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Sample records for randomized dose-ranging study

  1. Clonidine as an adjunct to intravenous regional anesthesia: A randomized, double-blind, placebo-controlled dose ranging study

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    Clarence S Ivie

    2011-01-01

    Full Text Available Background : The addition of clonidine to lidocaine intravenous regional anesthesia (IVRA has been previously reported to improve postoperative analgesia in patients undergoing upper extremity surgery. Our objective was to perform a dose ranging study in order to determine the optimal dose of clonidine used with lidocaine in IVRA. Design & Setting : We performed a double-blinded randomized placebo-controlled study with 60 patients scheduled for elective endoscopic carpal tunnel release under IVRA with 50 ml lidocaine 0.5%. University-affiliated outpatient surgery center. Data collected in operating rooms, recovery room, and by telephone after discharge from surgery center. Materials & Methods : Sixty adult ASA I or II patients undergoing outpatient endoscopic carpal tunnel release under intravenous regional anesthesia.Patients were randomized into five study groups receiving different doses of clonidine in addition to 50 ml 0.5% lidocaine in their IVRA. Group A received 0 mcg/kg, group B 0.25 mcg/kg, group C 0.5 mcg/kg, group D 1.0 mcg/kg and group E 1.5 mcg/kg of clonidine.Intraoperative fentanyl, recovery room pain scores, time to first postsurgical analgesic, total number of acetaminophen/codeine tablets consumed postsurgery, incidence of sedation, hypotension and bradycardia. Results & Conclusions : There was no benefit from any dose of clonidine compared to placebo. There were no clonidine-related side effects seen within the dose range studied. In short duration minor hand surgery, the addition of clonidine to lidocaine-based intravenous regional anesthesia provides no measurable benefit.

  2. A Randomized Dose-Ranging Study of Neuropeptide Y in Patients with Posttraumatic Stress Disorder.

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    Sayed, Sehrish; Van Dam, Nicholas T; Horn, Sarah R; Kautz, Marin M; Parides, Michael; Costi, Sara; Collins, Katherine A; Iacoviello, Brian; Iosifescu, Dan V; Mathé, Aleksander A; Southwick, Steven M; Feder, Adriana; Charney, Dennis S; Murrough, James W

    2018-01-01

    Anxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder. Twenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes. Twenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score. Our study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted. The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519). © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

  3. A randomized, double-blind, placebo-controlled, dose-ranging study using Genz-644470 and sevelamer carbonate in hyperphosphatemic chronic kidney disease patients on hemodialysis

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    Moustafa M

    2014-04-01

    Full Text Available Moustafa Moustafa,1 Lawrence Lehrner,2 Fahd Al-Saghir,3 Mark Smith,4 Sunita Goyal,5 Maureen Dillon,5 John Hunter,5 Randy Holmes-Farley5 1South Carolina Nephrology and Hypertension Center Inc., Orangeburg, SC, USA; 2Kidney Specialists of Southern Nevada, Las Vegas, NV, USA; 3Michigan Kidney Consultants, Pontiac, MI, USA; 4Kidney Care Associates, LLC, Augusta, GA, USA; 5Genzyme, a Sanofi company, Cambridge, MA, USA Background: Genz-644470 is a new, nonabsorbed phosphate binding polymer. In an in vitro competitive phosphate binding assay, Genz-644470 bound significantly more phosphate per gram than sevelamer. As a consequence, this clinical study evaluated the ability of Genz-644470 to lower serum phosphorus in patients on hemodialysis and compared serum phosphorus lowering of Genz-644470 with sevelamer carbonate and placebo. Because three different fixed doses of Genz-644470 and sevelamer carbonate were used, phosphate-lowering dose-responses of each agent were also analyzed. Methods: A randomized, double-blind, dose-ranging study was conducted. After a 2-week phosphate binder washout, 349 hyperphosphatemic (serum phosphorus >5.5 mg/dL hemodialysis patients were randomized to one of seven fixed-dose groups: placebo, Genz-644470 2.4 g/day, Genz-644470 4.8 g/day, Genz-644470 7.2 g/day, sevelamer carbonate 2.4 g/day, sevelamer carbonate 4.8 g/day, or sevelamer carbonate 7.2 g/day. Indicated total daily doses were administered in fixed divided doses three times a day with meals for 3 weeks. The change in serum phosphorus during the treatment period and its dose-response patterns were assessed. Results: Dose-dependent reductions in serum phosphorus were observed with both Genz-644470 and sevelamer carbonate. Serum phosphorus-lowering responses to fixed doses of sevelamer carbonate and Genz-644470 were enhanced in a roughly linear fashion with increasing doses over a threefold range after 3 weeks of treatment. Genz-644470 did not show any advantage in

  4. Phase 2 Randomized, Dose-Ranging Study of Oxymetazoline Cream for Treatment of Persistent Facial Erythema Associated With Rosacea.

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    DuBois, Janet; Dover, Jeffrey S; Jones, Terry M; Weiss, Robert A; Berk, David R; Ahluwalia, Gurpreet

    2018-03-01

    Rosacea is a chronic dermatologic condition with limited treatment options. This phase 2 study evaluated the optimal oxymetazoline dosing regimen in patients with moderate to severe persistent facial erythema of rosacea. Patients were randomly assigned to oxymetazoline cream, 0.5%, 1.0%, or 1.5%, or vehicle, administered once daily (QD) or twice daily (BID) for 28 consecutive days. The primary efficacy endpoint was the proportion of patients with ≥2-grade improvement from baseline on the Clinician Erythema Assessment (CEA) and the Subject Self-Assessment of erythema (SSA-1) on day 28. Safety assessments included treatment-emergent adverse events and dermal tolerability. A total of 356 patients were treated (mean age, 50.0 years; 80.1% female). The proportions of patients achieving the primary endpoint were significantly higher with oxymetazoline 0.5% QD (P=0.049), 1.0% QD (P=0.006), 1.5% QD (P=0.012), 1.0% BID (P=0.021), and 1.5% BID (P=0.006) versus their respective vehicles. For both QD and BID dosing, the efficacy of oxymetazoline 1.0% was greater than the 0.5% dose and comparable to the 1.5% dose. Safety and application-site tolerability were similar across groups. Short-term treatment period. Oxymetazoline 1.0% QD provided the optimal dosing regimen and was selected for evaluation in phase 3 clinical studies. J Drugs Dermatol. 2018;17(3):308-316.

  5. A phase 2a randomized, parallel group, dose-ranging study of molindone in children with attention-deficit/hyperactivity disorder and persistent, serious conduct problems.

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    Stocks, Jennifer Dugan; Taneja, Baldeo K; Baroldi, Paolo; Findling, Robert L

    2012-04-01

    To evaluate safety and tolerability of four doses of immediate-release molindone hydrochloride in children with attention-deficit/hyperactivity disorder (ADHD) and serious conduct problems. This open-label, parallel-group, dose-ranging, multicenter trial randomized children, aged 6-12 years, with ADHD and persistent, serious conduct problems to receive oral molindone thrice daily for 9-12 weeks in four treatment groups: Group 1-10 mg (5 mg if weight conduct problems. Secondary outcome measures included change in Nisonger Child Behavior Rating Form-Typical Intelligence Quotient (NCBRF-TIQ) Conduct Problem subscale scores, change in Clinical Global Impressions-Severity (CGI-S) and -Improvement (CGI-I) subscale scores from baseline to end point, and Swanson, Nolan, and Pelham rating scale-revised (SNAP-IV) ADHD-related subscale scores. The study randomized 78 children; 55 completed the study. Treatment with molindone was generally well tolerated, with no clinically meaningful changes in laboratory or physical examination findings. The most common treatment-related adverse events (AEs) included somnolence (n=9), weight increase (n=8), akathisia (n=4), sedation (n=4), and abdominal pain (n=4). Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). The incidence of AEs and treatment-related AEs increased with increasing dose. NCBRF-TIQ subscale scores improved in all four treatment groups, with 34%, 34%, 32%, and 55% decreases from baseline in groups 1, 2, 3, and 4, respectively. CGI-S and SNAP-IV scores improved over time in all treatment groups, and CGI-I scores improved to the greatest degree in group 4. Molindone at doses of 5-20 mg/day (children weighing <30 kg) and 20-40 mg (≥ 30 kg) was well tolerated, and preliminary efficacy results suggest that molindone produces dose-related behavioral improvements over 9-12 weeks. Additional double-blind, placebo-controlled trials are needed to further investigate molindone in this pediatric population.

  6. Analytical probabilistic proton dose calculation and range uncertainties

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    Bangert, M.; Hennig, P.; Oelfke, U.

    2014-03-01

    We introduce the concept of analytical probabilistic modeling (APM) to calculate the mean and the standard deviation of intensity-modulated proton dose distributions under the influence of range uncertainties in closed form. For APM, range uncertainties are modeled with a multivariate Normal distribution p(z) over the radiological depths z. A pencil beam algorithm that parameterizes the proton depth dose d(z) with a weighted superposition of ten Gaussians is used. Hence, the integrals ∫ dz p(z) d(z) and ∫ dz p(z) d(z)2 required for the calculation of the expected value and standard deviation of the dose remain analytically tractable and can be efficiently evaluated. The means μk, widths δk, and weights ωk of the Gaussian components parameterizing the depth dose curves are found with least squares fits for all available proton ranges. We observe less than 0.3% average deviation of the Gaussian parameterizations from the original proton depth dose curves. Consequently, APM yields high accuracy estimates for the expected value and standard deviation of intensity-modulated proton dose distributions for two dimensional test cases. APM can accommodate arbitrary correlation models and account for the different nature of random and systematic errors in fractionated radiation therapy. Beneficial applications of APM in robust planning are feasible.

  7. Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults

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    Sasai H

    2017-07-01

    Full Text Available Hiroyuki Sasai,1–3,* Keisuke Ueda,4,5,* Takehiko Tsujimoto,6,7 Hiroyuki Kobayashi,1 Chiaki Sanbongi,4 Shuji Ikegami,4 Yoshio Nakata1 1Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, 2Japan Society for the Promotion of Science, Chiyoda, Tokyo, 3Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, 4Food Science Research Laboratories, Meiji Co., Ltd., Odawara, Kanagawa, 5Graduate School of Comprehensive Human Sciences, 6Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 7Faculty of Human Sciences, Shimane University, Matsue, Shimane, Japan *These authors contributed equally to this work Objective: The objective of this study was to determine the effective dose of an amino acid mixture comprising arginine, alanine, and phenylalanine combined with physical activity promotion in reducing abdominal fat among overweight adults.Methods: A 12-week randomized, double-blind, placebo-controlled, dose-ranging, pilot trial was conducted in Mito, Japan, from January through April 2016, and the data were analyzed from May through November 2016. The study participants were 35 overweight adults, aged 20–64 years, with no regular exercise habit. Participants were randomly assigned to high-dose (3,000 mg/d, n=9, medium-dose (1,500 mg/d, n=9, low-dose (750 mg/d, n=8, or placebo (0 mg/d, n=9 groups, and the test beverage containing the amino acid mixture or placebo was administered for 12 weeks. All participants maintained a physically active lifestyle during the study period through monthly physical activity promotion sessions and smartphone-based self-monitoring with wearable trackers. Primary outcomes were changes in abdominal total, subcutaneous, and visceral fat areas, assessed by computed tomography.Results: Of the 35 enrolled participants, 32 completed the 12-week follow-up visit. The intention-to-treat analysis revealed that the changes in abdominal total fat

  8. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team.

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    Chaisson, R E; Benson, C A; Dube, M P; Heifets, L B; Korvick, J A; Elkin, S; Smith, T; Craft, J C; Sattler, F R

    1994-12-15

    To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). A randomized, double-blind, dose-ranging study. Outpatient clinics. 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. Median number of colony-forming units of M. avium complex per milliliter of blood. Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem.

  9. Influence of random setup error on dose distribution

    International Nuclear Information System (INIS)

    Zhai Zhenyu

    2008-01-01

    Objective: To investigate the influence of random setup error on dose distribution in radiotherapy and determine the margin from ITV to PTV. Methods: A random sample approach was used to simulate the fields position in target coordinate system. Cumulative effect of random setup error was the sum of dose distributions of all individual treatment fractions. Study of 100 cumulative effects might get shift sizes of 90% dose point position. Margins from ITV to PTV caused by random setup error were chosen by 95% probability. Spearman's correlation was used to analyze the influence of each factor. Results: The average shift sizes of 90% dose point position was 0.62, 1.84, 3.13, 4.78, 6.34 and 8.03 mm if random setup error was 1,2,3,4,5 and 6 mm,respectively. Univariate analysis showed the size of margin was associated only by the size of random setup error. Conclusions: Margin of ITV to PTV is 1.2 times random setup error for head-and-neck cancer and 1.5 times for thoracic and abdominal cancer. Field size, energy and target depth, unlike random setup error, have no relation with the size of the margin. (authors)

  10. Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.

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    Marcatto, Leiliane Rodrigues; Sacilotto, Luciana; Bueno, Carolina Tosin; Facin, Mirella; Strunz, Celia Maria Cassaro; Darrieux, Francisco Carlos Costa; Scanavacca, Maurício Ibrahim; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Santos, Paulo Caleb Junior Lima

    2016-11-17

    Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School. This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients. ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.

  11. The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies.

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    Zohar, S; Chevret, S

    2001-10-15

    The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials. In this paper we propose Bayesian stopping rules for the CRM, based on either posterior or predictive probability distributions that can be applied sequentially during the trial. These rules aim at early detection of either the mis-choice of dose range or a prefixed gain in the point estimate or accuracy of estimated probability of response associated with the MTD (or MED). They were compared through a simulation study under six situations that could represent the underlying unknown dose-response (either toxicity or failure) relationship, in terms of sample size, probability of correct selection and bias of the response probability associated to the MTD (or MED). Our results show that the stopping rules act correctly, with early stopping by using the two first rules based on the posterior distribution when the actual underlying dose-response relationship is far from that initially supposed, while the rules based on predictive gain functions provide a discontinuation of inclusions whatever the actual dose-response curve after 20 patients on average, that is, depending mostly on the accumulated data. The stopping rules were then applied to a data set from a dose-ranging phase II clinical trial aiming at estimating the MED dose of midazolam in the sedation of infants during cardiac catheterization. All these findings suggest the early use of the two first rules to detect a mis-choice of dose range, while they confirm the requirement of including at least 20 patients at the same dose to reach an accurate estimate of MTD (MED). A two-stage design is under study. Copyright 2001 John Wiley & Sons, Ltd.

  12. RETRACTED: Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomized, double-blind, placebo-controlled, dose-ranging study

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    MD Yoshitaka Fujii

    2004-07-01

    Fujii Y, Tanaka H, Somekawa Y. Treatment of postoperative emetic symptoms with granisetron in women undergoing abdominal hysterectomy: a randomised, double-blind, placebo-controlled, dose-ranging study. Current Therapeutic Research 2004;65:321–9. https://www.sciencedirect.com/science/article/pii/S0011393X04800018

  13. Dose Titration of Pregabalin in Patients with Painful Diabetic Peripheral Neuropathy: Simulation Based on Observational Study Patients Enriched with Data from Randomized Studies.

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    Alexander, Joe; Edwards, Roger A; Manca, Luigi; Grugni, Roberto; Bonfanti, Gianluca; Emir, Birol; Whalen, Edward; Watt, Stephen; Parsons, Bruce

    2018-03-01

    Achieving a therapeutic response to pregabalin in patients with painful diabetic peripheral neuropathy (pDPN) requires adequate upward dose titration. Our goal was to identify relationships between titration and response to pregabalin in patients with pDPN. Data were integrated from nine randomized, placebo-controlled clinical trials as well as one 6-week open-label observational study conducted by 5808 physicians (2642 patients with pDPN) in standard outpatient settings in Germany. These studies evaluated pregabalin for treatment of pDPN. Using these data, we examined "what if" scenarios using a microsimulation platform that integrates data from randomized and observational sources as well as autoregressive-moving-average with exogenous inputs models that predict pain outcomes, taking into account weekly changes in pain, sleep interference, dose, and other patient characteristics that were unchanging. Final pain levels were significantly different depending on dose changes (P titration regardless of baseline pain severity. Altogether, 78.5% of patients with pDPN had 0-1 dose change, and 15.2% had ≥ 2 dose changes. Simulation demonstrated that the 4.8% of inadequately titrated patients who did not improve/very much improve their pain levels would have benefited from ≥ 2 dose changes. Patient satisfaction with tolerability (range 90.3-96.2%) was similar, regardless of baseline pain severity, number of titrations, or extent of improvement, suggesting that tolerability did not influence treatment response patterns. Upward dose titration reduced pain in patients with pDPN who actually received it. Simulation also predicted pain reduction in an inadequately titrated nonresponder subgroup of patients had they actually received adequate titration. The decision not to uptitrate must have been driven by factors other than tolerability. Pfizer, Inc.

  14. Re: A Randomized Double-Blind Placebo-Controlled Phase 2 Dose-Ranging Study of OnabotulinumtoxinA in Men with Benign Prostatic Hyperplasia

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    Ozan Bozkurt

    2015-09-01

    Full Text Available Botulinum toxin is a neurotoxin inhibiting the release of acetylcholine and is used in various fields of medicine. Recently, it has been proposed as an alternative minimally invasive treatment modality for patients unresponsive to oral therapies. The present study is the largest prospective, randomized and placebo-controlled study investigating the efficacy and safety of different onabotulinumtoxinA (BTX-A doses in men with moderate to severe lower urinary tract symptoms (LUTS associated with benign prostatic hyperplasia (BPH. 100 U, 200 U and 300 U BTX-A doses via transperineal or transrectal route were injected within the transition zone of each lateral lobe. 69.7% of patients (115 of 380 completed the 72-week study. The authors reported significant improvement for all treatment arms including placebo from weeks 2 through 72 including the primary time point of week 12. There were no statistically significant differences between BTX-A groups and placebo in terms of treatment efficacy described as International Prostate Symptom Score (IPSS reduction, improvement of peak urinary flow rate (Qmax and post-void residual volume (PVR and prostate volume reduction at any time point throughout the study. Only in a subgroup of patients, including previous alpha-blocker users, 200 U BTX-A worked better than placebo in terms of IPSS reduction. Adverse event rates were similar between all treatment arms. The unexpected pronounced placebo response in the present study raises question marks in minds regarding the use of BTX-A as an alternative treatment option. These conflicting results suggest that intraprostatic BTX-A injection is still experimental and further trials are required.

  15. Study of Optimal Replacement of Thyroxine in the ElDerly (SORTED): protocol for a mixed methods feasibility study to assess the clinical utility of lower dose thyroxine in elderly hypothyroid patients: study protocol for a randomized controlled trial.

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    Wilkes, Scott; Pearce, Simon; Ryan, Vicky; Rapley, Tim; Ingoe, Lorna; Razvi, Salman

    2013-03-22

    The population of the UK is ageing. There is compelling evidence that thyroid stimulating hormone distribution levels increase with age. Currently, in UK clinical practice elderly hypothyroid patients are treated with levothyroxine to lower their thyroid stimulating hormone levels to a standard non-age-related range. Evidence suggests that mortality is negatively associated with thyroid stimulating hormone levels. We report the protocol of a feasibility study working towards a full-scale randomized controlled trial to test whether lower dose levothyroxine has beneficial cardiovascular outcomes in the oldest old. SORTED is a mixed methods study with three components: SORTED A: A feasibility study of a dual-center single-blinded randomized controlled trial of elderly hypothyroid patients currently treated with levothyroxine. Patients will be recruited from 20 general practices and two hospital trust endocrine units in Northumberland, Tyne and Wear. Target recruitment of 50 elderly hypothyroid patients currently treated with levothyroxine, identified in both primary and secondary care settings. Reduced dose of levothyroxine to achieve an elevated serum thyroid stimulating hormone (target range 4.1 to 8.0 mU/L) versus standard levothyroxine replacement (target range 0.4 to 4.0 mU/L). Using random permuted blocks, in a ratio of 1:1, randomization will be carried out by Newcastle Clinical Trials Unit. Study feasibility (recruitment and retention rates and medication compliance), acceptability of the trial design, assessment of mobility and falls risk, and change in cardiovascular risk factors. Qualitative study using in-depth interviews to understand patients' willingness to take part in a randomized controlled trial and participants' experience of the intervention. Retrospective cohort study of 400 treated hypothyroid patients aged 80 years or over registered in 2008 in primary care practices, studying their 4-year cardiovascular outcomes to inform the power of SORTED

  16. Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

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    Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick

    2015-01-01

    Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

  17. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study.

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    Lublin, Fred D; Bowen, James D; Huddlestone, John; Kremenchutzky, Marcelo; Carpenter, Adam; Corboy, John R; Freedman, Mark S; Krupp, Lauren; Paulo, Corri; Hariri, Robert J; Fischkoff, Steven A

    2014-11-01

    Infusion of PDA-001, a preparation of mesenchymal-like cells derived from full-term human placenta, is a new approach in the treatment of patients with multiple sclerosis. This safety study aimed to rule out the possibility of paradoxical exacerbation of disease activity by PDA-001 in patients with multiple sclerosis. This was a phase 1b, multicenter, randomized, double-blind, placebo-controlled, 2-dose ranging study including patients with relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis. The study was conducted at 6 sites in the United States and 2 sites in Canada. Patients were randomized 3:1 to receive 2 low-dose infusions of PDA-001 (150×10(6) cells) or placebo, given 1 week apart. After completing this cohort, subsequent patients received high-dose PDA-001 (600×10(6) cells) or placebo. Monthly brain magnetic resonance imaging scans were performed. The primary end point was ruling out the possibility of paradoxical worsening of MS disease activity. This was monitored using Cutter׳s rule (≥5 new gadolinium lesions on 2 consecutive scans) by brain magnetic resonance imaging on a monthly basis for six months and also the frequency of multiple sclerosis relapse. Ten patients with relapsing-remitting multiple sclerosis and 6 with secondary progressive multiple sclerosis were randomly assigned to treatment: 6 to low-dose PDA-001, 6 to high-dose PDA-001, and 4 to placebo. No patient met Cutter׳s rule. One patient receiving high-dose PDA-001 had an increase in T2 and gadolinium lesions and in Expanded Disability Status Scale score during a multiple sclerosis flare 5 months after receiving PDA-001. No other patient had an increase in Expanded Disability Status Scale score>0.5, and most had stable or decreasing Expanded Disability Status Scale scores. With high-dose PDA-001, 1 patient experienced a grade 1 anaphylactoid reaction and 1 had grade 2 superficial thrombophlebitis. Other adverse events were mild to moderate and included

  18. Personalized versus standardized dosing strategies for the treatment of childhood amblyopia: study protocol for a randomized controlled trial.

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    Moseley, Merrick J; Wallace, Michael P; Stephens, David A; Fielder, Alistair R; Smith, Laura C; Stewart, Catherine E

    2015-04-25

    Amblyopia is the commonest visual disorder of childhood in Western societies, affecting, predominantly, spatial visual function. Treatment typically requires a period of refractive correction ('optical treatment') followed by occlusion: covering the nonamblyopic eye with a fabric patch for varying daily durations. Recent studies have provided insight into the optimal amount of patching ('dose'), leading to the adoption of standardized dosing strategies, which, though an advance on previous ad-hoc regimens, take little account of individual patient characteristics. This trial compares the effectiveness of a standardized dosing strategy (that is, a fixed daily occlusion dose based on disease severity) with a personalized dosing strategy (derived from known treatment dose-response functions), in which an initially prescribed occlusion dose is modulated, in a systematic manner, dependent on treatment compliance. A total of 120 children aged between 3 and 8 years of age diagnosed with amblyopia in association with either anisometropia or strabismus, or both, will be randomized to receive either a standardized or a personalized occlusion dose regimen. To avoid confounding by the known benefits of refractive correction, participants will not be randomized until they have completed an optical treatment phase. The primary study objective is to determine whether, at trial endpoint, participants receiving a personalized dosing strategy require fewer hours of occlusion than those in receipt of a standardized dosing strategy. Secondary objectives are to quantify the relationship between observed changes in visual acuity (logMAR, logarithm of the Minimum Angle of Resolution) with age, amblyopia type, and severity of amblyopic visual acuity deficit. This is the first randomized controlled trial of occlusion therapy for amblyopia to compare a treatment arm representative of current best practice with an arm representative of an entirely novel treatment regimen based on statistical

  19. A randomized phase II dose-response exercise trial among colon cancer survivors: Purpose, study design, methods, and recruitment results.

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    Brown, Justin C; Troxel, Andrea B; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S; Rickels, Michael R; Rhim, Andrew D; Rustgi, Anil K; Courneya, Kerry S; Schmitz, Kathryn H

    2016-03-01

    Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the courage trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. The primary objective of the courage trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·week(-1)) and high-dose (300 min·week(-1)) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (Pclinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation

    Directory of Open Access Journals (Sweden)

    Farrauto Leonardo

    2011-06-01

    Full Text Available Abstract Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels. Methods In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD was measured at baseline, discharge from acute care (approximately 4-weeks, and 3-months. Results Sixty-five patients were enrolled in the study (44% male. An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15 and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09, respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L, and 44% of the 100,000 group. Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D. Trial registration Clinical

  1. Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

    Science.gov (United States)

    Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

    2015-10-01

    As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

  2. Brownian motion in short range random potentials

    International Nuclear Information System (INIS)

    Romero, A.H.; Romero, A.H.; Sancho, J.M.

    1998-01-01

    A numerical study of Brownian motion of noninteracting particles in random potentials is presented. The dynamics are modeled by Langevin equations in the high friction limit. The random potentials are Gaussian distributed and short ranged. The simulations are performed in one and two dimensions. Different dynamical regimes are found and explained. Effective subdiffusive exponents are obtained and commented on. copyright 1998 The American Physical Society

  3. A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone.

    Science.gov (United States)

    Piirainen, Annika; Kokki, Hannu; Immonen, Satu; Eskelinen, Matti; Häkkinen, Merja R; Hautajärvi, Heidi; Kokki, Merja

    2015-12-01

    Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC). Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was dexketoprofen. At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration. In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.

  4. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Science.gov (United States)

    van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

    2011-01-01

    Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

  5. Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

    Science.gov (United States)

    Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

    2016-01-01

    Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose

  6. Determination of dose ranges of gamma rays to induce specific changes in three ornamental species

    International Nuclear Information System (INIS)

    Gonzalez J, J.

    2011-11-01

    In order to confirming the possibility of to settle a dose range that takes place directly and not at random, a specific effect independently of the species that is were produced several similar organisms to three ornamental species took place via meristems cultivation: Petunia hybrid, Impatiens walleriana and Sprekelia formosissima, same that were irradiated in an irradiator Gamma cell 220, to different dose: 0, 3.5, 5.0, 7.5, 10, 12.5, 15, 17.5 and 20 Gy. Later on, of the plants treated via in vitro the subsequent generations were obtained until the M 4 . To determine the DL 50 and the possible good doses, the survival parameters, development, morphogenesis and height were evaluated during 8 weeks, interpreting based on them, the possible physiologic and genetic alterations induced by the radiation. The established DL 50 were: 7.5 Gy (Petunia), 19.0 Gy (Impatiens) and 12.0 Gy (Sprekelia). Based on the DL 50 of each species, a range of coincident dose settled down that produces a similar effect in the three species: a range of DL 23 to the DL 50 induces and alteration in the cytokinins production affecting directly in the leaves number, buds and plants taken place by meristem, also a range of DL 32 - DL 50 impacts in the auxins production altering to the radicule system. However, when being superimposed the dose is considered that the investigation should continue. (Author)

  7. Effective dose range for dental cone beam computed tomography scanners

    International Nuclear Information System (INIS)

    Pauwels, Ruben; Beinsberger, Jilke; Collaert, Bruno; Theodorakou, Chrysoula; Rogers, Jessica; Walker, Anne; Cockmartin, Lesley; Bosmans, Hilde; Jacobs, Reinhilde; Bogaerts, Ria; Horner, Keith

    2012-01-01

    Objective: To estimate the absorbed organ dose and effective dose for a wide range of cone beam computed tomography scanners, using different exposure protocols and geometries. Materials and methods: Two Alderson Radiation Therapy anthropomorphic phantoms were loaded with LiF detectors (TLD-100 and TLD-100H) which were evenly distributed throughout the head and neck, covering all radiosensitive organs. Measurements were performed on 14 CBCT devices: 3D Accuitomo 170, Galileos Comfort, i-CAT Next Generation, Iluma Elite, Kodak 9000 3D, Kodak 9500, NewTom VG, NewTom VGi, Pax-Uni3D, Picasso Trio, ProMax 3D, Scanora 3D, SkyView, Veraviewepocs 3D. Effective dose was calculated using the ICRP 103 (2007) tissue weighting factors. Results: Effective dose ranged between 19 and 368 μSv. The largest contributions to the effective dose were from the remainder tissues (37%), salivary glands (24%), and thyroid gland (21%). For all organs, there was a wide range of measured values apparent, due to differences in exposure factors, diameter and height of the primary beam, and positioning of the beam relative to the radiosensitive organs. Conclusions: The effective dose for different CBCT devices showed a 20-fold range. The results show that a distinction is needed between small-, medium-, and large-field CBCT scanners and protocols, as they are applied to different indication groups, the dose received being strongly related to field size. Furthermore, the dose should always be considered relative to technical and diagnostic image quality, seeing that image quality requirements also differ for patient groups. The results from the current study indicate that the optimisation of dose should be performed by an appropriate selection of exposure parameters and field size, depending on the diagnostic requirements.

  8. Comparison of microdose flare-up and antagonist multiple-dose protocols for poor-responder patients: a randomized study.

    Science.gov (United States)

    Demirol, Aygul; Gurgan, Timur

    2009-08-01

    To compare the efficacy of the microdose flare-up and multiple-dose antagonist protocols for poor-responder patients in intracytoplasmic sperm injection-ET cycles. A randomized, prospective study. Center for assisted reproductive technology in Turkey. Ninety patients with poor ovarian response in a minimum of two previous IVF cycles. All women were prospectively randomized into two groups by computer-assisted randomization. The patients in group 1 were stimulated according to the microdose flare-up protocol (n = 45), while the patients in group 2 were stimulated according to antagonist multiple-dose protocol (n = 45). The mean number of mature oocytes retrieved was the primary outcome measure, and fertilization rate, implantation rate per embryo, and clinical pregnancy rates were secondary outcome measures. The mean age of the women, the mean duration of infertility, basal FSH level, and the number of previous IVF cycles were similar in both groups. The total gonadotropin dose used was significantly higher in group 2, while the number of oocytes retrieved was significantly greater in group 1. Although the fertilization and clinical pregnancy rates were nonsignificantly higher in group 1 compared with group 2, the implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (22% vs. 11%). The microdose flare-up protocol seems to have a better outcome in poor-responder patients, with a significantly higher mean number of mature oocytes retrieved and higher implantation rate.

  9. Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

    2015-08-20

    Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

  10. Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

    Directory of Open Access Journals (Sweden)

    Pierre van Damme

    Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

  11. European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

    Science.gov (United States)

    Landolfi, R; Marchioli, R

    1997-01-01

    Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

  12. Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

    Science.gov (United States)

    Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

    2010-08-01

    The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

  13. Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

    Science.gov (United States)

    Solish, Nowell; Rivers, Jason K; Humphrey, Shannon; Muhn, Channy; Somogyi, Chris; Lei, Xiaofang; Bhogal, Meetu; Caulkins, Carrie

    2016-03-01

    Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

  14. Randomized Trial of 2 Versus 1 Dose of Measles Vaccine

    DEFF Research Database (Denmark)

    Brønd, Marie; Martins, Cesario L; Byberg, Stine

    2018-01-01

    Background: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investig...

  15. Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Carcas Antonio J

    2012-12-01

    Full Text Available Abstract Background Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE in patients with venous thromboembolism (VTE. Methods and design This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1 will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1 Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2 Time from the start of oral anticoagulant treatment

  16. Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Carcas, Antonio J; Borobia, Alberto M; Velasco, Marta; Abad-Santos, Francisco; Díaz, Manuel Quintana; Fernández-Capitán, Carmen; Ruiz-Giménez, Nuria; Madridano, Olga; Sillero, Pilar Llamas

    2012-12-13

    Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic

  17. Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: a randomized controlled study of benazepril and losartan in chronic renal insufficiency.

    Science.gov (United States)

    Hou, Fan Fan; Xie, Di; Zhang, Xun; Chen, Ping Yan; Zhang, Wei Ru; Liang, Min; Guo, Zhi Jian; Jiang, Jian Ping

    2007-06-01

    The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.

  18. Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial.

    Science.gov (United States)

    Cakir, F B; Yapar, O; Canpolat, C; Akalin, F; Berrak, S G

    2012-10-01

    Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics. In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 μg kg(-1) dose(-1) of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24 h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24 h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion. A total of 16 patients (median 8.7 years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p = 0.000) in patients that had granisetron at 40 μg/kg and PR interval was shortened in patients that had granisetron at 10 μg/kg dose (p = 0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24 h after granisetron infusion. As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 μg kg(-1) dose(-1) causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 μg kg(-1) dose(-1). However, our results should be supported by prospective randomized studies with larger samples of patient groups.

  19. A thermoluminescence study of mineral silicates extracted from herbs in the dose range 0.5–5 Gy

    International Nuclear Information System (INIS)

    Della Monaca, Sara; Fattibene, Paola; Bortolin, Emanuela

    2013-01-01

    The presence of silicates in many personal objects suggests their potential use at low dose as fortuitous dosimeter in an accidental radiological exposure, when conventional dosimetry is not available. The goal of the present work is the dosimetric characterization of mineral silicates extracted from the plant Hibiscus Sabdariffa L, known as Jamaica flower, in the dose range 0.5–5 Gy. By studying the radiation-induced signal in time, the temperature integration region between 210 °C and 250 °C was found to be the most stable and also reduced the effects of thermal fading in the dose reconstruction process; the dose response curve was linear between 0.5 Gy and 5 Gy. By checking the change in sensitivity after repeated exposures to ionizing radiations and to high temperature heating, no variation in the glow curve shape or peak intensities were detected. To eliminate a pre-existing background signal, all the characterization measurements were performed with aliquots “annealed” by a preliminary readout of the TL. - Highlights: • Glow curves change in shape and intensity just in the first 3 days after irradiation. • The dose response is linear in the dose range 0.5–5 Gy. • The curve shape or intensity don't change after repeated exposures and heatings. • Encouraging results were obtained in the dose recovery test

  20. The effectiveness of low-dose and high-dose tranexamic acid in posterior lumbar interbody fusion: a double-blinded, placebo-controlled randomized study.

    Science.gov (United States)

    Kim, Ki-Tack; Kim, Cheung-Kue; Kim, Yong-Chan; Juh, Hyung-Suk; Kim, Hyo-Jong; Kim, Hyeon-Soo; Hong, Se Jung; Hey, Hwee Weng Dennis

    2017-11-01

    Tranexamic acid is a proven drug used for reduction of intraoperative blood loss in spinal surgery. However, optimal dosing considering risk/benefits is not well established owing to the heterogeneity in patient selection and surgical procedures of previous studies. This study aimed to evaluate the effectiveness and safety of various tranexamic acid regimens in reducing perioperative blood loss in single-level posterior lumbar interbody fusion (PLIF). Patients were randomly grouped into three different interventions: low-dose tranexamic acid (LD), high-dose tranexamic acid (HD), and placebo-controlled (PC) groups. The HD and LD groups received 10 and 5 mg/kg of bolus loading dose and 2 and 1 mg/kg of continuous infusion until 5 h after surgery, respectively. Data on patient demographics and preoperative and 24-h postoperative laboratory values were collected. Outcome parameters include intraoperative blood loss, 24-h postoperative blood loss, and blood loss during removal of the last drain. Seventy-two patients (mean age 63.3 ± 7.6 years) showed similar baseline characteristics. Intraoperatively, blood loss was reduced by the administration of tranexamic acid (P = 0.04), contributed predominantly by a difference between the LD and HD groups (123 mL; P tranexamic acid use were noted. Tranexamic acid administration for single-level PLIF was effective and safe in reducing perioperative blood loss in a dose-dependent manner. An HD regimen comprising 10 mg/kg of bolus loading dose and 2 mg/kg/h of continuous infusion is recommended. Level 1 study according to Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.

  1. High-temperature absorbed dose measurements in the megagray range

    International Nuclear Information System (INIS)

    Balian, P.; Ardonceau, J.; Zuppiroli, L.

    1988-01-01

    Organic conductors of the tetraselenotetracene family have been tested as ''high-temperature'' absorbed dose dosimeters. They were heated up to 120 0 C and irradiated at this temperature with 1-MeV electrons in order to simulate, in a short time, a much longer γ-ray irradiation. The electric resistance increase of the crystal can be considered a good measurement of the absorbed dose in the range 10 6 Gy to a few 10 8 Gy and presumably one order of magnitude more. This dosimeter also permits on-line (in-situ) measurements of the absorbed dose without removing the sensor from the irradiation site. The respective advantages of organic and inorganic dosimeters at these temperature and dose ranges are also discussed. In this connection, we outline new, but negative, results concerning the possible use of silica as a high-temperature, high-dose dosimeter. (author)

  2. Low-dose intravenous alpha-2 agonists as adjuvants to spinal levobupivacaine: A randomized study

    Directory of Open Access Journals (Sweden)

    Pranav Jetley

    2017-01-01

    Full Text Available Background: Alpha-2 agonists have been used with spinal anesthesia for anxiolysis, analgesia, and hypnosis and for postoperative pain relief. These beneficial effects may, however, be offset by their propensity to prolong the duration of motor block and adversely affect hemodynamics when used in higher doses. This study compares the effects of low-dose premedication with intravenous (IV dexmedetomidine and IV clonidine with placebo, on spinal blockade duration, analgesia, and sedation with intrathecal levobupivacaine. Materials and Methods: In this prospective, randomized, double-blinded, placebo-controlled study, ninety American Society of Anesthesiologists Status I and II patients were randomly allocated into three groups: Group A (control received 10 ml normal saline IV, Group B received IV dexmedetomidine 0.6 μg/kg, and Group C received IV clonidine 1.2 μg/kg over 10 min, before spinal anesthesia with 0.5% levobupivacaine. Hemodynamics, total duration of analgesia, onset and duration of sensory and motor block, visual analog scale score, and sedation score were assessed. Complications, if any, were noted. Results: The level of sensory block achieved was higher with dexmedetomidine (T4.2 ± 0.8 and clonidine (T4.4 ± 0.7 as compared to control (T5.1 ± 0.7; P< 0.001. Time to two segment regression was greater with dexmedetomidine (146.5 ± 12.5 min and clonidine (138.9 ± 17.4 min compared to control (90.1 ± 9.4; P< 0.001. Dexmedetomidine maximally prolonged the duration to first patient request for analgesia (245.2 ± 26.8 min, followed by clonidine (175.3 ± 20.1 min, P< 0.001 and control (121.3 ± 16.1 min, P< 0.001. The duration of motor block was similar in all three groups. Incidence of bradycardia was significantly greater with both dexmedetomidine and clonidine compared to saline (P < 0.05. Conclusion: Premedication with low-dose IV dexmedetomidine and clonidine prolonged sensory blockade and analgesic duration and provided

  3. Finite-range Coulomb gas models of banded random matrices and quantum kicked rotors.

    Science.gov (United States)

    Pandey, Akhilesh; Kumar, Avanish; Puri, Sanjay

    2017-11-01

    Dyson demonstrated an equivalence between infinite-range Coulomb gas models and classical random matrix ensembles for the study of eigenvalue statistics. We introduce finite-range Coulomb gas (FRCG) models via a Brownian matrix process, and study them analytically and by Monte Carlo simulations. These models yield new universality classes, and provide a theoretical framework for the study of banded random matrices (BRMs) and quantum kicked rotors (QKRs). We demonstrate that, for a BRM of bandwidth b and a QKR of chaos parameter α, the appropriate FRCG model has the effective range d=b^{2}/N=α^{2}/N, for large N matrix dimensionality. As d increases, there is a transition from Poisson to classical random matrix statistics.

  4. A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

    Science.gov (United States)

    Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

    2008-05-01

    To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.

  5. Feasibility of RACT for 3D dose measurement and range verification in a water phantom

    Energy Technology Data Exchange (ETDEWEB)

    Alsanea, Fahed [School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana 47907-2051 (United States); Moskvin, Vadim [Radiation Oncology, Indiana University School of Medicine, 535 Barnhill Drive, RT 041, Indianapolis, Indiana 46202-5289 (United States); Stantz, Keith M., E-mail: kstantz@purdue.edu [School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana 47907-2051 and Radiology and Imaging Sciences, Indiana University School of Medicine, 950 West Walnut Street, Indianapolis, Indiana 46202-5289 (United States)

    2015-02-15

    Purpose: The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Methods: Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). Results: The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error < 150 μm) for a 1 cGy Bragg peak dose, where the integral dose within the Bragg peak was measured to within 2%. For existing hydrophone detector sensitivities, a Bragg peak dose of 1.6 cGy is possible. Conclusions: This study demonstrates that computed tomographic scanner based on ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly

  6. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum.

    Science.gov (United States)

    Hale, Braden R; Owusu-Agyei, Seth; Fryauff, David J; Koram, Kwadwo A; Adjuik, Martin; Oduro, Abraham R; Prescott, W Roy; Baird, J Kevin; Nkrumah, Francis; Ritchie, Thomas L; Franke, Eileen D; Binka, Fred N; Horton, John; Hoffman, Stephen L

    2003-03-01

    Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, double-blind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%-43%); for 50 mg/week, 84% (95% CI, 75%-91%); for 100 mg/week, 87% (95% CI, 78%-93%); and for 200 mg/week, 86% (95% CI, 76%-92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%-93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population.

  7. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial

    NARCIS (Netherlands)

    Roos, Annemieke; Linn-Rasker, Suzanne P.; van Domburg, Ron T.; Tijssen, Jan P.; Berghout, Arie

    2005-01-01

    BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively. METHODS: We conducted a prospective, randomized,

  8. TLD personnel monitoring dose estimation- extending the upper limit of the dose range

    International Nuclear Information System (INIS)

    Popli, K.L.; Sathian, Deepa; Divakaran, T.; Massand, O.P.

    2001-01-01

    TLD personnel monitoring was introduced in the year 1975 in India and at present nearly 41,000 radiation workers are being monitored by 13 monitoring laboratories all over India. The BARC- TLD being used for personnel monitoring is based on CaSO 4 :Dy embedded in PTFE and semi-automatic TL reader using hot N 2 Gas for heating the dosimeters. This reader has the range to measure γ dose from ten μSv to 3 μSv and x-ray dose form 1 μ Sv to 0.3 Sv due to the higher sensitivity of CaSO 4 : Dy to lower energy photons (20keV-50 keV) generated by diagnostic x-ray units. The x-ray radiation workers are at present nearly 35% of the total radiation workers monitored and this number is expected to grow as more and more number of x-ray workers are covered under this service. The upper limit of the x-ray dose range of the instrument is 0.3 Sv, whereas in the past one year it has been observed that at least 25% of the total overexposures reported in case of x-ray workers have recorded the dose more than 0.3 Sv. This paper presents the technique developed to extend the upper limit of the range from 0.3 Sv to 1 Sv for x-rays and 10 Sv for γ rays

  9. The influence of patient positioning uncertainties in proton radiotherapy on proton range and dose distributions

    Energy Technology Data Exchange (ETDEWEB)

    Liebl, Jakob, E-mail: jakob.liebl@medaustron.at [EBG MedAustron GmbH, 2700 Wiener Neustadt (Austria); Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Department of Therapeutic Radiology and Oncology, Medical University of Graz, 8036 Graz (Austria); Paganetti, Harald; Zhu, Mingyao; Winey, Brian A. [Francis H. Burr Proton Therapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

    2014-09-15

    Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: Thirty-eight clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50%- and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs), and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: The authors identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 and 5.8 mm for the 90%-dose falloff position, respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. For target volumes TCP decreases by more than 10% (absolute) occurred in less than 2.2% of the considered treatment scenarios for anatomy-based patient positioning and were nonexistent for fiducial-based patient positioning. EUD changes for target volumes were up to 35% (anatomy-based positioning) and 16% (fiducial-based positioning). Conclusions: The influence of patient positioning uncertainties on proton range in therapy of small lesions

  10. Bimonthly 24 h infusion of high-dose 5-fluorouracil vs EAP regimen in patients with advanced gastric cancer. A randomized phase II study.

    Science.gov (United States)

    Popov, I P; Jelić, S B; Krivokapić, Z V; Jezdić, S D; Pesko, P M; Micev, M T; Babić, D R

    2008-01-01

    To investigate the activity and toxicity of high dose (HD) infusional 5-FU in comparison to EAP regimen as first-line chemotherapy in patients with advanced gastric cancer. Histologically confirmed measurable advanced gastric cancer, age EAP arm: doxorubicin (40 mg/m(2)), etoposide (360 mg/m(2)), and cisplatin (80 mg/m(2)) every 28 d; HD 5-FU arm: 5-FU 2.6 g/m(2) 24 h infusion, biweekly. Sixty patients were randomized. Patient characteristics (arms EAP/HD 5-FU): Median age 57/55 yr, median PS 1/1, LAD (patients) 3/8, M1 (patients) 27/22. Median number of cycles (range): EAP arm 4 (2-8), HD 5-FU arm 2 (1-8). Worst toxicity per cycle (grade 3 and 4 in%): Neutropenia 20/3, thrombocytopenia 9/0, anemia 9/13, diarrhea 3/10, nausea 17/7, vomiting 10/0 for EAP and HD 5-FU arms, respectively. All patients were eligible for response in both arms. Confirmed response rate (95%CI): EAP arm 34% [16-50%]/HD 5-FU arm 10% (0-21%), no change: 46/40%, progression of disease: 20/50, respectively. Overall survival (range): EAP arm A 7 mo [3-27], HD 5-FU arm 6 mo (4-25). Infusional HD 5-FU showed a low incidence of severe toxicity. But given the low efficacy of 5-FU in the dosage we applied in the study, it cannot be recommended as a single treatment for further studies. Assessment of higher dose intensity and/or dose density of 5-FU, with introduction of other active drugs in combination, could be an option for further studies.

  11. Ease of intubation: A randomized, double-blind study to compare two doses of rocuronium bromide for endotracheal intubation.

    Science.gov (United States)

    Shukla, Aparna; Misra, Shilpi

    2016-01-01

    Clinical need for a nondepolarizing agent with a rapid onset time and a brief duration of action has led to the development of rocuronium bromide. The aim of this study was to evaluate optimal dose of rocuronium bromide for intubation and to compare the onset time, duration of action, intubating conditions, and hemodynamic effects of two doses of rocuronium bromide. A prospective, randomized, double-blind study. All the patients were divided in a randomized, double-blind fashion into two groups of twenty patients each. Group I patients received rocuronium bromide 0.6 mg/kg intravenously and intubated at 60 s, Group II patients received rocuronium bromide 0.9 mg/kg and intubated at 60 s. The neuromuscular block was assessed using single twitch stimulation of 0.1 Hz at adductor pollicis muscle of hand at every 10 s. The results were compiled and analyzed statistically using Chi-square test for qualitative data and Student's t -test for quantitative data. Time of onset was significantly shorter ( P Rocuronium bromide 0.9 mg/kg is a safer alternative to rocuronium bromide 0.6 mg/kg for endotracheal intubation with shorter time of onset and better intubating conditions.

  12. Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.

    Science.gov (United States)

    Scallion, Ralph; Moore, Keith A

    2009-10-01

    Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID. The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg. In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day. Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions

  13. Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

    Science.gov (United States)

    Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

    2016-01-01

    The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

  14. Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

    Science.gov (United States)

    Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

    2014-01-01

    Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

  15. A single dose, randomized, open-label, cross-over bioequivalence study of sildenafil citrate tablets in healthy Chinese volunteers
.

    Science.gov (United States)

    Li, Dai; Wang, Yu-Lu; Xu, Su-Mei; Li, Dan; Li, Xiao-Min; Pan, Jing; Xu, Ping-Sheng

    2017-02-01

    The present study was designed to evaluate the bioequivalence of a newly developed sildenafil citrate tablet 50 mg (Jinge®, Test) and a marketed counterpart (Viagra®, 100 mg, Reference) in healthy adult male Chinese volunteers. This single-dose, randomized, open-label, four-period, and two-treatment self-crossover study included two parts: fasting and postprandial studies. In each part of the study, the subjects were randomly assigned to receive test or reference products (100 mg sildenafil) in a 1 : 1 ratio, and then received the alternative products, following a 1-week washout period. Plasma sildenafil concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Tolerability was assessed during the entire study period. 32 healthy volunteers (aged 19 - 30) were enrolled in the study; 31 volunteers completed the fasting study, while 32 volunteers completed the postprandial study. The test formulation was bioequivalent to the marketed formulation as the 90% CIs for the ratio of geometric means of Cmax (fasting: 98.79 - 119.61%; fed: 94.47 - 119.65%), AUClast (fasting: 98.70 - 109.71%; fed: 96.39 - 112.89%), and AUC∞ (fasting: 98.45 - 108.87%; fed: 96.36 - 112.74%) were within equivalence limits (80 - 125%) under both fasting and postprandial conditions. When sildenafil was given with high-fat meals, mean Cmax was reduced by 23%, and median tmax ranged from 0.75 to 1.50 hours (p ≤ 0.05). However, both AUClast and AUC∞ were comparable between fasting and postprandial conditions. No serious adverse events were found among the subjects. This study confirmed that test and reference sildenafil citrate tablets were bioequivalent under fasting and postprandial conditions.
.

  16. Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty A randomized, double-blind, placebo-controlled, dose-finding study

    DEFF Research Database (Denmark)

    Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg

    2015-01-01

    (1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery......Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized......, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache...

  17. Wide-range neutron dose determination with CR-39

    International Nuclear Information System (INIS)

    Arneja, A.R.; Waker, A.J.

    1995-01-01

    Optical density measurements of CR-30 irradiated with 252 Cf neutrons and chemically etched with 6.5 N KOH solution have been used to determine neutron absorbed doses between 0.1 and 10 Gy. Optimum etching conditions will depend upon the absorbed dose. Since it is not always possible to know the range of absorbed dose on a CR-39 dosemeter collected from personnel and area monitor stations in a criticality accident situation, a three-step two-hour chemical etch at 60 o C has been found to be appropriate. If after a total of six hours of chemical etching the optical density is found to be below 0.04 for 500 nm light (transmission > 90%) then further treatment in the form of electrochemical etching can be carried out to determine the lower absorbed dose. In this manner, absorbed doses below 0.1 Gy can be determined by counting tracks over a unit area. (author)

  18. Motivation for Different Types and Doses of Exercise During Breast Cancer Chemotherapy: a Randomized Controlled Trial.

    Science.gov (United States)

    Courneya, Kerry S; Segal, Roanne J; Vallerand, James R; Forbes, Cynthia C; Crawford, Jennifer J; Dolan, Lianne B; Friedenreich, Christine M; Reid, Robert D; Gelmon, Karen; Mackey, John R; McKenzie, Donald C

    2016-08-01

    Exercise is beneficial for breast cancer patients during chemotherapy, but their motivation to perform different types and doses of exercise is unknown. The purpose of this study was to examine the anticipated and experienced motivation of breast cancer patients before and after three different exercise programs during chemotherapy. Breast cancer patients initiating chemotherapy (N = 301) were randomized to a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a combined dose of 50-60 min of aerobic and resistance exercise. Patient preference and motivational outcomes from the theory of planned behavior (i.e., perceived benefit, enjoyment, support, difficulty, and motivation) were assessed before and after the interventions. At pre-randomization, breast cancer patients were significantly (p types and doses of exercise during chemotherapy varied considerably at pre-randomization, but the motivational outcomes experienced after the three interventions were similar. Clinicians can recommend any of the three exercise interventions to breast cancer patients knowing that positive motivational outcomes will result. Clinicaltrials.gov identifier: NCT00249015 .

  19. A comparative pharmacokinetic study of a fixed dose combination for essential hypertensive patients: a randomized crossover study in healthy human volunteers.

    Science.gov (United States)

    Gorain, B; Choudhury, H; Halder, D; Sarkar, A K; Sarkar, P; Biswas, E; Ghosh, B; Pal, T K

    2013-04-01

    This study was aimed to investigate the relative bioavailability of fixed-dose-combination (FDC) product of amlodipine, telmisartan and hydrochlorothiazide with individual marketed products in healthy male volunteers. Control of blood pressure with fixed dose combination of the above drugs acting through different mechanism have a benefit of convenient dosing in terms of compliance, lower the dose and subsequently reduce the side effects. The authors investigated the relative bioavailability under a fasting state of the 3 drugs in a randomized, open-label, 2-treatment, 2-period, 2-sequence, crossover bioequivalence study with a washout period of 21 days. Plasma concentration of the analytes were assayed in timed samples with a simple, highly sensitive and rapid validated method using HPLC coupled to tandem mass spectrometry that had a lower limit of quantification of 1 ng/mL for all the 3 components. Test and reference formulations gave a mean Cmax of 5.234±0.914 ng/mL and 4.991±0.563 ng/mL, 108.839±13.601 ng/mL and 114.783±12.315 ng/mL and 97.814±10.779 ng/mL and 93.731±10.018 ng/mL for amlodipine, telmisartan and hydrochlorothiazide respectively. The AUC0-t of amlodipine, telmisartan and hydrochlorothiazide was 161.484 ng.h/mL, 1 917.644 ng.h/mL and 822.847 ng.h/mL for test formulation and 162.108 ng.h/mL, 2 014.764 ng.h/mL and 829.323 ng.h/mL for reference in the fasting state. The 90% confidence intervals for the test/reference ratio of the pharmacokinetic parameters in fasting state (mean Cmax, AUC0-t, and AUC0-∞) were within the acceptable range of 80.00-125.00. Thus, these findings clearly indicate that the FDC product is bioequivalent with the individual marketed products in terms of rate and extent of drug absorption and is well tolerated with no significant adverse reactions. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Simplified method for creating a density-absorbed dose calibration curve for the low dose range from Gafchromic EBT3 film

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Gotanda

    2016-01-01

    Full Text Available Radiochromic film dosimeters have a disadvantage in comparison with an ionization chamber in that the dosimetry process is time-consuming for creating a density-absorbed dose calibration curve. The purpose of this study was the development of a simplified method of creating a density-absorbed dose calibration curve from radiochromic film within a short time. This simplified method was performed using Gafchromic EBT3 film with a low energy dependence and step-shaped Al filter. The simplified method was compared with the standard method. The density-absorbed dose calibration curves created using the simplified and standard methods exhibited approximately similar straight lines, and the gradients of the density-absorbed dose calibration curves were −32.336 and −33.746, respectively. The simplified method can obtain calibration curves within a much shorter time compared to the standard method. It is considered that the simplified method for EBT3 film offers a more time-efficient means of determining the density-absorbed dose calibration curve within a low absorbed dose range such as the diagnostic range.

  1. Feasibility of RACT for 3D dose measurement and range verification in a water phantom.

    Science.gov (United States)

    Alsanea, Fahed; Moskvin, Vadim; Stantz, Keith M

    2015-02-01

    The objective of this study is to establish the feasibility of using radiation-induced acoustics to measure the range and Bragg peak dose from a pulsed proton beam. Simulation studies implementing a prototype scanner design based on computed tomographic methods were performed to investigate the sensitivity to proton range and integral dose. Derived from thermodynamic wave equation, the pressure signals generated from the dose deposited from a pulsed proton beam with a 1 cm lateral beam width and a range of 16, 20, and 27 cm in water using Monte Carlo methods were simulated. The resulting dosimetric images were reconstructed implementing a 3D filtered backprojection algorithm and the pressure signals acquired from a 71-transducer array with a cylindrical geometry (30 × 40 cm) rotated over 2π about its central axis. Dependencies on the detector bandwidth and proton beam pulse width were performed, after which, different noise levels were added to the detector signals (using 1 μs pulse width and a 0.5 MHz cutoff frequency/hydrophone) to investigate the statistical and systematic errors in the proton range (at 20 cm) and Bragg peak dose (of 1 cGy). The reconstructed radioacoustic computed tomographic image intensity was shown to be linearly correlated to the dose within the Bragg peak. And, based on noise dependent studies, a detector sensitivity of 38 mPa was necessary to determine the proton range to within 1.0 mm (full-width at half-maximum) (systematic error ionizing radiation-induced acoustics can be used to verify dose distribution and proton range with centi-Gray sensitivity. Realizing this technology into the clinic has the potential to significantly impact beam commissioning, treatment verification during particle beam therapy and image guided techniques.

  2. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN.

    Science.gov (United States)

    Jabbour, Elias; Short, Nicholas J; Montalban-Bravo, Guillermo; Huang, Xuelin; Bueso-Ramos, Carlos; Qiao, Wei; Yang, Hui; Zhao, Chong; Kadia, Tapan; Borthakur, Gautam; Pemmaraju, Naveen; Sasaki, Koji; Estrov, Zeev; Cortes, Jorge; Ravandi, Farhad; Alvarado, Yesid; Komrokji, Rami; Sekeres, Mikkael A; Steensma, David P; DeZern, Amy; Roboz, Gail; Kantarjian, Hagop; Garcia-Manero, Guillermo

    2017-09-28

    Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m 2 intravenously/subcutaneously daily or decitabine 20 mg/m 2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% ( P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine ( P = .2). Cytogenetic response rates were 61% and 25% ( P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively ( P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225). © 2017 by The American Society of Hematology.

  3. Cluster Randomized Trail of the uptake of a take-home Infant dose ...

    African Journals Online (AJOL)

    Objective: To test whether a single take home dose of infant nevirapine increased infant uptake without decreasing institutional deliveries. Design: Cluster randomized post-test only study with control group. Setting: Ten hospitals in urban areas of Coast, Rift Valley, and Western provinces, Kenya. Participants: Pregnant ...

  4. Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial.

    Science.gov (United States)

    Liaqat, Naeem; Dar, Sajid Hameed

    2017-04-01

    Acute postoperative pain control in children is an essential component of postoperative care, particularly in daycare procedures. Giving patients continuous narcotic analgesics can be risky; however, a single dose may be sufficient. This study used a prospective, randomized controlled design and was conducted at the Pediatric Surgery Unit, Services Hospital, Lahore. In total, 150 patients who underwent inguinal herniotomy (age range: 1-12 years) were randomly assigned to two groups: group A (nalbuphine) and group B (tramadol). Patients were given a single dose of either nalbuphine (0.2 mg/kg) or tramadol (2 mg/kg) immediately after surgery and pain was measured at 0, 1, 2, 4, and 8 h. The demographic characteristics were similar between the two groups. The mean pain score was lower in group A than in group B at 0 and 1 h (P pain scores in group A were still lower, but not significantly. In all, 9 patients (12.0%) required rescue analgesics in group A compared to 16 patients (21.3%) in group B (P = 0.051). The mean time for requirement of rescue analgesics was 6.5 ± 0.5 h in group A and 5.3 ± 1.7 h in group B (P = 0.06). A single dose of nalbuphine is sufficient, and superior to tramadol, for postoperative pain management in children who have undergone daycare procedures.

  5. Development of dose monitoring system applicable to various radiations with wide energy ranges

    International Nuclear Information System (INIS)

    Sato, Tatsuhiko; Satoh, Daiki; Endo, Akira; Yamaguchi, Yasuhiro

    2005-01-01

    A new inventive radiation dose monitor, designated as DARWIN (Dose monitoring system Applicable to various Radiations with WIde energy raNges), has been developed for monitoring doses in workspaces and surrounding environments of high energy accelerator facilities. DARWIN is composed of a phoswitch-type scintillation detector, which consists of liquid organic scintillator BC501A coupled with ZnS(Ag) scintillation sheets doped with 6 Li, and a data acquisition system based on a Digital-Storage-Oscilloscope. Scintillations from the detector induced by thermal and fast neutrons, photons and muons were discriminated by analyzing their waveforms, and their light outputs were directly converted into the corresponding doses by applying the G-function method. Characteristics of DARWIN were studied by both calculation and experiment. The calculated results indicate that DARWIN gives reasonable estimations of doses in most radiation fields. It was found from the experiment that DARWIN has an excellent property of measuring doses from all particles that significantly contribute to the doses in surrounding environments of accelerator facilities - neutron, photon and muon with wide energy ranges. The experimental results also suggested that DARWIN enables us to monitor small fluctuation of neutron dose rates near the background-level owing to its high sensitivity. (author)

  6. A Randomized, Double-Blind Pilot Study of Dose Comparison of Ramosetron to Prevent Chemotherapy-Induced Nausea and Vomiting

    Directory of Open Access Journals (Sweden)

    Ka-Rham Kim

    2015-01-01

    Full Text Available Purpose. This study was conducted to determine the optimal dose titration of ramosetron to prevent the Rhodes Index of Nausea, Vomiting, and Retching (RINVR. Methods. Patients treated with folic acid, 5-fluorouracil, and oxaliplatin were randomized into three groups (0.3 mg, 0.45 mg, and 0.6 mg ramosetron before chemotherapy. The pharmacokinetics and pharmacodynamics using RINVR were evaluated. Results. Seventeen, 15, and 18 patients received ramosetron at doses of 0.3 mg, 0.45 mg, and 0.6 mg, respectively. Tmax (h, Cmax (ng/mL, and AUClast (ng·h/mL were associated with dose escalation significantly, showing a reverse correlation with the RINVR during chemotherapy. Acute CINV was observed in four patients (22.2%, two patients (14.3%, and one (5.6% patient and a delayed CINV on day 7 was found in eight (47%, three (21.4%, and five (27.8% patients in each group. The complete response rate was increased with dose escalation (35.3%, 50.0%, and 72.2% in each group and also showed the tendency for decreasing moderate-to-severe CINV. Conclusions. This study shows a trend regarding the dose-response relationship for ramosetron to prevent CINV, including delayed emesis. It suggested that dose escalation should be considered in patients with CINV in a subsequent cycle of chemotherapy, and an individual approach using RINVR could be useful to monitor CINV.

  7. Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Ramroth, Johanna; Cutter, David J.; Darby, Sarah C. [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Higgins, Geoff S. [Department of Oncology, University of Oxford, Oxford, Oxfordshire (United Kingdom); McGale, Paul [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom); Partridge, Mike [CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, Oxfordshire (United Kingdom); Taylor, Carolyn W., E-mail: carolyn.taylor@ndph.ox.ac.uk [Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire (United Kingdom)

    2016-11-15

    Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no

  8. Dose and Fractionation in Radiation Therapy of Curative Intent for Non-Small Cell Lung Cancer: Meta-Analysis of Randomized Trials

    International Nuclear Information System (INIS)

    Ramroth, Johanna; Cutter, David J.; Darby, Sarah C.; Higgins, Geoff S.; McGale, Paul; Partridge, Mike; Taylor, Carolyn W.

    2016-01-01

    Purpose: The optimum dose and fractionation in radiation therapy of curative intent for non-small cell lung cancer remains uncertain. We undertook a published data meta-analysis of randomized trials to examine whether radiation therapy regimens with higher time-corrected biologically equivalent doses resulted in longer survival, either when given alone or when given with chemotherapy. Methods and Materials: Eligible studies were randomized comparisons of 2 or more radiation therapy regimens, with other treatments identical. Median survival ratios were calculated for each comparison and pooled. Results: 3795 patients in 25 randomized comparisons of radiation therapy dose were studied. The median survival ratio, higher versus lower corrected dose, was 1.13 (95% confidence interval [CI] 1.04-1.22) when radiation therapy was given alone and 0.83 (95% CI 0.71-0.97) when it was given with concurrent chemotherapy (P for difference=.001). In comparisons of radiation therapy given alone, the survival benefit increased with increasing dose difference between randomized treatment arms (P for trend=.004). The benefit increased with increasing dose in the lower-dose arm (P for trend=.01) without reaching a level beyond which no further survival benefit was achieved. The survival benefit did not differ significantly between randomized comparisons where the higher-dose arm was hyperfractionated and those where it was not. There was heterogeneity in the median survival ratio by geographic region (P<.001), average age at randomization (P<.001), and year trial started (P for trend=.004), but not for proportion of patients with squamous cell carcinoma (P=.2). Conclusions: In trials with concurrent chemotherapy, higher radiation therapy doses resulted in poorer survival, possibly caused, at least in part, by high levels of toxicity. Where radiation therapy was given without chemotherapy, progressively higher radiation therapy doses resulted in progressively longer survival, and no

  9. Stimulant Reduction Intervention using Dosed Exercise (STRIDE - CTN 0037: Study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Morris David W

    2011-09-01

    Full Text Available Abstract Background There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA Clinical Trials Network (CTN CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE study. Methods/Design STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI or Health Education Intervention Augmentation (HEI. Both groups will receive TAU (i.e., usual care. The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual sessions

  10. Evaluation of dose according to the volume and respiratory range during SBRT in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Deuk Hee [Dept. of Radiation Oncology, Busan Paik Hospital, Inje University, Busan (Korea, Republic of); Park, Eun Tae; Kim, Jung Hoon; Kang, Se Seik [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of)

    2016-09-15

    Stereotactic body radiotherapy is effective technic in radiotherapy for low stage lung cancer. But lung cancer is affected by respiratory so accurately concentrate high dose to the target is very difficult. In this study, evaluated the target volume according to how to take the image. And evaluated the dose by photoluminescence glass dosimeter according to how to contour the volume and respiratory range. As a result, evaluated the 4D CT volume was 10.4 cm{sup 3} which was closest value of real size target. And in dose case is internal target volume dose was 10.82, 16.88, 21.90 Gy when prescribed dose was 10, 15, 20 Gy and it was the highest dose. Respiratory gated radiotherapy dose was more higher than internal target volume. But it made little difference by respiratory range. Therefore, when moving cancer treatment, acquiring image by 4D CT, contouring internal target volume and respiratory gated radiotherapy technic would be the best way.

  11. Evaluation of dose according to the volume and respiratory range during SBRT in lung cancer

    International Nuclear Information System (INIS)

    Lee, Deuk Hee; Park, Eun Tae; Kim, Jung Hoon; Kang, Se Seik

    2016-01-01

    Stereotactic body radiotherapy is effective technic in radiotherapy for low stage lung cancer. But lung cancer is affected by respiratory so accurately concentrate high dose to the target is very difficult. In this study, evaluated the target volume according to how to take the image. And evaluated the dose by photoluminescence glass dosimeter according to how to contour the volume and respiratory range. As a result, evaluated the 4D CT volume was 10.4 cm 3 which was closest value of real size target. And in dose case is internal target volume dose was 10.82, 16.88, 21.90 Gy when prescribed dose was 10, 15, 20 Gy and it was the highest dose. Respiratory gated radiotherapy dose was more higher than internal target volume. But it made little difference by respiratory range. Therefore, when moving cancer treatment, acquiring image by 4D CT, contouring internal target volume and respiratory gated radiotherapy technic would be the best way

  12. Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

    Science.gov (United States)

    Hew, M; Gillman, A; Sutherland, M; Wark, P; Bowden, J; Guo, M; Reddel, H K; Jenkins, C; Marks, G B; Thien, F; Rimmer, J; Katsoulotos, G P; Cook, M; Yang, I; Katelaris, C; Bowler, S; Langton, D; Wright, C; Bint, M; Yozghatlian, V; Burgess, S; Sivakumaran, P; Yan, K Y; Kritikos, V; Peters, M; Baraket, M; Aminazad, A; Robinson, P; Jaffe, A; Powell, H; Upham, J W; McDonald, V M; Gibson, P G

    2016-11-01

    Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg. © 2016 John Wiley & Sons Ltd.

  13. Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

    Science.gov (United States)

    Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

    1999-03-17

    Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

  14. Degradation and annealing studies on gamma rays irradiated COTS PPD CISs at different dose rates

    International Nuclear Information System (INIS)

    Wang, Zujun; Ma, Yingwu; Liu, Jing; Xue, Yuan; He, Baoping; Yao, Zhibin; Huang, Shaoyan; Liu, Minbo; Sheng, Jiangkun

    2016-01-01

    The degradation and annealing studies on Colbalt-60 gamma-rays irradiated commercial-off-the-shelf (COTS) pinned photodiode (PPD) CMOS image sensors (CISs) at the various dose rates are presented. The irradiation experiments of COTS PPD CISs are carried out at 0.3, 3.0 and 30.0 rad(Si)/s. The COTS PPD CISs are manufactured using a standard 0.18-μm CMOS technology with four-transistor pixel PPD architecture. The behavior of the tested CISs shows a remarkable degradation after irradiation and differs in the dose rates. The dark current, dark signal non-uniformity (DSNU), random noise, saturation output, signal to noise ratio (SNR), and dynamic range (DR) versus the total ionizing dose (TID) at the various dose rates are investigated. The tendency of dark current, DSNU, and random noise increase and saturation output, SNR, and DR to decrease at 3.0 rad(Si)/s are far greater than those at 0.3 and 30.0 rad(Si)/s. The damage mechanisms caused by TID irradiation at the various dose rates are also analyzed. The annealing tests are carried out at room temperature with unbiased conditions after irradiation.

  15. Degradation and annealing studies on gamma rays irradiated COTS PPD CISs at different dose rates

    Science.gov (United States)

    Wang, Zujun; Ma, Yingwu; Liu, Jing; Xue, Yuan; He, Baoping; Yao, Zhibin; Huang, Shaoyan; Liu, Minbo; Sheng, Jiangkun

    2016-06-01

    The degradation and annealing studies on Colbalt-60 gamma-rays irradiated commercial-off-the-shelf (COTS) pinned photodiode (PPD) CMOS image sensors (CISs) at the various dose rates are presented. The irradiation experiments of COTS PPD CISs are carried out at 0.3, 3.0 and 30.0 rad(Si)/s. The COTS PPD CISs are manufactured using a standard 0.18-μm CMOS technology with four-transistor pixel PPD architecture. The behavior of the tested CISs shows a remarkable degradation after irradiation and differs in the dose rates. The dark current, dark signal non-uniformity (DSNU), random noise, saturation output, signal to noise ratio (SNR), and dynamic range (DR) versus the total ionizing dose (TID) at the various dose rates are investigated. The tendency of dark current, DSNU, and random noise increase and saturation output, SNR, and DR to decrease at 3.0 rad(Si)/s are far greater than those at 0.3 and 30.0 rad(Si)/s. The damage mechanisms caused by TID irradiation at the various dose rates are also analyzed. The annealing tests are carried out at room temperature with unbiased conditions after irradiation.

  16. SSRIs and ejaculation: a double-blind, randomized, fixed-dose study with paroxetine and citalopram.

    Science.gov (United States)

    Waldinger, M D; Zwinderman, A H; Olivier, B

    2001-12-01

    Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p = 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

  17. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus.

    Science.gov (United States)

    Wallace, Daniel J; Stohl, William; Furie, Richard A; Lisse, Jeffrey R; McKay, James D; Merrill, Joan T; Petri, Michelle A; Ginzler, Ellen M; Chatham, W Winn; McCune, W Joseph; Fernandez, Vivian; Chevrier, Marc R; Zhong, Z John; Freimuth, William W

    2009-09-15

    To assess the safety, tolerability, biologic activity, and efficacy of belimumab in combination with standard of care therapy (SOC) in patients with active systemic lupus erythematosus (SLE). Patients with a Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score >/=4 (n = 449) were randomly assigned to belimumab (1, 4, or 10 mg/kg) or placebo in a 52-week study. Coprimary end points were the percent change in the SELENA-SLEDAI score at week 24 and the time to first SLE flare. Significant differences between the treatment and placebo groups were not attained for either primary end point, and no dose response was observed. Reductions in SELENA-SLEDAI scores from baseline were 19.5% in the combined belimumab group versus 17.2% in the placebo group. The median time to first SLE flare was 67 days in the combined belimumab group versus 83 days in the placebo group. However, the median time to first SLE flare during weeks 24-52 was significantly longer with belimumab treatment (154 versus 108 days; P = 0.0361). In the subgroup (71.5%) of serologically active patients (antinuclear antibody titer >/=1:80 and/or anti-double-stranded DNA [anti-dsDNA] >/=30 IU/ml), belimumab treatment resulted in significantly better responses at week 52 than placebo for SELENA-SLEDAI score (-28.8% versus -14.2%; P = 0.0435), physician's global assessment (-32.7% versus -10.7%; P = 0.0011), and Short Form 36 physical component score (+3.0 versus +1.2 points; P = 0.0410). Treatment with belimumab resulted in a 63-71% reduction of naive, activated, and plasmacytoid CD20+ B cells, and a 29.4% reduction in anti-dsDNA titers (P = 0.0017) by week 52. The rates of adverse events and serious adverse events were similar in the belimumab and placebo groups. Belimumab was biologically active and well tolerated. The effect of belimumab on the reduction of SLE disease activity or flares was not significant

  18. Ionizing acceleration of color center transformation in the low radiation dose range

    International Nuclear Information System (INIS)

    Mamontov, A.P.; Starodubtsev, V.A.; Chernov, I.P.

    1985-01-01

    The purpose of the study is investigation of annealing and colour centers transformation of known nature in lithium fluoride crystals at the γ-irradiation low doses. The controlled colour centers have been introduced by LiF monocrystal samples irradiation by protons with 6 MeV energy. The γ-radiation dose rate constitutes 25 Grxssup(-1). The variation of absorption spectra caused by proton and γ-irradiation in initial crystals and in the sample being twice exposed has been studied. It is shown that for LiF monocrystals in the γ-radiation low dose range (below 5 kGr) anomalous dependences of concentration of F-aggregate colour centers on the irradiation dose are observed. High efficiency in defects transformation can be caused by the chain of self-sustaining reactions. The observed N-type dependences caused defects decay and competition of the processes of capture of anionic vacancies by F- and F-aggregate centers

  19. The Ghrelin agonist TZP-101 for management of postoperative ileus after partial colectomy: a randomized, dose-ranging, placebo-controlled clinical trial.

    Science.gov (United States)

    Popescu, Irinel; Fleshner, Phillip R; Pezzullo, John C; Charlton, Philippa A; Kosutic, Gordana; Senagore, Anthony J

    2010-02-01

    Ghrelin agonist TZP-101 is a potent prokinetic. This phase 2b study evaluated TZP-101 safety and efficacy in postoperative ileus management. Adults undergoing open partial colectomy were adaptively randomized to receive 20, 40, 80, 160, 320, 480 or 600 microg/kg TZP-101 (n = 168) or the placebo (n = 68) by 30-minute IV infusion within 1 hour of surgical closure and then daily for up to 7 days. The primary efficacy end point was the time to first bowel movement. Secondary end points included the percentage of patients with return of gastrointestinal function within 72 hours, and the time to readiness for discharge. TZP-101 accelerated the time to first bowel movement in all groups, with Cox proportional hazard ratios of 1.57 (P = .056) for the low-efficacious dose (80 microg/kg) and 1.67 (P = .03) for the most efficacious dose (480 microg/kg). Using Kaplan-Meier analysis, the median time to first bowel movement was reduced in all TZP-101 groups by 10 to 22 hours vs. the placebo. A greater number of patients who received TZP-101 achieved recovery (P readiness for hospital discharge was significantly accelerated by 20.4 hours at the 480 microg/kg TZP-101 dose compared with the placebo (hazard ratio = 1.69; P = .03). The most common treatment-emergent adverse events were nausea and vomiting, which were reduced in the TZP-101 group compared with the placebo group. In patients undergoing major abdominal surgery, the first-in-class ghrelin agonist TZP-101 was well-tolerated and accelerated recovery of the upper and lower gastrointestinal tract, with a large proportion of subjects recovering within 72 hours compared with the placebo.

  20. A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

    Science.gov (United States)

    Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

    2009-03-01

    Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

  1. Applichation of the sulphate ceric dosimetric in the high doses range

    International Nuclear Information System (INIS)

    Prieto Miranda, F.

    1991-01-01

    The ceric-cerous dosimetric system is one of the system more employed in the high dose dosimetry. The spectrophotometric procedure to measure the ceric-concentration is an usual analityc method to determine the absorbed dose. On the other hand, due at increase employ of the irradiation process control. In this paper is realized the ceric-cerous dosimetric calibration in the dose range of 0,6 - 5 kGy and the application in the irradiation process control to differents absorbed dose values

  2. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

    Directory of Open Access Journals (Sweden)

    Galynker Igor I

    2009-05-01

    Full Text Available Abstract Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks. Methods Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS, the Hamilton Anxiety Scale (Ham-A, the Hamilton Depression Rating Scale (Ham-D, the Sheehan Panic Anxiety Scale-Patient (SPAS-P, and the Clinical Global Impression scale (CGI. Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine. Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component. Trial Registration ClinicalTrials.gov Identifier: NCT100457106

  3. Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.

    Science.gov (United States)

    Shi, Shaojun; Liu, Yani; Wu, Jianhong; Li, Zhongfang; Zhao, Yan; Zhong, Dafang; Zeng, Fandian

    2010-10-01

    The proprietary formulation of fluoxetine hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. Pharmacokinetic studies investigating the bioequivalence of generic and branded formulations are needed to market generic fluoxetine in China. The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population. This 10-week, open-label, randomized-sequence, single-dose, 2-period crossover study was conducted in healthy native Han Chinese male volunteers. Eligible subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test or reference formulation, followed by a 35-day washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties (including C(max), T(max), AUC(0-t), AUC(0-∞), and t(½)), blood samples were obtained over a 672-hour period after dosing. Plasma concentrations of fluoxetine and its active metabolite, norfluoxetine, were analyzed using a validated LC-MS/MS method. The formulations were to be considered bioequivalent if the ln-transformed ratios (test/ reference) of C(max) and AUC were within the predetermined bioequivalence range of 80% to 125%, as established by the US Food and Drug Administration, and if the P values were fasting, healthy Chinese male volunteers. Both formulations appeared to be well tolerated. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

  4. Dose-dependent effects of lesogaberan on reflux measures in patients with refractory gastroesophageal reflux disease: a randomized, placebo-controlled study.

    Science.gov (United States)

    Miner, Philip B; Silberg, Debra G; Ruth, Magnus; Miller, Frank; Pandolfino, John

    2014-11-18

    The γ-aminobutyric acid type B-receptor agonist lesogaberan (AZD3355) has been developed for use in patients with gastroesophageal reflux disease (GERD) symptoms despite proton pump inhibitor (PPI) therapy (partial responders). This study aimed to explore the dose-response effect of lesogaberan on reflux episodes in partial responders. In this randomized, single-centre, double-blind, crossover, placebo-controlled study, partial responders taking optimised PPI therapy were given 30, 90, 120 and 240 mg doses of lesogaberan. Each dose was given twice (12 h apart) during a 24-h period, during which impedance-pH measurements were taken. Twenty-five patients were included in the efficacy analysis and 27 in the safety analysis. The effect of lesogaberan on the mean number of reflux episodes was dose-dependent, and all doses significantly reduced the mean number of reflux episodes relative to placebo. Lesogaberan also dose-dependently reduced the mean number of acid reflux episodes (except the 30 mg dose) and weakly acid reflux episodes (all doses) significantly, relative to placebo. Regardless of dose, lesogaberan had a similar effect on the percentage of time with esophageal pH < 4 [mean reduction: 68.5% (30 mg), 54.2% (90 mg), 65.9% (120 mg), 72.1% (240 mg); p < 0.05 except 90 mg dose]. No adverse events led to discontinuation and no serious adverse events occurred during active treatment. Lesogaberan inhibited reflux in a dose-dependent manner in partial responders taking optimised PPI therapy, and these effects were significant versus placebo. All lesogaberan doses were well tolerated and were not associated with clinically relevant adverse events. ClinicalTrials.gov identifier: NCT01043185.

  5. Properties of Wide-dose-range GafChromic Films for Synchrotron Radiation Facility

    International Nuclear Information System (INIS)

    Nariyama, Nobuteru

    2007-01-01

    GafChromic films have been used at SPring-8 to detect the intensively irradiated parts and protect them from damage by being covered with shield or moved. To extend the usable dose range more widely, a new type of sensitive film EBT was investigated for the introduction. Calibration curves were obtained irradiated with 60Co γ rays and compared with those of other GafChromic films. For the application, these films were set in the white x-ray hutch and the dose distribution was measured. Ratio of doses given by EBT and XT-R indicated the degree of the photon spectrum hardness, which depended on the positions. As a result, dose range from 50 mGy to 300 kGy became available for dose distribution measurements, and a set of films having different energy responses was found to give information of photon spectra

  6. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

    DEFF Research Database (Denmark)

    Dirks, Jesper; Fredensborg, Birgitte B; Christensen, Dennis

    2002-01-01

    BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central...... neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients...... received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side...

  7. Combined influence of CT random noise and HU-RSP calibration curve nonlinearities on proton range systematic errors

    Science.gov (United States)

    Brousmiche, S.; Souris, K.; Orban de Xivry, J.; Lee, J. A.; Macq, B.; Seco, J.

    2017-11-01

    Proton range random and systematic uncertainties are the major factors undermining the advantages of proton therapy, namely, a sharp dose falloff and a better dose conformality for lower doses in normal tissues. The influence of CT artifacts such as beam hardening or scatter can easily be understood and estimated due to their large-scale effects on the CT image, like cupping and streaks. In comparison, the effects of weakly-correlated stochastic noise are more insidious and less attention is drawn on them partly due to the common belief that they only contribute to proton range uncertainties and not to systematic errors thanks to some averaging effects. A new source of systematic errors on the range and relative stopping powers (RSP) has been highlighted and proved not to be negligible compared to the 3.5% uncertainty reference value used for safety margin design. Hence, we demonstrate that the angular points in the HU-to-RSP calibration curve are an intrinsic source of proton range systematic error for typical levels of zero-mean stochastic CT noise. Systematic errors on RSP of up to 1% have been computed for these levels. We also show that the range uncertainty does not generally vary linearly with the noise standard deviation. We define a noise-dependent effective calibration curve that better describes, for a given material, the RSP value that is actually used. The statistics of the RSP and the range continuous slowing down approximation (CSDA) have been analytically derived for the general case of a calibration curve obtained by the stoichiometric calibration procedure. These models have been validated against actual CSDA simulations for homogeneous and heterogeneous synthetical objects as well as on actual patient CTs for prostate and head-and-neck treatment planning situations.

  8. Dose-Weighted Adjusted Mantel-Haenszel Tests for Numeric Scaled Strata in a Randomized Trial

    Science.gov (United States)

    Gansky, Stuart A.; Cheng, Nancy F.; Koch, Gary G.

    2011-01-01

    A recent three-arm parallel groups randomized clinical prevention trial had a protocol deviation causing participants to have fewer active doses of an in-office treatment than planned. The original statistical analysis plan stipulated a minimal assumption randomization-based extended Mantel-Haenszel (EMH) trend test of the high frequency, low frequency, and zero frequency treatment groups and a binary outcome. Thus a dose-weighted adjusted EMH (DWAEMH) test was developed with an extra set of weights corresponding to the number of active doses actually available, in the spirit of a pattern mixture model. The method can easily be implemented using standard statistical software. A set of Monte Carlo simulations using a logistic model was undertaken with (and without) actual dose-response effects through 1000 replicates for empirical power estimates (and 2100 for empirical size). Results showed size was maintained and power was improved for DWAEMH versus EMH and logistic regression Wald tests in the presence of a dose effect and treatment by dose interaction. PMID:21709814

  9. Low or High Fractionation Dose {beta}-Radiotherapy for Pterygium? A Randomized Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Viani, Gustavo Arruda, E-mail: gusviani@gmail.com [Department of Radiation Oncology, Marilia Medicine School, Sao Paulo, SP (Brazil); De Fendi, Ligia Issa; Fonseca, Ellen Carrara [Department of Ophthalmology, Marilia Medicine School, Sao Paulo, SP (Brazil); Stefano, Eduardo Jose [Department of Radiation Oncology, Marilia Medicine School, Sao Paulo, SP (Brazil)

    2012-02-01

    Purpose: Postoperative adjuvant treatment using {beta}-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. Methods: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. Results: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. Conclusions: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy{sub 10.}.

  10. A wide range survey meter for estimating γ- and β-dose rates

    International Nuclear Information System (INIS)

    Jones, A.R.

    1980-09-01

    A survey meter has been developed to measure β-dose rates in the range 0.1 - 100 rad/h (1 mGy/h - 1 Gy/h) and γ-dose rates in the range 1 mrad/h - 100 rad/h (10 μGy/h-1 Gy/h). It also provides an audible warning of high γ-dose rates and an audible and visible warning when a predetermined γ-dose is exceeded. The report describes the design of the survey meter and presents data measured on the performance of an engineering prototype. Factors which affect performance and have been investigated are temperature, battery voltage (and type of battery), GM counter counting loss, direction of incident radiation, and energy of γ-rays. Finally, the application and calibration of the survey meter are discussed. (auth)

  11. An analysis of ingestion doses from a range of postulated Magnox reactor releases

    International Nuclear Information System (INIS)

    Nair, S.

    1985-06-01

    An analysis has been carried out of ingestion doses from a range of postulated Magnox reactor releases to atmosphere. Calculations were made of the dose to the adult, ten year old child and one year old child, which showed the one year old child to receive the highest dose. Detailed studies were made of the significance of the ingestion dose to the one year old child in relation to other exposure routes. The ingestion dose was also analysed in terms of the contributing critical organs, foods and nuclides. Approximate calculations were also made of the dependence of the ingestion dose on the time of year when the release occurs. The results of the analysis were used to derive a set of release-specific Emergency Action Guidance Levels (EAGLs) of critical nuclide concentrations in the critical foods, which comply with NRPB's ingestion ERL recommendations. The EAGLs were supplemented with a corresponding set of EAGLs for grass, for use in situations where crop samples were not readily available. (author)

  12. Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: a multicenter randomized placebo controlled trial.

    Science.gov (United States)

    Visser, Laura; de Boer, Marjon A; de Groot, Christianne J M; Nijman, Tobias A J; Hemels, Marieke A C; Bloemenkamp, Kitty W M; Bosmans, Judith E; Kok, Marjolein; van Laar, Judith O; Sueters, Marieke; Scheepers, Hubertina; van Drongelen, Joris; Franssen, Maureen T M; Sikkema, J Marko; Duvekot, Hans J J; Bekker, Mireille N; van der Post, Joris A M; Naaktgeboren, Christiana; Mol, Ben W J; Oudijk, Martijn A

    2017-07-14

    Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Clinical trial registration number of the Dutch Trial Register: NTR 5675 . EudraCT-registration number: 2015-003220-31.

  13. Epidural Labor Analgesia-Fentanyl Dose and Breastfeeding Success: A Randomized Clinical Trial.

    Science.gov (United States)

    Lee, Amy I; McCarthy, Robert J; Toledo, Paloma; Jones, Mary Jane; White, Nancy; Wong, Cynthia A

    2017-10-01

    Breastfeeding is an important public health concern. High cumulative doses of epidural fentanyl administered for labor analgesia have been reported to be associated with early termination of breastfeeding. We tested the hypothesis that breastfeeding success is adversely influenced by the cumulative epidural fentanyl dose administered for labor analgesia. The study was a randomized, double-blind, controlled trial of parous women at greater than 38 weeks gestation who planned to breastfeed, had successfully breastfed a prior infant, and who received neuraxial labor analgesia. Participants were randomized to receive one of three epidural maintenance solutions for labor analgesia (bupivacaine 1 mg/ml, bupivacaine 0.8 mg/ml with fentanyl 1 μg/ml, or bupivacaine 0.625 mg/ml with fentanyl 2 μg/ml). The primary outcome was the proportion of women breastfeeding at 6 weeks postpartum. Maternal and umbilical venous blood fentanyl and bupivacaine concentration at delivery were measured. A total of 345 women were randomized and 305 had complete data for analysis. The frequency of breastfeeding at 6 weeks was 97, 98, and 94% in the groups receiving epidural fentanyl 0, 1, and 2 μg/ml, respectively (P = 0.34). The cumulative fentanyl dose (difference: 37 μg [95% CI of the difference, -58 to 79 μg], P = 0.28) and maternal and umbilical cord venous fentanyl and bupivacaine concentrations did not differ between women who discontinued breastfeeding and those who were still breastfeeding at 6 weeks postpartum. Labor epidural solutions containing fentanyl concentrations as high as 2 μg/ml do not appear to influence breastfeeding rates at 6 weeks postpartum.

  14. Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

    Science.gov (United States)

    Thyssen, An; Solanki, Bhavna; Treem, William

    2012-07-01

    A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable

  15. Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled, dose-ranging Study.

    Science.gov (United States)

    Stohl, William; Merrill, Joan T; McKay, James D; Lisse, Jeffrey R; Zhong, Z John; Freimuth, William W; Genovese, Mark C

    2013-05-01

    To evaluate the efficacy/safety of belimumab in patients with rheumatoid arthritis (RA). Patients fulfilling American College of Rheumatology (ACR) criteria for RA for ≥ 1 year who had at least moderate disease activity while receiving stable disease-modifying antirheumatic drug (DMARD) therapy and failed ≥ 1 DMARD were randomly assigned to placebo or belimumab 1, 4, or 10 mg/kg, administered intravenously on Days 1, 14, and 28, and then every 4 weeks for 24 weeks (n = 283). This was followed by an optional 24-week extension (n = 237) in which all patients received belimumab. Primary efficacy endpoint was the Week 24 ACR20 response. Week 24 ACR20 responses with placebo and belimumab 1, 4, and 10 mg/kg were 15.9%, 34.7% (p = 0.010), 25.4% (p = 0.168), and 28.2% (p = 0.080), respectively. Patients taking any belimumab dose who continued with belimumab in the open-label extension had an ACR20 response of 41% at 48 weeks. A similar ACR20 response (42%) at 48 weeks was seen in patients taking placebo who switched in the extension to belimumab 10 mg/kg. Greater response rates were observed in patients who at baseline were rheumatoid factor-positive, anticitrullinated protein antibody-positive, or tumor necrosis factor inhibitor-naive, or had elevated C-reactive protein levels, Disease Activity Score 28 > 5.1, or low B lymphocyte stimulator levels (< 0.858 ng/ml). Adverse event rates were similar across treatment groups. In this phase II trial, belimumab demonstrated efficacy and was generally well tolerated in patients with RA who had failed previous therapies. [ClinicalTrials.gov identifier NCT00071812].

  16. Low-Dose Epinephrine Plus Tranexamic Acid Reduces Early Postoperative Blood Loss and Inflammatory Response: A Randomized Controlled Trial.

    Science.gov (United States)

    Zeng, Wei-Nan; Liu, Jun-Li; Wang, Fu-You; Chen, Cheng; Zhou, Qiang; Yang, Liu

    2018-02-21

    The reductions of perioperative blood loss and inflammatory response are important in total knee arthroplasty. Tranexamic acid reduced blood loss and the inflammatory response in several studies. However, the effect of epinephrine administration plus tranexamic acid has not been intensively investigated, to our knowledge. In this study, we evaluated whether the combined administration of low-dose epinephrine plus tranexamic acid reduced perioperative blood loss or inflammatory response further compared with tranexamic acid alone. This randomized placebo-controlled trial consisted of 179 consecutive patients who underwent primary total knee arthroplasty. Patients were randomized into 3 interventions: Group IV received intravenous low-dose epinephrine plus tranexamic acid, Group TP received topical diluted epinephrine plus tranexamic acid, and Group CT received tranexamic acid alone. The primary outcome was perioperative blood loss on postoperative day 1. Secondary outcomes included perioperative blood loss on postoperative day 3, coagulation and fibrinolysis parameters (measured by thromboelastography), inflammatory cytokine levels, transfusion values (rate and volume), thromboembolic complications, length of hospital stay, wound score, range of motion, and Hospital for Special Surgery (HSS) score. The mean calculated total blood loss (and standard deviation) in Group IV was 348.1 ± 158.2 mL on postoperative day 1 and 458.0 ± 183.4 mL on postoperative day 3, which were significantly reduced (p 0.05). The combined administration of low-dose epinephrine and tranexamic acid demonstrated an increased effect in reducing perioperative blood loss and the inflammatory response compared with tranexamic acid alone, with no apparent increased incidence of thromboembolic and other complications. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

  17. Simulation study on characteristics of long-range interaction in randomly asymmetric exclusion process

    Science.gov (United States)

    Zhao, Shi-Bo; Liu, Ming-Zhe; Yang, Lan-Ying

    2015-04-01

    In this paper we investigate the dynamics of an asymmetric exclusion process on a one-dimensional lattice with long-range hopping and random update via Monte Carlo simulations theoretically. Particles in the model will firstly try to hop over successive unoccupied sites with a probability q, which is different from previous exclusion process models. The probability q may represent the random access of particles. Numerical simulations for stationary particle currents, density profiles, and phase diagrams are obtained. There are three possible stationary phases: the low density (LD) phase, high density (HD) phase, and maximal current (MC) in the system, respectively. Interestingly, bulk density in the LD phase tends to zero, while the MC phase is governed by α, β, and q. The HD phase is nearly the same as the normal TASEP, determined by exit rate β. Theoretical analysis is in good agreement with simulation results. The proposed model may provide a better understanding of random interaction dynamics in complex systems. Project supported by the National Natural Science Foundation of China (Grant Nos. 41274109 and 11104022), the Fund for Sichuan Youth Science and Technology Innovation Research Team (Grant No. 2011JTD0013), and the Creative Team Program of Chengdu University of Technology.

  18. Pharmacokinetic comparison of controlled-release and immediate-release oral formulations of simvastatin in healthy Korean subjects: a randomized, open-label, parallel-group, single- and multiple-dose study.

    Science.gov (United States)

    Jang, Seong Bok; Lee, Yoon Jung; Lim, Lay Ahyoung; Park, Kyung-Mi; Kwon, Bong-Ju; Woo, Jong Soo; Kim, Yong-Il; Park, Min Soo; Kim, Kyung Hwan; Park, Kyungsoo

    2010-01-01

    A controlled-release (CR) formulation of simvastatin was recently developed in Korea. The formulation is expected to yield a lower C(max) and similar AUC values compared with the immediate-release (IR) formulation. The goal of this study was to compare the pharmacokinetics of the new CR formulation and an IR formulation of simvastatin after single- and multiple-dose administration in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, open-label, parallelgroup, 2-part study. Eligible subjects were healthy male or female volunteers between the ages of 19 and 55 years and within 20% of their ideal weight. In part I, each subject received a single dose of the CR or IR formulation of simvastatin 40 mg orally (20 mg x 2 tablets) after fasting. In part II, each subject received the same dose of the CR or IR formulation for 8 consecutive days. Blood samples were obtained for 48 hours after the dose in part I and after the first and the last dose in part II. Pharmacokinetic parameters were determined for both simvastatin (the inactive prodrug) and simvastatin acid (the active moiety). An adverse event (AE) was defined as any unfavorable sign (including an abnormal laboratory finding) or symptom, regardless of whether it had a causal relationship with the study medication. Serious AEs were defined as any events that are considered life threatening, require hospitalization or prolongation of existing hospitalization, cause persistent or significant disability or incapacity, or result in congenital abnormality, birth defect, or death. AEs were determined based on patient interviews and physical examinations. Twenty-four healthy subjects (17 men, 7 women; mean [SD] age, 29 [7] years; age range, 22-50 years) were enrolled in part I, and 29 subjects (17 men, 12 women; mean age, 33 [9] years; age range, 19-55 years) were enrolled in part II. For simvastatin acid, C

  19. Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

    Science.gov (United States)

    Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

    2017-10-01

    Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHDvitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Computed tomography versus intravenous urography in diagnosis of acute flank pain from urolithiasis: a randomized study comparing imaging costs and radiation dose

    International Nuclear Information System (INIS)

    Thomson, J.M.Z.; Maling, T.M.J.; Glocer, J.; Mark, S.; Abbott, C.

    2001-01-01

    The equivalent sensitivity of non-contrast computed tomography (NCCT) and intravenous urography (IVU) in the diagnosis of suspected ureteric colic has been established. Approximately 50% of patients with suspected ureteric colic do not have a nephro-urological cause for pain. Because many such patients require further imaging studies, NCCT may obviate the need for these studies and, in so doing, be more cost effective and involve less overall radiation exposure. The present study compares the total imaging cost and radiation dose of NCCT versus IVU in the diagnosis of acute flank pain. Two hundred and twenty-four patients (157 men; mean age 45 years; age range 19-79 years) with suspected renal colic were randomized either to NCCT or IVU. The number of additional diagnostic imaging studies, cost (IVU A$ 136; CTU A$ 173), radiation exposure and imaging times were compared. Of 119(53%) patients with renal obstruction, 105 had no nephro-urological causes of pain. For 21 (20%) of these patients an alternative diagnosis was made at the initial imaging, 10 of which were significant. Of 118 IVU patients, 28 (24%) required 32 additional imaging tests to reach a diagnosis, whereas seven of 106 (6%) NCCT patients required seven additional imaging studies. The average total diagnostic imaging cost for the NCCT group was A$181.94 and A$175.46 for the IVU group (P< 0.43). Mean radiation dose to diagnosis was 5.00 mSv (NCCT) versus 3.50 mSv (IVU) (P < 0.001). Mean imaging time was 30 min (NCCT) versus 75 min (IVU) (P < 0.001). Diagnostic imaging costs were remarkably similar. Although NCCT involves a higher radiation dose than IVU, its advantages of faster diagnosis, the avoidance of additional diagnostic imaging tests and its ability to diagnose other causes makes it the study of choice for acute flank pain at Christchurch Hospital. Copyright (2001) Blackwell Science Pty Ltd

  1. SU-E-T-324: The Influence of Patient Positioning Uncertainties in Proton Radiotherapy On Proton Range and Dose Distributions

    Energy Technology Data Exchange (ETDEWEB)

    Liebl, J [EBG MedAustron GmbH, Wiener Neustadt (Austria); Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Medical University of Graz, Graz (Austria); Paganetti, H; Winey, B [Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2014-06-01

    Purpose: Proton radiotherapy allows radiation treatment delivery with high dose gradients. The nature of such dose distributions increases the influence of patient positioning uncertainties on their fidelity when compared to photon radiotherapy. The present work quantitatively analyzes the influence of setup uncertainties on proton range and dose distributions. Methods: 38 clinical passive scattering treatment fields for small lesions in the head were studied. Dose distributions for shifted and rotated patient positions were Monte Carlo-simulated. Proton range uncertainties at the 50% and 90%-dose falloff position were calculated considering 18 arbitrary combinations of maximal patient position shifts and rotations for two patient positioning methods. Normal tissue complication probabilities (NTCPs), equivalent uniform doses (EUDs) and tumor control probabilities (TCPs) were studied for organs at risk (OARs) and target volumes of eight patients. Results: We identified a median 1σ proton range uncertainty at the 50%-dose falloff of 2.8 mm for anatomy-based patient positioning and 1.6 mm for fiducial-based patient positioning as well as 7.2 mm and 5.8 mm for the 90%-dose falloff position respectively. These range uncertainties were correlated to heterogeneity indices (HIs) calculated for each treatment field (38% < R{sup 2} < 50%). A NTCP increase of more than 10% (absolute) was observed for less than 2.9% (anatomy-based positioning) and 1.2% (fiducial-based positioning) of the studied OARs and patient shifts. TCP decreases larger than 10% (absolute) were seen for less than 2.2% of the target volumes or non-existent. EUD changes were up to 178% for OARs and 35% for target volumes. Conclusion: The influence of patient positioning uncertainties on proton range in therapy of small lesions in the human brain and target and OAR dosimetry were studied. Observed range uncertainties were correlated with HIs. The clinical practice of using multiple compensator

  2. Utility of the sore throat pain model in a multiple-dose assessment of the acute analgesic flurbiprofen: a randomized controlled study.

    Science.gov (United States)

    Schachtel, Bernard; Aspley, Sue; Shephard, Adrian; Shea, Timothy; Smith, Gary; Schachtel, Emily

    2014-07-03

    The sore throat pain model has been conducted by different clinical investigators to demonstrate the efficacy of acute analgesic drugs in single-dose randomized clinical trials. The model used here was designed to study the multiple-dose safety and efficacy of lozenges containing flurbiprofen at 8.75 mg. Adults (n=198) with moderate or severe acute sore throat and findings of pharyngitis on a Tonsillo-Pharyngitis Assessment (TPA) were randomly assigned to use either flurbiprofen 8.75 mg lozenges (n=101) or matching placebo lozenges (n=97) under double-blind conditions. Patients sucked one lozenge every three to six hours as needed, up to five lozenges per day, and rated symptoms on 100-mm scales: the Sore Throat Pain Intensity Scale (STPIS), the Difficulty Swallowing Scale (DSS), and the Swollen Throat Scale (SwoTS). Reductions in pain (lasting for three hours) and in difficulty swallowing and throat swelling (for four hours) were observed after a single dose of the flurbiprofen 8.75 mg lozenge (Pflurbiprofen-treated patients experienced a 59% greater reduction in throat pain, 45% less difficulty swallowing, and 44% less throat swelling than placebo-treated patients (all Pflurbiprofen 8.75 mg lozenges were shown to be an effective, well-tolerated treatment for sore throat pain. Other pharmacologic actions (reduced difficulty swallowing and reduced throat swelling) and overall patient satisfaction from the flurbiprofen lozenges were also demonstrated in this multiple-dose implementation of the sore throat pain model. This trial was registered with ClinicalTrials.gov, registration number: NCT01048866, registration date: January 13, 2010.

  3. A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

    Science.gov (United States)

    Cole, J B; Stellpflug, S J; Ellsworth, H; Anderson, C P; Adams, A B; Engebretsen, K M; Holger, J S

    2013-05-01

    High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

  4. Radiolysis of aqueous solutions of ammonium bicarbonate over a large dose range

    International Nuclear Information System (INIS)

    Draganic, Z.D.; Negron-Mendoza, A.; Vujosevic, S.I.; Navarro-Gonzales, R.; Albarran-Sanchez, M.G.

    1991-01-01

    Oxygen-free aqueous solutions of 0.05 mol dm -3 ammonium and sodium bicarbonate were studied after receiving various doses of 60 Co gammas (0.01-400 kGy) or 0.5-20 Gy pulses of 10 Mev electrons. Formate and oxalate were found to be the main radiolytic products, in addition to trace amounts of formaldehyde and an unidentified polymer. A large initial yield of formate in the γ-radiolysis, G(HCOO - ) = 2.2, is due to the reaction COO - + HCO 3 - ↔ HCOO - +CO 3 - . The efficiency of organic synthesis within the large dose range studied is low and is explained by efficient pathways leading to the reformation of bicarbonate, where the reaction COO - + CO 3 - is particularly significant. (author)

  5. Comparing Patient Satisfaction and Intubating Conditions Using Succinylcholine or Low-Dose Rocuronium for Rigid Bronchoscopy: A Randomized Study.

    Science.gov (United States)

    Ghezel-Ahmadi, Verena; Ghezel-Ahmadi, David; Mangen, Jacques; Bolukbas, Servet; Welker, Andreas; Kuerschner, Veit Christian; Fischer, Andreas; Schirren, Joachim; Beck, Grietje

    2015-09-01

    Despite its serious side effects, succinylcholine is commonly used for neuromuscular relaxation in short procedures, such as rigid bronchoscopy and tracheobronchial interventions. The application of low-dose rocuronium reversed by low-dose sugammadex might be a modern alternative. The aim of this study was to compare patient satisfaction, incidence of postoperative myalgia (POM) as well as intubating conditions of these two muscle relaxants for rigid bronchoscopy. A single-center, prospective-randomized, blinded study of 95 patients, scheduled for rigid bronchoscopy and tracheobronchial intervention was conducted. The patients were anesthetized with propofol, remifentanil and either low-dose succinylcholine (S) (0.5 mg/kg) or low-dose rocuronium (0.25 mg/kg) with sugammadex (RS) (0.5 mg/kg). All patients were evaluated on the first and second postinterventional day for their satisfaction with the treatment (rigid bronchoscopy) using a Numeric Analog Rating Scale (NAS 0-10) and the presence and severity of POM (NAS 1-4). Intubating conditions were assessed as excellent, good, or poor on the basis of position of vocal cords and reaction to insertion of the rigid bronchoscope. Patients in the S group were less satisfied with the treatment than patients in RS group (72.7 vs. 93.7%, p = 0.007). The incidence of POM on the first day after intervention was significantly higher in the S group then in the RS group (56.9% vs. 4.3%, p rocuronium in 75% of patients. The anesthetic drug costs were significantly higher in the RS group then in the S group (p rocuronium provided better patient satisfaction and less POM. But with the use of low-dose succinylcholine, the intubating conditions are more comfortable, and it is less expensive than rocuronium/sugammadex. Georg Thieme Verlag KG Stuttgart · New York.

  6. An analysis of ingestion doses from a range of postulated Magnox reactor releases

    International Nuclear Information System (INIS)

    Nair, S.

    1986-01-01

    An analysis was carried out of ingestion doses from a range of postulated Magnox reactor releases to the atmosphere. Doses to the adult, ten year old child and one year old child were calculated, which showed the one year old child to receive the highest dose. Detailed studies were made of the significance of the ingestion dose to the one year old child in relation to other exposure routes. The ingestion dose was analysed for its contributing critical organs, foods and nuclides. Approximate calculations were also made of the dependence of the ingestion dose on the time of year when the release occurs. The ingestion pathway was found to dominate if the release occurs towards the end of the growing season but to be less significant relative to other exposure pathways at all other times. The calculations enabled a set of release-specific emergency action guidance levels of critical nuclide concentrations in the critical foods to be produced, which comply with NRPB's ingestion Emergency Reference Level guidelines. (author)

  7. Immunophenotyping and efficacy of low dose ATG in non-sensitized kidney recipients undergoing early steroid withdrawal: a randomized pilot study.

    Directory of Open Access Journals (Sweden)

    Monica Grafals

    Full Text Available Rabbit antithymocyte globulin (ATG is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1 to our standard dose ATG (total dose 3.75 mg/kg(sATG vs. lower dose 2.25 mg/kg (lowATG. All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%, CMV (8% vs. 0 and BK (4% vs. 0 infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings.ClinicalTrials.gov NCT00548405.

  8. Escitalopram in obsessive-compulsive disorder: a randomized, placebo-controlled, paroxetine-referenced, fixed-dose, 24-week study

    DEFF Research Database (Denmark)

    Stein, Dan J; Andersen, Elisabeth Anne Wreford; Tonnoir, Brigitte

    2007-01-01

    OBJECTIVE: A randomized, placebo controlled fixed-dose trial was undertaken to determine the efficacy and tolerability of escitalopram in obsessive-compulsive disorder (OCD), using paroxetine as the active reference. RESEARCH DESIGN AND METHODS: A total of 466 adults with OCD from specialized...... clinical centres, psychiatric hospital departments, psychiatric practices, or general practice were randomized to one of four treatment groups: escitalopram 10 mg/day (n = 116), escitalopram 20 mg/day (n = 116), paroxetine 40 mg/day (n = 119), or placebo (n = 115) for 24 weeks. The primary efficacy...... of adverse events, and on changes in vital signs (blood pressure and pulse). Main outcome measures; RESULTS: Escitalopram 20 mg/day was superior to placebo on the primary and all secondary outcome endpoints, including remission. Escitalopram 10 mg/day and paroxetine 40 mg/day were also effective...

  9. Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial

    International Nuclear Information System (INIS)

    Al-Mamgani, Abrahim; Heemsbergen, Wilma D.; Levendag, Peter C.; Lebesque, Joos V.

    2010-01-01

    Purpose: To investigate the effect of dose escalation within prognostic risk groups in prostate cancer. Patients and methods: Between 1997 and 2003, 664 patients with localized prostate cancer were randomly assigned to receive 68- or 78-Gy of radiotherapy. Two prognostic models were examined: a risk group model (low-, intermediate-, and high-risk) and PSA-level groupings. High-risk patients with hormonal therapy (HT) were analyzed separately. Outcome variable was freedom from failure (FFF) (clinical failure or PSA nadir + 2 μg/L). Results: In relation to the advantage of high-dose radiotherapy, intermediate-risk patients benefited most from dose escalation. However no significant heterogeneity could be demonstrated between the risk groups. For two types of PSA-level groupings: PSA 8 μg/L, the test for heterogeneity was significant (p = 0.03 and 0.05, respectively). Patients with PSA 8-18 μg/L (n = 297, HR = 0.59) derived the greatest benefit from dose escalation. No heterogeneity could be demonstrated for high-risk patients with and without HT. Conclusion: Intermediate-risk group derived the greatest benefit for dose escalation. However, from this trial no indication was found to exclude low-risk or high-risk patients from high-dose radiotherapy. Patients could be selected for high-dose radiotherapy based on PSA-level groupings: for patients with a PSA < 8 μg/L high-dose radiotherapy is probably not indicated, but should be confirmed in other randomized studies.

  10. Small-dose hypobaric lidocaine-fentanyl spinal anesthesia for short duration outpatient laparoscopy. I. A randomized comparison with conventional dose hyperbaric lidocaine.

    Science.gov (United States)

    Vaghadia, H; McLeod, D H; Mitchell, G W; Merrick, P M; Chilvers, C R

    1997-01-01

    A randomized, single-blind trial of two spinal anesthetic solutions for outpatient laparoscopy was conducted to compare intraoperative conditions and postoperative recovery. Thirty women (ASA physical status I and II) were assigned to one of two groups. Group I patients received a small-dose hypobaric solution of 1% lidocaine 25 mg made up to 3 mL by the addition of fentanyl 25 micrograms. Group II patients received a conventional-dose hyperbaric solution of 5% lidocaine 75 mg (in 7.5% dextrose) made up to 3 mL by the addition of 1.5 mL 10% dextrose. All patients received 500 mL of crystalloid preloading. Spinal anesthesia was performed at L2-3 or L3-4 with a 27-gauge Quincke point needle. Surgery commenced when the level of sensory anesthesia reached T-6. Intraoperative hypotension requiring treatment with ephedrine occurred in 54% of Group II patients but not in any Group I patients. Median (range) time for full motor recovery was 50 (0-95) min in Group I patients compared to 90 (50-120) min in Group II patients (P = 0.0005). Sensory recovery also occurred faster in Group I patients (100 +/- 22 min) compared with Group II patients (140 +/- 27 min, P = 0.0001). Postoperative headache occurred in 38% of all patients and 70% of these were postural in nature. Oral analgesia was the only treatment required. Spinal anesthesia did not result in a significant incidence of postoperative backache. On follow-up, 96% said they found spinal needle insertion acceptable, 93% found surgery comfortable, and 90% said they would request spinal anesthesia for laparoscopy in future. Overall, this study found spinal anesthesia for outpatient laparoscopy to have high patient acceptance and a comparable complication rate to other studies. The small-dose hypobaric lidocaine-fentanyl technique has advantages over conventional-dose hyperbaric lidocaine of no hypotension and faster recovery.

  11. Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

    Science.gov (United States)

    Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

    2017-03-15

    Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Investigation of Kodak extended dose range (EDR) film for megavoltage photon beam dosimetry

    International Nuclear Information System (INIS)

    Chetty, Indrin J.; Charland, Paule M.

    2002-01-01

    We have investigated the dependence of the measured optical density on the incident beam energy, field size and depth for a new type of film, Kodak extended dose range (Kodak EDR). Film measurements have been conducted over a range of field sizes (3x3 cm 2 to 25x25 cm 2 ) and depths (d max to 15 cm), for 6 MV and 15 MV photons within a solid water phantom, and the variation in sensitometric response (net optical density versus dose) has been reported. Kodak EDR film is found to have a linear response with dose, from 0 to 350 cGy, which is much higher than that typically seen for Kodak XV film (0-50 cGy). The variation in sensitometric response for Kodak EDR film as a function of field size and depth is observed to be similar to that of Kodak XV film; the optical density varied in the order of 2-3% for field sizes of 3x3 cm 2 and 10x10 cm 2 at depths of d max , 5 cm and 15 cm in the phantom. Measurements for a 25x25 cm 2 field size showed consistently higher optical densities at depths of d max , 5 cm and 15 cm, relative to a 10x10 cm 2 field size at 5 cm depth, with 4-5% differences noted at a depth of 15 cm. Fractional depth dose and profiles conducted with Kodak EDR film showed good agreement (2%/2 mm) with ion chamber measurements for all field sizes except for the 25x25 cm 2 at depths greater than 15 cm, where differences in the order of 3-5% were observed. In addition, Kodak EDR film measurements were found to be consistent with those of Kodak XV film for all fractional depth doses and profiles. The results of this study indicate that Kodak EDR film may be a useful tool for relative dosimetry at higher dose ranges. (author)

  13. Investigation of Kodak extended dose range (EDR) film for megavoltage photon beam dosimetry.

    Science.gov (United States)

    Chetty, Indrin J; Charland, Paule M

    2002-10-21

    We have investigated the dependence of the measured optical density on the incident beam energy, field size and depth for a new type of film, Kodak extended dose range (Kodak EDR). Film measurements have been conducted over a range of field sizes (3 x 3 cm2 to 25 x 25 cm2) and depths (d(max) to 15 cm), for 6 MV and 15 MV photons within a solid water phantom, and the variation in sensitometric response (net optical density versus dose) has been reported. Kodak EDR film is found to have a linear response with dose, from 0 to 350 cGy, which is much higher than that typically seen for Kodak XV film (0-50 cGy). The variation in sensitometric response for Kodak EDR film as a function of field size and depth is observed to be similar to that of Kodak XV film; the optical density varied in the order of 2-3% for field sizes of 3 x 3 cm2 and 10 x 10 cm2 at depths of d(max), 5 cm and 15 cm in the phantom. Measurements for a 25 x 25 cm2 field size showed consistently higher optical densities at depths of d(max), 5 cm and 15 cm, relative to a 10 x 10 cm2 field size at 5 cm depth, with 4-5% differences noted at a depth of 15 cm. Fractional depth dose and profiles conducted with Kodak EDR film showed good agreement (2%/2 mm) with ion chamber measurements for all field sizes except for the 25 x 25 cm2 at depths greater than 15 cm, where differences in the order of 3-5% were observed. In addition, Kodak EDR film measurements were found to be consistent with those of Kodak XV film for all fractional depth doses and profiles. The results of this study indicate that Kodak EDR film may be a useful tool for relative dosimetry at higher dose ranges.

  14. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H

    1998-01-01

    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5

  15. Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects with Complicated Intra-abdominal Infection.

    Science.gov (United States)

    Lucasti, Christopher; Vasile, Liviu; Sandesc, Dorel; Venskutonis, Donatas; McLeroth, Patrick; Lala, Mallika; Rizk, Matthew L; Brown, Michelle L; Losada, Maria C; Pedley, Alison; Kartsonis, Nicholas A; Paschke, Amanda

    2016-10-01

    Relebactam (REL [MK-7655]) is a novel class A/C β-lactamase inhibitor intended for use with imipenem for the treatment of Gram-negative bacterial infections. REL restores imipenem activity against some resistant strains of Klebsiella and Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271), subjects who were ≥18 years of age with complicated intra-abdominal infection were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo, each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h (q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of microbiologically evaluable (ME) subjects with a favorable clinical response at discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized, 347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49 years). The most common diagnoses were complicated appendicitis (53%) and complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant Gram-negative infections at baseline. Both REL doses plus IMI were generally well tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical response rates at DCIV were similar in subjects who received 250 mg REL plus IMI (96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone (95.2%; one-sided P imipenem exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage of >90% of carbapenem-resistant bacterial strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  16. Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

    Science.gov (United States)

    Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

    2017-09-08

    In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy

  17. Long range order and giant components of quantum random graphs

    CERN Document Server

    Ioffe, D

    2006-01-01

    Mean field quantum random graphs give a natural generalization of classical Erd\\H{o}s-R\\'{e}nyi percolation model on complete graph $G_N$ with $p =\\beta /N$. Quantum case incorporates an additional parameter $\\lambda\\geq 0$, and the short-long range order transition should be studied in the $(\\beta ,\\lambda)$-quarter plane. In this work we explicitly compute the corresponding critical curve $\\gamma_c$, and derive results on two-point functions and sizes of connected components in both short and long range order regions. In this way the classical case corresponds to the limiting point $(\\beta_c ,0) = (1,0)$ on $\\gamma_c$.

  18. Rescue dose orders as an alternative to range orders: an evidence-based practice project.

    Science.gov (United States)

    Yi, Cassia

    2015-06-01

    Relief of pain is a fundamental aspect of optimal patient care. However, pain management in the inpatient setting is often constrained by concerns related to regulatory oversight, particularly with regard to the use of opioid dose range orders. These concerns can inadvertently result in the development of policies and practices that can negatively impact the health care team's ability to deliver optimal and individualized pain management. An evidence-based practice project was undertaken to address concerns about regulatory oversight of pain management processes by changing the way pain was managed in a large academic hospital setting. A novel pain management approach using rescue dose medications was established as an alternative to opioid dose range orders. The use of the rescue dose protocol was successfully implemented. Outcomes included an overall reduction in the administration of inappropriate intravenous opioids and opioid-acetaminophen combination medications, with a subsequent increase in single-entity first-line opioid analgesics. Rescue dose protocols may offer an alternative to opioid dose range orders as a means of effectively managing pain. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  19. Neurodevelopmental Outcomes of Extremely Preterm Infants Randomized to Stress Dose Hydrocortisone.

    Directory of Open Access Journals (Sweden)

    Nehal A Parikh

    Full Text Available To compare the effects of stress dose hydrocortisone therapy with placebo on survival without neurodevelopmental impairments in high-risk preterm infants.We recruited 64 extremely low birth weight (birth weight ≤1000 g infants between the ages of 10 and 21 postnatal days who were ventilator-dependent and at high-risk for bronchopulmonary dysplasia. Infants were randomized to a tapering 7-day course of stress dose hydrocortisone or saline placebo. The primary outcome at follow-up was a composite of death, cognitive or language delay, cerebral palsy, severe hearing loss, or bilateral blindness at a corrected age of 18-22 months. Secondary outcomes included continued use of respiratory therapies and somatic growth.Fifty-seven infants had adequate data for the primary outcome. Of the 28 infants randomized to hydrocortisone, 19 (68% died or survived with impairment compared with 22 of the 29 infants (76% assigned to placebo (relative risk: 0.83; 95% CI, 0.61 to 1.14. The rates of death for those in the hydrocortisone and placebo groups were 31% and 41%, respectively (P = 0.42. Randomization to hydrocortisone also did not significantly affect the frequency of supplemental oxygen use, positive airway pressure support, or need for respiratory medications.In high-risk extremely low birth weight infants, stress dose hydrocortisone therapy after 10 days of age had no statistically significant effect on the incidence of death or neurodevelopmental impairment at 18-22 months. These results may inform the design and conduct of future clinical trials.ClinicalTrials.gov NCT00167544.

  20. High-dose estradiol improves cognition for women with AD: results of a randomized study.

    Science.gov (United States)

    Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

    2001-08-28

    To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

  1. [Epidural anaesthesia: Simulated intravascular test dose with S(+) ketamine, lidocaine and adrenaline. A prospective, randomized, double blind and placebo controlled study].

    Science.gov (United States)

    Higueras, R; Errando, C L; Soriano-Bru, J L

    2015-02-01

    The use of a test dose in epidural anaesthesia is a safety recommendation. However specificity and sensitivity of the drugs used with this indication have been not conclusive. The main objective of this study was to compare the effectiveness and the adverse effects of a simulated intravascular test dose of adrenaline, lidocaine and S(+)-ketamine. A prospective, randomized, double blinded, placebo controlled study was designed. ASA I patients scheduled for elective surgery were included. These were randomized to the following study groups: S(+)-ketamine 0.5 mg.kg-1 (S+K group), 5% lidocaine 1.5 mg.kg-1 (L5% group), adrenaline 15μg (ADR group), and physiological saline 3 ml (SF group; control group). An evaluation was made during the first 15 minutes after the study drug was administered. Variables including heart rate (HR) systolic and diastolic blood pressure (sBP and dBP), mean arterial pressure (MAP), and SpO2 were recorded at 0 min (baseline) and at 2, 5, 8, 10 and 15 minutes after drug injection. An increase of at least 20 beats per minute (bpm) in relation to the baseline measurement was considered a positive result, as was an increase sBP >15 mmHg. The clinical effects described as related to iv injection of the study drugs recorded were: sedation-hypnosis, dizziness, nystagmus, metallic taste perception, perioral or facial paresthesias, tinnitus, as well as any other effect the patients mentioned. Sensitivity and specificity were calculated as was the percent increase in the parameters in order to see if these were clinically useful. A total of 80 patients, 20 per group, were included. The sBP, dBP, and MAP were significantly raised at the 2, 5, 8 and 10 minutes measurements in the S(+)K group compared to the rest of the groups (Padrenaline at the scheduled doses showed low sensitivity and specificity as a simulated iv epidural test dose. S(+)-ketamine could be a feasible marker after accidental iv injection during epidural anaesthesia or analgesia

  2. Sibutramine in weight control: a dose-ranging, efficacy study.

    Science.gov (United States)

    Weintraub, M; Rubio, A; Golik, A; Byrne, L; Scheinbaum, M L

    1991-09-01

    We tested the safety and efficacy of sibutramine, 5 and 20 mg, and placebo on weight loss. Medication was added to caloric restriction, behavior modification, and exercise in a parallel-group, double-blind clinical trial. Participants were 130% to 180% of ideal body weight and in good health. The study lasted 12 weeks over Thanksgiving, Christmas, and New Year's Day. Weight loss during 8 weeks of study medication was: placebo, 1.4 +/- 2.1 kg (n = 19); 5 mg sibutramine, 2.9 +/- 2.3 kg (n = 18); and 20 mg sibutramine, 5.0 +/- 2.7 kg (n = 18) (p less than 0.05 sibutramine, 5 and 20 mg, versus placebo; p less than 0.05 sibutramine, 20 mg versus 5 mg). There is a significant dose-effect relationship. Five participants left the study before completion, all because of adverse events; placebo (one patient), 5 mg sibutramine (one patient), and 20 mg sibutramine (three patients). Sleep difficulties were noted by eight participants (20 mg sibutramine, seven patients; 5 mg, one patient; and placebo, no patients). Six of 21 participants receiving 20 mg complained of irritability, unusual impatience, or "excitation." Sibutramine, 5 and 20 mg, added to a multimodal program assisted participants in losing weight.

  3. Multi-isocenter stereotactic radiotherapy: implications for target dose distributions of systematic and random localization errors

    International Nuclear Information System (INIS)

    Ebert, M.A.; Zavgorodni, S.F.; Kendrick, L.A.; Weston, S.; Harper, C.S.

    2001-01-01

    Purpose: This investigation examined the effect of alignment and localization errors on dose distributions in stereotactic radiotherapy (SRT) with arced circular fields. In particular, it was desired to determine the effect of systematic and random localization errors on multi-isocenter treatments. Methods and Materials: A research version of the FastPlan system from Surgical Navigation Technologies was used to generate a series of SRT plans of varying complexity. These plans were used to examine the influence of random setup errors by recalculating dose distributions with successive setup errors convolved into the off-axis ratio data tables used in the dose calculation. The influence of systematic errors was investigated by displacing isocenters from their planned positions. Results: For single-isocenter plans, it is found that the influences of setup error are strongly dependent on the size of the target volume, with minimum doses decreasing most significantly with increasing random and systematic alignment error. For multi-isocenter plans, similar variations in target dose are encountered, with this result benefiting from the conventional method of prescribing to a lower isodose value for multi-isocenter treatments relative to single-isocenter treatments. Conclusions: It is recommended that the systematic errors associated with target localization in SRT be tracked via a thorough quality assurance program, and that random setup errors be minimized by use of a sufficiently robust relocation system. These errors should also be accounted for by incorporating corrections into the treatment planning algorithm or, alternatively, by inclusion of sufficient margins in target definition

  4. The effect of different doses of esmolol on hemodynamic, bispectral index and movement response during orotracheal intubation: prospective, randomized, double-blind study

    Directory of Open Access Journals (Sweden)

    Mensure Yılmaz Çakırgöz

    2014-12-01

    Full Text Available Objective: A prospective, randomized and double-blind study was planned to identify the optimum dose of esmolol infusion to suppress the increase in bispectral index values and the movement and hemodynamic responses to tracheal intubation. Materials and methods: One hundred and twenty patients were randomly allocated to one of three groups in a double-blind fashion. 2.5 mg kg-1 propofol was administered for anesthesia induction. After loss of consciousness, and before administration of 0.6 mg kg-1 rocuronium, a tourniquet was applied to one arm and inflated to 50 mm Hg greater than systolic pressure. The patients were divided into 3 groups; 1 mg kg-1 h-1 esmolol was given as the loading dose and in Group Es50 50 μg kg-1 min-1, in Group Es150 150 μg kg-1 min-1, and in Group Es250 250 μg kg-1 min-1 esmolol infusion was started. Five minutes after the esmolol has been begun, the trachea was intubated; gross movement within the first minute after orotracheal intubation was recorded. Results: Incidence of movement response and the ΔBIS max values were comparable in Group Es250 and Group Es150, but these values were significantly higher in Group Es50 than in the other two groups. In all three groups in the 1st minute after tracheal intubation heart rate and mean arterial pressure were significantly higher compared to values from before intubation (p < 0.05. In the study period there was no significant difference between the groups in terms of heart rate and mean arterial pressure. Conclusion: In clinical practise we believe that after 1 mg kg-1 loading dose, 150 μg kg-1 min-1 iv esmolol dose is sufficient to suppress responses to tracheal intubation without increasing side effects.

  5. Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

    Science.gov (United States)

    Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

    2015-07-01

    In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

  6. Darwin: Dose monitoring system applicable to various radiations with wide energy ranges

    International Nuclear Information System (INIS)

    Sato, T.; Satoh, D.; Endo, A.; Yamaguchi, Y.

    2007-01-01

    A new radiation dose monitor, designated as DARWIN (Dose monitoring system Applicable to various Radiations with Wide energy ranges), has been developed for real-time monitoring of doses in workspaces and surrounding environments of high-energy accelerator facilities. DARWIN is composed of a Phoswitch-type scintillation detector, which consists of liquid organic scintillator BC501A coupled with ZnS(Ag) scintillation sheets doped with 6 Li, and a data acquisition system based on a Digital-Storage-Oscilloscope. DARWIN has the following features: (1) capable of monitoring doses from neutrons, photons and muons with energies from thermal energy to 1 GeV, 150 keV to 100 MeV and 1 MeV to 100 GeV, respectively, (2) highly sensitive with precision and (3) easy to operate with a simple graphical user-interface. The performance of DARWIN was examined experimentally in several radiation fields. The results of the experiments indicated the accuracy and wide response range of DARWIN for measuring dose rates from neutrons, photons and muons with wide energies. It was also found from the experiments that DARWIN enables us to monitor small fluctuations of neutron dose rates near the background level because of its high sensitivity. With these properties, DARWIN will be able to play a very important role for improving radiation safety in high-energy accelerator facilities. (authors)

  7. 8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

    International Nuclear Information System (INIS)

    Maranzano, Ernesto; Trippa, Fabio; Casale, Michelina; Costantini, Sara; Lupattelli, Marco; Bellavita, Rita; Marafioti, Luigi; Pergolizzi, Stefano; Santacaterina, Anna; Mignogna, Marcello; Silvano, Giovanni; Fusco, Vincenzo

    2009-01-01

    Background and purpose: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. Materials and methods: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). Results: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p = 0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. Conclusions: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

  8. Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

    Science.gov (United States)

    Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

    2016-10-01

    We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

  9. Studies on γ-ray induced structural changes in Nd{sup 3+} doped lead alumino silicate glasses by means of thermoluminescence for dosimetric applications in high dose ranges

    Energy Technology Data Exchange (ETDEWEB)

    Sundara Rao, M. [Department of Physics, Acharya Nagarjuna University, Nagarjuna Nagar 522 510, Guntur, A.P. (India); Gandhi, Y. [Department of Physics, Kakani Venkata Ratnam College, Nandigama 521 185, A.P. (India); Sanyal, Bhaskar [Food Technology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Bhargavi, K. [Department of Physics, Acharya Nagarjuna University, Nagarjuna Nagar 522 510, Guntur, A.P. (India); Piasecki, M. [Institute of Physics, J. Dlugosz University, Ul. Armii Krajowej 13/15, 42-201 Czestochowa (Poland); Veeraiah, N., E-mail: nvr8@rediffmail.com [Department of Physics, Acharya Nagarjuna University, Nagarjuna Nagar 522 510, Guntur, A.P. (India)

    2014-12-15

    Graphical abstract: TL glow curves of PbO–SiO{sub 2}:Nd{sup 3+} glasses mixed with different concentrations of Al{sub 2}O{sub 3} exposed to γ-rays of dose 5.0 kGy. - Highlights: • TL studies of Nd{sup 3+} ions doped lead alumino silicate glasses were carried out. • Highest TL output was observed in the glasses mixed with 10 mol% of Al{sub 2}O{sub 3}. • Different mechanisms responsible for TL emission were discussed. • Near linearity of the dose response was observed in the dose range of 1.0–3.0 kGy. • These glasses may be useful as dosimeters in processing perishable food commodities. - Abstract: Thermoluminescence (TL) studies on PbO–Al{sub 2}O{sub 3}–SiO{sub 2}:Nd{sup 3+} glasses mixed with varying concentrations of Al{sub 2}O{sub 3} exposed to γ-rays of dose in the range 0–5.0 kGy were carried out. The TL emission exhibited a dosimetric peak at about 185 °C. The TL output under the glow peak increased with increasing Al{sub 2}O{sub 3} and also with the γ-ray dose. The mechanisms responsible for TL emission and enhancement of TL output with increase in the concentration of Al{sub 2}O{sub 3} were quantitatively discussed in terms of induced structural defects in the vicinity of Nd{sup 3+} ions due to interaction of γ-rays with the glass network in the scenario of varying concentration of Al{sub 2}O{sub 3}. The dose response of these glass samples exhibited linear behavior in the medium dose range viz., 1.0–3.0 kGy. Finally, it is concluded that the glass containing the highest concentration of Al{sub 2}O{sub 3} exhibits high TL output and such glasses are useful for dosimetry in the range 1.0–3.0 kGy and hence these glasses may be useful for dosimetry in such high range of doses required for commercial radiation processing of perishable food commodities to extend their shelf-lives.

  10. A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

    Science.gov (United States)

    Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-03-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start.

  11. ATG-Fresenius treatment and low-dose tacrolimus: results of a randomized controlled trial in liver transplantation.

    Science.gov (United States)

    Benítez, C E; Puig-Pey, I; López, M; Martínez-Llordella, M; Lozano, J J; Bohne, F; Londoño, M C; García-Valdecasas, J C; Bruguera, M; Navasa, M; Rimola, A; Sánchez-Fueyo, A

    2010-10-01

    We report the results of a prospective randomized controlled trial in liver transplantation assessing the efficacy and safety of antithymocyte globulin (ATG-Fresenius) plus tacrolimus monotherapy at gradually decreasing doses. Patients were randomized to either: (a) standard-dose tacrolimus plus steroids;or (b) peritransplant ATG-Fresenius plus reduced-dose tacrolimus monotherapy followed by weaning of tacrolimus starting 3 months after transplantation. The primary end-point was the achievement of very low-dose tacrolimus (every-other-day or once daily dose with Fresenius group but no benefits in terms of improved renal function, lower metabolic complications or increased prevalence of tolerance-related biomarkers were observed. In conclusion, the use of ATG-Fresenius and tacrolimus at gradually decreasing doses was associated with a high rate of rejection, did not allow for the administration of very low doses of tacrolimus and failed to provide detectable clinical benefits. ClinicalTrials.gov identifier: NCT00436722. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

  12. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial.

    Science.gov (United States)

    Taguchi, Isao; Iimuro, Satoshi; Iwata, Hiroshi; Takashima, Hiroaki; Abe, Mitsuru; Amiya, Eisuke; Ogawa, Takanori; Ozaki, Yukio; Sakuma, Ichiro; Nakagawa, Yoshihisa; Hibi, Kiyoshi; Hiro, Takafumi; Fukumoto, Yoshihiro; Hokimoto, Seiji; Miyauchi, Katsumi; Yamazaki, Tsutomu; Ito, Hiroshi; Otsuji, Yutaka; Kimura, Kazuo; Takahashi, Jun; Hirayama, Atsushi; Yokoi, Hiroyoshi; Kitagawa, Kazuo; Urabe, Takao; Okada, Yasushi; Terayama, Yasuo; Toyoda, Kazunori; Nagao, Takehiko; Matsumoto, Masayasu; Ohashi, Yasuo; Kaneko, Tetsuji; Fujita, Retsu; Ohtsu, Hiroshi; Ogawa, Hisao; Daida, Hiroyuki; Shimokawa, Hiroaki; Saito, Yasushi; Kimura, Takeshi; Inoue, Teruo; Matsuzaki, Masunori; Nagai, Ryozo

    2018-05-08

    Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P Japanese patients with stable coronary artery disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730. © 2018 The Authors.

  13. A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction.

    Science.gov (United States)

    Dording, Christina M; Fisher, Lauren; Papakostas, George; Farabaugh, Amy; Sonawalla, Shamsah; Fava, Maurizio; Mischoulon, David

    2008-01-01

    We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (PMaca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.

  14. Randomized multicenter trial on the effect of radiotherapy for plantar Fasciitis (painful heel spur) using very low doses – a study protocol

    International Nuclear Information System (INIS)

    Niewald, Marcus; Seegenschmiedt, M Heinrich; Micke, Oliver; Gräber, Stefan

    2008-01-01

    A lot of retrospective data concerning the effect of radiotherapy on the painful heel spur (plantar fasciitis) is available in the literature. Nevertheless, a randomized proof of this effect is still missing. Thus, the GCGBD (German cooperative group on radiotherapy for benign diseases) of the DEGRO (German Society for Radiation Oncology) decided to start a randomized multicenter trial in order to find out if the effect of a conventional total dose is superior compared to that of a very low dose. In a prospective, controlled and randomized phase III trial two radiotherapy schedules are to be compared: standard arm: total dose 6.0 Gy in single fractions of 1.0 Gy applied twice a week experimental arm: total dose 0.6 Gy in single fractions of 0.1 Gy applied twice a week (acting as a placebo) Patients aged over 40 years who have been diagnosed clinically and radiologically to be suffering from a painful heel spur for at least six months can be included. Former trauma, surgery or radiotherapy to the heel are not allowed nor are patients with a severe psychiatric disease or women during pregnancy and breastfeeding. According to the statistical power calculation 100 patients have to be enrolled into each arm. After having obtaining a written informed consent a patient is randomized by the statistician to one of the arms mentioned above. After radiotherapy, the patients are seen first every six weeks, then regularly up to 48 months after therapy, they additionally receive a questionnaire every six weeks after the follow-up examinations. The effect is measured using several target variables (scores): Calcaneodynia-score according to Rowe et al., SF-12 score, and visual analogue scale of pain. The most important endpoint is the pain relief three months after therapy. Patients with an inadequate result are offered a second radiotherapy series applying the standard dose (equally in both arms). This trial protocol has been approved by the expert panel of the DEGRO as well as

  15. Randomized multicenter trial on the effect of radiotherapy for plantar Fasciitis (painful heel spur using very low doses – a study protocol

    Directory of Open Access Journals (Sweden)

    Micke Oliver

    2008-09-01

    Full Text Available Abstract Background A lot of retrospective data concerning the effect of radiotherapy on the painful heel spur (plantar fasciitis is available in the literature. Nevertheless, a randomized proof of this effect is still missing. Thus, the GCGBD (German cooperative group on radiotherapy for benign diseases of the DEGRO (German Society for Radiation Oncology decided to start a randomized multicenter trial in order to find out if the effect of a conventional total dose is superior compared to that of a very low dose. Methods/Design In a prospective, controlled and randomized phase III trial two radiotherapy schedules are to be compared: standard arm: total dose 6.0 Gy in single fractions of 1.0 Gy applied twice a week experimental arm: total dose 0.6 Gy in single fractions of 0.1 Gy applied twice a week (acting as a placebo Patients aged over 40 years who have been diagnosed clinically and radiologically to be suffering from a painful heel spur for at least six months can be included. Former trauma, surgery or radiotherapy to the heel are not allowed nor are patients with a severe psychiatric disease or women during pregnancy and breastfeeding. According to the statistical power calculation 100 patients have to be enrolled into each arm. After having obtaining a written informed consent a patient is randomized by the statistician to one of the arms mentioned above. After radiotherapy, the patients are seen first every six weeks, then regularly up to 48 months after therapy, they additionally receive a questionnaire every six weeks after the follow-up examinations. The effect is measured using several target variables (scores: Calcaneodynia-score according to Rowe et al., SF-12 score, and visual analogue scale of pain. The most important endpoint is the pain relief three months after therapy. Patients with an inadequate result are offered a second radiotherapy series applying the standard dose (equally in both arms. This trial protocol has been

  16. The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

    Science.gov (United States)

    Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

    2014-04-01

    Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

  17. Development of new chemical dosimeter for low dose range

    International Nuclear Information System (INIS)

    Mhatre, Sachin G.V.; Adhikari, S.

    2012-01-01

    Accurate measurement of low dose radiation in complex systems is of utmost importance in radiation biology and related areas. Ferrous Benzoic acid Xylenol orange (FBX) system is being widely used for measurement of low dose gamma radiation because of its reproducibility and precision. However, an additional step, i.e., dissolution of benzoic acid in water at higher temperature followed by cooling at room temperature is involved for the preparation of this dosimeter. This makes it inconvenient as a ready to use dosimeter. In the present work, the organic molecule, sorbitol has been used for measurement of low doses of radiation. The advantages of using sorbitol are its ready availability and instantaneous water solubility. Owing to its dissolution at room temperature, possible errors those are involved in calculation of dose due to thermal oxidation of ferrous ions during preparation of the FBX dosimetric solution could be made insignificant in the proposed dosimeter. In the present system, sorbitol acts as radiolytic sensitizer for the oxidation of ferrous ion, and xylenol orange forms a 1:1 complex specifically with ferric ions. Thus, the analytical detection limit of ferric ions is enhanced compared to other systems. Final composition of the dosimetric solution is; 0.5 mol/m 3 xylenol orange, 10 mol/m 3 sorbitol and 0.2 mol/m 3 ferrous ion in 50 mol/m 3 sulfuric acid. Radiolytic sensitization in combination with analytical enhancement of the ferrous based system, allows us to measure radiation dose in the range of 0.05 Gy–12 Gy with ease and high reproducibility.

  18. A comparative study of the Si diodes of N type applied to high-dose range dosimetry

    International Nuclear Information System (INIS)

    Pascoalino, Kelly Cristina da Silva; Goncalves, Josemary Angelica Correa; Tobias, Carmen Cecilia Bueno

    2011-01-01

    This work presents the results of the comparative studies of floating-zone (Fz) and magnetic Czochralski (MCz) n-type silicon diodes as gamma dosimeters. The devices were irradiated with gamma rays from 60 Co source, Gammacell 220, at Radiation Technology Center (CTR-IPEN/CNEN-SP) with the dose rate of 2 kGy/h. The results with total absorbed doses of approximately 1 MGy showed that the devices studied are tolerant to radiation damages and then can be used as an online dosimeter in high doses radiation processing. (author)

  19. Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

    Science.gov (United States)

    Takahashi, Fumihiro; Morita, Satoshi

    2018-02-08

    Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

  20. Upgrading NASA/DOSE laser ranging system control computers

    Science.gov (United States)

    Ricklefs, Randall L.; Cheek, Jack; Seery, Paul J.; Emenheiser, Kenneth S.; Hanrahan, William P., III; Mcgarry, Jan F.

    1993-01-01

    Laser ranging systems now managed by the NASA Dynamics of the Solid Earth (DOSE) and operated by the Bendix Field Engineering Corporation, the University of Hawaii, and the University of Texas have produced a wealth on interdisciplinary scientific data over the last three decades. Despite upgrades to the most of the ranging station subsystems, the control computers remain a mix of 1970's vintage minicomputers. These encompass a wide range of vendors, operating systems, and languages, making hardware and software support increasingly difficult. Current technology allows replacement of controller computers at a relatively low cost while maintaining excellent processing power and a friendly operating environment. The new controller systems are now being designed using IBM-PC-compatible 80486-based microcomputers, a real-time Unix operating system (LynxOS), and X-windows/Motif IB, and serial interfaces have been chosen. This design supports minimizing short and long term costs by relying on proven standards for both hardware and software components. Currently, the project is in the design and prototyping stage with the first systems targeted for production in mid-1993.

  1. Duration of remission after halving of the etanercept dose in patients with ankylosing spondylitis: a randomized, prospective, long-term, follow-up study

    Directory of Open Access Journals (Sweden)

    Nannini C

    2013-01-01

    Full Text Available Fabrizio Cantini, Laura Niccoli, Emanuele Cassarà, Olga Kaloudi, Carlotta NanniniDivision of Rheumatology, Misericordia e Dolce Hospital, Prato, ItalyBackground: The aim of this study was to evaluate the proportion of patients with ankylosing spondylitis maintaining clinical remission after reduction of their subcutaneous etanercept dose to 50 mg every other week compared with that in patients receiving etanercept 50 mg weekly.Methods: In the first phase of this randomized, prospective, follow-up study, all biologic-naïve patients identified between January 2005 and December 2009 as satisfying the modified New York clinical criteria for ankylosing spondylitis treated with etanercept 50 mg weekly were evaluated for disease remission in January 2010. In the second phase, patients meeting the criteria for remission were randomized to receive subcutaneous etanercept as either 50 mg weekly or 50 mg every other week. The randomization allocation was 1:1. Remission was defined as Bath Ankylosing Spondylitis Disease Activity Index < 4, no extra-axial manifestations of peripheral arthritis, dactylitis, tenosynovitis, or iridocyclitis, and normal acute-phase reactants. The patients were assessed at baseline, at weeks 4 and 12, and every 12 weeks thereafter. The last visit constituted the end of the follow-up.Results: During the first phase, 78 patients with ankylosing spondylitis (57 males and 21 females, median age 38 years, median disease duration 12 years were recruited. In January 2010, after a mean follow-up of 25 ± 11 months, 43 (55.1% patients achieving clinical remission were randomized to one of the two treatment arms. Twenty-two patients received etanercept 50 mg every other week (group 1 and 21 received etanercept 50 mg weekly (group 2. At the end of follow-up, 19 of 22 (86.3% subjects in group 1 and 19 of 21 (90.4% in group 2 were still in remission, with no significant difference between the two groups. The mean follow-up duration in group

  2. Haloperidol dose combined with dexamethasone for PONV prophylaxis in high-risk patients undergoing gynecological laparoscopic surgery: a prospective, randomized, double-blind, dose-response and placebo-controlled study.

    Science.gov (United States)

    Joo, Jin; Park, Yong Gyu; Baek, Jungwon; Moon, Young Eun

    2015-07-08

    Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. Female adults (n = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0-2 h) and late (2-24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; P = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (P haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. ClinicalTrials.gov ( NCT01639599 ).

  3. Radiation doses due to long-range transport of airborne radionuclides

    International Nuclear Information System (INIS)

    Nordlund, G.; Valkama, I.; Rossi, J.; Savolainen, I.

    1985-12-01

    Within the framework of this study a model for estimating the long range transport of radioactive material and for calculating the resultant doses is developed. In the model initially the dispersion paths, i.e. trajectories, of the radioactive matter are calculated from the assumed source areas as well as the dispersion conditions along the trajectories. The trajectories are calculated at three-hour intervals in a two-dimensional grid using numerically analysed winds at a constant pressure level of 850 mb. The dispersion condition parameters applied are: the stability of the atmospheric boundary layer, the so-called mixing height, occurrence of precipitation and the character of the terrain. For each trajectory a type-index value is computed, describing the severity of the possible effects of radioactivity transported by the particular trajectory. The dispersion model uses the information on dispersion conditions provided by the trajectory model to compute the remaining radioactivity in the cloud, the deposition, as well as the doses due to different dose pathways. The pathways used are the external radiation from the cloud and from the activity deposited on the ground, inhalation of radioactive material and ingestion of contaminated food products (milk, meat, green vegetables, grain and roots). In addition to the effects of individual transport incidents, the cumulative probability distributions of the effects of accidental releases of radioactive matter can also be calculated using trajectory statistics and the trajectory type index

  4. Phase 2, Randomized, Double-Blind, Dose-Ranging Study Evaluating the Safety, Tolerability, Population Pharmacokinetics, and Efficacy of Oral Torezolid Phosphate in Patients with Complicated Skin and Skin Structure Infections▿ † ‡

    Science.gov (United States)

    Prokocimer, P.; Bien, P.; Surber, J.; Mehra, P.; DeAnda, C.; Bulitta, J. B.; Corey, G. R.

    2011-01-01

    Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate ([TP] TR-701), a second-generation oxazolidinone with 4- to 16-fold greater potency than linezolid against Gram-positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind phase 2 study evaluated three levels (200, 300, or 400 mg) of oral, once-daily TP over 5 to 7 days for complicated skin and skin structure infections (cSSSI). Patients 18 to 75 years old with cSSSI caused by suspected or confirmed Gram-positive pathogens were randomized 1:1:1. Of 188 treated patients, 76.6% had abscesses, 17.6% had extensive cellulitis, and 5.9% had wound infections. S. aureus, the most common pathogen, was isolated in 90.3% of patients (139/154) with a baseline pathogen; 80.6% were MRSA. Cure rates in clinically evaluable patients were 98.2% at 200 mg, 94.4% at 300 mg, and 94.4% at 400 mg. Cure rates were consistent across diagnoses, regardless of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with S. aureus isolated at baseline were 96.6% overall and 96.8% for MRSA. TP was safe and well tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of 8.28 liters/h (between-patient variability, 32.3%), a volume of the central compartment of 71.4 liters (24.0%), and a volume of the peripheral compartment of 27.9 liters (35.7%). Results of this study show a high degree of efficacy at all three dose levels without significant differences in the safety profile and support the continued evaluation of TP for the treatment of cSSSI in phase 3 trials. PMID:21115795

  5. Does quasi-long-range order in the two-dimensional XY model really survive weak random phase fluctuations?

    International Nuclear Information System (INIS)

    Mudry, Christopher; Wen Xiaogang

    1999-01-01

    Effective theories for random critical points are usually non-unitary, and thus may contain relevant operators with negative scaling dimensions. To study the consequences of the existence of negative-dimensional operators, we consider the random-bond XY model. It has been argued that the XY model on a square lattice, when weakly perturbed by random phases, has a quasi-long-range ordered phase (the random spin wave phase) at sufficiently low temperatures. We show that infinitely many relevant perturbations to the proposed critical action for the random spin wave phase were omitted in all previous treatments. The physical origin of these perturbations is intimately related to the existence of broadly distributed correlation functions. We find that those relevant perturbations do enter the Renormalization Group equations, and affect critical behavior. This raises the possibility that the random XY model has no quasi-long-range ordered phase and no Kosterlitz-Thouless (KT) phase transition

  6. Patient doses in interventional cardiology procedures

    International Nuclear Information System (INIS)

    Domienik, J.; Papierz, S.; Jankowski, J.; Peruga, J.Z.

    2008-01-01

    In most countries of European Union legislation requires the determination of the total skin dose to patient resulting from interventional procedures to assess the risk of deterministic effect. To this end, various dose indicators like dose area product (DAP), cumulative dose (CD) and entrance dose at the patient plane (EFD) are used in clinical practice. The study aims at relating those dose indicators with doses ascribe to the most irradiated areas of the patient skin usually expressed in terms of local maximal skin dose (MSD). For the study the local MSD and related to their areas are investigated and compared for coronary angiography CA and intervention (PCI). Two methods implying radiographic films Kodak EDR2 and matrixes of thermoluminescent dosimeters (TLDs) are applied for direct measurements of dose distribution for selected procedures. Both methods are compared. Additionally, for patient dosimetry the following data: MSD, CD, EFD, fluoroscopy time (FT), number of acquired images, total DAP, fluoro-DAP and record-DAP were collected for randomly selected procedure. The statistical quantities like: median, 3 rd quartile, mean and standard deviation for all dosimetric parameters are determined. Preliminary study showed that the values of data collected for coronary procedures are in the ranges 0,7 - 27,3 min for fluoroscopy time, 50 - 350 Gy cm 2 for total DAP, 300 - 2000 mGy for CD, 140 - 2000 mGy for EFD and 100 - 1500 mGy for local maximal skin dose. For interventions the ranges are, accordingly 3,0 - 43,6 min , 25 - 450 Gy cm 2 , 270 - 6600 mGy, 80 - 2600 mGy and 80 - 1500 mGy. As a result of the study the correlations between dose indicators and local MSD are analyzed. The concentration of dose on irradiated films are going to be investigated in some detail as well. (author)

  7. Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

    2015-04-01

    Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

  8. Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.

    Science.gov (United States)

    Zohar, Sarah; Chevret, Sylvie

    2003-02-01

    We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.

  9. Entropy and long-range memory in random symbolic additive Markov chains.

    Science.gov (United States)

    Melnik, S S; Usatenko, O V

    2016-06-01

    The goal of this paper is to develop an estimate for the entropy of random symbolic sequences with elements belonging to a finite alphabet. As a plausible model, we use the high-order additive stationary ergodic Markov chain with long-range memory. Supposing that the correlations between random elements of the chain are weak, we express the conditional entropy of the sequence by means of the symbolic pair correlation function. We also examine an algorithm for estimating the conditional entropy of finite symbolic sequences. We show that the entropy contains two contributions, i.e., the correlation and the fluctuation. The obtained analytical results are used for numerical evaluation of the entropy of written English texts and DNA nucleotide sequences. The developed theory opens the way for constructing a more consistent and sophisticated approach to describe the systems with strong short-range and weak long-range memory.

  10. HALF-DOSE DEPOT TRIPTORELIN COMPARABLE TO REDUCED DAILY BUSERELIN: A RANDOMIZED CLINICAL TRIAL

    Directory of Open Access Journals (Sweden)

    L. Safdarian

    2007-09-01

    Full Text Available Pituitary suppression by depot GnRH agonist may be excessive for ovarian stimulation. This study compares the efficacy of a single half-dose depot triptorelin and reduced-dose daily buserelin in a long protocol ICSI/ET. METHODS: A total of 182 patients were randomized into two groups using sealed envelopes. Pituitary desensitization was obtained in group 1 (91 patients with half-dose (1.87 mg depot triptorelin in the mid-luteal phase of their menstrual cycle, and in group 2 (91 patients with standard daily dose (0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotropin (HMG stimulation. RESULTS: No significant differences were found among those who received HCG in terms of clinical pregnancy rate (34.4% in both groups, implantation rate (14.8% in group 1 versus 11.1% in group 2, fertilization rate (93.3 versus 95.6%, poor response rate (11.1 versus 6.7%, and miscarriage rate (11.1 versus 7.8%. No significant differences were seen in number of HMG ampoules used, follicles at HCG administration, and oocytes retrieved. The number of days of stimulation was significantly reduced in group 2 (11.2 +/- 1.8 in group 1 versus 10.6 +/- 1.9, p = 0.030. CONCLUSION: A half-dose of depot triptorelin can be successfully used in ovarian stimulation instead of reduced-dose daily buserelin, with more patient comfort and reduced stress and cost of injections.

  11. Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

    International Nuclear Information System (INIS)

    Xiao Yao; Guo Hong-Xia; Zhang Feng-Qi; Zhao Wen; Wang Yan-Ping; Zhang Ke-Ying; Ding Li-Li; Luo Yin-Hong; Wang Yuan-Ming; Fan Xue

    2014-01-01

    Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed. (interdisciplinary physics and related areas of science and technology)

  12. Prospective randomized trial for the evaluation of the efficacy of low vs. high dose I-131 for post operative remnant ablation in differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Barrenechea, E.A.; Laureta, E.G.; Gaston, J.C.; Al-Nahhas, A.; Padhy, A.K.

    2005-01-01

    The study was done under the auspices of the IAEA to evaluate the efficacy of low dose (50-60mCi) vs. High dose (100 mCi) for the post-operative remnant ablation of differentiated thyroid cancer and to determine other factors associated with successful ablation. There were eighty-six patients included in the study with a diagnosis of papillary, follicular or mixed type of thyroid cancer. They all have undergone near total thyroidectomy or total thyroidectomy and without any evidence of metastatic disease. Four to six weeks after the surgery and without thyroid hormone maintenance as well as iodine free diet and drugs, they underwent a total body scan and uptake using 1-3 mci of I-131. Serum TSH and thyroglobulin were also taken. Randomization was made thru the IAEA and the patients either got a low dose or a high dose depending on such randomization. Of the 86 patients included, there were a total of 76 evaluable cases. There were three dropouts because of other medical conditions as upper GI bleeding, lung cancer and leg fracture. The 7 other patients have not completed their follow-up body scan. Among these patients were 67 females and 19 males whose age range was 19 to 84 years old. There were 65 cases with histologic type of papillary cancer, 15 follicular and 6 mixed varieties. Forty-one patients were randomized to the high dose group while 35 patients were assigned to the low dose therapy group. These patients were confined till their radiation activity was below 2mR/hr. Monitoring of the patients were done during their hospital stay. Post-therapy body scan was done but not with all patients. Most of the side effects noted were sialitis, mild neck pains, nausea and occasional vomiting as well as ageusia. These patients were maintained on thyroid hormone depending on their sensitivity but almost all were given 200-300mgs per day. The older patients tolerated only around 150mcgs/day. After four to six months, serum TSH, thyroglobulin and total body scan were

  13. Dosimetric performance of an enhanced dose range radiographic film for intensity-modulated radiation therapy quality assurance

    International Nuclear Information System (INIS)

    Olch, Arthur J.

    2002-01-01

    Film-based quality assurance (QA) is an important element of any intensity modulated radiation therapy (IMRT) program. XV2 film is often used for IMRT QA, however, it has saturation and energy response limitations which hinder accurate film dosimetry. A new commercially released ready-pack film has been introduced that has an extended dose range (EDR2), reportedly allowing measured doses above 600 cGy without saturation. Also, this film may have less energy dependence due to its composition. The purpose of this paper is to study and compare the two types of film with respect to absolute dose accuracy for IMRT plans, percent depth dose accuracy for square fields between 2 and 20 cm, ability to measure composite plan isodoses and single beam fluence maps for IMRT cases, and sensitivity to processor variations over time. In 19 IMRT patient QA tests, the EDR2 film was able to achieve an absolute dose accuracy of better than 2% vs over 4% for XV2 film. The EDR2 film was able to reproduce ionization chamber and diode-measured percent depth doses to 20 cm depth generally to within 1% over the range of field sizes tested compared to about 10% for the XV2 film. When compared to calculations, EDR2 film agreed better than XV2 film for both composite plan isodoses and single beam fluence intensity maps. The EDR2 film was somewhat more resistant to processor changes over time than the XV2 film, with a standard deviation of dose reproducibility of less than 2% compared to 6%, respectively

  14. Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

    Science.gov (United States)

    Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

    2014-09-01

    Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

  15. Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

    Science.gov (United States)

    Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

    2016-10-01

    Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  16. Some effects of random dose measurement errors on analysis of atomic bomb survivor data

    International Nuclear Information System (INIS)

    Gilbert, E.S.

    1985-01-01

    The effects of random dose measurement errors on analyses of atomic bomb survivor data are described and quantified for several procedures. It is found that the ways in which measurement error is most likely to mislead are through downward bias in the estimated regression coefficients and through distortion of the shape of the dose-response curve. The magnitude of the bias with simple linear regression is evaluated for several dose treatments including the use of grouped and ungrouped data, analyses with and without truncation at 600 rad, and analyses which exclude doses exceeding 200 rad. Limited calculations have also been made for maximum likelihood estimation based on Poisson regression. 16 refs., 6 tabs

  17. Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

    Science.gov (United States)

    Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

    2014-04-01

    Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

  18. Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

    Science.gov (United States)

    Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

    2018-02-01

    Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

  19. Case study on implementation of the dose constraint concept in optimization in working environment

    Energy Technology Data Exchange (ETDEWEB)

    Krajewska, Grazyna; Krajewski, Pawel [Central Laboratory for Radiological Protection, PL-03194, Warsaw (Poland)

    2014-07-01

    A case study of already fixed dose constrain values in nuclear medicine sector, indicated that, the practical implementation of ICRP principle of optimization ( Publication 103, ICRP, 2007) still hit on methodology problems due to lack of adequate numerous monitoring data of internal contamination and complicated mathematical formalism. In practice, to ensure that 'the likelihood of incurring exposure, the number of people exposed, and the magnitude of their individual doses are kept as low as reasonably achievable', the baseline of effective doses together with statistical distribution is required. Furthermore, as it has revealed in this study, doses PHP's generated with MC methods had un-regularly shapes, depending on random operations rather than routine procedures. The role of dose constraints for occupational exposures, was further elaborated in Publication 101 (ICRP, 2006) as 'the dose constraint is a value of individual dose used to limit the range of options considered in the process of optimization'. The revisions of the International Basic Safety Standards as well as the Euratom Basic Safety Standard Directive both aim to implement new ICRP recommendations and have requirements to use dose constraints, defined broadly along the lines provided by the ICRP, and suggest that values be selected from the bands recommended by the ICRP. These will be obligatory adopted in the national regulations by regulatory authorities of EU countries. However, due to accidental characteristics of monitoring data, the 95% confidence tail of the doses for the most highly exposed individuals is near the limit of 20 mSv per year. This is apparently observed in the particular endocrinology units dealing with I-131 therapy. One might concluded that dose limitation and optimization are viewed as sufficient for the management of occupational exposures and reasonably be achieved. (authors)

  20. A Randomized Cross‐over Study of High‐dose Metoclopramide plus Dexamethasone versus Granisetron plus Dexamethasone in Patients Receiving Chemotherapy with High‐dose Cisplatin

    Science.gov (United States)

    Eguchi, Kenji; Shinkai, Tetsu; Tamura, Tomohide; Ohe, Yuichiro; Nisio, Masato; Kunikane, Hiroshi; Arioka, Hitoshi; Karato, Atsuya; Nakashima, Hajime; Sasaki, Yasutsuna; Tajima, Kinuko; Tada, Noriko; Saijo, Nagahiro

    1994-01-01

    We carried out a randomized, single‐blind, cross‐over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high‐dose metoclopramide plus dexamethasone (HDMP + Dx). Fifty‐four patients with primary or metastatic lung cancer, given single‐dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD=4.3) and 0,1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN + Dx groups, respectively (P=0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P= 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2–5, but it was not statistically significant. Twenty‐four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP + Dx. In the HDMP + Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and IS patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed. PMID:7829401

  1. Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone

    Energy Technology Data Exchange (ETDEWEB)

    Shipley, William U; Verhey, Lynn J; Munzenrider, John E; Suit, Herman D; Urie, Marcia M; McManus, Patricia L; Young, Robert H; Shipley, Jenot W; Zietman, Anthony L; Biggs, Peter J; Heney, Niall M; Goitein, Michael

    1995-04-30

    Purpose: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. Methods and Materials: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. Results: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy

  2. Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone

    International Nuclear Information System (INIS)

    Shipley, William U.; Verhey, Lynn J.; Munzenrider, John E.; Suit, Herman D.; Urie, Marcia M.; McManus, Patricia L.; Young, Robert H.; Shipley, Jenot W.; Zietman, Anthony L.; Biggs, Peter J.; Heney, Niall M.; Goitein, Michael

    1995-01-01

    Purpose: Following a thorough Phase I/II study, we evaluated by a Phase III trial high versus conventional dose external beam irradiation as mono-therapy for patients with Stage T3-T4 prostate cancer. Patient outcome following standard dose radiotherapy or following a 12.5% increase in total dose to 75.6 Cobalt Gray Equivalent (CGE) using a conformal perineal proton boost was compared for local tumor control, disease-free survival, and overall survival. Methods and Materials: Stage T3-T4, Nx, N0-2, M0 patients received 50.4 Gy by four-field photons and were randomized to receive either an additional 25.2 CGE by conformal protons (arm 1--the high dose arm, 103 patients, total dose 75.6 CGE) or an additional 16.8 Gy by photons (arm 2--the conventional dose arm, 99 patients, total dose 67.2 Gy). Actuarial overall survival (OS), disease-specific survival (DSS), total recurrence-free survival (TRFS), (clinically free, prostate specific antigen (PSA) less than 4ng/ml and a negative prostate rebiopsy, done in 38 patients without evidence of disease) and local control (digital rectal exam and rebiopsy negative) were evaluated. Results: The protocol completion rate was 90% for arm 1 and 97% for arm 2. With a median follow-up of 61 months (range 3 to 139 months) 135 patients are alive and 67 have died, 20 from causes other than prostate cancer. We found no significant differences in OS, DSS, TRFS or local control between the two arms. Among those completing randomized treatment (93 in arm 1 and 96 in arm 2), the local control at 5 and 8 years for arm 1 is 92% and 77%, respectively and is 80% and 60%, respectively for arm 2 (p = .089) and there are no significant differences in OS, DSS, and TRFS. The local control for the 57 patients with poorly differentiated (Gleason 4 or 5 of 5) tumors at 5 and 8 years for arm 1 is 94% and 84% and is 64% and 19% on arm 2 (p 0.0014). In patients whose digital rectal exam had normalized following treatment and underwent prostate rebiopsy

  3. Effects of gamma radiation in a wide range of doses on the morphological characteristics of Lemna minor L

    International Nuclear Information System (INIS)

    Rasskazova, M.M.; Berestina, A.V.

    2011-01-01

    The effects of gamma radiation on the morphological parameters of Lemna minor L. were studied. As the sensitive parameters were invited to use chlorosis and necrosis. Significant differences between samples begin to show after 14 days of observation. The presence of effect, irrespective of the dose in the range 0,1-30 Gy, shows the efficiency of a sufficiently small dose (0,1 Gy) was revealed.

  4. Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

    Science.gov (United States)

    van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

    2013-04-01

    Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

  5. Necessary accuracy of dose estimation during cohort epidemiologic study after irradiation

    International Nuclear Information System (INIS)

    Orlov, M.Yu.; Stepanenko, V.F.; Khoshi, M.; Takada, Dzh.

    2003-01-01

    Effect of breadth of dose ranges on values of radiation risk was estimated. Ratios of observed numbers of mortalities because of leukemia in the cohort in 1950 - 1974 under deferent radiation dose to expected number of mortalities in this cohort only under background radiation were used as degree of risk. Data of cooperative Japan-American Program LSS (Life Span Study) were applied in the researches. It is established that required for the risk assessment with uncertainty 20 - 30 % the accuracy of dose estimation comprises 30 - 35 % in the range 1 - 5 rad and 5 - 10 % in the range 5 - 30 rad [ru

  6. Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

    Science.gov (United States)

    Mösges, Ralph; Rohdenburg, Christina; Eichel, Andrea; Zadoyan, Gregor; Kasche, Elena-Manja; Shah-Hosseini, Kija; Lehmacher, Walter; Schmalz, Petra; Compalati, Enrico

    2017-11-01

    To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

  7. Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

    Science.gov (United States)

    Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

    2010-01-01

    Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

  8. Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug

    Directory of Open Access Journals (Sweden)

    N. Shafiq

    2014-01-01

    Full Text Available Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85±1.94 h, 13.77±2.05 h, and 878.74±133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

  9. Two factors influencing dose reconstruction in low dose range: the variability of BKG intensity on one individual and water content

    International Nuclear Information System (INIS)

    Zhang, Tengda; Zhang, Wenyi; Zhao, Zhixin; Zhang, Haiying; Ruan, Shuzhou; Jiao, Ling

    2016-01-01

    A fast and accurate retrospective dosimetry method for the triage is very important in radiation accidents. Electron paramagnetic resonance (EPR) fingernail dosimetry is a promising way to estimate radiation dose. This article presents two factors influencing dose reconstruction in low dose range: the variability of background signal (BKG) intensity on one individual and water content. Comparing the EPR spectrum of dried and humidified fingernail samples, it is necessary to add a procedure of dehydration before EPR measurements, so as to eliminate the deviation caused by water content. Besides, the BKGs of different fingers' nails are not the same as researchers thought previously, and the difference between maximum and minimum BKG intensities of one individual can reach 55.89 %. Meanwhile, the variability of the BKG intensity among individuals is large enough to impact precise dose reconstruction. Water within fingernails and instability of BKG are two reasons that cause the inaccuracy of radiation dose reconstruction in low-dosage level. (authors)

  10. An epidemiological study for the reduction of population radiation dose

    International Nuclear Information System (INIS)

    Gamo, Makoto

    1989-01-01

    The correlation of tube voltage with patient exposure was studied using effective dose as an indicator of dose reduction in intraoral radiography. The results were as follows: l. The salivary gland tissues contributed the most to the effective dose of intraoral radiography. 2. In the 50 to 90 kV range, there was no appreciable correlation between tube voltage and effective dose. 3. Therefore, it was suggested that adjusting the tube voltage for maximum image quality does not effect radiation protection. 4. This study reconfirmed the fact that increases in voltages up to 90 kV reduce skin doses. (author)

  11. Radiation dose to the patient in radionuclide studies

    International Nuclear Information System (INIS)

    Roedler, H.D.

    1981-01-01

    In medical radionuclide studies, the radiation risk has to be considered in addition to the general risk of administering a pharmaceutical. As radiation exposure is an essential factor in radiation risk estimation, some aspects of internal dose calculation, including radiation risk assessments, are treated. The formalism of current internal dose calculation is presented. The input data, especially the residence time and the absorbed dose per transformation, their origin and accuracy are discussed. Results of internal dose calculations for the ten most frequently used radionuclide studies are presented as somatically effective dose equivalents. The accuracy of internal dose calculation is treated in detail by considering the biokinetics of the radiopharmaceutical, the phantoms used for dose calculations, the absorbed dose per transformation, the administered activity, and the transfer of the dose, calculated for a phantom, to the patient. The internal dose calculated for a reference phantom may be assumed to be in accordance with the actual patient dose within a range described by a factor of about two to three. Finally, risk estimates for nuclear medicine procedures are quantified, being generally of sixth order. The radiation risk from the radioiodine test is comparably higher, but probably lower than calculated according to the UNSCEAR risk coefficients. However, further studies are needed to confirm these preliminary results and to improve the quantification of the radiation risk from the medical use of radionuclides. (author)

  12. SU-F-BRD-09: A Random Walk Model Algorithm for Proton Dose Calculation

    International Nuclear Information System (INIS)

    Yao, W; Farr, J

    2015-01-01

    Purpose: To develop a random walk model algorithm for calculating proton dose with balanced computation burden and accuracy. Methods: Random walk (RW) model is sometimes referred to as a density Monte Carlo (MC) simulation. In MC proton dose calculation, the use of Gaussian angular distribution of protons due to multiple Coulomb scatter (MCS) is convenient, but in RW the use of Gaussian angular distribution requires an extremely large computation and memory. Thus, our RW model adopts spatial distribution from the angular one to accelerate the computation and to decrease the memory usage. From the physics and comparison with the MC simulations, we have determined and analytically expressed those critical variables affecting the dose accuracy in our RW model. Results: Besides those variables such as MCS, stopping power, energy spectrum after energy absorption etc., which have been extensively discussed in literature, the following variables were found to be critical in our RW model: (1) inverse squared law that can significantly reduce the computation burden and memory, (2) non-Gaussian spatial distribution after MCS, and (3) the mean direction of scatters at each voxel. In comparison to MC results, taken as reference, for a water phantom irradiated by mono-energetic proton beams from 75 MeV to 221.28 MeV, the gamma test pass rate was 100% for the 2%/2mm/10% criterion. For a highly heterogeneous phantom consisting of water embedded by a 10 cm cortical bone and a 10 cm lung in the Bragg peak region of the proton beam, the gamma test pass rate was greater than 98% for the 3%/3mm/10% criterion. Conclusion: We have determined key variables in our RW model for proton dose calculation. Compared with commercial pencil beam algorithms, our RW model much improves the dose accuracy in heterogeneous regions, and is about 10 times faster than MC simulations

  13. Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study.

    Science.gov (United States)

    Jensterle, Mojca; Goricar, Katja; Janez, Andrej

    2016-04-01

    Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m 2 ; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m 2 in patients treated with COMBO and by 1.4±1.2 kg/m 2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.

  14. Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors

    Directory of Open Access Journals (Sweden)

    Jappe Annette

    2011-01-01

    Full Text Available Abstract Background This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. Methods A total of 24 patients with advanced breast cancer (n = 6, gastric cancer (n = 6, non-small cell lung cancer (n = 6, or renal cell carcinoma (n = 6 who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. Results Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4 and 2 h (range, 0.9-6 in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7% and fatigue (16.7% and 33.3% in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83% and 6 (50% patients in the 5 and 10 mg/day groups, respectively. Conclusions Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. Trial registration Chinese Health Authorities 2008L09346

  15. A phase 1, open-label, randomized study to compare the immunogenicity and safety of different administration routes and doses of virosomal influenza vaccine in elderly.

    Science.gov (United States)

    Levin, Yotam; Kochba, Efrat; Shukarev, Georgi; Rusch, Sarah; Herrera-Taracena, Guillermo; van Damme, Pierre

    2016-10-17

    Influenza remains a significant problem in elderly despite widespread vaccination coverage. This randomized, phase-I study in elderly compared different strategies of improving vaccine immunogenicity. A total of 370 healthy participants (⩾65years) were randomized equally 1:1:1:1:1:1 to six influenza vaccine treatments (approximately 60-63 participants per treatment arm) at day 1 that consisted of three investigational virosomal vaccine formulations at doses of 7.5, 15, and 45μg HA antigen/strain administered intradermally (ID) by MicronJet600™ microneedle device (NanoPass Technologies) or intramuscularly (IM), and three comparator registered seasonal vaccines; Inflexal V™ (Janssen) and MF59 adjuvanted Fluad™ (Novartis) administered IM and Intanza™ (Sanofi Pasteur) administered ID via Soluvia™ prefilled microinjection system (BD). Serological evaluations were performed at days 22 and 90 and safety followed-up for 6months. Intradermal delivery of virosomal vaccine using MicronJet600™ resulted in significantly higher immunogenicity than the equivalent dose of virosomal Inflexal V™ administered intramuscularly across most of the parameters and strains, as well as in some of the readouts and strains as compared with the 45μg dose of virosomal vaccine formulation. Of 370 participants, 300 (81.1%) reported ⩾1 adverse event (AE); more participants reported solicited local AEs (72.2%) than solicited systemic AEs (12.2%). Intradermal delivery significantly improved influenza vaccine immunogenicity compared with intramuscular delivery. Triple dose (45μg) virosomal vaccine did not demonstrate any benefit on vaccine's immunogenicity over 15μg commercial presentation. All treatments were generally safe and well-tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Vitamin D supplementation in nursing home patients: randomized controlled trial of standard daily dose versus individualized loading dose regimen.

    Science.gov (United States)

    Wijnen, Hugo; Salemink, Dayenne; Roovers, Lian; Taekema, Diana; de Boer, Hans

    2015-05-01

    Supplementation of cholecalciferol 800 IU daily appears to be insufficient to raise vitamin D levels to >75 nmol/l in nursing home (NH) patients. Our objective was to compare the efficacy of an individualized cholecalciferol loading dose (LD) regimen and a daily dose (DD) regimen of cholecalciferol 800 IU in reaching 25-OH vitamin D (25OHD) levels >75 nmol/l. A total of 30 NH patients with 25OHD levels 50 nmol/l were included. Patients were randomized using the minimization method in the LD or DD group. The cholecalciferol LD, calculated with an algorithm based on serum 25OHD level and body weight, was administered in divided doses of 50,000 IU twice a week, followed by a monthly maintenance dose of either 50,000 or 25,000 IU. The DD regimen consisted of cholecalciferol 800 IU daily for 26 weeks. Serum 25OHD, calcium, creatinine, phosphate, and parathyroid hormone were measured, and 2-minute walking test, handgrip strength, and timed get up and go test were assessed at baseline (T 0), after 5 weeks (T 5), 12 weeks (T 12), and 26 weeks (T 26). The primary endpoint was the percentage of patients with 25OHD levels >75 nmol/l at T 5. Secondary endpoints were the proportion of patients with 25OHD levels >75 nmol/l at T 26, safety of LD regimen, and improvement of performance tests with normalization of vitamin D levels. Median baseline 25OHD levels (interquartile range) were comparable between the 14 DD and 16 LD patients: 20.9 (15.9-29.6) and 21.7 (16.4-32.8) nmol/l, respectively. Levels of 25OHD >75 nmol/l at T 5 were reached in 79 % of the 14 LD patients, but in none of the 13 DD patients (p 75 nmol/l were reached in 83 % of the 12 LD patients and in 30 % of the ten DD patients (p tests was observed. In NH patients with severe 25OHD deficiency, an individualized calculated cholecalciferol LD is likely to be superior to a DD of cholecalciferol 800 IU in terms of the ability to rapidly normalize vitamin D levels.

  17. Homeostatic balance as an indicator of prolonged technogenic exposure in low dose range

    International Nuclear Information System (INIS)

    Karpov, A.B.; Voronova, I.A.; Takhauov, R.M.; Semyonova, Yu.V.; Sherstoboev, E.Yu.; Udut, V.V.

    2008-01-01

    Full text: Indication of changes induced by ionizing radiation starting up a wide range of pathologic reactions in the disease developments still poses a significant problem in radiation medicine. It mainly concerns exposure to low dose-rate ionizing radiation, since its effects are still open to question, and today any researcher acknowledges that radiation induced pathological changes can accumulate at both subclinical and prenosological stages and develop not only in exposed persons, but also in their offspring. The subject of this study was workers of reactor and radiochemical productions of Siberian Group of Chemical Enterprises (SGCE) exposed to external and combined (external and internal) radiation respectively. Two comparative groups were formed: reactor and radiochemical production workers. In the reactor production group of workers the cumulative dose of external γ-radiation was up to 300 mSv, in the radiochemical production group - up to 150 mSv. Age ranged from 40 to 50 years. The two groups were compared between each other. Above all, there were formed 'insider control' groups (workers of the same productions with zero doses) to assess the impact of radiation factor on central homeostatic mechanisms. These groups were created using pair technique in order to level somatic disorders influence on the parameters under study. Numbers of full and biochemical blood examinations, energy metabolism between cells, hormones of homeostasis by the adaptive hormone level - insulin and cortisol, lipid peroxidation and antioxidant protection systems, immune and vegetative systems were all analyzed. Analyses of the systems performed, it was found out that in persons having been exposed to long term occupational radiation there were significant changes indicating lipid peroxidation system activation, antioxidant protection system depression, as well as lowered energy metabolism. The higher external γ-doses the bigger these changes are. Results from the two groups of

  18. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  19. Comparative bioavailability and pharmacokinetics of two oral formulations of flurbiprofen: a single-dose, randomized, open-label, two-period, crossover study in Pakistani subjects.

    Science.gov (United States)

    Qayyum, Aisha; Najmi, Muzammil Hasan; Abbas, Mateen

    2013-11-01

    Comparative bioavailability studies are conducted to establish the bioequivalence of generic formulation with that of branded reference formulation, providing confidence to clinicians to use these products interchangeably. This study was carried out to compare a locally manufactured formulation of flurbiprofen with that of a branded product. Twenty two healthy male adults received a single dose of flurbiprofen (100mg) either generic or branded product according to randomization scheme on each of 2 periods. Blood samples were collected and plasma flurbiprofen concentration was determined by a validated HPLC method. Pharmacokinetic parameters like AUC(0-t), AUC(0-oo), Cmax, Tmax, t½, Vd and clearance were determined. The 90% CI for the ratio of geometric means of test to reference product's pharmacokinetic variables was calculated. Pharmacokinetic parameters for two formulations were comparable. Ratio of means of AUC(0-24), AUC(0-oo) and Cmax for test to reference products and 90% CI for these ratios were within the acceptable range. The p-values calculated by TOST were much less than the specified value (p-0.05). ANOVA gave p-values which were more than the specified value (p-0.05) for sequence, subject, period and formulation. Test formulation of flurbiprofen (tablet Flurso) was found to meet the criteria for bioequivalence to branded product (tablet Ansaid) based on pharmacokinetic parameters.

  20. Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial.

    Science.gov (United States)

    Jo, Young-Il; Na, Ha-Young; Moon, Ju-Young; Han, Sang-Woong; Yang, Dong-Ho; Lee, Sang-Ho; Park, Hyeong-Cheon; Choi, Hoon-Young; Lim, So-Dug; Kie, Jeong-Hae; Lee, Yong-Kyu; Shin, Sug-Kyun

    2016-03-01

    Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% ± 26.1% (p valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria.

  1. Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

    Science.gov (United States)

    Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

    2010-11-01

    Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and

  2. Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin γ-Carboxylation: A Double-Blind, Randomized Controlled Trials.

    Science.gov (United States)

    Inaba, Naoko; Sato, Toshiro; Yamashita, Takatoshi

    2015-01-01

    Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin γ-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 μg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 μg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 μg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 μg groups compared with the 0 μg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 μg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake ≥100 μg was suggested to improve osteocalcin γ-carboxylation.

  3. Randomized Controlled Trial Comparing Exercise to Health Education for Stimulant Use Disorder: Results From the CTN-0037 STimulant Reduction Intervention Using Dosed Exercise (STRIDE) Study.

    Science.gov (United States)

    Trivedi, Madhukar H; Greer, Tracy L; Rethorst, Chad D; Carmody, Thomas; Grannemann, Bruce D; Walker, Robrina; Warden, Diane; Shores-Wilson, Kathy; Stoutenberg, Mark; Oden, Neal; Silverstein, Meredith; Hodgkins, Candace; Love, Lee; Seamans, Cindy; Stotts, Angela; Causey, Trey; Szucs-Reed, Regina P; Rinaldi, Paul; Myrick, Hugh; Straus, Michele; Liu, David; Lindblad, Robert; Church, Timothy; Blair, Steven N; Nunes, Edward V

    To evaluate exercise as a treatment for stimulant use disorders. The STimulant Reduction Intervention using Dosed Exercise (STRIDE) study was a randomized clinical trial conducted in 9 residential addiction treatment programs across the United States from July 2010 to February 2013. Of 497 adults referred to the study, 302 met all eligibility criteria, including DSM-IV criteria for stimulant abuse and/or dependence, and were randomized to either a dosed exercise intervention (Exercise) or a health education intervention (Health Education) control, both augmenting treatment as usual and conducted thrice weekly for 12 weeks. The primary outcome of percent stimulant abstinent days during study weeks 4 to 12 was estimated using a novel algorithm adjustment incorporating self-reported Timeline Followback (TLFB) stimulant use and urine drug screen (UDS) data. Mean percent of abstinent days based on TLFB was 90.8% (SD = 16.4%) for Exercise and 91.6% (SD = 14.7%) for Health Education participants. Percent of abstinent days using the eliminate contradiction (ELCON) algorithm was 75.6% (SD = 27.4%) for Exercise and 77.3% (SD = 25.1%) for Health Education. The primary intent-to-treat analysis, using a mixed model controlling for site and the ELCON algorithm, produced no treatment effect (P = .60). In post hoc analyses controlling for treatment adherence and baseline stimulant use, Exercise participants had a 4.8% higher abstinence rate (78.7%) compared to Health Education participants (73.9%) (P = .03, number needed to treat = 7.2). The primary analysis indicated no significant difference between exercise and health education. Adjustment for intervention adherence showed modestly but significantly higher percent of abstinent days in the exercise group, suggesting that exercise may improve outcomes for stimulant users who have better adherence to an exercise dose. ClinicalTrials.gov identifier: NCT01141608. © Copyright 2017 Physicians Postgraduate Press, Inc.

  4. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Science.gov (United States)

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  5. Preliminary evaluation of second harmonic direct detection scheme for low-dose range in alanine/EPR dosimetry

    International Nuclear Information System (INIS)

    Chen, Felipe; Graeff, Carlos F.O.; Baffa, Oswaldo

    2002-01-01

    The usefulness of a direct detection scheme of the second harmonic (2h) overmodulated signal from irradiated alanine in EPR dosimetry was studied. For this purpose, a group of DL-alanine/paraffin cylindrical pellets was produced. The dosimeters were irradiated with a 60 Co radiotherapy gamma source with doses of 0.05, 0.1, 0.5, 1 and 5 Gy. The EPR measurements were carried out in a VARIAN-E4 spectrometer operating in X-band with optimized parameters to obtain highest amplitude signals of both harmonics. The 2h signal was detected directly at twice the modulation frequency. In preliminary results, the 2h showed some advantages over the 1h such as better resolution for doses below 1 Gy, better repeatability results and better linear behaviour in the dose range indicated. (author)

  6. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

    Science.gov (United States)

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2015-07-01

    High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

  7. Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

    Science.gov (United States)

    Goodman, David W; Starr, H Lynn; Ma, Yi-Wen; Rostain, Anthony L; Ascher, Steve; Armstrong, Robert B

    2017-01-01

    To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040. © Copyright 2017 Physicians Postgraduate Press, Inc.

  8. Once-daily dose regimen of ribavirin is interchangeable with a twice-daily dose regimen: randomized open clinical trial

    Directory of Open Access Journals (Sweden)

    Balk JM

    2015-08-01

    Full Text Available Jiska M Balk,1 Guido RMM Haenen,1 Özgür M Koc,2 Ron Peters,3 Aalt Bast,1 Wim JF van der Vijgh,1 Ger H Koek,4 1Department of Toxicology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, 2Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 3DSM Resolve, Geleen, 4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands Background: The combination of ribavirin (RBV and pegylated interferon (PEG-IFN is effective in the treatment of chronic hepatitis C infection. Reducing the frequency of RBV intake from twice to once a day will improve compliance and opens up the opportunity to combine RBV with new and more specific direct-acting agents in one pill. Therefore, the purpose of this study was to evaluate the pharmacokinetic profile of RBV in a once-daily to twice-daily regimen. The secondary aim was to determine tolerability as well as the severity and differences in side effects of both treatment regimens. Methods: In this randomized open-label crossover study, twelve patients with chronic type 1 hepatitis C infection and weighing more than 75 kg were treated with 180 µg of PEG-IFN weekly and 1,200 mg RBV daily for 24 weeks. The patients received RBV dosed as 1,200 mg once-daily for 12 weeks followed by RBV dosed as 600 mg twice-daily for 12 weeks, or vice versa. In addition to the pharmacokinetic profile, the hematological profile and side effects were recorded. The RBV concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Results: Eight of twelve patients completed the study. Neither the time taken for RBV to reach peak plasma concentration nor the AUC0-last (adjusted for difference in dose was significantly different between the two groups (P>0.05. Furthermore, the once-daily regimen did not give more side effects than the twice-daily regimen (P>0

  9. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    Science.gov (United States)

    Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-04-01

    To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

  10. Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

    Science.gov (United States)

    Helmy, Sally A; El-Bedaiwy, Heba M

    2014-11-01

    Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

  11. Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

    Science.gov (United States)

    Bernardo-Escudero, Roberto; Alonso-Campero, Rosalba; Francisco-Doce, María Teresa de Jesús; Cortés-Fuentes, Myriam; Villa-Vargas, Miriam; Angeles-Uribe, Juan

    2012-12-01

    The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

  12. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

    Science.gov (United States)

    van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

    2017-08-01

    To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; ptofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

    Science.gov (United States)

    Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

    Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

  14. Range walk error correction and modeling on Pseudo-random photon counting system

    Science.gov (United States)

    Shen, Shanshan; Chen, Qian; He, Weiji

    2017-08-01

    Signal to noise ratio and depth accuracy are modeled for the pseudo-random ranging system with two random processes. The theoretical results, developed herein, capture the effects of code length and signal energy fluctuation are shown to agree with Monte Carlo simulation measurements. First, the SNR is developed as a function of the code length. Using Geiger-mode avalanche photodiodes (GMAPDs), longer code length is proven to reduce the noise effect and improve SNR. Second, the Cramer-Rao lower bound on range accuracy is derived to justify that longer code length can bring better range accuracy. Combined with the SNR model and CRLB model, it is manifested that the range accuracy can be improved by increasing the code length to reduce the noise-induced error. Third, the Cramer-Rao lower bound on range accuracy is shown to converge to the previously published theories and introduce the Gauss range walk model to range accuracy. Experimental tests also converge to the presented boundary model in this paper. It has been proven that depth error caused by the fluctuation of the number of detected photon counts in the laser echo pulse leads to the depth drift of Time Point Spread Function (TPSF). Finally, numerical fitting function is used to determine the relationship between the depth error and the photon counting ratio. Depth error due to different echo energy is calibrated so that the corrected depth accuracy is improved to 1cm.

  15. Nonlinear complexity of random visibility graph and Lempel-Ziv on multitype range-intensity interacting financial dynamics

    Science.gov (United States)

    Zhang, Yali; Wang, Jun

    2017-09-01

    In an attempt to investigate the nonlinear complex evolution of financial dynamics, a new financial price model - the multitype range-intensity contact (MRIC) financial model, is developed based on the multitype range-intensity interacting contact system, in which the interaction and transmission of different types of investment attitudes in a stock market are simulated by viruses spreading. Two new random visibility graph (VG) based analyses and Lempel-Ziv complexity (LZC) are applied to study the complex behaviors of return time series and the corresponding random sorted series. The VG method is the complex network theory, and the LZC is a non-parametric measure of complexity reflecting the rate of new pattern generation of a series. In this work, the real stock market indices are considered to be comparatively studied with the simulation data of the proposed model. Further, the numerical empirical study shows the similar complexity behaviors between the model and the real markets, the research confirms that the financial model is reasonable to some extent.

  16. Prospective randomized clinical studies involving reirradiation. Lessons learned

    International Nuclear Information System (INIS)

    Nieder, Carsten; Langendijk, Johannes A.; Guckenberger, Matthias; Grosu, Anca L.

    2016-01-01

    Reirradiation is a potentially useful option for many patients with recurrent cancer. The purpose of this study was to review all recently published randomized trials in order to identify methodological strengths and weaknesses, comment on the results, clinical implications and open questions, and give advice for the planning of future trials. Systematic review of trials published between 2000 and 2015 (databases searched were PubMed, Scopus and Web of Science). We reviewed 9 trials, most of which addressed reirradiation of head and neck tumours. The median number of patients was 69. Trial design, primary endpoint and statistical hypotheses varied widely. The results contribute mainly to decision making for reirradiation of nasopharynx cancer and bone metastases. The trials with relatively long median follow-up confirm that serious toxicity remains a concern after high cumulative total doses. Multi-institutional collaboration is encouraged to complete sufficiently large trials. Despite a paucity of large randomized studies, reirradiation has been adopted in different clinical scenarios by many institutions. Typically, the patients have been assessed by multidisciplinary tumour boards and advanced technologies are used to create highly conformal dose distributions. (orig.) [de

  17. A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy

    NARCIS (Netherlands)

    Wymenga, ANM; vanderGraaf, WTA; Wils, JA; vanHeukelom, LS; vanderLinden, GHM; DullemondWestland, AC; Nooy, M; vanderHeul, C; deBruijn, KM; deVries, EGE

    Background: This study compares efficacy safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy. Patients and methods: 152 chemotherapy-naive cancer patients were randomized in a double-blind

  18. Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment

    International Nuclear Information System (INIS)

    Glimelius, Bengt; Isacsson, Ulf; Jung, Bo; Paahlman, Lars

    1997-01-01

    Purpose: This study explored the relationship between radiation dose and reduction in local recurrence rate after preoperative and postoperative radiotherapy in rectal cancer. Methods and Materials: All randomized trials initiated prior to 1988 comparing preoperative and postoperative radiotherapy with surgery alone or with each other were included. Local failure rates were available in 5626 randomized patients. The linear quadratic formula was used to compensate for different radiotherapy schedules. Results: For preoperative radiotherapy, a clear dose-response relationship could be established. For postoperative radiotherapy, the range of doses was narrow, and a dose-response relationship could not be demonstrated. At similar doses, preoperative radiotherapy appeared to be more efficient in reducing local failure rate than postoperative. The only trial comparing preoperative with postoperative radiotherapy confirms this notion. A 15-20 Gy higher dose may be required postoperatively than preoperatively to reach similar efficacy. Neither approach alone significantly influences survival, although it is likely that a small survival benefit may be seen after preoperative radiotherapy. Conclusions: The information from the entire randomized experience suggests that preoperative radiotherapy may be more dose efficient than postoperative radiotherapy

  19. Staggering the dose of sugammadex lowers risks for severe emergence cough: a randomized control trial.

    Science.gov (United States)

    P S, Loh; Miskan, M M; Y Z, Chin; Zaki, R A

    2017-10-11

    Cough on emergence has been reported as a common adverse reaction with sugammadex reversal. We investigated if staggering the dose of sugammadex will reduce emergence cough in a single-center, randomized, double-blinded study. A hundred and twenty ASA 1-3 adults were randomly reversed with 1 mg/kg sugammadex prior to extubation followed by another 1 mg/kg immediately after extubation (staggered group), single dose of 2 mg/kg sugammadex (single bolus group) or neostigmine 0.02 mg/kg with glycopyrrolate (neostigmine group). We found 70% of patients (n = 28) reversed with single boluses of sugammadex had Grade 3 emergence cough compared to 12.5% (n = 5) in the staggered sugammadex group and 17.5% (n = 7) in the neostigmine group (p sugammadex group (n = 14, 35%, p = 0.005). On the other hand, staggering sugammadex lowered risks of developing severe cough (RR 0.2, p sugammadex group and control given neostigmine. In terms of timing, there was no delay in time taken from discontinuing anesthetic agents to reversal and extubation if sugammadex was staggered (emergence time 6.0 ± 3.2 s, p = 0.625 and reversal time 6.5 ± 3.5, p = 0.809). Staggering the dose of sugammadex for reversal will effectively decrease common emergence and early postoperative complications. ANZCTR Number ACTRN12616000116426 . Retrospectively registered on 2nd February 2016.

  20. Optimal Target Range of Closed-Loop Inspired Oxygen Support in Preterm Infants: A Randomized Cross-Over Study.

    Science.gov (United States)

    van den Heuvel, Maria Elisabeth Nicoletta; van Zanten, Henriette A; Bachman, Tom E; Te Pas, Arjan B; van Kaam, Anton H; Onland, Wes

    2018-06-01

    To investigate the effect of different pulse oximetry (SpO 2 ) target range settings during automated fraction of inspired oxygen control (A-FiO 2 ) on time spent within a clinically set SpO 2 alarm range in oxygen-dependent infants on noninvasive respiratory support. Forty-one preterm infants (gestational age [median] 26 weeks, age [median] 21 days) on FiO 2  >0.21 receiving noninvasive respiratory support were subjected to A-FiO 2 using 3 SpO 2 target ranges (86%-94%, 88%-92%, or 89%-91%) in random order for 24 hours each. Before switching to the next target range, SpO 2 was manually controlled for 24 hours (washout period). The primary outcome was the time spent within the clinically set alarm limits of 86%-94%. The percent time within the 86%-94% SpO 2 alarm range was similar for all 3 A-FiO 2 target ranges (74%). Time spent in hyperoxemia was not significantly different between target ranges. However, the time spent in severe hypoxemia (SpO 2  target ranges of A-FiO 2 (88%-92%; 1.9%, 89%-91%; 1.7%) compared with the wide target range (86%-94%; 3.4%, P target range. Narrowing the target range of A-FiO 2 to the desired median ±2% is effective in reducing the time spent in hypoxemia, without increasing the risk of hyperoxemia. www.trialregister.nl: NTR4368. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Efficacy of prokinetics with a split-dose of polyethylene glycol in bowel preparation for morning colonoscopy: a randomized controlled trial.

    Science.gov (United States)

    Kim, Hyoung Jun; Kim, Tae Oh; Shin, Bong Chul; Woo, Jae Gon; Seo, Eun Hee; Joo, Hee Rin; Heo, Nae-Yun; Park, Jongha; Park, Seung Ha; Yang, Sung Yeon; Moon, Young Soo; Shin, Jin-Yong; Lee, Nae Young

    2012-01-01

    Currently, a split-dose of polyethylene glycol (PEG) is the mainstay of bowel preparation due to its tolerability, bowel-cleansing action, and safety. However, bowel preparation with PEG is suboptimal because residual fluid reduces the polyp detection rate and requires a more thorough colon inspection. The aim of our study was to demonstrate the efficacy of a sufficient dose of prokinetics on bowel cleansing together with split-dose PEG. A prospective endoscopist-blinded study was conducted. Patients were randomly allocated to two groups: prokinetic with split-dose PEG or split-dose PEG alone. A prokinetic [100 mg itopride (Itomed)], was administered twice simultaneously with each split-dose of PEG. Bowel-cleansing efficacy was measured by endoscopists using the Ottawa scale and the segmental fluidity scale score. Each participant completed a bowel preparation survey. Mean scores from the Ottawa scale, segmental fluid scale, and rate of poor preparation were compared between both groups. Patients in the prokinetics with split-dose PEG group showed significantly lower total Ottawa and segmental fluid scores compared with patients in the split-dose of PEG alone group. A sufficient dose of prokinetics with a split-dose of PEG showed efficacy in bowel cleansing for morning colonoscopy, largely due to the reduction in colonic fluid. Copyright © 2012 S. Karger AG, Basel.

  2. Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas

    International Nuclear Information System (INIS)

    Khalil, Azza A.; Bentzen, Soeren M.; Bernier, Jacques; Saunders, Michele I.; Horiot, Jean-Claude; Bogaert, Walter van den; Cummings, Bernard J.; Dische, Stanley

    2003-01-01

    Purpose: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. Methods and Materials: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D prolif of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. Results: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. Conclusions: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials

  3. Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

    Directory of Open Access Journals (Sweden)

    Weise-Kelly Lorraine

    2011-08-01

    Full Text Available Abstract Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing. Methods We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (i.e., CCDSS showed improvement if at least 50% of the relevant study outcomes were statistically significantly positive. Results Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14, insulin (6, theophylline/aminophylline (4, aminoglycosides (3, digoxin (2, lidocaine (1, or as part of a multifaceted approach (3. Cluster randomization was rarely used (18% and CCDSSs were usually stand-alone systems (76% primarily used by physicians (85%. Overall, 18 of 30 studies (60% showed an improvement in the process of care and 4 of 19 (21% an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range. Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing

  4. Radiolysis of aqueous solutions of ammonium bicarbonate over a large dose range

    International Nuclear Information System (INIS)

    Draganic, Z.D.; Draganic, I.G.; Negron-Mendoza, A.; Navarro-Gonzales, R.; Albarran-Sanchez, M.G.; Sehested, K.

    1986-12-01

    0 2 -free aqueous solutions of 0.05 mol dm -3 ammonium bicarbonate were studied after receiving various doses of 60 Co gammas (0.001-170 Mrd) or krd pulses of 10 MeV electrons. Formate, oxalate, formaldehyde and an unidentified polymer (M w 14000-16000 daltons) were found to be the main radiolytic products. A large initial yield of formate in the γ-radiolysis, G(HCOO - ) = 2.2, is due to the reaction CO 2 - + HCO 3 - ↔ HC00 - + CO 3 - . The efficiency of organic synthesis within the large dose range studied is low and is explained by efficient pathways to the reformation of bicarbonate, where the reaction CO 2 - + CO 3 - is particurlarly significant. Computer fitting of the data obtained in the γ-radiolysis and by pulsed electron beam experiments gives k(CO 2 - + HCO 3 - ) = (2 ± 0.4)x10 3 dm 3 mol -1 s -1 , k(CO 2 - + CO 3 - ) = (5 ± 1)x10 7 dm 3 mol -1 s -1 , k(NH 2 + = HCO 3 - ) 4 dm 3 mol -1 s -1 and k(NH 2 + CO 3 - ) = (1.5 ± 0.5)x10 9 dm 3 mol -1 s -1 . (author)

  5. Long-range epidemic spreading in a random environment.

    Science.gov (United States)

    Juhász, Róbert; Kovács, István A; Iglói, Ferenc

    2015-03-01

    Modeling long-range epidemic spreading in a random environment, we consider a quenched, disordered, d-dimensional contact process with infection rates decaying with distance as 1/rd+σ. We study the dynamical behavior of the model at and below the epidemic threshold by a variant of the strong-disorder renormalization-group method and by Monte Carlo simulations in one and two spatial dimensions. Starting from a single infected site, the average survival probability is found to decay as P(t)∼t-d/z up to multiplicative logarithmic corrections. Below the epidemic threshold, a Griffiths phase emerges, where the dynamical exponent z varies continuously with the control parameter and tends to zc=d+σ as the threshold is approached. At the threshold, the spatial extension of the infected cluster (in surviving trials) is found to grow as R(t)∼t1/zc with a multiplicative logarithmic correction and the average number of infected sites in surviving trials is found to increase as Ns(t)∼(lnt)χ with χ=2 in one dimension.

  6. Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

    Science.gov (United States)

    Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

    2011-01-01

    Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

  7. Random and systematic beam modulator errors in dynamic intensity modulated radiotherapy

    International Nuclear Information System (INIS)

    Parsai, Homayon; Cho, Paul S; Phillips, Mark H; Giansiracusa, Robert S; Axen, David

    2003-01-01

    This paper reports on the dosimetric effects of random and systematic modulator errors in delivery of dynamic intensity modulated beams. A sliding-widow type delivery that utilizes a combination of multileaf collimators (MLCs) and backup diaphragms was examined. Gaussian functions with standard deviations ranging from 0.5 to 1.5 mm were used to simulate random positioning errors. A clinical example involving a clival meningioma was chosen with optic chiasm and brain stem as limiting critical structures in the vicinity of the tumour. Dose calculations for different modulator fluctuations were performed, and a quantitative analysis was carried out based on cumulative and differential dose volume histograms for the gross target volume and surrounding critical structures. The study indicated that random modulator errors have a strong tendency to reduce minimum target dose and homogeneity. Furthermore, it was shown that random perturbation of both MLCs and backup diaphragms in the order of σ = 1 mm can lead to 5% errors in prescribed dose. In comparison, when MLCs or backup diaphragms alone was perturbed, the system was more robust and modulator errors of at least σ = 1.5 mm were required to cause dose discrepancies greater than 5%. For systematic perturbation, even errors in the order of ±0.5 mm were shown to result in significant dosimetric deviations

  8. Dose-response relationship with radiotherapy: an evidence?

    International Nuclear Information System (INIS)

    Chauvet, B.; Rauglaudre, G. de; Mineur, L.; Alfonsi, M.; Reboul, F.

    2003-01-01

    The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical data, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective data (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies. (author)

  9. Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers.

    Science.gov (United States)

    Zimmermann, Torsten; Höchel, Joachim; Becka, Michael; Boettger, Michael K; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S; Donath, Frank

    2018-05-01

    Regorafenib is a multikinase inhibitor under investigation for use in neovascular age-related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. This was a single-centre, randomized, double-masked, parallel-group, dose-escalation, placebo-controlled study. Subjects received regorafenib eye drops (30 mg ml -1 , 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Thirty-six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600-700-fold lower than after multiple oral administration of 160 mg day -1 , the dose approved in cancer indications. These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml -1 tid for use in clinical studies. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  10. Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

    Science.gov (United States)

    Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

    2017-09-01

    The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p appendicitis and reduces the dose by approximately 46%.

  11. Clinical application of AcMAR (accelerated multiple-arc radiotherapy) for head and neck tumors. Results of a randomized, two-dose study in Kitami Red-Cross General Hospital

    International Nuclear Information System (INIS)

    Arimoto, Takuro; Yamazaki, Akira; Yonesaka, Akio; Matsuzawa, Tooru; Kanai, Naoki

    2003-01-01

    Enhanced acute mucositis is the limiting factor for accelerated, hyperfractionated radiotherapy in head and neck (H and N) squamous cell carcinomas (SCCs). We have developed a simple, new form of conformal radiotherapy, accelerated multiple arc radiotherapy (AcMAR), which covers the target volume by combined, segmental, and rotational arc fields. Two to three rotational fields were placed with CT guidance, each covering the primary tumor and lymph nodes separately. The optimal inter-isocenter distance was determined by 3D dose calculation. The surface area of oro-pharyngeal mucosa irradiated by more than a 50% dose by this method was reduced by 37-73% compared to that with a conventional parallel opposing technic. Dose searching, randomized two-dose study was initiated in Kitami Red-cross General Hospital (KRCGH) in January 1995, and 101 patients were registered and completed AcMAR in Oct 2000. All the patients were followed for up to 96 months (24-96 mo, median 48 mo) at the time of analysis. Fifty-one out of 101 patients were Stage III (17) and IV (34). Primary site of tumors were; 38 larynx, 25 oropharynx, 15 hypopharynx, 13 oral cavity, and 10 other miscellaneous sites. Patients were randomly allocated either to 60 Gy/24 fr/bid/3 wks to gross tumor volume (GTV) (Group A), or 66 Gy/33 fr/bid/4 wks to GTV (Group B). Forty Gy/16 fr/bid/2 wks was given to the volume of prophylactic'' irradiation in both groups of patients. Results were as follows: All the patients, except for one, completed AcMAR without treatment interruption. Acute mucositis at the site of high-dose irradiation was intense; 72% of Group A and 62.5% of Group B experienced World Health Organization (WHO) Grade 3 (confluent) mucositis focally. Fifty-one out of 53 in Group A and 48/48 in Group B, however, could maintain oral food intake (WHO Grade 1 or 2) even at the peak of their mucositis, because of the limited area of severe mucositis. With regard to late morbidity, however, 6/46 (followed >24 mo

  12. Relative bioavailability of generic and branded 250-mg and 500-mg oral chlorphenesin carbamate tablets in healthy Korean volunteers: a single-dose, randomized-sequence, open-label, two-period crossover trial.

    Science.gov (United States)

    Yu, Ji-young; Song, Hyun Ho; Kim, Bo Gyeom; Park, Hyeon Ju; Choi, Kwang Sik; Kwon, Young Ee

    2009-11-01

    Chlorphenesin carbamate is a skeletal muscle relaxant approved in Korea for use in the treatment of pain and discomfort related to skeletal muscle trauma and inflammation. The aim of this study was to assess the bioequivalence of a generic formulation of chlorphenesin carbamate at doses of 250 and 500 mg and 2 branded formulations of the same doses in healthy Korean adults. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Korean male and female volunteers. Subjects were assigned to receive, in a randomized sequence, a single dose of the generic (test) and branded (reference) formulations of chlorphenesin carbamate at a dose of 250 or 500 mg. Blood samples were drawn at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 9, 12, and 15 hours after administration. Pharmacokinetic properties (C(max), T(max), AUC(0-t) AUC(0-infinity), t(1/2), and ke) were determined using HPLC. The formulations were to be considered bioequivalent if the 90% CIs of the treatment ratios of the geometric means of C(max) and AUC(0-t) were within a predetermined range of log 0.80 to log 1.25 based on regulatory criteria. Tolerability was assessed by monitoring for adverse events (AEs) on physical examination and/or e-mail and personal interview at the beginning and end of each study period. Twenty-eight subjects (22 men, 6 women) received chlorphenesin carbamate at the 250-mg dose, and 24 male subjects received the 500-mg dose. The mean (SD) ages of the subjects were 24.0 (2.6) and 24.0 (1.9) years in the 250- and 500-mg groups, respectively. No significant differences were found between the test and reference formulations (90% CIs: C(max), 1.0048-1.1153 with the 250-mg dose and 0.9630-1.1189 with the 500-mg dose; AUC(0-t), 0.9882-1.0546 and 0.9842-1.0578, respectively). No clinically significant AEs (upper gastric pain, abdominal bloating, pyrexia, edema, nausea, heartburn, constipation, headache, dizziness, drowsiness, or fatigue) were reported throughout

  13. Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

    Science.gov (United States)

    Goebel, Andreas; Bisla, Jatinder; Carganillo, Roy; Frank, Bernhard; Gupta, Rima; Kelly, Joanna; McCabe, Candy; Murphy, Caroline; Padfield, Nick; Phillips, Ceri; Sanders, Mark; Serpell, Mick; Shenker, Nick; Shoukrey, Karim; Wyatt, Lynne; Ambler, Gareth

    2017-10-03

    Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). 7 secondary and tertiary care pain management centers in the United Kingdom. 111 patients with moderate or severe CRPS of 1 to 5 years' duration. IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Results do not apply to patients who have had CRPS for less than 1 year or more

  14. Pattern imprinting in deep sub-micron static random access memories induced by total dose irradiation

    Science.gov (United States)

    Zheng, Qi-Wen; Yu, Xue-Feng; Cui, Jiang-Wei; Guo, Qi; Ren, Di-Yuan; Cong, Zhong-Chao; Zhou, Hang

    2014-10-01

    Pattern imprinting in deep sub-micron static random access memories (SRAMs) during total dose irradiation is investigated in detail. As the dose accumulates, the data pattern of memory cells loading during irradiation is gradually imprinted on their background data pattern. We build a relationship between the memory cell's static noise margin (SNM) and the background data, and study the influence of irradiation on the probability density function of ΔSNM, which is the difference between two data sides' SNMs, to discuss the reason for pattern imprinting. Finally, we demonstrate that, for micron and deep sub-micron devices, the mechanism of pattern imprinting is the bias-dependent threshold shift of the transistor, but for a deep sub-micron device the shift results from charge trapping in the shallow trench isolation (STI) oxide rather than from the gate oxide of the micron-device.

  15. Development of dose monitoring system applicable to various radiations with wide energy ranges

    International Nuclear Information System (INIS)

    Sato, Tatsuhiko; Satoh, Daiki; Endo, Akira

    2006-01-01

    A new radiation dose monitor, designated as DARWIN (Dose monitoring system Applicable to various Radiations with WIde energy raNges), has been developed for real-time monitoring of doses in workspaces and surrounding environments of high energy accelerator facilities. DARWIN is composed of a phoswitch-type scintillation detector, which consists of liquid organic scintillator BC501A coupled with ZnS(Ag) scintillation sheets doped with 6 Li, and a data acquisition system based on a Digital-Storage-Oscilloscope. DARWIN has the following features: (1) capable of monitoring doses from neutrons, photons and muons with energies from thermal energy to 1 GeV, 150 keV to 100 MeV, and 1 MeV to 100 GeV, respectively, (2) highly sensitive with precision, and (3) easy to operate with a simple graphical user-interface. The performance of DARWIN was examined experimentally in several radiation fields. The results of the experiments indicated the accuracy and rapid response of DARWIN for measuring dose rates from neutrons, photons and muons with wide energies. With these properties, we conclude that DARWIN will be able to play a very important role for improving radiation safety in high energy accelerator facilities. (author)

  16. TRADOS - an air trajectory dose model for long range transport of radioactive release to the atmosphere

    International Nuclear Information System (INIS)

    Rossi, J.; Valkama, I.

    1985-01-01

    A model for estimating radiation doses resulting from long range atmospheric transport of released radionuclides in accidents is precented. The model (TRADOS) is able to treat changing diffusion conditions. For example the plume can be exposed to temporary rain, changes in turbulence and mixing depth. This can result in considerable changes in individual doses. The method is applied to an example trajectory and the doses caused by a serious reactor accident are calculated

  17. Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

    Energy Technology Data Exchange (ETDEWEB)

    Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

    2013-04-15

    The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  18. Evaluation of a High Concentrated Contrast Media Injection Protocol in Combination with Low Tube Current for Dose Reduction in Coronary Computed Tomography Angiography: A Randomized, Two-center Prospective Study.

    Science.gov (United States)

    Sun, Yibo; Hua, Yanqing; Wang, Mingpeng; Mao, Dingbiao; Jin, Xiu; Li, Cheng; Shi, Kailei; Xu, Jianrong

    2017-12-01

    The study aimed to prospectively evaluate the radiation dose reduction potential and image quality (IQ) of a high-concentration contrast media (HCCM) injection protocol in combination with a low tube current (mAs) in coronary computed tomography angiography. Eighty-one consecutive patients (mean age: 62 years; 34 females; body mass index: 18-31) were included and randomized-assigned into two groups. All computed tomography (CT) examinations were performed in two groups with the same tube voltage (100 kV), flow rate of contrast medium (5.0 mL/s), and iodine dose (22.8 g). An automatic mAs and low concentration contrast medium (300 mgI/mL) were used in group A, whereas effective mAs was reduced by a factor 0.6 along with HCCM (400 mgI/mL) in group B. Radiation dose was assessed (CT dose index [CTDI vol ] and dose length product), and vessel-based objective IQ for various regions of interest (enhancement, noise, signal-to-noise ratio, and contrast-to-noise ratio), subjective IQ, noise, and motion artifacts were analyzed overall and vessel-based with a 5-point Likert scale. The CT attenuation of coronary arteries and image noise in group B were significantly higher than those in group A (ranges: 507.5-548.1 Hounsfield units vs 407.5-444.5 Hounsfield units; and 20.3 ± 8.6 vs 17.7 ± 8.0) (P ≤ 0.0166). There was no significant difference between the two groups in signal-to-noise ratio, contrast-to-noise ratio, and subjective IQ of coronary arteries (29.4-31.7, 30.0-37.0, and medium score of 5 in group A vs 29.4-32.4, 27.7-36.3, and medium score of 5 in group B, respectively, P ≥ 0.1859). Both mean CTDI vol and dose length product in group B were 58% of those of group A. HCCM combined with low tube current allows dose reduction in coronary computed tomography angiography and does not compromise IQ. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  19. Effect of an Early Dose of Measles Vaccine on Morbidity Between 18 Weeks and 9 Months of Age: A Randomized, Controlled Trial in Guinea-Bissau

    DEFF Research Database (Denmark)

    Do, Vu An; Biering-Sorensen, Sofie; Fisker, Ane Bærent

    2017-01-01

    with a higher risk of the well-known adverse events of fever, rash, and convulsions within the first 14 days. From 15 days after randomization to age 9 months, early measles vaccination was associated with reductions in maternally reported diarrhea (hazard ratio [HR], 0.89; 95% confidence interval [CI],.82-. 97......Background: Children in Guinea-Bissau receive measles vaccine (MV) at 9 months of age, but studies have shown that an additional dose before 9 months of age might have beneficial nonspecific effects. Within a randomized trial designed to examine nonspecific effects of early MV receipt on mortality......, we conducted a substudy to investigate the effect of early MV receipt on morbidity. Methods: Children were randomly assigned at a ratio of 2: 1 to receive 2 doses of MVat 18 weeks and age 9 months (intervention group) or 1 dose of MV at age 9 months, in accordance with current practice (control group...

  20. Effect of γ-dose rate and total dose interrelation on the polymeric hydrogel: A novel injectable male contraceptive

    International Nuclear Information System (INIS)

    Jha, Pradeep K.; Jha, Rakhi; Gupta, B.L.; Guha, Sujoy K.

    2010-01-01

    Functional necessity to use a particular range of dose rate and total dose of γ-initiated polymerization to manufacture a novel polymeric hydrogel RISUG (reversible inhibition of sperm under guidance) made of styrene maleic anhydride (SMA) dissolved in dimethyl sulphoxide (DMSO), for its broad biomedical application explores new dimension of research. The present work involves 16 irradiated samples. They were tested by fourier transform infrared spectroscopy, matrix assisted laser desorption/ionization-TOF, field emission scanning electron microscopy, high resolution transmission electron microscopy, etc. to see the interrelation effect of gamma dose rates (8.25, 17.29, 20.01 and 25.00 Gy/min) and four sets of doses (1.8, 2.0, 2.2 and 2.4 kGy) on the molecular weight, molecular weight distribution and porosity analysis of the biopolymeric drug RISUG. The results of randomized experiment indicated that a range of 18-24 Gy/min γ-dose rate and 2.0-2.4 kGy γ-total doses is suitable for the desirable in vivo performance of the contraceptive copolymer.

  1. Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Cengiz, Pelin; Gokcinar, Derya; Karabeyoglu, Isil; Topcu, Hulya; Cicek, Gizem Selen; Gogus, Nermin

    2014-05-01

    To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. A randomized, double-blind comparative study. Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6 μg/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects.

  2. Control of moderate-to-severe asthma with randomized ciclesonide doses of 160, 320 and 640 μg/day

    Directory of Open Access Journals (Sweden)

    Pedersen SE

    2017-03-01

    Full Text Available Søren E Pedersen,1 Niyati Prasad,2 Udo-Michael Goehring,3 Henrik Andersson,4 Dirkje S Postma5 1Pediatric Research Unit, Kolding Hospital, University of Southern Denmark, Kolding, Denmark; 2Vertex, Phase IV & Global Strategy, London, UK; 3Vifor Pharma Ltd, Clinical Research & Biometrics, Glattbrugg, Switzerland; 4Swedish Social Insurance Agency, Government Offices of Sweden, Stockholm, Sweden; 5Department of Pulmonology, Griac Research Institute, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Background: The inhaled corticosteroid (ICS ciclesonide (Cic, controls asthma symptoms in the majority of patients at the recommended dose of 160 µg/day. However, the relationship between the level of asthma control and increasing doses of Cic is unknown. This study investigated whether long-term treatment with higher doses of Cic would further improve asthma symptoms in patients with uncontrolled asthma despite ICS use. Patients and methods: In a double-blind, randomized, parallel-group study, 367 patients were allocated to one of three treatment arms (Cic 160, 320 and 640 μg/day. After a single-blind, 3-week baseline period with Cic 160 µg/day, eligible patients were randomized to receive 52 weeks of treatment with Cic 160, 320 or 640 μg/day (double-blind period during which forced expiratory volume in 1 second (FEV1, exacerbations and Asthma Control Questionnaire (ACQ scores were measured. Results: Treatment with all the three doses was associated with significant improvements in ACQ scores, FEV1 and asthma symptoms (P<0.01. There were no statistically significant differences between the three doses. The results of the primary end point analysis showed a numerical improvement in the ACQ score with Cic 640 μg/day compared with Cic 160 μg/day (least square [LS] mean: -0.122; two-sided P-value: 0.30. Post hoc subgroup analyses showed that the improvement in the ACQ score with Cic 640 μg/day compared

  3. A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

    Science.gov (United States)

    Pusuwan, Pawana; Tuntawiroon, Malulee; Sritongkul, Nopamol; Chaudakshetrin, Pachee; Nopmaneejumruslers, Cherdchai; Komoltri, Chulalak; Thepamongkhol, Kullathorn; Khiewvan, Benjapa; Tuchinda, Pongpija; Sriussadaporn, Sutin

    2011-03-01

    To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). A high dose regimen of radioactive iodine treatment is more effective than

  4. Dose comparison according to Smooth Thickness application of Range compensator during proton therapy for brain tumor patient

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tase Woan; Kim, Dae Woong; Kim, Jae Weon; Jeong, Kyeong Sik [Proton Therapy Center, National Cancer Center, Goyang (Korea, Republic of)

    2016-12-15

    Range Compensator used for proton therapy compensates the proton beam dose which delivers to the normal tissues according to the Target's Distal Margin dose. We are going to check the improvement of dose on the target part by comparing the dose of PTV and OAR according to applying in different method of Smooth Thickness of Range Compensator which is used in brain tumor therapy. For 10 brain tumor patients taking proton therapy in National Cancer Center, Apply Smooth Thickness applied in Range Compensator in order from one to five by using Compensator Editor of Eclipse Proton Planning System(Version 10.0, Varian, USA). The therapy plan algorithm used Proton Convolution Superposition(version 8.1.20 or 10.0.28), and we compared Dmax, Dmin, Homogeneity Index, Conformity Index and OAR dose around tumor by applying Smooth Thickness in phase. When Smooth Thickness was applied from one to five, the Dmax of PTV was decreased max 4.3%, minimum at 0.8 and average of 1.81%. Dmin increased max 1.8%, min 1.8% and average. Difference between max dose and minimum dose decreased at max 5.9% min 1.4% and average 2.6%. Homogeneity Index decreased average of 0.018 and Conformity Index didn't had a meaningful change. OAR dose decreased in Brain Stem at max 1.6%, min 0.1% and average 0.6% and in Optic Chiasm max 1.3%, min 0.3%, and average 0.5%. However, patient C and patient E had an increase each 0.3% and 0.6%. Additionally, in Rt. Optic Nerve, there was a decrease at max 1.5%, min 0.3%, and average 0.8%, however, patient B had 0.1% increase. In Lt. Optic Nerve, there was a decrease at max 1.8%, min 0.3%, and average 0.7%, however, patient H had 0.4 increase. As Smooth Thickness of Range Compensator which is used as the proton treatment for brain tumor patients is applied in stages, the resolution of Compensator increased and as a result the most optimized amount of proton beam dose can be delivered. This is considered to be able to irradiate the equal amount at PTV and

  5. Dose-response studies of Ropivacaine in blood flow of upper extremity after supraclavicular block: a double-blind randomized controlled study.

    Science.gov (United States)

    Li, Ting; Ye, Qiguang; Wu, Daozhu; Li, Jun; Yu, Jingui

    2017-12-02

    The sympathetic block of upper limb leading to increased blood flow has important clinical implication in microvascular surgery. However, little is known regarding the relationship between concentration of local anesthetic and blood flow of upper limb. The aim of this dose-response study was to determine the ED 50 and ED 95 of ropivacaine in blood flow after supraclavicular block (SB). Patients undergoing upper limb surgery and supraclavicular block were randomly assigned to receive 30ml ropivacaine in concentrations of 0.125%(A Group), 0.2%(B Group), 0.25%(C Group), 0.375%(D Group), 0.5%(E Group), or 0.75%(F Group) (n=13 per group). All patients received supraclavicular block (SB). Time average maximum velocity (TAMAX), cross-sectional area (CSA) of brachial artery and skin temperatures (T s ) were measured repeatedly at the same marked points, they were taken at baseline (before block, t 0 ) and at 30min after SB (t 1 ). Blood flow(BF) = TAMAX× CSA×60 sec.. Relative blood flow (ΔBF) = BF t1 / BF t0 . Success of SB was assessed simultaneously. Supplementary anesthesia and other adverse events (AE) were recorded. Significant increase in TAMAX, CSA, BF and T s were seen in all concentration groups at t 1 comparing with t 0 (Pblock were 0.18/0.33% (0.15-0.21/0.27-0.51), R 2 =0.904. The dose-response curve between SB ropivacaine and the changes of BF was determined. The ED 50 /ED 95 of ropivacaine of ΔBF are 0.35/1.94% (0.25-0.45/0.83-4.52). TAMAX, CSA and BF consistently increased with ropivacaine concentration. The maximal sympathetic block needs higher concentration than that complete sensation block needs which may benefit for microvascular surgery. Clinicaltrials.gov NCT02139982 . Retrospectively registered (Date of registration: May, 2014).

  6. The impact of low-dose aspirin on preterm birth: secondary analysis of a randomized controlled trial.

    Science.gov (United States)

    Allshouse, A A; Jessel, R H; Heyborne, K D

    2016-06-01

    The objective of this study is to determine whether low-dose aspirin (LDA) reduced the rate of preterm birth (PTB) in a cohort of women at high risk for preeclampsia. Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin trial. Preterm births were categorized by phenotype: indicated, spontaneous or due to preterm premature rupture of membranes (PPROMs). Of 1789 randomized women, 30.5% delivered before 37 weeks (18.5% indicated, 5.8% spontaneous and 6.2% following preterm PPROMs). Among women randomized to LDA, we observed a trend favoring fewer PTBs due to spontaneous preterm labor and preterm PPROMs, odds ratio (OR: 0.826 (0.620, 1.099)); the incidence of indicated PTBs appeared unchanged, OR: 0.999 (0.787, 1.268). Although not reaching significance, we observed an effect size similar to other studies of both low- and high-risk women. These results support findings from other studies assessing LDA as a PTB prevention strategy.

  7. Intraoperative Low-Dose Ketamine Infusion Reduces Acute Postoperative Pain Following Total Knee Replacement Surgery: A Prospective, Randomized Double-Blind Placebo-Controlled Trial

    International Nuclear Information System (INIS)

    Pelin Cengiz, P.; Gokcinar, D.; Karabeyoglu, I.; Topcu, H.; Cicek, G. S.; Gogus, N.

    2014-01-01

    Objective: To evaluate the effect of intraoperative low-dose ketamine with general anesthesia on postoperative pain after total knee replacement surgery. Study Design: A randomized, double-blind comparative study. Place and Duration of Study: Ankara Numune Training and Research Hospital, Turkey, from January and June 2011. Methodology: Sixty adults undergoing total knee arthroplasty were enrolled in this study. The patients were randomly allocated into two groups of equal size to receive either racemic ketamine infusion (6.25 g/kg/minute) or the same volume of saline. A visual analogue scale (VAS) was used to measure each patient's level of pain at 1, 3, 6, 12, and 24 hours after surgery. Time to first analgesic request, postoperative morphine consumption and the incidence of side effects were also recorded. Results: Low-dose ketamine infusion prolonged the time to first analgesic request. It also reduced postoperative cumulative morphine consumption at 1, 3, 6, 12, and 24 hours postsurgery (p < 0.001). Postoperative VAS scores were also significantly lower in the ketamine group than placebo, at all observation times. Incidences of side effects were similar in both study groups. Conclusion: Intraoperative continuous low-dose ketamine infusion reduced pain and postoperative analgesic consumption without affecting the incidence of side effects. (author)

  8. Numerical study of microphase separation in gels and random media

    International Nuclear Information System (INIS)

    Uchida, Nariya

    2004-01-01

    Microphase separation in gels and random media is numerically studied using a Ginzburg-Landau model. A random field destroys long-range orientational (lamellar) order and gives rise to a disordered bicontinuous morphology. The dependence of the correlation length on the field strength is distinct from that of random-field magnets

  9. Study of the Radiochromic Film for High Dose Measurement in Radiation Processing

    Directory of Open Access Journals (Sweden)

    CHEN Yi-zhen

    2016-02-01

    Full Text Available To establish the radiochromic film dosimeter for high dose level measurement during radiation processing, By corresponding formula and its preparation process research, batches of radiochromic film dosimeters were prepared using nylon as substrate and pararosaniline cyanide as dye. In Co-60 gamma reference radiation field, dosimetry response performance of radiochromic film was studied and results showed that the repeatability was good to 1.0%. The response curves demonstrated good linearity in the dose range of 5-210 kGy, and the signal of radiochromic film dosimeters after irradiation under the condition of low temperature storage within 2 weeks was stable. In addition, the radiochromic film dosimeters were not found to have noticeable dose rate dependence in the range of this experiment. In the linear dose range, radiochromic film dosimeter measures the absorbed dose, with extended uncertainty 4.2% (k=2 for Co-60 gamma rays. The film was suitable as dosimeters for the parameters measurement of the electron beam on the accelerator.

  10. Relative bioavailability of two oral formulations of risperidone 2 mg: A single-dose, randomized-sequence, open-label, two-period crossover comparison in healthy Brazilian volunteers.

    Science.gov (United States)

    Belotto, Karisa Cristina Rodrigues; Raposo, Nádia Rezende Barbosa; Ferreira, Aline Siqueira; Gattaz, Wagner Farid

    2010-11-01

    Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 1858 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m

  11. Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

    International Nuclear Information System (INIS)

    Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

    1998-01-01

    Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    Science.gov (United States)

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  13. Occupational dose measurement in interventional cardiology, dosimetry comparison study

    International Nuclear Information System (INIS)

    Ahmad, A.M.A.

    2008-05-01

    The number of cardiology interventional procedures has significantly increased recently. This is due to the reliability of the diagnostic equipment to diagnose many heart disease. In the procedures the x-ray used results in increasing radiation doses to the staff. The cardiologists and other staff members in interventional cardiology are usually working close to the area under examination and receive the dose primarily from scattered radiation from the patient. Therefore workers in interventional cardiology are expected to receive high doses. This study overviews the status of occupational exposure at the three cardiology centers at three different hospitals in Khartoum compared with that received by workers at other medical practices (radiotherapy, nuclear medicine and diagnostic radiology) in the Institute of Nuclear and Technology (INMO) at El Gezira. The TLD Harshaw 6600 reader was used in the assessment of effective dose for Hp (10). Two TLDs were used by each worker at the three cardiology centres, one worn under a protective apron and the other worn outside and above the apron as specified by the ICRP. Each worker at the other sections was facilitated with one dosimeter to be worn on the chest. The annual doses received by 14 cardiologists, 13 nurses and 9 technologists at the three cardiology centres were in the range: (0.84-4.77), (0.15-2.08), (0.32-1.10) mSv respectively. In the INMO the annual doses received by 7 doctors, 5 nurses and 14 technologists were in the range: (0.12-0.51), (0.11-0.65), (0.03-1.39) mSv respectively. The results showed that the annual doses received by the workers do not exceed 20 mSv. The study also indicated that doses received by workers in interventional cardiology, in particular the cardiologists are high compared to that received at the other medical sections.(Author)

  14. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery.

    Science.gov (United States)

    Barnwal, Neeraj Kumar; Umbarkar, Sanjeeta Rajendra; Sarkar, Manjula Sudeep; Dias, Raylene J

    2017-01-01

    Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP), mean airway pressure (MaP), oxygenation index (OI), and central venous pressure (CVP) were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU) stay were noted. MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000). Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165). Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  15. Pattern imprinting in deep sub-micron static random access memories induced by total dose irradiation

    International Nuclear Information System (INIS)

    Zheng Qi-Wen; Yu Xue-Feng; Cui Jiang-Wei; Guo Qi; Ren Di-Yuan; Cong Zhong-Chao; Zhou Hang

    2014-01-01

    Pattern imprinting in deep sub-micron static random access memories (SRAMs) during total dose irradiation is investigated in detail. As the dose accumulates, the data pattern of memory cells loading during irradiation is gradually imprinted on their background data pattern. We build a relationship between the memory cell's static noise margin (SNM) and the background data, and study the influence of irradiation on the probability density function of ΔSNM, which is the difference between two data sides' SNMs, to discuss the reason for pattern imprinting. Finally, we demonstrate that, for micron and deep sub-micron devices, the mechanism of pattern imprinting is the bias-dependent threshold shift of the transistor, but for a deep sub-micron device the shift results from charge trapping in the shallow trench isolation (STI) oxide rather than from the gate oxide of the micron-device. (condensed matter: structural, mechanical, and thermal properties)

  16. A prospective randomized study concerning the point a dose in high-dose rate intracavitary therapy for carcinoma of the uterine cervix. The final results

    International Nuclear Information System (INIS)

    Chatani, M.; Matayoshi, Y.; Masaki, N.; Teshima, T.; Inoue, T.

    1994-01-01

    Between January 1983 and February 1989, a total of 165 patients with carcinoma of the unterine cervix was entered in a prospective randomized study concerning the point A dose of HDR therapy (6 Gy/fraktion vs 7.5 Gy/fraction) and external irradiation dose at Department of Radiation Therapy, The Center for Adult Diseases, Osaka. UICC stage distribution of patients was as follows: Stage IA=4, stage IB=33, stage IIA=18, stage IIB=38, stage III=57, stage IV=15. Overall 5-year cause specific survivals were as follows: Stage IA=100%, stage IB=96%, stage IIA=92%, stage IIB=79%, stage III=57%, stage IV=27%. In each stage, 5-year survival rates in groups A and B were 100%, 93% in stage I, 82% and 85% in stage II, 62% and 52% in stage II and 22% and 31% in stage IV, respectively. There were no statistically significant differences among these survival curves in each stage. Five-year local failure rates were 16% in group A and 16% in group B (p=0.9096), and corresponding distant failure rates were 23% in group A and 19% in group B (p=0.2955). Moderate-to-severe complications requiring treatment (Kottmeier's grade 2 or more) were noted in 6 patients (7%) in group A and 6 patients (7%) in group B. All of the bladder and rectal complications needed medical treatment (Kottmeier's grade 2). Severe complications receiving surgery were noted in 4 patients (A: 1; B: 3), i.e., small intestine 3 and sigmoid colon 1 patient. Another 1 patient (A) was dead of ileus. There were no statistically significant differences between 2 treatment schedules in survival rates, failure patterns and complications rates. This fact suggests that small number of fractions (7.5 Gy/fraction) may be advantageous because of short duration and a low load of treatment. (orig.) [de

  17. A prospective randomized evaluation of the prophylactic use of low-dose dopamine in cancer patients receiving interleukin-2.

    Science.gov (United States)

    Cormier, J N; Hurst, R; Vasselli, J; Lee, D; Kim, C J; McKee, M; Venzon, D; White, D; Marincola, F M; Rosenberg, S A

    1997-07-01

    The administration of high-dose interleukin-2 (IL-2) causes tumor regression in 17-25% of patients with metastatic melanoma or renal cell carcinoma. Renal dysfunction is a common dose-limiting toxicity of IL-2 administration, limiting 26% of treatment cycles. We have conducted a prospective randomized trial to evaluate whether the prophylactic administration of low-dose dopamine (2 mg/kg/min) can minimize renal toxicity and thus affect the amount of IL-2 administered. Forty-two patients were randomly assigned to receive systemic high-dose IL-2 with standard supportive measures (group A = 21 patients) or with the addition of prophylactic dopamine (group B = 21 patients) at 2 mg/kg/min. For patients in group B, dopamine was instituted 1 h before the initiation of IL-2 administration and was discontinued 6-12 h after the maximum number of doses of IL-2 were given. There was no difference in the amount of IL-2 administered for each course of therapy for groups A and B. Despite differences in urine flow (milliliters per kilogram per day), fluid balance (liters per day), and overall weight gain, prophylactic low-dose dopamine did not significantly alter maximum plasma urea or creatinine levels in group B when compared with the control group (group A). The overall toxicity profile considering all grade 3 and 4 toxicities for patients in groups A and B was comparable. Thus, there is no evidence to support the routine use of prophylactic low-dose dopamine in patients receiving high-dose IL-2.

  18. Randomized study comparing full dose monotherapy (S-1 followed by irinotecan) and reduced dose combination therapy (S-1/oxaliplatin followed by S-1/irinotecan) as initial therapy for older patients with metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Österlund, Pia; Berglund, Åke

    2017-01-01

    to select which older patients should receive therapy. Methods: The NORDIC 9 trial is a Nordic multicenter randomized phase II study comparing full dose monotherapy (S-1 30 mg/m2 twice daily days 1-14 every 3 weeks, followed by second line irinotecan 250-350 mg/m2 iv day 1 every 3 weeks or 180-250 mg/m2 iv...... day 1 every 2 weeks) with reduced dose combination therapy (S-1 20 mg/m2 days 1-14 + oxaliplatin 100 mg/m2 iv day 1 every 3 weeks, followed by second line S-1 20 mg/m2 days 1-14 + irinotecan 180 mg/m2 day 1 every 3 week) for older patients (≥70 years) with mCRC who are not candidates for full...... chance for tailored treatment strategies in these patients. Trial registration: EU Clinical Trial Register, EudraCT no. 2014-000394-39. Registered 05 May 2014....

  19. The efficacy and safety of S-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose-finding study

    Directory of Open Access Journals (Sweden)

    Yataba I

    2017-04-01

    Full Text Available Ikuko Yataba,1 Noboru Otsuka,1 Isao Matsushita,1 Hideo Matsumoto,2 Yuichi Hoshino3 1Taisho Pharmaceutical Co, Ltd, 2Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, 3Department of Orthopedics Surgery, School of Medicine, Jichi Medical University, Tochigi, Japan Background: Nonsteroidal anti-inflammatory drug (NSAID patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA to determine its optimal dose. This was a multicenter, randomized, double-blind, parallel-group comparative study. Patients and methods: Enrolled 509 knee OA patients were treated with placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2 weeks. The primary endpoint for efficacy was improvement in knee pain on rising from the chair assessed by visual analog scale (VAS. The other endpoints were clinical symptoms, pain on walking, and global assessment by both investigator and patient. Safety was evaluated by observing adverse events (AEs. Results: VAS change in knee pain from baseline to trial end was dose-dependent, least squares mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg, respectively. A significant difference was observed between placebo and SFPP 40 mg (P=0.001. In contrast, the effect of SFPP at a dose ≤20 mg was not significantly different from that of placebo. The proportion of the patients who achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (P<0.001. In all other endpoints, SFPP 40 mg showed significant improvement compared with placebo. The incidence of AEs was

  20. Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX - RAdiation Dose study (RAD-MATRIX).

    Science.gov (United States)

    Sciahbasi, Alessandro; Calabrò, Paolo; Sarandrea, Alessandro; Rigattieri, Stefano; Tomassini, Francesco; Sardella, Gennaro; Zavalloni, Dennis; Cortese, Bernardo; Limbruno, Ugo; Tebaldi, Matteo; Gagnor, Andrea; Rubartelli, Paolo; Zingarelli, Antonio; Valgimigli, Marco

    2014-06-01

    Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access. The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Dosing Accuracy of Insulin Aspart FlexPens After Transport Through the Pneumatic Tube System.

    Science.gov (United States)

    Ward, Leah G; Heckman, Michael G; Warren, Amy I; Tran, Kimberly

    2013-01-01

    The purpose of this study was to evaluate whether transporting insulin aspart FlexPens via a pneumatic tube system affects the dosing accuracy of the pens. A total of 115 Novo Nordisk FlexPens containing insulin aspart were randomly assigned to be transported via a pneumatic tube system (n = 92) or to serve as the control (n = 23). Each pen was then randomized to 10 international unit (IU) doses (n = 25) or 30 IU doses (n = 67), providing 600 and 603 doses, respectively, for the pneumatic tube group. The control group also received random assignment to 10 IU doses (n = 6) or 30 IU doses (n = 17), providing 144 and 153 doses, respectively. Each dose was expelled using manufacturer instructions. Weights were recorded, corrected for specific gravity, and evaluated based on acceptable International Organization for Standardization (ISO) dosing limits. In the group of pens transported through the pneumatic tube system, none of the 600 doses of 10 IU (0.0%; 95% CI, 0.0 to 0.6) and none of the 603 doses of 30 IU (0.0%; 95% CI, 0.0 to 0.6) fell outside of the range of acceptable weights. Correspondingly, in the control group, none of the 144 doses at 10 IU (0.0%; 95% CI, 0.0 to 2.5) and none of the 153 doses at 30 IU (0.0%; 95% CI, 0.0 to 2.4) were outside of acceptable ISO limits. Transportation via pneumatic tube system does not appear to compromise dosing accuracy. Hospital pharmacies may rely on the pneumatic tube system for timely and accurate transport of insulin aspart FlexPens.

  2. A comprehensive comparative study of the pre-dose effect for three quartz crystals of different origin

    International Nuclear Information System (INIS)

    Kitis, G.; Pagonis, V.; Chen, R.; Polymeris, G.

    2006-01-01

    The study of the thermoluminescence (TL) sensitivity of quartz due to heat and irradiation treatments is of importance in dating and retrospective dosimetry. A comprehensive comparative study of the pre-dose effect was carried out for three types of quartz of different origin. Complete TL vs. dose and sensitivity S vs. pre-dose curves were obtained for the dose range of 0.1 < D < 400 Gy. Additional complete sensitivity vs. pre-dose curves were obtained for samples which underwent a combined pre-dose irradiation and a subsequent heat treatment to 500 deg. C. Although the TL vs. dose curves showed very different behaviours, the sensitivity vs. pre-dose curves showed several common characteristics. The sensitivity vs. pre-dose curves showed abrupt changes ∼10 Gy. The sensitivity after a combined pre-dose irradiation and heat treatment to 500 deg. C showed a very gradual change in the whole dose range studied. These results are explained qualitatively by using the modified Zimmerman model for quartz. (authors)

  3. Higher-Than-Conventional Radiation Doses in Localized Prostate Cancer Treatment: A Meta-analysis of Randomized, Controlled Trials

    International Nuclear Information System (INIS)

    Viani, Gustavo Arruda; Stefano, Eduardo Jose; Afonso, Sergio Luis

    2009-01-01

    Purpose: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. Results: Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p 2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). Conclusions: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.

  4. Two separate dose-dependent effects of paroxetine

    DEFF Research Database (Denmark)

    Nielsen, Anette Green; Pedersen, Rasmus Steen; Nøhr-Jensen, Lene

    2010-01-01

    PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received...... concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose......-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P inhibition...

  5. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Barnwal

    2017-01-01

    Full Text Available Background: Pulmonary hypertension secondary to congenital heart disease is a common problem in pediatric patients presenting for open heart surgery. Milrinone has been shown to reduce pulmonary vascular resistance and pulmonary artery pressure in pediatric patients and neonates postcardiac surgery. We aimed to evaluate the postoperative outcome in such patients with three different fixed maintenance doses of milrinone. Methodology: Patients were randomized into three groups. All patients received fixed bolus dose of milrinone 50 μg/kg on pump during rewarming. Following this, patients in low-dose group received infusion of milrinone at the rate of 0.375 μg/kg/min, medium-dose group received 0.5 μg/kg/min, and high-dose group received 0.75 μg/kg/min over 24 h. Heart rate, mean arterial pressure (MAP, mean airway pressure (MaP, oxygenation index (OI, and central venous pressure (CVP were compared at baseline and 24 h postoperatively. Dose of inotropic requirement, duration of ventilatory support and Intensive Care Unit (ICU stay were noted. Results: MAP, MaP, OI, and CVP were comparable in all three groups postoperatively. All patients in the low-dose group required low inotropic support while 70% of patients in the high-dose group needed high inotropic support to manage episodes of hypotension (P = 0.000. Duration of ventilatory support and ICU stay in all three groups was comparable (P = 0.412, P = 0.165. Conclusion: Low-dose infusions while having a clinical impact were more beneficial in avoiding adverse events and decreasing inotropic requirement without affecting duration of ventilatory support and duration of ICU stay.

  6. The influence of non-radiation induced ESR background signal from paraffin-alanine probes for dosimetry in the radiotherapy dose range

    International Nuclear Information System (INIS)

    Wieser, A.; Lettau, C.; Fill, U.; Regulla, D.F.

    1993-01-01

    The yield of radicals induced by ionizing radiation in the amino acid alanine and its quantification by ESR spectroscopy has proven excellent reproducibility. Those radicals trapped in the crystal lattice are prevented from recombination providing a thermally very stable system. This allows alanine to be applied as a transfer dosemeter. With paraffin-alanine probes ESR dosimetry can be performed with a standard deviation of ± 0.5% in the dose range from 20 Gy up to 100 kGy. At 1 Gy dose level the error increases to ± 6%. This dose level is three orders of magnitude higher than the calculated detection threshold for alanine with modern X-band ESR spectrometers. It was found that the poor standard deviation at the 1 Gy dose level, is not mainly produced by a bad signal-to-noise ratio but by a variable non-radiation induced ESR background signal from the alanine probes within a batch. In the present study the main sources of error for ESR dosimetry in the dose range below 20 Gy were analyzed. The influences of the production process, UV light and humidity upon the ESR background signal from paraffin-alanine probes were investigated. Measurements are shown indicating a second stable structure of the alanine radical at room temperature. (author)

  7. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II).

    Science.gov (United States)

    Lamo-Espinosa, José M; Mora, Gonzalo; Blanco, Juan F; Granero-Moltó, Froilán; Nuñez-Córdoba, Jorge M; Sánchez-Echenique, Carmen; Bondía, José M; Aquerreta, Jesús Dámaso; Andreu, Enrique J; Ornilla, Enrique; Villarón, Eva M; Valentí-Azcárate, Andrés; Sánchez-Guijo, Fermín; Del Cañizo, María Consuelo; Valentí-Nin, Juan Ramón; Prósper, Felipe

    2016-08-26

    Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial. A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 10(6) or 100 × 10(6) cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 10(6) cells are administered. These results pave the way for a future phase III clinical trial. gov identifier NCT02123368. Nº EudraCT: 2009-017624-72.

  8. Study on method of dose estimation for the Dual-moderated neutron survey meter

    International Nuclear Information System (INIS)

    Zhou, Bo; Li, Taosheng; Xu, Yuhai; Gong, Cunkui; Yan, Qiang; Li, Lei

    2013-01-01

    In order to study neutron dose measurement in high energy radiation field, a Dual-moderated survey meter in the range from 1 keV to 300 MeV mean energies spectra has been developed. Measurement results of some survey meters depend on the neutron spectra characteristics in different neutron radiation fields, so the characteristics of the responses to various neutron spectra should be studied in order to get more reasonable dose. In this paper the responses of the survey meter were calculated under different neutron spectra data from IAEA of Technical Reports Series No. 318 and other references. Finally one dose estimation method was determined. The range of the reading per H*(10) for the method estimated is about 0.7–1.6 for the neutron mean energy range from 50 keV to 300 MeV. -- Highlights: • We studied a novel high energy neutron survey meter. • Response characteristics of the survey meter were calculated by using a series of neutron spectra. • One significant advantage of the survey meter is that it can provide mean energy of radiation field. • Dose estimate deviation can be corrected. • The range of corrected reading per H*(10) is about 0.7–1.6 for the neutron fluence mean energy range from 0.05 MeV to 300 MeV

  9. Nominal Range Sensitivity Analysis of peak radionuclide concentrations in randomly heterogeneous aquifers

    International Nuclear Information System (INIS)

    Cadini, F.; De Sanctis, J.; Cherubini, A.; Zio, E.; Riva, M.; Guadagnini, A.

    2012-01-01

    Highlights: ► Uncertainty quantification problem associated with the radionuclide migration. ► Groundwater transport processes simulated within a randomly heterogeneous aquifer. ► Development of an automatic sensitivity analysis for flow and transport parameters. ► Proposal of a Nominal Range Sensitivity Analysis approach. ► Analysis applied to the performance assessment of a nuclear waste repository. - Abstract: We consider the problem of quantification of uncertainty associated with radionuclide transport processes within a randomly heterogeneous aquifer system in the context of performance assessment of a near-surface radioactive waste repository. Radionuclide migration is simulated at the repository scale through a Monte Carlo scheme. The saturated groundwater flow and transport equations are then solved at the aquifer scale for the assessment of the expected radionuclide peak concentration at a location of interest. A procedure is presented to perform the sensitivity analysis of this target environmental variable to key parameters that characterize flow and transport processes in the subsurface. The proposed procedure is exemplified through an application to a realistic case study.

  10. Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Yongchuan Li

    Full Text Available A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2-5 days after contrast administration and need for dialysis.Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR =0.51, 95% CI 0.34-0.76, p =0.001; I(2 = 0%. The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05-2.10, p = 0.24; I(2 = 0%. The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD -0.64, 95% CI: -1.57 to 0.29, P = 0.18, I(2 = 97%.Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.

  11. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

  12. Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2017-01-01

    Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

  13. Dose-Escalation Study for Cardiac Radiosurgery in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Blanck, Oliver, E-mail: oliver.blanck@uksh.de [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); CyberKnife Center Northern Germany, Guestrow (Germany); Bode, Frank [Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Gebhard, Maximilian [Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Hunold, Peter [Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Brandt, Sebastian [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Bruder, Ralf [Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Grossherr, Martin [Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Vonthein, Reinhard [Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Rades, Dirk [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); Dunst, Juergen [Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck (Germany); University Copenhagen (Denmark)

    2014-07-01

    Purpose: To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation. Methods and Materials: Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm{sup 3}). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination. Results: Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy. Conclusions: Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.

  14. Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma

    Science.gov (United States)

    San Miguel, Jesus F.; Weisel, Katja C.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Moreau, Philippe; Banos, Anne; Oriol, Albert; Garderet, Laurent; Cavo, Michele; Ivanova, Valentina; Alegre, Adrian; Martinez-Lopez, Joaquin; Chen, Christine; Renner, Christoph; Bahlis, Nizar Jacques; Yu, Xin; Teasdale, Terri; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios A.

    2015-01-01

    Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. PMID:26160879

  15. Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX – RAdiation Dose study (RAD-MATRIX)

    International Nuclear Information System (INIS)

    Sciahbasi, Alessandro; Calabrò, Paolo; Sarandrea, Alessandro; Rigattieri, Stefano; Tomassini, Francesco; Sardella, Gennaro; Zavalloni, Dennis; Cortese, Bernardo; Limbruno, Ugo; Tebaldi, Matteo; Gagnor, Andrea; Rubartelli, Paolo; Zingarelli, Antonio; Valgimigli, Marco

    2014-01-01

    Background: Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. Methods: The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access. Conclusions: The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes

  16. Randomized comparison of operator radiation exposure comparing transradial and transfemoral approach for percutaneous coronary procedures: rationale and design of the minimizing adverse haemorrhagic events by TRansradial access site and systemic implementation of angioX – RAdiation Dose study (RAD-MATRIX)

    Energy Technology Data Exchange (ETDEWEB)

    Sciahbasi, Alessandro, E-mail: alessandro.sciahbasi@fastwebnet.it [Interventional Cardiology, Sandro Pertini Hospital – ASL RMB, Rome (Italy); Calabrò, Paolo [Division of Cardiology - Department of Cardio-Thoracic Sciences - Second University of Naples (Italy); Sarandrea, Alessandro [HSE Management, Rome (Italy); Rigattieri, Stefano [Interventional Cardiology, Sandro Pertini Hospital – ASL RMB, Rome (Italy); Tomassini, Francesco [Department of Cardiology, Infermi Hospital, Rivoli (Italy); Sardella, Gennaro [La Sapienza University, Rome (Italy); Zavalloni, Dennis [UO Emodinamica e Cardiologia Invasiva, IRCCS, Istituto Clinico Humanitas, Rozzano (Italy); Cortese, Bernardo [Interventional Cardiology, Fatebenefratelli Hospital, Milan (Italy); Limbruno, Ugo [Cardiology Unit, Misericordia Hospital, Grosseto (Italy); Tebaldi, Matteo [Cardiology Department, University of Ferrara, Department of Cardiology (Italy); Gagnor, Andrea [Department of Cardiology, Infermi Hospital, Rivoli (Italy); Rubartelli, Paolo [Villa Scassi Hospital, Genova (Italy); Zingarelli, Antonio [San Martino Hospital, Genova (Italy); Valgimigli, Marco [Thoraxcenter, Rotterdam (Netherlands)

    2014-06-15

    Background: Radiation absorbed by interventional cardiologists is a frequently under-evaluated important issue. Aim is to compare radiation dose absorbed by interventional cardiologists during percutaneous coronary procedures for acute coronary syndromes comparing transradial and transfemoral access. Methods: The randomized multicentre MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial has been designed to compare the clinical outcome of patients with acute coronary syndromes treated invasively according to the access site (transfemoral vs. transradial) and to the anticoagulant therapy (bivalirudin vs. heparin). Selected experienced interventional cardiologists involved in this study have been equipped with dedicated thermoluminescent dosimeters to evaluate the radiation dose absorbed during transfemoral or right transradial or left transradial access. For each access we evaluate the radiation dose absorbed at wrist, at thorax and at eye level. Consequently the operator is equipped with three sets (transfemoral, right transradial or left transradial access) of three different dosimeters (wrist, thorax and eye dosimeter). Primary end-point of the study is the procedural radiation dose absorbed by operators at thorax. An important secondary end-point is the procedural radiation dose absorbed by operators comparing the right or left radial approach. Patient randomization is performed according to the MATRIX protocol for the femoral or radial approach. A further randomization for the radial approach is performed to compare right and left transradial access. Conclusions: The RAD-MATRIX study will probably consent to clarify the radiation issue for interventional cardiologist comparing transradial and transfemoral access in the setting of acute coronary syndromes.

  17. Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

    Science.gov (United States)

    Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

    2018-05-01

    The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all pNegative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all pnegative symptoms in patients with stabilized schizophrenia.

  18. Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

    Science.gov (United States)

    Evans, Malkanthi; Beck, Mareike; Elliott, James; Etheve, Stephane; Roberts, Richard; Schalch, Wolfgang

    2013-06-01

    Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

  19. Dose response of PEG 3350 for the treatment of childhood fecal impaction.

    Science.gov (United States)

    Youssef, Nader N; Peters, John M; Henderson, Wendy; Shultz-Peters, Sandra; Lockhart, Danielle K; Di Lorenzo, Carlo

    2002-09-01

    To investigate the efficacy and safety of polyethylene glycol (PEG) 3350 in the treatment of childhood fecal impaction. This was a prospective, double-blind, parallel, randomized study of 4 doses of PEG 3350; 0.25 g/kg per day, 0.5 g/kg per day, 1 g/kg per day, 1.5 g/kg per day, given for 3 days in children with constipation for >3 months and evidence of fecal impaction. Forty patients completed the study (27 boys, median age 7.5, range 3.3-13.1 years). Disimpaction occurred in 75% of children, with a significant difference between the two higher doses and the lower doses (95% vs 55%, P PEG 3350 is safe and effective in the treatment of childhood fecal impaction at doses of 1 and 1.5 g/kg per day.

  20. Clinical validation of a dose reduction study in paediatric abdomen MSCT scanning

    International Nuclear Information System (INIS)

    Ciccarone, A.; Fonda, C.; Zatelli, Giovanna; Mazzocchi, S.

    2008-01-01

    Full text: In our previous work an individual dose adaptation in abdomen of paediatric patients has been showed at the Meyer children hospital of Florence. For each kV really feasible in our MSCT scanner, a table of mAs versus abdomen thickness and width ratio has been developed only on the basis of water cylinder phantoms. The choice of the water arise by the fact that in pediatric patient the quantity of water inside the body is major than that of adult. In this way a reduction dose has showed with respect to the ordinary paediatric scanning protocol in use before and the same image quality has been preserved in the case of an optimized CT scanning technique of a standard adult patient of height 175 cm and weight 70 kg. However these results were only theoretical because relied on water phantoms. Now this work concerns the clinical validation of our dose reduction study on phantoms. So 50 examinations were acquired with the dose reduction scanning technique and scored randomly, without knowing weight and height of patient by three radiologists. These scores were compared with that of other 50 abdomen examination before dose reduction study. The scores refers to the noise perceived by radiologist and to the diagnostic quality of radiograph. As last, a score on the low contrast tissue separation between muscle and fat and a score on visibility of structure therein have been asked to the radiologists. The same work has concerned the abdomen examinations with iodine contrast medium. In this study the score of each radiographs has been catalogued in four range of age, 0 - 1; 1 - 3; 3 - 8; 8 - 13 years. Aligned rank and Wilcoxon's signed rank tests were used for statistical analyses. The table of modulating mAs with respect to the size of patient obtained with only water phantom study has been revised so that none reduced detection in low-visibility structures like fat or muscle or liver was evident. Nevertheless a reduction in CTDI of 30 % has been reached in our new

  1. Prophylactic CNS therapy in childhood leukemia. Randomized controlled study of high-dose intravenous methotrexate and cranial irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Takashi; Hiyoshi, Yasuhiko [Kurume Univ., Fukuoka (Japan). School of Medicine; Fujimoto, Takeo

    1982-12-01

    This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm/sup 3/) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm/sup 3/) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m/sup 2/) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m/sup 2/, the CSF concentration of MTX rose to 2.3 +- 2.4 x 10/sup -6/M after initiation of infusion and remained in 10/sup -7/ M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% in Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC.

  2. Dose-Dependent Effects of Statins for Patients with Aneurysmal Subarachnoid Hemorrhage: Meta-Regression Analysis.

    Science.gov (United States)

    To, Minh-Son; Prakash, Shivesh; Poonnoose, Santosh I; Bihari, Shailesh

    2018-05-01

    The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage. Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse. The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352). The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.

    Science.gov (United States)

    Ashida, K; Sakurai, Y; Nishimura, A; Kudou, K; Hiramatsu, N; Umegaki, E; Iwakiri, K; Chiba, T

    2015-09-01

    The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders. To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO). In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4. A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups. Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

  4. A single dose of erythropoietin reduces perioperative transfusions in cardiac surgery: results of a prospective single-blind randomized controlled trial.

    Science.gov (United States)

    Weltert, Luca; Rondinelli, Beatrice; Bello, Ricardo; Falco, Mauro; Bellisario, Alessandro; Maselli, Daniele; Turani, Franco; De Paulis, Ruggero; Pierelli, Luca

    2015-07-01

    We conducted a prospective single-blind randomized study to assess whether a single 80,000 IU dose of human recombinant erythropoietin (HRE), given just 2 days before cardiac surgery, could be effective in reducing perioperative allogeneic red blood cell transfusion (aRBCt). Six-hundred patients presenting with preoperative hemoglobin (Hb) level of not more than 14.5 g/dL were randomly assigned to either HRE or control. The primary endpoint was the incidence of perioperative aRBCt. The secondary endpoints were mortality and the incidence of adverse events in the first 45 days after surgery, Hb level on Postoperative Day 4, and number of units of RBC transfusions in the first 4 days after surgery. A total of 17% (HRE) versus 39% (control) required transfusion (relative risk, 0.436; pHRE (0%) and control (3.5%) among the patients with baseline Hb of 13.0 g/dL or more, which included the nonanemic fraction of the study population. The mean (range) Hb level on Postoperative Day 4 was 10.2 (9.9-10.6) g/dL (HRE) versus 8.7 (8.5-9.2) g/dL (control; pHRE (pHRE) versus 3.33% (control). The 45-day adverse event rate was 4.33% (HRE) versus 5.67% (control; both p=NS). In anemic patients (HbHRE administered 2 days before cardiac surgery is effective in reducing the incidence of aRBCt without increasing adverse events. © 2015 AABB.

  5. A dose error evaluation study for 4D dose calculations

    Science.gov (United States)

    Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

    2014-10-01

    Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

  6. Absorbed dose/melting heat dependence studies for the PVDF homopolymer

    International Nuclear Information System (INIS)

    Batista, Adriana S.M.; Gual, Maritza R.; Pereira, Claubia

    2013-01-01

    Differential Scanning Calorimetry (DSC) of gamma irradiated Poly (vinylidene Fluoride) [PVDF] homopolymer has been studied in connection with the use of material in industrial high gamma dose measurement. Interaction between gamma radiation and PVDF leads to the radio-induction of C=O and conjugated C=C bonds, as it can be inferred from previous infrared (FTIR) and ultraviolet-visible (UV-Vis) spectrometric data. These induced defects result in a decrease of the polymer crystallinity that can be followed with DSC scans, by measuring the latent heat during the melting transition (Hmelt). After a systematic investigation, we have found that Hmelt is unambiguously related to the delivered doses ranging from 100 to 2,000 kGy of gamma radiation. One the other hand, further fading investigation analysis has proved that the Hmelt x Dose relationship can be fitted by an exponential function that remains constant for several months. Both the very large range of dose measurement and also the possibility of evaluating high gamma doses until five months after irradiation make PVDF homopolymers very good candidates to be investigated as commercial high gamma dose dosimeters. The high gamma dose irradiation facilities in Brazil used to develop high dose dosimeters are all devoted to industrial and medical purposes. Therefore, in view of the uncertainties involved in the dose measurements related to the electronic equilibrium correction factors and backscattering in the isodose curves used at the irradiation setup, a validation process is required to correctly evaluate the delivered absorbed doses. The sample irradiations were performed with a Co-60 source, at 12kGy/h and 2,592 kGy/h, in the high gamma dose facilities at Centro de Desenvolvimento da Tecnologia Nuclear CDTN/CNEN, Belo Horizonte, Brazil. The comparison of the curve of the Hmelt vs Dose is presented in this paper. (author)

  7. X-γ dose rate continuous monitor with wide range based on single-chip microcomputer

    International Nuclear Information System (INIS)

    Wu Debo; Ling Qiu; Guo Lanying; Yang Binhua

    2007-01-01

    This paper describes a concept about circuit designing of X-γ dose rate continuous monitor with wide range based on single-chip microcomputer, and also presents the design procedure of hardware and software, and gives several methods for solving the design procedure of hardware and software with emphasis. (authors)

  8. Randomized multicenter follow-up trial on the effect of radiotherapy for plantar fasciitis (painful heels spur) depending on dose and fractionation – a study protocol

    International Nuclear Information System (INIS)

    Holtmann, Henrik; Niewald, Marcus; Prokein, Benjamin; Graeber, Stefan; Ruebe, Christian

    2015-01-01

    An actual clinical trial showed the effect of low dose radiotherapy in painful heel spur (plantar fasciitis) with single doses of 1.0 Gy and total doses of 6.0 Gy applied twice weekly. Furthermore, a lot of animal experimental and in vitro data reveals the effect of lower single doses of 0.5 Gy which may be superior in order to ease pain and reduce inflammation in patients with painful heel spur. Our goal is therefore to transfer this experimentally found effect into a randomized multicenter trial. This was a controlled, prospective, two-arm phase III-multicenter trial. The standard arm consisted of single fractions of 1.0 Gy applied two times a week, for a total dose of 6.0 Gy (total therapy time: 3 weeks). The experimental arm consisted of single fractions of 0.5 Gy applied 3 times a week, for a total dose of 6.0 Gy (total therapy time: 4 weeks). Following a statistical power calculation, there were 120 patients for each investigation arm. The main inclusion criteria were: age > = 40 years, clinical and radiologically diagnosed painful heel spur (plantar fasciitis), and current symptoms for at least 6 months. The main exclusion criteria were: former local trauma, surgery or radiotherapy of the heel; pregnant or breastfeeding women; and a pre-existing severe psychiatric or psychosomatic disorder. After approving a written informed consent the patients are randomized by a statistician into one of the trial arms. After radiotherapy, the patients are seen after six weeks, after twelve weeks and then every twelve weeks up to 48 weeks. Additionally, they receive a questionnaire every six weeks after the follow-up examinations up to 48 weeks. The effect is measured using the visual analogue scale of pain (VAS), the calcaneodynia score according to Rowe and the SF-12 score. The primary endpoint is the pain relief three months after therapy. Patients of both therapy arms with an insufficient result are offered a second radiotherapy series applying the standard dose

  9. Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study.

    Science.gov (United States)

    Shalaby, S M; Bosseila, M; Fawzy, M M; Abdel Halim, D M; Sayed, S S; Allam, R S H M

    2016-11-01

    Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm 2 ) UVA-1 phototherapy (340-400 nm) or 3 sessions of fractional CO 2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO 2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

  10. Analysis of the dose-response relationship observed in Sprekelia, Petunia and Impatiens treated with gamma radiation

    International Nuclear Information System (INIS)

    Gonzalez J, J.

    2007-01-01

    The present investigation was carried out in order to verifying if it is possible to establish one or a dose range that directly not at random produces a specific effect independently of the species that is treated. The results show that this can be possible if the ranges settle down based on the specific stocking lethal dose for each specie. (Author)

  11. The effect of chronic progressive-dose sodium bicarbonate ingestion on CrossFit-like performance: A double-blind, randomized cross-over trial.

    Science.gov (United States)

    Durkalec-Michalski, Krzysztof; Zawieja, Emilia E; Podgórski, Tomasz; Łoniewski, Igor; Zawieja, Bogna E; Warzybok, Marta; Jeszka, Jan

    2018-01-01

    Sodium bicarbonate (SB) has been proposed as an ergogenic aid, as it improves high-intensity and resistance exercise performance. However, no studies have yet investigated SB application in CrossFit. This study examined the effects of chronic, progressive-dose SB ingestion on CrossFit-like performance and aerobic capacity. In a randomized, double-blind, cross-over trial, 21 CrossFit-trained participants were randomly allocated to 2 groups and underwent 2 trials separated by a 14-day washout period. Participants ingested either up to 150 mg∙kg-1 of SB in a progressive-dose regimen or placebo for 10 days. Before and after each trial, Fight Gone Bad (FGB) and incremental cycling (ICT) tests were performed. In order to examine biochemical responses, blood samples were obtained prior to and 3 min after completing each exercise test. No gastrointestinal (GI) side effects were reported during the entire protocol. The overall FGB performance improved under SB by ~6.1% (pCrossFit-like performance, as well as delayed ventilatory threshold occurrence.

  12. A double-blind, randomized, placebo-controlled, fixed-dose phase III study of vilazodone in patients with generalized anxiety disorder.

    Science.gov (United States)

    Gommoll, Carl; Durgam, Suresh; Mathews, Maju; Forero, Giovanna; Nunez, Rene; Tang, Xiongwen; Thase, Michael E

    2015-06-01

    Vilazodone, a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist, is approved for treating major depressive disorder in adults. This study (NCT01629966 ClinicalTrials.gov) evaluated the efficacy and safety of vilazodone in adults with generalized anxiety disorder (GAD). A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227). Primary and secondary efficacy parameters were total score change from baseline to week 8 on the Hamilton Rating Scale for Anxiety (HAMA) and Sheehan Disability Scale (SDS), respectively, analyzed using a predefined mixed-effect model for repeated measures (MMRM). Safety outcomes were presented by descriptive statistics. The least squares mean difference (95% confidence interval) in HAMA total score change from baseline (MMRM) was statistically significant for vilazodone 40 mg/day versus placebo (-1.80 [-3.26, -0.34]; P = .0312 [adjusted for multiple comparisons]), but not for vilazodone 20 mg/day versus placebo. Mean change from baseline in SDS total score was not significantly different for either dose of vilazodone versus placebo when adjusted for multiplicity; significant improvement versus placebo was noted for vilazodone 40 mg/day without adjustment for multiplicity (P = .0349). The incidence of adverse events was similar for vilazodone 20 and 40 mg/day (∼71%) and slightly lower for placebo (62%). Nausea, diarrhea, dizziness, vomiting, and fatigue were reported in ≥5% of patients in either vilazodone group and at least twice the rate of placebo. Vilazodone was effective in treating anxiety symptoms of GAD. No new safety concerns were identified. © 2015 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc.

  13. Evaluation of GAFCHROMIC EBT2 dosimetry for the low dose range using a flat-bed scanner with the reflection mode

    International Nuclear Information System (INIS)

    Gotanda, Tatsuhiro; Katsuda, Toshizo; Akagawa, Takuya; Gotanda, Rumi; Tabuchi, Akihiko; Yamamoto, Kenyu; Kuwano, Tadao; Takedo, Yoshihiro; Yatake, Hidetoshi; Yabunaka, Koichi

    2013-01-01

    Recently developed radiochromic films can easily be used to measure absorbed doses because they do not need development processing and indicate a density change that depends on the absorbed dose. However, in GAFCHROMIC EBT2 dosimetry (GAF-EBT2) as a radiochromic film, the precision of the measurement was compromised, because of non-uniformity problems caused by image acquisition using a flat-bed scanner with a transmission mode. The purpose of this study was to improve the precision of the measurement using a flat-bed scanner with a reflection mode at the low absorbed dose dynamic range of GAF-EBT2. The calibration curves of the absorbed dose versus the film density for GAF-EBT2 were provided. X-rays were exposed in the range between ~0 and 120 mGy in increments of about 12 mGy. The results of the method using a flat-bed scanner with the transmission mode were compared with those of the method using the same scanner with the reflection mode. The results should that the determination coefficients (r 2 ) for the straight-line approximation of the calibration curve using the reflection mode were higher than 0.99, and the gradient using the reflection mode was about twice that of the one using the transmission mode. The non-uniformity error that is produced by a flat-bed scanner with the transmission mode setting could be almost eliminated by converting from the transmission mode to the reflection mode. In light of these findings, the method using a flat-bed scanner with the reflection mode (only using uniform white paper) improved the precision of the measurement for the low absorbed dose range.

  14. Effect of Low-dose Atracurium on Laryngeal Mask Airway Insertion Conditions: A Randomized Double-blind Clinical Trial

    Directory of Open Access Journals (Sweden)

    Karim Nasseri

    2017-01-01

    Full Text Available Background: The amount of sedation and muscle relaxation of the jaw may have an impact on complications caused by laryngeal mask airway (LMA. The aim of this study is to evaluate the effect of low-dose Atracurium on conditions of insertion, complications, and hemodynamic responses to LMA insertion following induction of anesthesia with propofol, in patients undergoing cataract surgery. Patients and Methods: In this double-blind randomized clinical trial study, 60 patients were randomly divided into two groups. Initially, the patients in the study group received 0.15 mg/kg intravenous injection of atracurium, and the patients in the control group received 2 ml of intravenous injection of normal saline, after which anesthesia in both groups were induced with midazolam, fentanyl, lidocaine, and propofol. The amount of jaw relaxation, ease of insertion, and the time needed for insertion, hemodynamic responses and complications of LMA insertion were evaluated. Results: Jaw relaxation and ease of LMA insertion in the study group was significantly better than that of the control group (P = 0.02. Average time needed for LMA placement in the study group (5/06 ± 0.52 second was significantly lower than the control group (5/76 ± 0.67 second (P = 0.001. Hemodynamic response to LMA insertion was similar in both groups. Sore throat at recovery and 24 h after surgery in the control group was significantly higher than that of the study group (3/30 vs. 10/30 (P = 0.01. Conclusions: Using low doses of atracurium decreases the time needed for LMA insertion and sore throat after the operation. Atracurium also increases jaw relaxation and facilitates the placement of LMA.

  15. Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on postsurgical dental pain: two randomized, single-dose, double-blind, placebo-controlled clinical studies.

    Science.gov (United States)

    Yue, Yong; Collaku, Agron; Brown, Jean; Buchanan, William L; Reed, Kenneth; Cooper, Stephen A; Otto, James

    2013-09-01

    Paracetamol (APAP), also known as acetaminophen, is the most commonly used over-the-counter analgesic for the treatment of mild-to-moderate pain. However, the speed of onset of pain relief is limited mainly to the standard, immediate-release formulation. Efficacy and speed of onset of pain relief are critical in acute pain situations such as postsurgical dental pain, because reducing pain can improve clinical outcome and reduce the risk of transition from acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of excessive dosing with the analgesic. We sought to investigate the dose-response efficacy and speed of onset of pain relief of a fast-dissolving APAP formulation compared with lower doses of APAP and placebo in dental patients after impacted third molar extraction. Two single-center, single-dose, randomized, placebo-controlled, double-blind, double-dummy, parallel-group studies (Study I and Study II) were conducted to evaluate the efficacy and speed of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD-APAP), standard APAP, and placebo in patients with postsurgical dental pain following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg, FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients. All 701 patients from both studies were included in the analysis and safety assessment. FD-APAP 1000 mg demonstrated significantly greater effect compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy measurements, including sum of pain relief and pain intensity difference, total pain relief, sum of pain intensity difference, pain intensity difference, and pain relief score during 6 hours after the dose. Onset of confirmed first perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which was 32% and 25% significantly shorter than onset of pain relief of FD

  16. Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol.

    Science.gov (United States)

    Oyanguren, Juana; García-Garrido, LLuisa; Nebot Margalef, Magdalena; Lekuona, Iñaki; Comin-Colet, Josep; Manito, Nicolás; Roure, Julia; Ruiz Rodriguez, Pilar; Enjuanes, Cristina; Latorre, Pedro; Torcal Laguna, Jesús; García-Gutiérrez, Susana

    2017-11-01

    Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta-blockers (BBs), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse-managed) and control (cardiologist-managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups. We have designed a multicentre (20 hospitals) non-inferiority randomized controlled trial, including patients with new-onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II-III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N-terminal pro B-type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics. The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice. © 2017 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of

  17. First-In-Human, Double-Blind, Placebo-Controlled, Randomized, Dose-Escalation Study of BG00010, a Glial Cell Line-Derived Neurotrophic Factor Family Member, in Subjects with Unilateral Sciatica.

    Science.gov (United States)

    Rolan, Paul E; O'Neill, Gilmore; Versage, Eve; Rana, Jitesh; Tang, Yongqiang; Galluppi, Gerald; Aycardi, Ernesto

    2015-01-01

    To evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica. This was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28. Beyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was

  18. The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women-A randomized controlled trial.

    Science.gov (United States)

    Grimnes, G; Emaus, N; Cashman, K D; Jorde, R

    2017-07-01

    Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D 3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D 3 (20 000 IU) or matching placebos to be taken twice a week. A total of 297 postmenopausal women with osteopenia or osteoporosis. Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; PD had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations. © 2017 John Wiley & Sons Ltd.

  19. Relationship between accuracy and number of samples on statistical quantity and contour map of environmental gamma-ray dose rate. Example of random sampling

    International Nuclear Information System (INIS)

    Matsuda, Hideharu; Minato, Susumu

    2002-01-01

    The accuracy of statistical quantity like the mean value and contour map obtained by measurement of the environmental gamma-ray dose rate was evaluated by random sampling of 5 different model distribution maps made by the mean slope, -1.3, of power spectra calculated from the actually measured values. The values were derived from 58 natural gamma dose rate data reported worldwide ranging in the means of 10-100 Gy/h rates and 10 -3 -10 7 km 2 areas. The accuracy of the mean value was found around ±7% even for 60 or 80 samplings (the most frequent number) and the standard deviation had the accuracy less than 1/4-1/3 of the means. The correlation coefficient of the frequency distribution was found 0.860 or more for 200-400 samplings (the most frequent number) but of the contour map, 0.502-0.770. (K.H.)

  20. Efficacy between high and medium doses of glucocorticoid therapy in remission induction of IgG4-related diseases: a preliminary randomized controlled trial.

    Science.gov (United States)

    Wu, Qingjun; Chang, Jie; Chen, Hua; Chen, Yu; Yang, Hongxian; Fei, Yunyun; Zhang, Panpan; Zeng, Xiaofeng; Zhang, Fengchun; Zhang, Wen

    2017-05-01

    In order to evaluate the efficacy and safety of high versus medium doses of glucocorticoid therapy in remission induction of immunoglobulin G4-related disease (IgG4-RD), we set up a randomized controlled study. Newly diagnosed IgG4-RD patients were randomly assigned to two groups: high doses of prednisone (0.8-1.0 mg/kg/day) and medium doses (0.5-0.6 mg/kg/day). Patients were assessed at weeks 0, 4, 12 and 24. The primary outcome was the remission rate at week 24. The secondary endpoints included IgG4-RD responder index (IgG4-RD RI), IgG and IgG4 levels. Twenty cases in each group finished the study. At week 24, the total response rates were 95% and 80% in high and medium dose groups, respectively. There was no significant difference between the two groups. IgG4-RD RI reduced from 14.9 to 3.0 in the high dose group, while in the medium dose group it was from 13.1 to 3.2. At week 24, the average level of IgG4 reduced from 1576 to 324 mg/dL and from 1445 to 684 mg/dL in the two groups, respectively. Relapsed patients had higher baseline IgG4-RD RI. There was no severe adverse effect shown in both groups. The effect of remission induction was similar in high and medium glucocorticoid groups. However, patients with more organs involved and higher IgG4-RD RI score at baseline might get more benefit with high dose glucocorticoid for remission induction. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  1. Required accuracy and dose thresholds in individual monitoring

    DEFF Research Database (Denmark)

    Christensen, P.; Griffith, R.V.

    1994-01-01

    this uncertainty factor, a value of 21% can be evaluated for the allowable maximum overall standard deviation for dose measurements at dose levels near the annual dose limits increasing to 45% for dose levels at the lower end of the dose range required to be monitored. A method is described for evaluating...... the overall standard deviation of the dosimetry system by combining random and systematic uncertainties in quadrature, and procedures are also given for determining each individual uncertainty connected to the dose measurement. In particular, attention is paid to the evaluation of the combined uncertainty due...... to energy and angular dependencies of the dosemeter. In type testing of personal dosimetry systems, the estimated overall standard deviation of the dosimetry system is the main parameter to be tested. An important characteristic of a personal dosimetry system is its capability of measuring low doses...

  2. A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.

    Science.gov (United States)

    Markus, Richard; Chow, Vincent; Pan, Zhiying; Hanes, Vladimir

    2017-10-01

    This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males. In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC inf ) and the maximum observed concentration (C max ). Secondary endpoints included safety and immunogenicity. AUC inf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUC inf , respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUC inf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected. This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.

  3. Field study to evaluate radiation doses in dental practices

    International Nuclear Information System (INIS)

    Panzer, W.; Scheurer, C.

    1984-05-01

    An inexpensive and simple test device was developed and used in a field study to evaluate entrance dose, dose to an intra-oral film, filtration and field size under routine conditions in more than 150 dental practices. The test device consists of two films of different speed and a set of 5 thin copper filters for a filter analytical determination of the radiation quality. Dentists voluntarily participating in the study were asked to expose the test device like they usually do when examining a molar tooth. The main result was the evidence of a significant dose reduction compared to the findings of similar studies performed in 1970 and 1976. This reduction is due to a general shift to lower values and a complete disappearance of values above 45 mGy (5 R) which in 1970 were still more than 15%. In the same way the number of facilities showing insufficient filtration or collimation had decreased. Nevertheless, a large spread of dose values could still be observed, ranging from less than 0.45 mGy (50 mR) to more than 26 mGy (3 R), for the entrance dose. The most striking result, however, was that such an important parameter like the speed of the films used at the respective unit turned out to have no impact on the entrance dose. (orig./HP)

  4. Study of dose effect relationship at low doses for non quantitative reactions of skin intestinal mucosa and lung

    International Nuclear Information System (INIS)

    Dutreix, J.; Wambersie, A.

    1977-01-01

    Most of the biological reactions observed in animal experiments or in clinical studies are non quantitative and they only allow assessing an inequality between the effects produced by different irradiations. The method used in non quantitative studies is actually based on the relative contribution of irreparable events and reparable to the cell killing. It provides for the cell population involved in non quantitative biological effects some data which can be expressed in term of a cell survival curve. Such data can be useful in Radiation therapy particularly for maximizing the difference between biological effects by a proper choice of the fraction size. The initial part of the cell survival curve, within the range of doses actually used appears to be a straight exponential. This should allow the extrapolation to very low doses in the range of interest to Radiation Protection

  5. The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

    Science.gov (United States)

    Ibrahim, Moustafa Ibrahim; Hamdy, Ahmed; Shafik, Adel; Taha, Salah; Anwar, Mohammed; Faris, Mohammed

    2014-05-01

    The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily

  6. Effectiveness of low-dose doxycycline (LDD on clinical symptoms of Sjögren's Syndrome: a randomized, double-blind, placebo controlled cross-over study

    Directory of Open Access Journals (Sweden)

    Vuotila Tuija

    2007-12-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are proteolytic enzymes that may contribute to tissue destruction in Sjögren's syndrome (SS. Low-dose doxycycline (LDD inhibits MMPs. We evaluated the efficacy of LDD for the subjective symptoms in primary SS patients. This was a randomized, double blind, placebo controlled cross-over study. 22 patients were randomly assigned to receive either 20 mg LDD or matching placebo twice a day for 10 weeks. The first medication period was followed by 10-week washout period, after which the patient received either LDD or placebo, depending on the first drug received, followed by the second washout period. Stimulated saliva flow rates and pH were measured before and after one and ten weeks of each medication and after washout periods. VAS scale was used to assess the effect of LDD and placebo on following six subjective symptoms: xerostomia; xerophtalmia; difficulty of swallowing; myalgia; arthralgia; and fatigue. The effect was evaluated for each medication and washout period separately. Results Overall, the effects of medications on subjective symptoms were minor. Wilcoxon test demonstrated increased fatigue with LDD during medication (p Conclusion LDD may not be useful in reducing the primary SS symptoms.

  7. Pharmacokinetics and Safety of Amenamevir in Healthy Subjects: Analysis of Four Randomized Phase 1 Studies.

    Science.gov (United States)

    Kusawake, Tomohiro; Keirns, James J; Kowalski, Donna; den Adel, Martin; Groenendaal-van de Meent, Dorien; Takada, Akitsugu; Ohtsu, Yoshiaki; Katashima, Masataka

    2017-12-01

    Amenamevir (ASP2151) is a nonnucleoside antiherpesvirus compound available for the treatment of varicella-zoster virus infections. In this article we summarize the findings of four phase 1 studies in healthy participants. Four randomized phase 1 studies investigated the safety and pharmacokinetics of single and multiple doses of amenamevir, including the assessment of age group effect (nonelderly vs elderly), food effect, and the relative bioavailability of two formulations. Amenamevir was administered orally at various doses as a single dose (5-2400 mg) or daily (300 or 600 mg/day) for 7 days. Following single and multiple oral doses, amenamevir demonstrated a less than dose proportional increase in the pharmacokinetic parameters area under the plasma drug concentration versus time curve from time zero to infinity (AUC inf ) and C max . After single and multiple oral 300-mg doses of amenamevir, no apparent differences in pharmacokinetics were observed between nonelderly and elderly participants. In contrast, with the amenamevir 600-mg dose both the area under the plasma drug concentration versus time curve from time zero to 24 h and C max were slightly increased and renal clearance was decreased in elderly participants. The pharmacokinetics of amenamevir was affected by food, with AUC inf increased by about 90%. In the bioavailability study, AUC inf and C max were slightly lower following tablet versus capsule administration (decreased by 14 and 12%, respectively), with relative bioavailability of 86%. The different amenamevir doses and formulations were safe and well tolerated; no deaths or serious adverse events were reported. Amenamevir had less than dose proportional pharmacokinetic characteristics. Age may have an influence on amenamevir pharmacokinetics; however, the effect was considered minimal. The pharmacokinetics of amenamevir were affected by food, with AUC inf almost doubling when amenamevir was administered with food. The concentration versus

  8. Linear optical absorption response of poly(vinylidene fluoride - trifluoroethylene) copolymers to high gamma dose

    International Nuclear Information System (INIS)

    Medeiros, Adriana S.

    2009-01-01

    Poly(vinylidene fluoride) [PVDF] is a semicrystalline linear homopolymer composed by the repetition of CH 2 - CF 2 monomers. The Poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] is a copolymer which is obtained with the random introduction of fluorinated CHF-CF 2 monomers in the PVDF main chain. PVDF, and also its copolymers with TrFE contents ranging from 18 to 63 wt. %, have long been studied for their striking ferroelectric properties and their applications in actuators, transducers and ferroelectric memory. Recent research work around the world have demonstrated that, for TrFE contents ranging from with 30 to 50 wt. %, the copolymer can have its ferroelectric properties modified by high doses of ionizing radiation, with the appearing of radio-induced relaxor ferroelectric features. These studies have lead us to investigate the possible use of these copolymers as high dose dosemeters, once the reported amount of induced C=C conjugated bonds after X-ray, UV and gamma irradiation seems to be a function of the delivered radiation dose. In a first investigation for doses ranging from 0.1 to 100 kGy we found out a linear relation between the gamma radiation dose and the absorption peak intensities in the UV region of the spectrum, i.e., at 223 and 274 nm. The absorption peak at 223 nm is the most sensitive to gamma rays and can be used for detecting gamma doses ranging from 0.3 to 75 kGy. Simultaneously, the absorption peak at 274 nm can be used for doses ranging from 1 to 100 kGy. Now, in the present work, we extended the investigation to gamma doses up to 3 MGy. Particularly, this study is focused in the optical absorption peak at 274 nm, corresponding to the radio-induction of triplets of conjugated C=C double bonds. The investigation revealed a linear correlation between the gamma dose and peak intensity at 274 nm for gamma doses ranging from 0.1 to more than 750 KGy, with a huge extension of the original usable dose range. Calorimetric data revealed a

  9. The dual trigger study: Rationale and study design of a prospective double-blind randomized clinical trial comparing pregnancy rates after co-administration of low dose hCG at the time of GnRH agonist trigger or 35 h later for the prevention of OHSS

    Directory of Open Access Journals (Sweden)

    Daniel Griffin

    2017-12-01

    Full Text Available Ovarian hyperstimulation syndrome (OHSS is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group. The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

  10. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

    Science.gov (United States)

    Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-01

    The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

  11. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    International Nuclear Information System (INIS)

    Stambaugh, Cassandra; Nelms, Benjamin E.; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-01-01

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D 99% ), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from the

  12. Reduction of the unnecessary dose from the over-range area with a spiral dynamic z-collimator: comparison of beam pitch and detector coverage with 128-detector row CT.

    Science.gov (United States)

    Shirasaka, Takashi; Funama, Yoshinori; Hayashi, Mutsukazu; Awamoto, Shinichi; Kondo, Masatoshi; Nakamura, Yasuhiko; Hatakenaka, Masamitsu; Honda, Hiroshi

    2012-01-01

    Our purpose in this study was to assess the radiation dose reduction and the actual exposed scan length of over-range areas using a spiral dynamic z-collimator at different beam pitches and detector coverage. Using glass rod dosimeters, we measured the unilateral over-range scan dose between the beginning of the planned scan range and the beginning of the actual exposed scan range. Scanning was performed at detector coverage of 80.0 and 40.0 mm, with and without the spiral dynamic z-collimator. The dose-saving ratio was calculated as the ratio of the unnecessary over-range dose, with and without the spiral dynamic z-collimator. In 80.0 mm detector coverage without the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 108, 120, and 126 mm, corresponding to a beam pitch of 0.60, 0.80, and 0.99, respectively. With the spiral dynamic z-collimator, the actual exposed scan length for the over-range area was 48, 66, and 84 mm with a beam pitch of 0.60, 0.80, and 0.99, respectively. The dose-saving ratios with and without the spiral dynamic z-collimator for a beam pitch of 0.60, 0.80, and 0.99 were 35.07, 24.76, and 13.51%, respectively. With 40.0 mm detector coverage, the dose-saving ratios with and without the spiral dynamic z-collimator had the highest value of 27.23% with a low beam pitch of 0.60. The spiral dynamic z-collimator is important for a reduction in the unnecessary over-range dose and makes it possible to reduce the unnecessary dose by means of a lower beam pitch.

  13. Dose/volume–response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions

    International Nuclear Information System (INIS)

    Thor, Maria; Apte, Aditya; Deasy, Joseph O.; Karlsdóttir, Àsa; Moiseenko, Vitali; Liu, Mitchell; Muren, Ludvig Paul

    2013-01-01

    Background and purpose: Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. Materials and methods: The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. Results: The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55–70 Gy), using both the planned and the motion-inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs = 0.12–0.21; Rs = 0.11–0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs = 0.13, p = 0.02). Conclusion: Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power

  14. Foetal Radiation Dose and Risk from Diagnostic Radiology Procedures: A Multinational Study

    International Nuclear Information System (INIS)

    Osei, Ernest K.; Darko, Johnson

    2012-01-01

    In diagnostic radiology examinations there is a benefit that the patient derives from the resulting diagnosis. Given that so many examinations are performed each year, it is inevitable that there will be occasions when an examination(s) may be inadvertently performed on pregnant patients or occasionally it may become clinically necessary to perform an examination(s) on a pregnant patient. In all these circumstances it is necessary to request an estimation of the foetal dose and risk. We initiated a study to investigate fetal doses from different countries. Exposure techniques on 367 foetuses from 414 examinations were collected and investigated. The FetDoseV4 program was used for all dose and risk estimations. The radiation doses received by the 367 foetuses ranges: <0.001–21.9 mGy depending on examination and technique. The associated probability of induced hereditary effect ranges: <1 in 200000000 (5 × 10 −9 ) to 1 in 10000 (1 × 10 −4 ) and the risk of childhood cancer ranges <1 in 12500000 (8 × 10 −8 ) to 1 in 500 (2 × 10 −3 ). The data indicates that foetal doses from properly conducted diagnostic radiology examinations will not result in any deterministic effect and a negligible risk of causing radiation induced hereditary effect in the descendants of the unborn child

  15. Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

    Science.gov (United States)

    Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

    2017-06-01

    This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

  16. Cystic Fibrosis: Are Volumetric Ultra-Low-Dose Expiratory CT Scans Sufficient for Monitoring Related Lung Disease?

    DEFF Research Database (Denmark)

    Loeve, Martine; Lequin, Maarten H; Bruijne, Marleen de

    2009-01-01

    Purpose: To assess whether chest computed tomography (CT) scores from ultra-low-dose end-expiratory scans alone could suffice for assessment of all cystic fibrosis (CF)-related structural lung abnormalities. Materials and Methods: In this institutional review board–approved study, 20 patients...... with CF aged 6–20 years (eight males, 12 females) underwent low-dose end-inspiratory CT and ultra-low-dose end-expiratory CT. Informed consent was obtained. Scans were randomized and scored by using the Brody-II CT scoring system to assess bronchiectasis, airway wall thickening, mucus plugging......-Altman plots. Results: Median age was 12.6 years (range, 6.3–20.3 years), median forced expiratory volume in 1 second was 100% (range, 46%–127%) of the predicted value, and median forced vital capacity was 99% (range, 61%–123%) of the predicted value. Very good agreement was observed between end...

  17. Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)

    NARCIS (Netherlands)

    Rubbert-Roth, Andrea; Tak, Paul P.; Zerbini, Cristiano; Tremblay, Jean-Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M.

    2010-01-01

    Methods. Patients with active RA despite stable MTX (10-25 mg/week) were randomly assigned to one of the three treatment regimens comprising two courses of RTX given 24 weeks apart: 2 x 500 and 2 x 500 mg; 2 x 500 and 2 x 1000 mg (dose escalation); and 2 x 1000 and 2 x 1000 mg. The primary endpoint

  18. Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.

    Science.gov (United States)

    Collet, Jean-Philippe; Hulot, Jean-Sébastien; Abtan, Jérémie; Anzaha, Ghalia; Kerneis, Mathieu; Silvain, Johanne; Cayla, Guillaume; O'Connor, Stephen A; Barthélémy, Olivier; Beygui, Farzin; Galier, Sophie; Brugier, Delphine; Stanek, Eric J; Charland, Scott L; Gallois, Vanessa; Montalescot, Gilles

    2014-09-01

    The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

  19. Effect of Intrathecal Bupivacaine Dose on the Success of External Cephalic Version for Breech Presentation: A Prospective, Randomized, Blinded Clinical Trial.

    Science.gov (United States)

    Chalifoux, Laurie A; Bauchat, Jeanette R; Higgins, Nicole; Toledo, Paloma; Peralta, Feyce M; Farrer, Jason; Gerber, Susan E; McCarthy, Robert J; Sullivan, John T

    2017-10-01

    Breech presentation is a leading cause of cesarean delivery. The use of neuraxial anesthesia increases the success rate of external cephalic version procedures for breech presentation and reduces cesarean delivery rates for fetal malpresentation. Meta-analysis suggests that higher-dose neuraxial techniques increase external cephalic version success to a greater extent than lower-dose techniques, but no randomized study has evaluated the dose-response effect. We hypothesized that increasing the intrathecal bupivacaine dose would be associated with increased external cephalic version success. We conducted a randomized, double-blind trial to assess the effect of four intrathecal bupivacaine doses (2.5, 5.0, 7.5, 10.0 mg) combined with fentanyl 15 μg on the success rate of external cephalic version for breech presentation. Secondary outcomes included mode of delivery, indication for cesarean delivery, and length of stay. A total of 240 subjects were enrolled, and 239 received the intervention. External cephalic version was successful in 123 (51.5%) of 239 patients. Compared with bupivacaine 2.5 mg, the odds (99% CI) for a successful version were 1.0 (0.4 to 2.6), 1.0 (0.4 to 2.7), and 0.9 (0.4 to 2.4) for bupivacaine 5.0, 7.5, and 10.0 mg, respectively (P = 0.99). There were no differences in the cesarean delivery rate (P = 0.76) or indication for cesarean delivery (P = 0.82). Time to discharge was increased 60 min (16 to 116 min) with bupivacaine 7.5 mg or higher as compared with 2.5 mg (P = 0.004). A dose of intrathecal bupivacaine greater than 2.5 mg does not lead to an additional increase in external cephalic procedural success or a reduction in cesarean delivery.

  20. Review of low dose-rate epidemiological studies and biological mechanisms of dose-rate effects on radiation induced carcinogenesis

    International Nuclear Information System (INIS)

    Iwasaki, Toshiyasu; Otsuka, Kensuke; Yoshida, Kazuo

    2015-01-01

    Radiation protection system adopts the linear non-threshold model with using dose and dose-rate effectiveness factor (DDREF). The dose-rate range where DDREF is applied is below 100 mGy per hour, and it is regarded that there are no dose-rate effects at very low dose rate, less than of the order of 10 mGy per year, even from the biological risk evaluation model based on cellular and molecular level mechanisms for maintenance of genetic integrity. Among low dose-rate epidemiological studies, studies of residents in high natural background areas showed no increase of cancer risks at less than about 10 mGy per year. On the other hand, some studies include a study of the Techa River cohort suggested the increase of cancer risks to the similar degree of Atomic bomb survivor data. The difference of those results was supposed due to the difference of dose rate. In 2014, International Commission on Radiological Protection opened a draft report on stem cell biology for public consultations. The report proposed a hypothesis based on the new idea of stem cell competition as a tissue level quality control mechanism, and suggested that it could explain the dose-rate effects around a few milligray per year. To verify this hypothesis, it would be needed to clarify the existence and the lowest dose of radiation-induced stem cell competition, and to elucidate the rate of stem cell turnover and radiation effects on it. As for the turnover, replenishment of damaged stem cells would be the important biological process. It would be meaningful to collect the information to show the difference of dose rates where the competition and the replenishment would be the predominant processes. (author)

  1. Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

    Science.gov (United States)

    Godino, Cosmo; Pavon, Anna Giulia; Mangieri, Antonio; Salerno, Anna; Cera, Michela; Monello, Alberto; Chieffo, Alaide; Magni, Valeria; Cappelletti, Alberto; Margonato, Alberto; Colombo, Antonio

    2017-08-01

    The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ≥12 hours after statin LD. 682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone. © 2017 Wiley Periodicals, Inc.

  2. Is It Better to Enter a Volume CT Dose Index Value before or after Scan Range Adjustment for Radiation Dose Optimization of Pediatric Cardiothoracic CT with Tube Current Modulation?

    Science.gov (United States)

    2018-01-01

    Objective To determine whether the body size-adapted volume computed tomography (CT) dose index (CTDvol) in pediatric cardiothoracic CT with tube current modulation is better to be entered before or after scan range adjustment for radiation dose optimization. Materials and Methods In 83 patients, cardiothoracic CT with tube current modulation was performed with the body size-adapted CTDIvol entered after (group 1, n = 42) or before (group 2, n = 41) scan range adjustment. Patient-related, radiation dose, and image quality parameters were compared and correlated between the two groups. Results The CTDIvol after the CT scan in group 1 was significantly higher than that in group 2 (1.7 ± 0.1 mGy vs. 1.4 ± 0.3 mGy; p Hounsfield units [HU] vs. 4.5 ± 0.7 HU) and image quality (1.5 ± 0.6 vs. 1.5 ± 0.6) showed no significant differences between the two (p > 0.05). In both groups, all patient-related parameters, except body density, showed positive correlations (r = 0.49–0.94; p 0.05) in group 2. Conclusion In pediatric cardiothoracic CT with tube current modulation, the CTDIvol entered before scan range adjustment provides a significant dose reduction (18%) with comparable image quality compared with that entered after scan range adjustment.

  3. Dose De-escalation of Intrapleural Tissue Plasminogen Activator Therapy for Pleural Infection. The Alteplase Dose Assessment for Pleural Infection Therapy Project.

    Science.gov (United States)

    Popowicz, Natalia; Bintcliffe, Oliver; De Fonseka, Duneesha; Blyth, Kevin G; Smith, Nicola A; Piccolo, Francesco; Martin, Geoffrey; Wong, Donny; Edey, Anthony; Maskell, Nick; Lee, Y C Gary

    2017-06-01

    Intrapleural therapy with a combination of tissue plasminogen activator (tPA) 10 mg and DNase 5 mg administered twice daily has been shown in randomized and open-label studies to successfully manage over 90% of patients with pleural infection without surgery. Potential bleeding risks associated with intrapleural tPA and its costs remain important concerns. The aim of the ongoing Alteplase Dose Assessment for Pleural infection Therapy (ADAPT) project is to investigate the efficacy and safety of dose de-escalation for intrapleural tPA. The first of several planned studies is presented here. To evaluate the efficacy and safety of a reduced starting dose regimen of 5 mg of tPA with 5 mg of DNase administered intrapleurally for pleural infection. Consecutive patients with pleural infection at four participating centers in Australia, the United Kingdom, and New Zealand were included in this observational, open-label study. Treatment was initiated with tPA 5 mg and DNase 5 mg twice daily. Subsequent dose escalation was permitted at the discretion of the attending physician. Data relating to treatment success, radiological and systemic inflammatory changes (blood C-reactive protein), volume of fluid drained, length of hospital stay, and treatment complications were extracted retrospectively from the medical records. We evaluated 61 patients (41 males; age, 57 ± 16 yr). Most patients (n = 58 [93.4%]) were successfully treated without requiring surgery for pleural infection. Treatment success was corroborated by clearance of pleural opacities visualized by chest radiography (from 42% [interquartile range, 22-58] to 16% [8-31] of hemithorax; P < 0.001), increase in pleural fluid drainage (from 175 ml in the 24 h preceding treatment to 2,025 ml [interquartile range, 1,247-2,984] over 72 h of therapy; P <  0.05) and a reduction in blood C-reactive protein (P < 0.05). Seven patients (11.5%) had dose escalation of tPA to 10 mg. Three patients underwent

  4. Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease

    Science.gov (United States)

    Brod, Lissa S.; Aldred, Jason L.; Nutt, John G.

    2013-01-01

    Background Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects. Methods We compared 4-week outpatient treatments with carbidopa 75 mg and 450 mg/day administered with levodopa on the subjects’ normal schedule. After each treatment phase subjects had two 2-hour levodopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding four weeks and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and levodopa and carbidopa plasma concentrations were monitored during the infusions. Results Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four levodopa infusions although AUC for plasma levodopa was modestly increased with 450 mg of carbidopa. Nine subjects reported the high carbidopa outpatient phase was associated with greater response to levodopa. Conclusion Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day. PMID:22508376

  5. Effect of Increasing Doses of Saw Palmetto on Lower Urinary Tract Symptoms: A Randomized Trial

    Science.gov (United States)

    Barry, Michael J.; Meleth, Sreelatha; Lee, Jeannette Y.; Kreder, Karl J.; Avins, Andrew L.; Nickel, J. Curtis; Roehrborn, Claus G.; Crawford, E. David; Foster, Harris E.; Kaplan, Steven A.; McCullough, Andrew; Andriole, Gerald L.; Naslund, Michael J.; Williams, O. Dale; Kusek, John W.; Meyers, Catherine M.; Betz, Joseph M.; Cantor, Alan; McVary, Kevin T.

    2012-01-01

    Context Saw palmetto fruit extracts are widely used for treating lower urinary tract symptoms attributed to benign prostatic hyperplasia. However, recent clinical trials have questioned their efficacy, at least at standard doses (320 mg daily). Objective To determine the effect of a saw palmetto extract at up to three times the standard dose on lower urinary tract symptoms attributed to benign prostatic hyperplasia. Design Multicenter placebo-controlled randomized trial conducted from June, 2008 through October, 2010. Setting Eleven North American clinical sites. Participants Were men at least 45 years old, with a peak urinary flow rate ≥ 4 ml/sec, an AUA Symptom Index (AUASI) score ≥ 8 and ≤ 24, and no exclusions. Interventions One, two, and then three 320 mg daily doses of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. Main Outcome Measures Primary outcome was the difference in AUASI score from baseline to 72 weeks. Secondary outcomes were measures of urinary bother; nocturia; uroflow; postvoid residual; prostate-specific antigen; participants’ global assessments; and indices of sexual function, continence, sleep quality, and prostatitis symptoms. Results From baseline to 72 weeks, mean AUASI scores decreased from 14.4 to 12.2 points with saw palmetto and from 14.7 to 11.7 points with placebo. The group mean difference in AUASI score change from baseline to 72 weeks between the saw palmetto and placebo groups was 0.79 points favoring placebo (bound of the 95% confidence interval most favorable to saw palmetto was 1.77 points, one-sided P=0.91). Saw palmetto was no more effective than placebo for any secondary outcome. No attributable side effects were identified. Conclusions Increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. (CAMUS study number NCT00603304 http://www.ClinicalTrials.gov) PMID:21954478

  6. Bioequivalence of a biosimilar enoxaparin sodium to Clexane® after single 100 mg subcutaneous dose: results of a randomized, double-blind, crossover study in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Martínez González J

    2018-03-01

    Full Text Available Javier Martínez González, Mayte Monreal, Ignacio Ayani Almagia, Jordi Llaudó Garín, Lourdes Ochoa Díaz de Monasterioguren, Ibón Gutierro Adúriz R&D Department, Laboratorios Farmacéuticos Rovi S.A., Madrid, Spain Purpose: To demonstrate the pharmacokinetic/pharmacodynamic (PK/PD equivalence of a biosimilar enoxaparin to the reference drug, and to assess its safety and tolerability in healthy volunteers. Patients and methods: A randomized, double-blind, crossover, 2-sequence, single-dose study was conducted in healthy volunteers of both sexes. Participants were sequentially and randomly administered single subcutaneous injections of enoxaparin 100 mg manufactured by Rovi (test; Madrid, Spain and Clexane® (enoxaparin 100 mg manufactured by Sanofi, reference separated by a 1-week washout period. The primary PK/PD variables were maximum activity (Amax and area under the effect curve from time 0 to the last measured activity (T (AUEC0–T and AUEC from time 0 to infinity (AUEC0–inf of anti-FXa activity, and Amax and AUEC0–T of anti-FIIa activity. Secondary variables were Amax and AUEC0–T, AUEC0–inf of tissue factor pathway inhibitor, and the ratio of AUEC0–T anti-FXa to anti-FIIa activity. Biosimilarity would be shown when the 95% CI of the ratio of geometric least squares means (95% CI RGLSMs of primary PK/PD parameters fell within the standard range of bioequivalence, ie, 80%–125%.Results: The study sample consisted of 46 volunteers (33 males aged 18–44 years and with body mass index ranging from 19.0 to 31.1 kg/m2. Three subjects did not complete the study. The curves of anti-FXa, anti-FIIa and tissue factor pathway inhibitor activities corresponding to administration of the test and reference products were comparable. The 95% CI RGLSMs of Amax, AUEC0–T and AUEC0–inf for anti-FXa activity were 94.6%–105.9%, 99.8%–108.0% and 100.0%–108.6% respectively; Amax and AUEC0–T for anti-FIIa activity were 94.7%–112.6% and

  7. Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: a randomized, single-dose, two-period, two-sequence crossover study.

    Science.gov (United States)

    Srichaiya, Arunee; Longchoopol, Chaowanee; Oo-Puthinan, Sarawut; Sayasathid, Jarun; Sripalakit, Pattana; Viyoch, Jarupa

    2008-10-01

    Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder. A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers. The aim of this study was to compare the pharmacokinetic parameters between 2 brands of lamotrigine in healthy Thai male volunteers. A randomized, single-dose, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in healthy Thai males. Subjects were randomized to receive either the test or reference formulation in the first period. All subjects were required to be nonsmokers and without a history of alcohol or drug abuse. Plasma samples were collected over a 120-hour period after 100-mg lamotrigine administration in each period. A validated high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma. Pharmacokinetic parameters were determined using a noncompartmental method. Bioequivalence between the test and reference products, as defined by the US Food and Drug Administration (FDA), is determined when the ratio for the 90% CIs of the difference in the means of the log-transformed AUC(0-t), AUC(0-infinity), and C(max) of the 2 products are within 0.80 and 1.25. Adverse events were determined by measuring vital signs after dosing. Subjects were also asked if they suffered from undesirable effects such as nausea, vomiting, dizziness, and headache. This bioequivalence study was performed in 24 healthy Thai males (mean [SD] age, 20.5 [1.3] years; range, 19-24 years; weight, 62.5 [7.4] kg; height, 172.8 [6.9] cm; body mass index, 20.9 [2.0] kg/m(2)). The mean (SD) C(max) and T(max) of the test formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.2 (0.9) hours, respectively. The mean (SD) C(max) and T(max) of the reference formulation of lamotrigine were 1.7 (0.3) microg/mL and 1.4 (1.0) hours, respectively. The mean

  8. A Monte Carlo Study of dose enhancement according to the enhancement agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Hoon; Kim, Chang Soo [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of); Hwang, Chul Hwan [Dept. of Radiation Oncology, Pusan National University Hospital, Busan (Korea, Republic of)

    2017-03-15

    Dose enhancement effects at megavoltage (MV) X and γ-ray energies, and the effects of different energy levels on incident energy, dose enhancement agents, and concentrations were analyzed using Monte Carlo simulations. Gold, gadolinium, Iodine, and iron oxide (Fe2O3) were compared as dose enhancement agents. For incident energy, 4, 6, 10 and 15 MV X-ray spectra produced by a linear accelerator and a Co60 γ-ray were used. The dose enhancement factor (DEF) was calculated using an ICRU Slab phantom for concentrations of 7, 18, and 30 mg/g. The DEF was higher at higher concentrations of dose enhancement agents and at lower incident energies. The calculated DEF ranged from 1.035 to 1.079, and dose enhancement effects were highest for iron oxide, followed by iodine, gadolinium, and gold. Thus, this study contributes to improving the therapeutic ratio by delivering larger doses of radiation to tumor volume, and provides data to support further in vivo and in vitro studies.

  9. Laparoscopic cholecystectomy under spinal anesthesia: comparative study between conventional-dose and low-dose hyperbaric bupivacaine

    Directory of Open Access Journals (Sweden)

    Imbelloni LE

    2011-10-01

    Full Text Available Luiz Eduardo Imbelloni1, Raphael Sant'Anna2, Marcos Fornasari2, José Carlos Fialho21Department of Anesthesiology, Faculty of Medecine Nova Esperança, Hospital de Mangabeira, João Pessoa, 2Hospital Rio Laranjeiras, Rio de Janeiro, BrazilBackground: Laparoscopic cholecystectomy has the advantages of causing less postoperative pain and requiring a short hospital stay, and therefore is the treatment of choice for cholelithiasis. This study was designed to compare spinal anesthesia using hyperbaric bupivacaine given as a conventional dose by lumbar puncture or as a low-dose by thoracic puncture.Methods: A total of 140 patients with symptomatic gallstone disease were randomized to undergo laparoscopic cholecystectomy with low-pressure CO2 pneumoperitoneum under spinal anesthesia using either conventional lumbar spinal anesthesia (hyperbaric bupivacaine 15 mg and fentanyl 20 mg or low-dose thoracic spinal anesthesia (hyperbaric bupivacaine 7.5 mg and fentanyl 20 µg. Intraoperative parameters, postoperative pain, complications, recovery time, and patient satisfaction at follow-up were compared between the two treatment groups.Results: All procedures were completed under spinal anesthesia, with no cases needing conversion to general anesthesia. Values for time for block to reach the T3 dermatomal level, duration of motor and sensory block, and hypotensive events were significantly lower with low-dose bupivacaine. Postoperative pain was higher for low-dose hyperbaric bupivacaine at 6 and 12 hours. All patients were discharged after 24 hours. Follow-up 1 week postoperatively showed all patients to be satisfied and to be keen advocates of spinal anesthesia.Conclusion: Laparoscopic cholecystectomy can be performed successfully under spinal anesthesia. A small dose of hyperbaric bupivacaine 7.5 mg and 20 µg fentanyl provides adequate spinal anesthesia for laparoscopy and, in comparison with hyperbaric bupivacaine 15% and fentanyl 20 µg, causes markedly

  10. Dose-response relationship for life-shortening and carcinogenesis in mice irradiated at day 7 postnatal age with dose range below 1 Gy of gamma rays

    International Nuclear Information System (INIS)

    Sasaki, Shunsaku; Fukuda, Nobuo

    2006-01-01

    This study was designed to elucidate the dose-response relationships for life-shortening and tumorigenic effect in the dose range below 1 Gy of gamma rays delivered during the infant period. Female B6C3F 1 mice were irradiated with 0.10, 0.48 or 0.95 Gy at 7 days of age. All irradiated mice were allowed to live out their entire life span together with a simultaneously ongoing control group under a specific pathogen-free condition. Shortening of the mean life span was 1.58% in mice irradiated with 0.10 Gy, which was statistically significant. The coefficient of the linear dose-response relationship for life-shortening was 11.21% Gy -1 . The attributable death fraction for all causes of death in 0.10 Gy group reached 0.092. The excess relative risk for death rate from all causes was 0.102 in the group irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of the excess relative risk for death rate from all causes was 1.30 Gy -1 . The mean number of types of solid tumors at the time of death in mice irradiated with 0.10 Gy was distinctly larger than that in the control group. The excess relative risk for death rate from solid tumors was 0.45 in mice irradiated with 0.10 Gy. The coefficient of the linear dose-response relationship of excess relative risk for death rate from solid tumors was 4.52 Gy -1 . Increase in incidences of the pituitary, ovarian and adrenal tumors was observed in mice irradiated with 0.10 Gy. The results of the present study showed that infant mice are susceptible to solid tumor induction, especially of the endocrine organs. (author)

  11. Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

    NARCIS (Netherlands)

    Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

    2003-01-01

    textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

  12. Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

    Science.gov (United States)

    Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

    2016-01-01

    In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

  13. Comparison of two doses of heparin on outcome in off-pump coronary artery bypass surgery patients: A prospective randomized control study

    Directory of Open Access Journals (Sweden)

    Murali Chakravarthy

    2017-01-01

    Full Text Available Introduction: While off pump coronary artery bypass surgery is practiced with an intention to reduce the morbidity associated with cardiopulmonary bypass, the resultant ′hypercoagulability′ needs to be addressed. Complications such as cavitary thrombus possibly due to the hyper coagulability after off pump coronary artery bypass surgery have been described. Many clinicians use higher doses of heparin - up to 5 mg/kg in order to thwart this fear. Overall, there appears to be no consensus on the dose of heparin in off pump coronary artery bypass surgeries. Aim of the Study: The aim of the study was understand the differences in outcome of such as transfusion requirement, myocardial ischemia, and morbidity when two different doses were used for systemic heparinization. Methods: Elective patients scheduled for off pump coronary artery bypass surgery were included. Ongoing anti platelet medication was not an exclusion criteria, however, anti platelet medications were ceased about a week prior to surgery when possible. Thoracic epidural anesthesia was administered as an adjunct in patients who qualified for it. By computer generated randomization chart, patients were chosen to receive either 2 or 3 mg/kg of intravenous unfractioned heparin to achieve systemic heparinization with activated clotting time targeted at >240 secs. Intraoperative blood loss, postoperative blood loss, myocardial ischemic episodes, requirement of intraaortic balloon counter pulsation and transfusion requirement were analyzed. Results: Sixty two patients participated in the study. There was one conversion to cardiopulmonary bypass. The groups had comparable ACT at baseline (138.8 vs. 146.64 seconds, P = 0.12; 3 mg/kg group had significantly higher values after heparin, as expected. But after reversal with protamine, ACT and need for additional protamine was similar among the groups. Intraoperative (685.56 ± 241.42 ml vs. 675.15 ± 251.86 ml, P = 0.82 and postoperative

  14. Choline PET based dose-painting in prostate cancer - Modelling of dose effects

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

    2010-01-01

    Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

  15. Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

    Science.gov (United States)

    Drullinsky, Pamela; Sugarman, Steven M; Fornier, Monica N; D'Andrea, Gabriella; Gilewski, Teresa; Lake, Diana; Traina, Tiffany; Wasserheit-Lieblich, Carolyn; Sklarin, Nancy; Atieh-Graham, Deena; Mills, Nancy; Troso-Sandoval, Tiffany; Seidman, Andrew D; Yuan, Jeffrey; Patel, Hamangi; Patil, Sujata; Norton, Larry; Hudis, Clifford

    2010-12-01

    Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule. Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%. The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals. Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.

  16. Biochemical and molecular study of genetic stability in tomatoes plants rom seeds treated with low doses of X-ray

    International Nuclear Information System (INIS)

    Ramirez, R; Gonzalez, LM; Chavez, Licet; Camejo, Yanelis; Gonzalez, Maria C; Fernandez, Arais

    2008-01-01

    For the extensive agricultural exploitation of vegetable radio stimulation, it is indispensable to study the genetic stability of treated varieties, having in mind X ray potentialities of inducing not only physiological but genetic changes as well. Therefore, biochemical and molecular markers were employed in tomato plants derived from irradiated seeds at low doses of X rays. For the biochemical analysis, peroxidases, polyphenoloxidases and dismutase superoxide isoenzymes were determined whereas the Random Amplification of Polymorphic DNA (RAPD) method based on Polymerase Chain Reaction (PCR) was used for the molecular analysis. When comparing the electrophoretic patterns from the control and irradiated treatments applied to the three enzymatic systems, there were not appreciable variations on the number of bands and their intensities, indicating the little variability induced in these systems by the low X ray doses. Also, from the molecular viewpoint, electrophoretic patterns showed a clear amplification of DNA by generating a total of 155 bands in all varieties studied. This molecular marker showed a high monomorphism independently of the treatments applied, with values ranging between 86 and 97 %, indicating that irradiation at low doses did not induce an important genetic variability and confirming its possible practical usefulness for stimulating some physiological processes without causing. (Author)

  17. Quantifying the spatial and temporal variation in dose from external exposure to radiation: a new tool for use on free-ranging wildlife

    International Nuclear Information System (INIS)

    Hinton, Thomas G.; Byrne, Michael E.; Webster, Sarah; Beasley, James C.

    2015-01-01

    Inadequate dosimetry is often the fundamental problem in much of the controversial research dealing with radiation effects on free-ranging wildlife. Such research is difficult because of the need to measure dose from several potential pathways of exposure (i.e., internal contamination, external irradiation, and inhalation). Difficulties in quantifying external exposures can contribute significantly to the uncertainties of dose-effect relationships. Quantifying an animal's external exposure due to spatial–temporal use of habitats that can vary by orders of magnitude in radiation levels is particularly challenging. Historically, wildlife dosimetry studies have largely ignored or been unable to accurately quantify variability in external dose because of technological limitations. The difficulties of quantifying the temporal–spatial aspects of external irradiation prompted us to develop a new dosimetry instrument for field research. We merged two existing technologies [Global Positioning Systems (GPS) and electronic dosimeters] to accommodate the restrictive conditions of having a combined unit small enough to be unobtrusively worn on the neck of a free-ranging animal, and sufficiently robust to withstand harsh environmental conditions. The GPS–dosimeter quantifies the spatial and temporal variation in external dose as wildlife traverse radioactively contaminated habitats and sends, via satellites, an animal's location and short term integrated dose to the researcher at a user-defined interval. Herein we describe: (1) the GPS–dosimeters; (2) tests to compare their uniformity of response to external irradiation under laboratory conditions; (3) field tests of their durability when worn on wildlife under natural conditions; and (4) a field application of the new technology at a radioactively contaminated site. Use of coupled GPS–dosimetry will allow, for the first time, researchers to better understand the relationship of animals to their contaminated

  18. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments

    Energy Technology Data Exchange (ETDEWEB)

    Stambaugh, Cassandra [Department of Physics, University of South Florida, Tampa, Florida 33612 (United States); Nelms, Benjamin E. [Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida 33612 (United States)

    2013-09-15

    Purpose: The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments.Methods: VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D{sub 99%}), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found.Results: For the motion amplitudes and periods obtained from

  19. ICRU reference dose in an era of intensity-modulated radiation therapy clinical trials: Correlation with planning target volume mean dose and suitability for intensity-modulated radiation therapy dose prescription

    International Nuclear Information System (INIS)

    Yaparpalvi, Ravindra; Hong, Linda; Mah, Dennis; Shen Jin; Mutyala, Subhakar; Spierer, Marnee; Garg, Madhur; Guha, Chandan; Kalnicki, Shalom

    2008-01-01

    Background and Purpose: IMRT clinical trials lack dose prescription and specification standards similar to ICRU standards for two- and three-dimensional external beam planning. In this study, we analyzed dose distributions for patients whose treatment plans incorporated IMRT, and compared the dose determined at the ICRU reference point to the PTV doses determined from dose-volume histograms. Additionally, we evaluated if ICRU reference type single-point dose prescriptions are suitable for IMRT dose prescriptions. Materials and methods: For this study, IMRT plans of 117 patients treated at our institution were randomly selected and analyzed. The treatment plans were clinically applied to the following disease sites: abdominal (11), anal (10), brain (11), gynecological (15), head and neck (25), lung (15), male pelvis (10) and prostate (20). The ICRU reference point was located in each treatment plan following ICRU Report 50 guidelines. The reference point was placed in the central part of the PTV and at or near the isocenter. In each case, the dose was calculated and recorded to this point. For each patient - volume and dose (PTV, PTV mean, median and modal) information was extracted from the planned dose-volume histogram. Results: The ICRU reference dose vs PTV mean dose relationship in IMRT exhibited a weak positive association (Pearson correlation coefficient 0.63). In approximately 65% of the cases studied, dose at the ICRU reference point was greater than the corresponding PTV mean dose. The dose difference between ICRU reference and PTV mean doses was ≤2% in approximately 79% of the cases studied (average 1.21% (±1.55), range -4% to +4%). Paired t-test analyses showed that the ICRU reference doses and PTV median doses were statistically similar (p = 0.42). The magnitude of PTV did not influence the difference between ICRU reference and PTV mean doses. Conclusions: The general relationship between ICRU reference and PTV mean doses in IMRT is similar to that

  20. Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

    Science.gov (United States)

    Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

    2017-03-28

    Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

  1. Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

    Science.gov (United States)

    Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

    2012-05-01

    A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

  2. Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: A prospective, randomized, double-blinded, placebo controlled, clinical trial.

    Science.gov (United States)

    De Oliveira, Gildasio S; Rodes, Meghan E; Bialek, Jane; Kendall, Mark C; McCarthy, Robert J

    2017-11-15

    Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery. We aimed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery. We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline. The study was a prospective randomized double blinded, placebo controlled, clinical trial. Healthy female subjects were randomized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. The association between opioid consumption and quality of recovery was evaluated using Spearman rho. P quality of recovery, P = .007. A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery. The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery. © 2017 Wiley Periodicals, Inc.

  3. Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study.

    Science.gov (United States)

    Hss, Amar-Singh; Koh, Mia-Tuang; Tan, Kah Kee; Chan, Lee Gaik; Zhou, Lynn; Bouckenooghe, Alain; Crevat, Denis; Hutagalung, Yanee

    2013-12-02

    Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia. In this observer-blind, placebo-controlled, Phase III study, children aged 2-11 years were randomized (4:1) to receive CYD-TDV or placebo at 0, 6 and 12 months. Primary endpoints included assessment of reactogenicity following each dose, adverse events (AEs) and serious AEs (SAEs) reported throughout the study, and immunogenicity expressed as geometric mean titres (GMTs) and distribution of dengue virus (DENV) neutralizing antibody titres. 250 participants enrolled in the study (CYD-TDV: n=199; placebo: n=51). There was a trend for reactogenicity to be higher with CYD-TDV than with placebo post-dose 1 (75.4% versus 68.6%) and post-dose 2 (71.6% versus 62.0%) and slightly lower post-dose 3 (57.9% versus 64.0%). Unsolicited AEs declined in frequency with each subsequent dose and were similar overall between groups (CYD-TDV: 53.8%; placebo: 49.0%). Most AEs were of Grade 1 intensity and were transient. SAEs were reported by 5.5% and 11.8% of participants in the CYD-TDV and placebo groups, respectively. No deaths were reported. Baseline seropositivity against each of the four DENV serotypes was similar between groups, ranging from 24.0% (DENV-4) to 36.7% (DENV-3). In the CYD-TDV group, GMTs increased post-dose 2 for all serotypes compared with baseline, ranging from 4.8 (DENV-1) to 8.1-fold (DENV-3). GMTs further increased post-dose 3 for DENV-1 and DENV-2. Compared with baseline, individual titre increases ranged from 6.1-fold (DENV-1) to 7.96-fold (DENV-3). This study demonstrated a satisfactory safety profile and a balanced humoral immune response against all four DENV serotypes for CYD-TDV administered via a three-dose regimen to children in Malaysia. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All

  4. Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers.

    Science.gov (United States)

    Burns, Olivia; Zhu, John; Manyak, Michael J; Ravindranath, Ramiya; Koosha, Fariba; Haque, Nazneen; Chung, Sally

    2018-05-01

    The relative bioavailabilities of dutasteride/tamsulosin hydrochloride 0.5 mg/0.2 mg fixed-dose combination (FDC) capsules compared with coadministered reference products (1 dutasteride 0.5-mg capsule [Avodart ® ] + 1 tamsulosin hydrochloride 0.2-mg orally disintegrating tablet [Harnal D ® ]) were investigated in 2 clinical trials under fasted and fed conditions (ClinicalTrials.gov NCT02184585 and NCT02509104). Both trials were open-label, randomized, single-dose, crossover studies in healthy male adults aged 18-65 years. Trial 1 evaluated 2 formulations (FDC1 and FDC2), and trial 2 evaluated a third formulation (FDC3). The primary end points were dutasteride area under the concentration-time curve from time 0 to t (AUC (0-t) ) and peak plasma concentration (C max ) and tamsulosin AUC (0-∞) , AUC (0-t) , and C max . The formulations were considered to be bioequivalent if the 90%CIs for the geometric mean ratios for each end point were within the range of 0.80-1.25. For FDC1 in trial 1, bioequivalence criteria were not met for dutasteride C max or AUC in the fasted state or for tamsulosin C max in the fasted or fed states. For FDC2 in trial 1, all bioequivalence criteria were met except for tamsulosin C max in the fasted state. For FDC3 in trial 2, bioequivalence criteria were met for all dutasteride and tamsulosin end points in both the fed and fasted states. Safety profiles were similar for all FDC formulations and combination treatments. © 2017, The American College of Clinical Pharmacology.

  5. Sirolimus Associated with Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial.

    Science.gov (United States)

    Kojima, Cristiane Akemi; Nga, Hong Si; Takase, Henrique Mochida; Bravin, Ariane Moyses; Martinez Garcia, Márcia de Fátima Faraldo; Garcia, Paula Dalsoglio; Contti, Mariana Moraes; de Andrade, Luis Gustavo Modelli

    2018-06-01

    There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimus-mycophenolate (23 patients). Cytomegalovirus infection rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

  6. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  7. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. The mesoscopic conductance of disordered rings, its random matrix theory and the generalized variable range hopping picture

    International Nuclear Information System (INIS)

    Stotland, Alexander; Peer, Tal; Cohen, Doron; Budoyo, Rangga; Kottos, Tsampikos

    2008-01-01

    The calculation of the conductance of disordered rings requires a theory that goes beyond the Kubo-Drude formulation. Assuming 'mesoscopic' circumstances the analysis of the electro-driven transitions shows similarities with a percolation problem in energy space. We argue that the texture and the sparsity of the perturbation matrix dictate the value of the conductance, and study its dependence on the disorder strength, ranging from the ballistic to the Anderson localization regime. An improved sparse random matrix model is introduced to capture the essential ingredients of the problem, and leads to a generalized variable range hopping picture. (fast track communication)

  9. Dose titration to reduce dipyridamole-related headache.

    Science.gov (United States)

    Chang, Yeu-Jhy; Ryu, Shan-Jin; Lee, Tsong-Hai

    2006-01-01

    Combination of low-dose aspirin and modified-release dipyridamole (ASA+MR-DP) provides a significantly increased benefit in stroke prevention over aspirin alone. However, headaches were reported in more patients receiving dipyridamole-containing agents than in those receiving placebo. We undertook a randomized, double-blind, placebo-controlled trial to evaluate which dosing regimens of ASA+MR-DP have better tolerance. This trial randomized 146 patients with a history of ischemic cerebrovascular disease into three groups: placebo (days 1-28), reduced dose (placebo on days 1-4, ASA+MR-DP once daily before bed during days 5-14, and b.i.d. on days 15-28), and regular dose (placebo on days 1-4, and ASA+MR-DP b.i.d. on days 5-28). Using Chinese diary card, headache was assessed as mean cumulated headache (Sigma frequency x intensity/occurrence days x study days) over the study period, and was graded 0-4 according to Cancer Therapy Evaluation Program, Common Toxicity Criteria, Version 2.0. Intent-to-treat patients after randomization was 46 in placebo group, 45, reduced dose, and 49, regular dose. Among commonly reported adverse effects, headache of any grade occurred significantly more in the regular dose group (38.8%), as compared to the other two groups (p < 0.05). Mean cumulated headache was higher (p < 0.05) in the regular dose group than in the reduced group during days 5-14. Of 27 patients who dropped out, 15 (55.6%) were due to headache, which was substantially more in regular dose (8, 53.3%), though the difference was statistically insignificant. Initial reduced dose treatment with ASA+MR-DP may cause fewer headaches than regular dosing, and seems better tolerated by those susceptible to phosphodiesterase inhibitor-induced headache. Copyright 2006 S. Karger AG, Basel.

  10. Relation between dose of bendrofluazide, antihypertensive effect, and adverse biochemical effects

    DEFF Research Database (Denmark)

    Carlsen, J E; Køber, L; Torp-Pedersen, C

    1990-01-01

    OBJECTIVE--To determine the relevant dose of bendrofluazide for treating mild to moderate hypertension. DESIGN--Double blind parallel group trial of patients who were given placebo for six weeks and then randomly allocated to various doses of bendrofluazide (1.25, 2.5, 5, or 10 mg daily) or place...... of bendrofluazide to treat mild to moderate hypertension is 1.25-2.5 mg a day. Higher doses caused more pronounced adverse biochemical effects including adverse lipid effects. Previous trials with bendrofluazide have used too high doses....... relations between dose and effect were shown for potassium, urate, glucose, total cholesterol, and apolipoprotein B concentrations. The 1.25 mg dose increased only urate concentrations, whereas the 10 mg dose affected all the above biochemical variables. CONCLUSION--The relevant range of doses...

  11. CLINICAL-PHARMACOLOGY OF ROCURONIUM (ORG-9426) - STUDY OF THE TIME-COURSE OF ACTION, DOSE REQUIREMENT, REVERSIBILITY, AND PHARMACOKINETICS

    NARCIS (Netherlands)

    VANDENBROEK, L; WIERDA, JMKH; SMEULERS, NJ; VANSANTEN, GJ; LECLERCQ, MGL; HENNIS, PJ

    1994-01-01

    Study Objective: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol halothane, or isoflurane). Design: Prospective, randomized study. Setting: Operating

  12. Pharmacokinetic comparison of sustained- and immediate-release oral formulations of cilostazol in healthy Korean subjects: a randomized, open-label, 3-part, sequential, 2-period, crossover, single-dose, food-effect, and multiple-dose study.

    Science.gov (United States)

    Lee, Donghwan; Lim, Lay Ahyoung; Jang, Seong Bok; Lee, Yoon Jung; Chung, Jae Yong; Choi, Jong Rak; Kim, Kiyoon; Park, Jin Woo; Yoon, Hosang; Lee, Jaeyong; Park, Min Soo; Park, Kyungsoo

    2011-12-01

    A sustained-release (SR) formulation of cilostazol was recently developed in Korea and was expected to yield a lower C(max) and a similar AUC to the immediate-release (IR) formulation. The goal of the present study was to compare the pharmacokinetic profiles of a newly developed SR formulation and an IR formulation of cilostazol after single- and multiple-dose administration and to evaluate the influence of food in healthy Korean subjects. This study was developed as part of a product development project at the request of the Korean regulatory agency. This was a randomized, 3-part, sequential, open-label, 2-period crossover study. Each part consisted of different subjects between the ages of 19 and 55 years. In part 1, each subject received a single dose of SR (200 mg × 1 tablet, once daily) and IR (100 mg × 2 tablets, BID) formulations of cilostazol orally 7 days apart in a fasted state. In part 2, each subject received a single dose of the SR (200 mg × 1 tablet, once daily) formulation of cilostazol 7 days apart in a fasted and a fed state. In part 3, each subject received multiple doses of the 2 formulations for 8 consecutive days 21 days apart. Blood samples were taken for 72 hours after the dose. Cilostazol pharmacokinetics were determined for both the parent drug and its metabolites (OPC-13015 and OPC-13213). Adverse events were evaluated through interviews and physical examinations. Among the 92 enrolled subjects (66 men, 26 women; part 1, n = 26; part 2, n = 26; part 3, n = 40), 87 completed the study. In part 1, all the primary pharmacokinetic parameters satisfied the criterion for assumed bioequivalence both in cilostazol and its metabolites, yielding 90% CI ratios of 0.9624 to 1.2323, 0.8873 to 1.1208, and 0.8919 to 1.1283 for C(max) and 0.8370 to 1.0134, 0.8204 to 0.9807, and 0.8134 to 0.9699 for AUC(0-last) of cilostazol, OPC-13015, and OPC-13213, respectively. In part 2, food intake increased C(max) and AUC significantly (P food and 23 with a high

  13. Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

    International Nuclear Information System (INIS)

    Hori, T.; Moriya, Junko; Nakai, Sayaka

    1978-01-01

    Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

  14. A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women.

    Science.gov (United States)

    Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L; Myers, Leann; Martin, David H

    2010-12-15

    To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms. Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P TV among HIV+ women.

  15. Methadone dose and neonatal abstinence syndrome-systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Cleary, Brian J

    2012-02-01

    AIM: To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). METHODS: PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS. RESULTS: A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. CONCLUSIONS: Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.

  16. Electroacupuncture for tapering off long-term benzodiazepine use: study protocol of randomized controlled trial.

    Science.gov (United States)

    Yeung, Wing-Fai; Chung, Ka-Fai; Zhang, Zhang-Jin; Chan, Wai-Chi; Zhang, Shi-Ping; Ng, Roger Man-Kin; Chan, Connie Lai-Wah; Ho, Lai-Ming; Yu, Yee-Man; Lao, Li-Xing

    2017-03-31

    Conventional approaches for benzodiazepine tapering have their limitations. Anecdotal studies have shown that acupuncture is a potential treatment for facilitating successful benzodiazepine tapering. As of today, there was no randomized controlled trial examining its efficacy and safety. The purpose of the study is to evaluate the efficacy of using electroacupuncture as an adjunct treatment to gradual tapering of benzodiazepine doses in complete benzodiazepine cessation in long-term benzodiazepine users. The study protocol of a randomized, assessor- and subject-blinded, controlled trial is presented. One hundred and forty-four patients with histories of using benzodiazepines in ≥50% of days for more than 3 months will be randomly assigned in a 1:1 ratio to receive either electroacupuncture or placebo electroacupuncture combined with gradual benzodiazepine tapering schedule. Both experimental and placebo treatments will be delivered twice per week for 4 weeks. Major assessments will be conducted at baseline, week 6 and week 16 post-randomization. Primary outcome is the cessation rate of benzodiazepine use. Secondary outcomes include the percentage change in the doses of benzodiazepine usage and the severity of withdrawal symptoms experienced based on the Benzodiazepine Withdrawal Symptom Questionnaire, insomnia as measured by the Insomnia Severity Index, and anxiety and depressive symptoms as evaluated by the Hospital Anxiety and Depression Scale. Adverse events will also be measured at each study visit. Results of this study will provide high quality evidence of the efficacy and safety of electroacupuncture as an adjunct treatment for benzodiazepine tapering in long-term users. ClinicalTrials.gov NCT02475538 .

  17. Cavities at the Si projected range by high dose and energy Si ion implantation in Si

    International Nuclear Information System (INIS)

    Canino, M.; Regula, G.; Lancin, M.; Xu, M.; Pichaud, B.; Ntzoenzok, E.; Barthe, M.F.

    2009-01-01

    Two series of n-type Si samples α and β are implanted with Si ions at high dose (1 x 10 16 ) and high energies, 0.3 and 1.0 MeV, respectively. Both sort of samples are then implanted with 5 x 10 16 He cm -2 (at 10 or 50 keV) and eventually with B atoms. Some of the samples are annealed at temperatures ranging from 800 to 1000 deg. C to allow the thermal growth of He-cavities, located between sample surface and the projected range (R p ) of Si. After the triple ion implantation, which corresponds to defect engineering, samples were characterized by cross-section transmission electron microscopy (XTEM). Voids (or bubbles) are observed not only at the R p (He) on all annealed samples, but also at the R p (Si) on β samples implanted with He at 50 keV. The samples are also studied by positron annihilation spectroscopy (PAS) and the spectra confirm that as-implanted samples contain di-vacancies and that the annealed ones, even at high temperature have bigger open volumes, which are assumed to be the same voids observed by XTEM. It is demonstrated that a sole Si implantation at high energy and dose is efficient to create cavities which are thermally stable up to 1000 deg. C only in the presence of He.

  18. Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study

    Directory of Open Access Journals (Sweden)

    Xu HR

    2016-05-01

    Full Text Available Hongrong Xu,1,* Lei Sheng,1,* Weili Chen,1 Fei Yuan,1 Mengjie Yang,1 Hui Li,1 Xuening Li,1 John Choi,2 Guiyu Zhao,2 Tianxin Hu,2 Yongguo Li,2 Yi Zhang,2 Li Chen2 1Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, Shanghai, 2Department of Clinical Research & Development, Hua Medicine, Shanghai, People’s Republic of China *These authors have contributed equally to this work Background: HMS5552, a novel fourth-generation glucokinase (GK activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK, and pharmacodynamics (PD of HMS5552 during its first-in-human exposure.Methods: Sixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg, ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints.Results: HMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0–t and maximum plasma concentration (Cmax. Slopes estimated by linear regression for AUC0–t and Cmax were ~1.0 (0.932 and 0.933, respectively. Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (% and mean glucose area under effect curve 0–4 hours change from baseline (% (P<0.001. Fifteen adverse events were reported by nine subjects (ten with HMS5552 and five with the placebo. All adverse events were mild in intensity and resolved without any treatment

  19. Dose-to-man studies

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Dose-to-Man Studies focused on developing computer data handling and computer modules which permit easy, rapid assessment of the dose to southeastern United States populations from routine or accidental releases of radionuclides to atmospheric and stream systems

  20. Quenched Large Deviations for Simple Random Walks on Percolation Clusters Including Long-Range Correlations

    Science.gov (United States)

    Berger, Noam; Mukherjee, Chiranjib; Okamura, Kazuki

    2018-03-01

    We prove a quenched large deviation principle (LDP) for a simple random walk on a supercritical percolation cluster (SRWPC) on {Z^d} ({d ≥ 2}). The models under interest include classical Bernoulli bond and site percolation as well as models that exhibit long range correlations, like the random cluster model, the random interlacement and the vacant set of random interlacements (for {d ≥ 3}) and the level sets of the Gaussian free field ({d≥ 3}). Inspired by the methods developed by Kosygina et al. (Commun Pure Appl Math 59:1489-1521, 2006) for proving quenched LDP for elliptic diffusions with a random drift, and by Yilmaz (Commun Pure Appl Math 62(8):1033-1075, 2009) and Rosenbluth (Quenched large deviations for multidimensional random walks in a random environment: a variational formula. Ph.D. thesis, NYU, arXiv:0804.1444v1) for similar results regarding elliptic random walks in random environment, we take the point of view of the moving particle and prove a large deviation principle for the quenched distribution of the pair empirical measures of the environment Markov chain in the non-elliptic case of SRWPC. Via a contraction principle, this reduces easily to a quenched LDP for the distribution of the mean velocity of the random walk and both rate functions admit explicit variational formulas. The main difficulty in our set up lies in the inherent non-ellipticity as well as the lack of translation-invariance stemming from conditioning on the fact that the origin belongs to the infinite cluster. We develop a unifying approach for proving quenched large deviations for SRWPC based on exploiting coercivity properties of the relative entropies in the context of convex variational analysis, combined with input from ergodic theory and invoking geometric properties of the supercritical percolation cluster.

  1. Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

    Science.gov (United States)

    Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

    2017-10-01

    Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used

  2. Nonlinearity and thresholds in dose-response relationships for carcinogenicity due to sampling variation, logarithmic dose scaling, or small differences in individual susceptibility

    International Nuclear Information System (INIS)

    Lutz, W.K.; Gaylor, D.W.; Conolly, R.B.; Lutz, R.W.

    2005-01-01

    Nonlinear and threshold-like shapes of dose-response curves are often observed in tests for carcinogenicity. Here, we present three examples where an apparent threshold is spurious and can be misleading for low dose extrapolation and human cancer risk assessment. Case 1: For experiments that are not replicated, such as rodent bioassays for carcinogenicity, random variation can lead to misinterpretation of the result. This situation was simulated by 20 random binomial samplings of 50 animals per group, assuming a true linear dose response from 5% to 25% tumor incidence at arbitrary dose levels 0, 0.5, 1, 2, and 4. Linearity was suggested only by 8 of the 20 simulations. Four simulations did not reveal the carcinogenicity at all. Three exhibited thresholds, two showed a nonmonotonic behavior with a decrease at low dose, followed by a significant increase at high dose ('hormesis'). Case 2: Logarithmic representation of the dose axis transforms a straight line into a sublinear (up-bent) curve, which can be misinterpreted to indicate a threshold. This is most pronounced if the dose scale includes a wide low dose range. Linear regression of net tumor incidences and intersection with the dose axis results in an apparent threshold, even with an underlying true linear dose-incidence relationship. Case 3: Nonlinear shapes of dose-cancer incidence curves are rarely seen with epidemiological data in humans. The discrepancy to data in rodents may in part be explained by a wider span of individual susceptibilities for tumor induction in humans due to more diverse genetic background and modulation by co-carcinogenic lifestyle factors. Linear extrapolation of a human cancer risk could therefore be appropriate even if animal bioassays show nonlinearity

  3. A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

    Science.gov (United States)

    Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

    2017-05-01

    Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

  4. A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

    International Nuclear Information System (INIS)

    Osman, N D; Shamsuri, S B M; Razali, M A S M; Isa, S M; Tan, Y W

    2017-01-01

    Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDI vol and CTDI w ) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDI w ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients. (paper)

  5. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

    Science.gov (United States)

    Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic; Habib, Robert H; Halaby, Georges; Arabi, Asma; Singh, Ravinder J; Kassem, Moustapha; Mahfoud, Ziyad; Hoteit, Maha; Daher, Rose T; Bassil, Darina; El Ferkh, Karim; El-Hajj Fuleihan, Ghada

    2017-07-01

    The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m 2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p 76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  6. Radiation-induced polymerization of water-saturated styrene in a wide range of dose rate

    International Nuclear Information System (INIS)

    Takezaki, J.; Okada, T.; Sakurada, I.

    1978-01-01

    Radiation-induced polymerization of water-saturated styrene (water content 3.5 x 10 -2 mole/liter) was carried out in a wide range of dose rate between 1.2 x 10 3 and 1.8 x 10 7 rad/sec, and compared with the polymerization of the moderately dried styrene (water content 3.2 x 10 -3 mole/liter). Molecular weight distribution curves of the polymerization products showed that they were generally consisted of four parts, namely, oligomers, radical, cationic, and super polymers. Contributions of the four constituents to the polymerization and the number average degrees of polymerization (DP) of the four kinds of polymers were calculated by the graphical analysis of the curves. The rate of radical polymerization and DP of radical polymers are independent of the water content; the dose rate dependences of the polymerization rate and DP agree with the well known square root and inverse square root laws, respectively, of the radical polymerization of styrene. The rate of ionic polymerization is directly proportional to the dose rate, but it decreases, at a given dose rate, inversely proportional to the water content of styrene. DP of ionic polymer is independent of the dose rate but decreases with increasing water content. The super polymer of DP about 10 4 is not formed in the case of the moderately dried styrene. G values for the initiating radical and ion formation are calculated to be independently of the dose rate and water content, 0.66 and 0.027, respectively. It was suggested that oligomer was formed in the early stage by the interaction of cation with anion and only those cations which had survived underwent polymerization. 10 figures, 4 tables

  7. Efficacy and Safety of Multiple Doses of Exenatide Once-Monthly Suspension in Patients With Type 2 Diabetes: A Phase II Randomized Clinical Trial.

    Science.gov (United States)

    Wysham, Carol H; MacConell, Leigh; Hardy, Elise

    2016-10-01

    This study investigated the efficacy and safety of multiple exenatide once-monthly suspension (QMS) doses of exenatide-containing microspheres in Miglyol referenced against the clinical dose of exenatide once-weekly (QW) microspheres in aqueous solution. In this phase II, randomized, controlled, single-blind study, 121 adults (∼30/arm) with type 2 diabetes and HbA1c 7.1-11.0% (54-97 mmol/mol) were randomized 1:1:1:1 to subcutaneous exenatide QW 2 mg (self-administered) or exenatide QMS 5, 8, or 11 mg (caregiver-administered) for 20 weeks. The primary end point was change in HbA1c. At baseline, mean age was 50 years, HbA1c was 8.5% (69 mmol/mol), fasting plasma glucose (FPG) was 184 mg/dL, and body weight was 98 kg. At week 20, mean ± SD HbA1c reductions were -1.54% ± 1.26% with exenatide QW and -1.29% ± 1.07%, -1.31% ± 1.66%, and -1.45% ± 0.93% with exenatide QMS 5, 8, and 11 mg, respectively (evaluable population: n = 110). There were no significant differences in HbA1c reductions among the exenatide QMS doses. FPG reductions were -34 ± 48 mg/dL with exenatide QW and -25 ± 43, -30 ± 52, and -49 ± 49 mg/dL with exenatide QMS 5, 8, and 11 mg, respectively. Weight decreased with all treatments. For exenatide QMS, nausea (16.7-23.3%) and headache (16.7-26.7%) were the most common adverse events. No major or minor hypoglycemia occurred. All doses of exenatide QMS resulted in efficacy and tolerability profiles consistent with exenatide QW. These results combined with pharmacokinetic and pharmacodynamic modeling could inform dose selection for further development. © 2016 by the American Diabetes Association.

  8. Implementation of random set-up errors in Monte Carlo calculated dynamic IMRT treatment plans

    International Nuclear Information System (INIS)

    Stapleton, S; Zavgorodni, S; Popescu, I A; Beckham, W A

    2005-01-01

    The fluence-convolution method for incorporating random set-up errors (RSE) into the Monte Carlo treatment planning dose calculations was previously proposed by Beckham et al, and it was validated for open field radiotherapy treatments. This study confirms the applicability of the fluence-convolution method for dynamic intensity modulated radiotherapy (IMRT) dose calculations and evaluates the impact of set-up uncertainties on a clinical IMRT dose distribution. BEAMnrc and DOSXYZnrc codes were used for Monte Carlo calculations. A sliding window IMRT delivery was simulated using a dynamic multi-leaf collimator (DMLC) transport model developed by Keall et al. The dose distributions were benchmarked for dynamic IMRT fields using extended dose range (EDR) film, accumulating the dose from 16 subsequent fractions shifted randomly. Agreement of calculated and measured relative dose values was well within statistical uncertainty. A clinical seven field sliding window IMRT head and neck treatment was then simulated and the effects of random set-up errors (standard deviation of 2 mm) were evaluated. The dose-volume histograms calculated in the PTV with and without corrections for RSE showed only small differences indicating a reduction of the volume of high dose region due to set-up errors. As well, it showed that adequate coverage of the PTV was maintained when RSE was incorporated. Slice-by-slice comparison of the dose distributions revealed differences of up to 5.6%. The incorporation of set-up errors altered the position of the hot spot in the plan. This work demonstrated validity of implementation of the fluence-convolution method to dynamic IMRT Monte Carlo dose calculations. It also showed that accounting for the set-up errors could be essential for correct identification of the value and position of the hot spot

  9. Implementation of random set-up errors in Monte Carlo calculated dynamic IMRT treatment plans

    Science.gov (United States)

    Stapleton, S.; Zavgorodni, S.; Popescu, I. A.; Beckham, W. A.

    2005-02-01

    The fluence-convolution method for incorporating random set-up errors (RSE) into the Monte Carlo treatment planning dose calculations was previously proposed by Beckham et al, and it was validated for open field radiotherapy treatments. This study confirms the applicability of the fluence-convolution method for dynamic intensity modulated radiotherapy (IMRT) dose calculations and evaluates the impact of set-up uncertainties on a clinical IMRT dose distribution. BEAMnrc and DOSXYZnrc codes were used for Monte Carlo calculations. A sliding window IMRT delivery was simulated using a dynamic multi-leaf collimator (DMLC) transport model developed by Keall et al. The dose distributions were benchmarked for dynamic IMRT fields using extended dose range (EDR) film, accumulating the dose from 16 subsequent fractions shifted randomly. Agreement of calculated and measured relative dose values was well within statistical uncertainty. A clinical seven field sliding window IMRT head and neck treatment was then simulated and the effects of random set-up errors (standard deviation of 2 mm) were evaluated. The dose-volume histograms calculated in the PTV with and without corrections for RSE showed only small differences indicating a reduction of the volume of high dose region due to set-up errors. As well, it showed that adequate coverage of the PTV was maintained when RSE was incorporated. Slice-by-slice comparison of the dose distributions revealed differences of up to 5.6%. The incorporation of set-up errors altered the position of the hot spot in the plan. This work demonstrated validity of implementation of the fluence-convolution method to dynamic IMRT Monte Carlo dose calculations. It also showed that accounting for the set-up errors could be essential for correct identification of the value and position of the hot spot.

  10. Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial.

    Science.gov (United States)

    Michalski, Jeff M; Moughan, Jennifer; Purdy, James; Bosch, Walter; Bruner, Deborah W; Bahary, Jean-Paul; Lau, Harold; Duclos, Marie; Parliament, Matthew; Morton, Gerard; Hamstra, Daniel; Seider, Michael; Lock, Michael I; Patel, Malti; Gay, Hiram; Vigneault, Eric; Winter, Kathryn; Sandler, Howard

    2018-03-15

    Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008. Men with stage cT1b to T2b, Gleason score 2 to 6, and prostate-specific antigen (PSA) level of 10 or greater and less than 20 or Gleason score of 7 and PSA less than 15 received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions. Time to OS measured from randomization to death due to any cause. American Society for Therapeutic Radiology and Oncology (ASTRO)/Phoenix definitions were used for biochemical failure. Acute (≤90 days of treatment start) and late radiation therapy toxic effects (>90 days) were graded using the National Cancer Institute Common Toxicity Criteria, version 2.0, and the RTOG/European Organisation for the Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme, respectively. With a median follow-up of 8.4 (range, 0.02-13.0) years in 1499 patients (median [range] age, 71 [33-87] years; 70% had PSA <10 ng/mL, 84% Gleason score of 7, 57% T1 disease), there was no difference in OS between the 751 men in the 79.2-Gy arm and the 748 men in the 70.2-Gy arm. The 8-year rates of OS were 76% with 79.2 Gy and 75% with 70.2 Gy (hazard ratio [HR], 1.00; 95% CI, 0.83-1.20; P = .98). The 8-year cumulative rates of distant metastases were 4% for the 79.2-Gy arm and 6% for the 70.2-Gy arm (HR, 0.65; 95% CI, 0.42-1.01; P = .05). The ASTRO and Phoenix biochemical failure rates at 5 and 8 years were 31% and 20% with 79.2 Gy

  11. The Effect of Increasing Doses of Saw Palmetto Fruit Extract on Serum PSA Levels: Analysis of the CAMUS Randomized Trial

    Science.gov (United States)

    Andriole, Gerald L.; McCullum-Hill, Christie; Sandhu, Gurdarshan S.; Crawford, E. David; Barry, Michael J.; Cantor, Alan

    2014-01-01

    Purpose Saw palmetto extracts are used for treating lower urinary tract symptoms in men despite level I evidence concluding that saw palmetto was ineffective in reducing lower urinary symptoms. We sought to determine whether higher doses of saw palmetto as studied in CAMUS affect serum PSA levels. Materials and Methods The CAMUS trial was a randomized, placebo-controlled double blind multi-centered North American trial conducted between June 5, 2008 and October 10, 2012 in which 369 men >45 years of age with AUA symptom score ≥ 8 and ≤ 24 were randomly assigned to placebo or dose escalation saw palmetto, which consisted of 320mg for first 24 weeks to 640mg for next 24 weeks to 960mg for last 24 weeks of this 72 week trial. Serum PSA levels (Beckman-Coulter) were obtained at baseline and at weeks 24, 48 and 72 and were compared between treatment groups using the pooled t and Fisher's exact tests. Results Serum PSA levels were similar at baseline for the placebo (1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in PSA levels over the course of the study were similar: placebo group mean change 0.16 ± 1.08 ng/ml and saw palmetto group mean change 0.23 ± 0.83 ng/ml (p value 0.50). Additionally, no differential effect on serum PSA levels was observed between treatment arms when groups were stratified by baseline PSA values. Conclusions Saw palmetto extract does not affect serum PSA levels more than placebo even at relatively high doses. PMID:23253958

  12. Radiation doses from radon and progeny in Irish houses

    International Nuclear Information System (INIS)

    McLaughlin, J.P.

    1985-08-01

    In the United Kingdom, the estimated average annual effective dose equivalent to members of the public from all sources is 2.4 mSv (240 mrem). 40% of this dose is contributed by exposure to radon, and it is not unreasonable to assume that the situation in Ireland is very similar. During 1982-84 a preliminary study of radon and penetrating radiation on 300 Irish houses showed seasonally averaged indoor radon concentrations in the range 3 Bq/m 3 of air to 700 bq/m 3 , with a median value of about 40 bq/m 3 . A national survey of indoor radon has now been undertaken; 3000 households, randomly selected from the electoral register are to be monitored and the result correlated with energy conservation practices. The final part of this document deals with the regulatory aspects of radon control and reviews the practices for reduction of indoor radon daughter doses presently in hand in Scandinavia. An appendix of radiation units and terms is also given

  13. Miglustat in late-onset Tay-Sachs disease: a 12-month, randomized, controlled clinical study with 24 months of extended treatment.

    Science.gov (United States)

    Shapiro, Barbara E; Pastores, Gregory M; Gianutsos, John; Luzy, Cécile; Kolodny, Edwin H

    2009-06-01

    To evaluate the safety and efficacy of miglustat in patients with GM2 gangliosidosis. A randomized, multicenter, open-label, 12-month study involving patients aged 18 years or older, randomized 2:1 to miglustat (200 mg TID) or "no miglustat treatment." This study was followed by 24 months of extended treatment during which all patients received miglustat. Primary efficacy endpoints were change in eight measures of isometric muscle strength in the limbs and isometric grip strength, evaluated at baseline, and months 12 and 36. Secondary efficacy endpoints included gait, balance, disability, and other neurological assessments. Safety evaluations included adverse event reporting. Thirty patients (67% male, age range 18-56 years) with late-onset Tay-Sachs disease were enrolled; 20 were randomized to miglustat and 10 to "no miglustat treatment." Muscle and grip strength generally decreased over the study period. No differences were observed between the two groups in any efficacy measure, either during the 12-month randomized phase or the full 36 months. The most common treatment-related adverse events were decrease in weight and diarrhea. Miglustat treatment was not shown to lead to measurable benefits in this cohort of patients with late-onset Tay-Sachs disease. The observed safety profile was consistent with that of the approved dose (100 mg TID) in type 1 Gaucher disease.

  14. Changes in Rectal Dose Due to Alterations in Beam Angles for Setup Uncertainty and Range Uncertainty in Carbon-Ion Radiotherapy for Prostate Cancer.

    Directory of Open Access Journals (Sweden)

    Yoshiki Kubota

    Full Text Available Carbon-ion radiotherapy of prostate cancer is challenging in patients with metal implants in one or both hips. Problems can be circumvented by using fields at oblique angles. To evaluate the influence of setup and range uncertainties accompanying oblique field angles, we calculated rectal dose changes with oblique orthogonal field angles, using a device with fixed fields at 0° and 90° and a rotating patient couch.Dose distributions were calculated at the standard angles of 0° and 90°, and then at 30° and 60°. Setup uncertainty was simulated with changes from -2 mm to +2 mm for fields in the anterior-posterior, left-right, and cranial-caudal directions, and dose changes from range uncertainty were calculated with a 1 mm water-equivalent path length added to the target isocenter in each angle. The dose distributions regarding the passive irradiation method were calculated using the K2 dose algorithm.The rectal volumes with 0°, 30°, 60°, and 90° field angles at 95% of the prescription dose were 3.4±0.9 cm3, 2.8±1.1 cm3, 2.2±0.8 cm3, and 3.8±1.1 cm3, respectively. As compared with 90° fields, 30° and 60° fields had significant advantages regarding setup uncertainty and significant disadvantages regarding range uncertainty, but were not significantly different from the 90° field setup and range uncertainties.The setup and range uncertainties calculated at 30° and 60° field angles were not associated with a significant change in rectal dose relative to those at 90°.

  15. Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study.

    Science.gov (United States)

    Ou, Jian-Jun; Xun, Guang-Lei; Wu, Ren-Rong; Li, Le-Hua; Fang, Mao-Sheng; Zhang, Hong-Geng; Xie, Shi-Ping; Shi, Jian-Guo; Du, Bo; Yuan, Xue-Qin; Zhao, Jing-Ping

    2011-02-01

    S-citalopram (escitalopram) is the very active moiety of citalopram. It has been shown in many studies to be an effective and safe antidepressant for treating major depressive disorder (MDD). The aim of our study was to compare the efficacy and safety of escitalopram vs citalopram in Chinese MDD patients. In the double-blind study, 240 MDD patients were randomly assigned to treatment for 6 weeks either with escitalopram (10-20 mg/d) or citalopram (20-40 mg/d). The primary efficacy measurement was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of study. The secondary efficacy measurements were response and remission rates. The adverse events (AEs) were recorded by the investigator. Two hundred and three (85%) patients completed the trial. The average dose was 13.9 mg/d in the escitalopram group and 27.6 mg/d in the citalopram group. No significant differences were found between the two groups in the change in HAMD-17 total score, response, and remission rate. These results were similar in severe MDD patients. No significant differences were found between the two groups in AEs. No serious AEs were observed in this study. The study suggests that escitalopram 10-20 mg/d are as effective and safe as citalopram 20-40 mg/d in the short-term treatment for Chinese MDD patients.

  16. Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of Observational Studies

    Science.gov (United States)

    García Rodríguez, Luis A.; Martín-Pérez, Mar; Hennekens, Charles H.; Rothwell, Peter M.; Lanas, Angel

    2016-01-01

    Background Low-dose aspirin has proven effectiveness in secondary and primary prevention of cardiovascular events, but is also associated with an increased risk of major bleeding events. For primary prevention, this absolute risk must be carefully weighed against the benefits of aspirin; such assessments are currently limited by a lack of data from general populations. Methods Systematic searches of Medline and Embase were conducted to identify observational studies published between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI) bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75–325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with aspirin versus non-use were calculated using random-effects models, based on reported estimates of RR (including odds ratios, hazard ratios, incidence rate ratios and standardized incidence ratios) in 39 articles. Findings The incidence of GI bleeding with low-dose aspirin was 0.48–3.64 cases per 1000 person-years, and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95% confidence interval [CI]: 1.2–1.7). For upper and lower GI bleeding, the RRs with low-dose aspirin were 2.3 (2.0–2.6) and 1.8 (1.1–3.0), respectively. Neither aspirin dose nor duration of use had consistent effects on RRs for upper GI bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2–1.7) overall. Aspirin was associated with increased bleeding risks when combined with non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin reuptake inhibitors compared with monotherapy. By contrast, concomitant use of proton pump inhibitors decreased upper GI bleeding risks relative to aspirin monotherapy. Conclusions The risks of major bleeding with low-dose aspirin in real-world settings are of a similar magnitude to those reported in randomized trials. These data will help inform clinical judgements regarding the use of low-dose aspirin

  17. Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target.

    Science.gov (United States)

    Budiarto, E; Keijzer, M; Storchi, P R M; Heemink, A W; Breedveld, S; Heijmen, B J M

    2014-01-20

    Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.

  18. Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target

    International Nuclear Information System (INIS)

    Budiarto, E; Keijzer, M; Heemink, A W; Storchi, P R M; Breedveld, S; Heijmen, B J M

    2014-01-01

    Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements. (paper)

  19. Radial dose distribution from carbon ion incident on liquid water

    International Nuclear Information System (INIS)

    Scifoni, E.; Surdutovich, E.; Solov'yov, A.V.; Surdutovich, E.

    2010-01-01

    We report calculations of the radial dose deposited along carbon-ion tracks in liquid water using different techniques depending on the energy range of secondary electrons. The models are developed in relation with the experimental data on electron penetration lengths. For electrons with energies higher than 45 eV, we use the Katz model. However, the main focus is on the low-energy electrons, which are largely responsible for DNA damage within 10 nm from the tracks. For these electrons, the dose calculation is based on their random walk behaviour. The results of this combined approach are compared to experimental measurements. Contributions to the deposited energy by electrons of different ranges of energy are discussed. (authors)

  20. Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

    Science.gov (United States)

    Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

    2014-09-01

    The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for

  1. Fluorouracil and high-dose leucovorin with radiotherapy as adjuvant therapy for rectal cancer. Results of a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Giralt, J. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rubio, D. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Maldonado, X. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Naval, J. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Casado, S. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Lara, F. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rosello, J.M. [Dept. of Preventive Medicine, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Armengol, M. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain)

    1997-07-01

    The purpose of this phase II study was to evaluate the efficacy and toxicity of fluorouracil and high-dose leucovorin (5-FU/LV) with pelvic irradiation as adjuvant therapy for patients with macroscopical resected rectal or recto-sigmoid cancer. Following surgery for stages II-III primary (52) or recurrent rectal cancer (4), 56 patients received 8 cycles of 5-FU/LV and pelvic irradiation. 5-FU doses were 200 mgr/m{sup 2} for cycles 2-3 and 300 mgr/m{sup 2} for cycles 1 and 4-8. LV doses remained fixed at 200 mgr/m{sup 2}. Pelvic radiation was started in the third week, between the first and second cycle. The total dose was 50.4 Gy. No serve complications had been recorded. The incidence of grade 3 diarrhea was 19%. Three patients presented leukopenia grade 3 (5%). In 44 patients (78%) the planned treatment could be administered. The median follow-up was 40 months (range 22-66). Seven patients had a local relapse (13%) and 6 developed distant metastasis (10%). The 3-year disease-free survival was 72% and the overall survival was 76%. These preliminary results show that combined post-operative 5-FU/LV and pelvic radiotherapy are well tolerated and present a reasonable local control and survival rates. This adjuvant treatment should be evaluated in randomized trials. (orig.).

  2. Local dose enhancement in radiation therapy: Monte Carlo simulation study

    International Nuclear Information System (INIS)

    Silva, Laura E. da; Nicolucci, Patricia

    2014-01-01

    The development of nanotechnology has boosted the use of nanoparticles in radiation therapy in order to achieve greater therapeutic ratio between tumor and healthy tissues. Gold has been shown to be most suitable to this task due to the high biocompatibility and high atomic number, which contributes to a better in vivo distribution and for the local energy deposition. As a result, this study proposes to study, nanoparticle in the tumor cell. At a range of 11 nm from the nanoparticle surface, results have shown an absorbed dose 141 times higher for the medium with the gold nanoparticle compared to the water for an incident energy spectrum with maximum photon energy of 50 keV. It was also noted that when only scattered radiation is interacting with the gold nanoparticles, the dose was 134 times higher compared to enhanced local dose that remained significant even for scattered radiation. (author)

  3. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Kristin Brekke

    Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

  4. High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

    Science.gov (United States)

    Ganmaa, Davaasambuu; Munkhzul, Baatar; Fawzi, Wafaie; Spiegelman, Donna; Willett, Walter C; Bayasgalan, Purev; Baasansuren, Erkhembayar; Buyankhishig, Burneebaatar; Oyun-Erdene, Sereeter; Jolliffe, David A; Xenakis, Theodoros; Bromage, Sabri; Bloom, Barry R; Martineau, Adrian R

    2017-09-01

    Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. To determine the effect of high-dose vitamin D 3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D 3 . We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D 3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P vitamin D 3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). Vitamin D 3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

  5. A double-blind, randomized, multiple-dose, parallel-group study to characterize the occurrence of diarrhea following two different dosing regimens of neratinib, an irreversible pan-ErbB receptor tyrosine kinase inhibitor.

    Science.gov (United States)

    Abbas, Richat; Hug, Bruce A; Leister, Cathie; Sonnichsen, Daryl

    2012-07-01

    Neratinib, a potent, low-molecular-weight, orally administered, irreversible, pan-ErbB receptor tyrosine kinase inhibitor has antitumor activity in ErbB2 + breast cancer. The objective of this study was to characterize the onset, severity, and duration of diarrhea after administration of neratinib 240 mg once daily (QD) and 120 mg twice daily (BID) for ≤14 days in healthy subjects. A randomized, double-blind, parallel-group, inpatient study was conducted in 50 subjects given oral neratinib either 240 mg QD or 120 mg BID with food for ≤14 days. The primary endpoint was the proportion of subjects with diarrhea of at least moderate severity (grade 2; 5-7 loose stools/day). In subjects with grade 2 diarrhea, fecal analytes were determined. Pharmacokinetic profiles were characterized for neratinib on Days 1 and 7. No severe (grade 3) diarrhea was reported. By Day 4, all subjects had grade 1 diarrhea. Grade 2 diarrhea occurred in 11/22 evaluable subjects (50 % [90 % confidence interval (CI): 28-72 %]) in the QD group and 17/23 evaluable subjects (74 % [90 % CI: 52-90 %]) in the BID group (P = 0.130). In fecal analyses, 18 % tested positive for hemoglobin and 46 % revealed fecal lactoferrin. Specimen pH was neutral to slightly alkaline. In pharmacokinetic analyses, Day 1 peak plasma concentration and Day 7 steady-state exposure were higher with the QD regimen than the BID regimen. In an exploratory analysis, ABCG2 genotype showed no correlation with severity or onset of diarrhea. Incidences and onsets of at least grade 1 and at least grade 2 diarrhea were not improved on BID dosing compared with QD dosing.

  6. Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

    2010-04-01

    Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

  7. Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.

    Science.gov (United States)

    Ormerod, Anthony D; van Voorst Vader, Pieter C; Majewski, Slovomir; Vanscheidt, Wolfgang; Benjamin, Nigel; van der Meijden, Willem

    2015-08-01

    Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003. Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily). The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety. Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose

  8. Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments

    International Nuclear Information System (INIS)

    Visser, Andries G.; Aardweg, Gerard J.M.J. van den; Levendag, Peter C.

    1996-01-01

    to be less need for strong fractionation in PDR schedules. If the overall time is at least as long as that of the LDR schedule and if the total physical dose is (slightly) adapted, PDR schedules can be designed using longer pulse intervals of up to 3 h. Schedules with sufficiently long intervals have significant logistic advantages in terms of patient care and treatment tolerance. However, in general, PDR schedules that apply more fractionation have a lower risk of overdosing normal tissues in comparison to fractionated HDR schedules. Applying probable ranges for the values of α/β and T (1(2)) , the model calculations indicate that the differences in effects between the proposed fractionated HDR and PDR schedules could be rather small. To detect the magnitude of these differences, (randomized) clinical studies with rather large patient groups might be needed. Conclusions: Pulsed dose rate treatment schedules with longer intervals of up to 3 h appear adequate to replace LDR treatment schedules. Whether PDR schedules can, indeed, replace LDR treatment schedules and whether they offer detectable advantages over schedules with less fractionation (fractionated HDR) should be tested in clinical studies

  9. An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study.

    Science.gov (United States)

    Wang, M; Wang, Q; Yu, Y Y; Wang, W S

    2013-09-01

    Ketamine can completely eliminate pain associated with propofol injection. However, the effective dose of ketamine to eliminate propofol injection pain has not been determined. The purpose of this study was to determine the effective dose of ketamine needed to eliminate pain in 50% and 95% of patients (ED50 and ED95, respectively) during propofol injections. This study was conducted in a double-blinded fashion and included 50 patients scheduled for elective gynecological laparoscopy under general anesthesia. The initial dose of ketamine used in the first patient was 0.25mg/kg. The dosing modifications were in increments or decrements of 0.025 mg/kg. Ketamine was administered 15 seconds before injecting propofol (2.5mg/kg), which was injected at a rate of 1mL/s. Patients were asked to rate their pain during propofol injection every 5s econds using a 0-3 pain scale. The highest pain score was recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by probit analyses. The dose of ketamine ranged from 0.175 to 0.275 mg/kg. The ED50 and ED95 of ketamine for eliminating pain during propofol injection were 0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211-0.243 mg/kg and 0.26-0.364 mg/kg, respectively). Ketamine at an approximate dose of 0.3mg/kg was effective in eliminating pain during propofol injection. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  10. SMALL-DOSE CYTOKINES IN COMBINATION WITH 5-FLUOROURACIL IN OLISSEMINATED RENAL CELL CARCINOMA: FINAL RESULTS OF A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    L. V. Demidov

    2009-01-01

    Full Text Available Background: High and intermediate IL-2 regimens are difficult to recommend because of great toxicity and efficacy is not sufficient. We suggest that a combination of very low-dose cytokines is effective and safe in metastatic renal cell carcinoma (MRCC patients (pts. A prospective randomized study was started in 2003. The primary end-point was a response rate. Methods: The eligibility criteria included histopathologically confirmed MRCC, ECOG PS 0-2, no autoimmune diseases, no brain metastases, and normal organ function. All pts were randomized in three arms: IL-2 alone, 1.5 MIU, iv, t.i.w., weeks 1—3 or IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w, weeks 1—3 or biochemotherapy group 5-FU, 500 mg/m2, iv, once a week, weeks 1—3 plus IL-2 1.0 MIU, iv, t.i.w., weeks 1—3 plus IFN 5 MIU, sc, t.i.w., weeks 1—3. Courses were repeated every three weeks. A response was assessed according to the RECIST every 2 courses.Results: 64 pts were enrolled, of whom 63 were analyzed. Their median age was 55.4 years (range 16—74. 42.9% of the patients had pre- viously received chemo- or immunotherapy. 55.6 percent of the pts had poor prognosis (according to Motzer et al., 2002. Bone metastases were present in 52.4% of the pts. Sixteen patients treated with IL-2 alone showed no CR, PR, 2 SD, or 14 PD. Of 23 patients in the IL-2+IFN group, there were 5 PR, 8 SD, and 10 PD, with a response rate of 21.7%. Amongst 24 patients in the 5-FU+IL-2+IFN group, there were 1 CR, 3 PR, 10 SD, and 10 PD, with a response rate of 16.7%. One-year survival was 20.0%, 81.3% and 81.0%, respectively. The influenza-like syndrome was the most common side effect in the pts who received IFN (89.1%, grade 1, CTC. Hypotension associated with IL-2 (all groups was seen in 56.3% (50%, grade 1 and 6.3%, grade 2. The other adverse reactions were 12.7% grade 1 neutropenia and vomiting in 4.7% pts (Group 3.Conclusion: All regimens are well tolerated. Small-dose IL-2

  11. Quality assessment of delineation and dose planning of early breast cancer patients included in the randomized Skagen Trial 1

    DEFF Research Database (Denmark)

    Francolini, Giulio; Thomsen, Mette S; Yates, Esben S

    2017-01-01

    , Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured....... No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable. CONCLUSIONS: QA showed high protocol compliance and adequate dose...... coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation....

  12. Radiation dose measurement in gastrointestinal studies

    International Nuclear Information System (INIS)

    Sulieman, A.; Elzaki, M.; Kappas, C.; Theodorou, K.

    2011-01-01

    Barium studies investigations (barium swallow, barium meal and barium enema) are the basic routine radiological examination, where barium sulphate suspension is introduced to enhance image contrast of gastrointestinal tracts. The aim of this study was to quantify the patients' radiation doses during barium studies and to estimate the organ equivalent dose and effective dose with those procedures. A total of 33 investigations of barium studies were measured by using thermoluminescence dosemeters. The result showed that the patient entrance surface doses were 12.6±10, 44.5±49 and 35.7±50 mGy for barium swallow, barium meal, follow through and enema, respectively. Effective doses were 0.2, 0.35 and 1.4 mSv per procedure for barium swallow, meal and enema respectively. Radiation doses were comparable with the previous studies. A written protocol for each procedure will reduce the inter-operator variations and will help to reduce unnecessary exposure. (authors)

  13. Dose-ranging evaluation of intravitreal siRNA PF-04523655 for diabetic macular edema (the DEGAS study)

    DEFF Research Database (Denmark)

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I

    2012-01-01

    To evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation.......To evaluate the safety and efficacy of three doses of PF-04523655, a 19-nucleotide methylated double stranded siRNA targeting the RTP801 gene, for the treatment of diabetic macular edema (DME) compared to focal/grid laser photocoagulation....

  14. SU-F-T-157: Physics Considerations Regarding Dosimetric Accuracy of Analytical Dose Calculations for Small Field Proton Therapy: A Monte Carlo Study

    Energy Technology Data Exchange (ETDEWEB)

    Geng, C [Massachusetts General Hospital, Boston, MA (United States); Nanjing University of Aeronautics and Astronautics, Nanjing (China); Daartz, J; Cheung, K; Bussiere, M; Shih, H; Paganetti, H; Schuemann, J [Massachusetts General Hospital, Boston, MA (United States)

    2016-06-15

    Purpose: To evaluate the accuracy of dose calculations by analytical dose calculation methods (ADC) for small field proton therapy in a gantry based passive scattering facility. Methods: 50 patients with intra-cranial disease were evaluated in the study. Treatment plans followed standard prescription and optimization procedures of proton stereotactic radiosurgery. Dose distributions calculated with the Monte Carlo (MC) toolkit TOPAS were used to represent delivered treatments. The MC dose was first adjusted using the output factor (OF) applied clinically. This factor is determined from the field size and the prescribed range. We then introduced a normalization factor to measure the difference in mean dose between the delivered dose (MC dose with OF) and the dose calculated by ADC for each beam. The normalization was determined by the mean dose of the center voxels of the target area. We compared delivered dose distributions and those calculated by ADC in terms of dose volume histogram parameters and beam range distributions. Results: The mean target dose for a whole treatment is generally within 5% comparing delivered dose (MC dose with OF) and ADC dose. However, the differences can be as great as 11% for shallow and small target treated with a thick range compensator. Applying the normalization factor to the MC dose with OF can reduce the mean dose difference to less than 3%. Considering range uncertainties, the generally applied margins (3.5% of the prescribed range + 1mm) to cover uncertainties in range might not be sufficient to guarantee tumor coverage. The range difference for R90 (90% distal dose falloff) is affected by multiple factors, such as the heterogeneity index. Conclusion: This study indicates insufficient accuracy calculating proton doses using ADC. Our results suggest that uncertainties of target doses are reduced using MC techniques, improving the dosimetric accuracy for proton stereotactic radiosurgery. The work was supported by NIH/NCI under CA

  15. A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.

    Science.gov (United States)

    Amalraj, Augustine; Varma, Karthik; Jacob, Joby; Divya, Chandradhara; Kunnumakkara, Ajaikumar B; Stohs, Sidney J; Gopi, Sreeraj

    2017-10-01

    Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.

  16. Dosimetric properties of the 'Pille' portable, wide dose range TLD reader

    International Nuclear Information System (INIS)

    Szabo, P.P.; Feher, I.; Deme, S.; Szabo, B.; Vagvoelgyi, J.

    1986-01-01

    The dosimetric properties of a portable TLD reader are described. The TLD system named 'Pille' or 'moth' consists of a lightweight battery-operated portable TLD reader and its CaSO 4 :Dy bulb dosemeters. The reproducibility of the TLD system at constant temperature was found to be better than + -2%, and the mean time between failures exceeded 5 years. The dose range of the system is wide, covering more than 6 orders of magnitude, from 5 μGy to 10 Gy. The energy dependence of the CaSO 4 :Dy bulb dosemeters is less than + - 20% above 100 keV in the energy compensation capsules. Without additional annealing, the bulb dosemeters can be re-used at least 100 times, which is an important aspect during in situ measurements. (author)

  17. Recurrence of random walks with long-range steps generated by fractional Laplacian matrices on regular networks and simple cubic lattices

    Science.gov (United States)

    Michelitsch, T. M.; Collet, B. A.; Riascos, A. P.; Nowakowski, A. F.; Nicolleau, F. C. G. A.

    2017-12-01

    We analyze a Markovian random walk strategy on undirected regular networks involving power matrix functions of the type L\\frac{α{2}} where L indicates a ‘simple’ Laplacian matrix. We refer to such walks as ‘fractional random walks’ with admissible interval 0walk. From these analytical results we establish a generalization of Polya’s recurrence theorem for fractional random walks on d-dimensional infinite lattices: The fractional random walk is transient for dimensions d > α (recurrent for d≤slantα ) of the lattice. As a consequence, for 0walk is transient for all lattice dimensions d=1, 2, .. and in the range 1≤slantα walk is transient only for lattice dimensions d≥slant 3 . The generalization of Polya’s recurrence theorem remains valid for the class of random walks with Lévy flight asymptotics for long-range steps. We also analyze the mean first passage probabilities, mean residence times, mean first passage times and global mean first passage times (Kemeny constant) for the fractional random walk. For an infinite 1D lattice (infinite ring) we obtain for the transient regime 0walk is generated by the non-diagonality of the fractional Laplacian matrix with Lévy-type heavy tailed inverse power law decay for the probability of long-range moves. This non-local and asymptotic behavior of the fractional random walk introduces small-world properties with the emergence of Lévy flights on large (infinite) lattices.

  18. A prospective randomized study comparing percutaneous nephrolithotomy under combined spinal-epidural anesthesia with percutaneous nephrolithotomy under general anesthesia.

    Science.gov (United States)

    Singh, Vishwajeet; Sinha, Rahul Janak; Sankhwar, S N; Malik, Anita

    2011-01-01

    A prospective randomized study was executed to compare the surgical parameters and stone clearance in patients who underwent percutaneous nephrolithotomy (PNL) under combined spinal-epidural anesthesia (CSEA) versus those who underwent PNL under general anesthesia (GA). Between January 2008 to December 2009, 64 patients with renal calculi were randomized into 2 groups and evaluated for the purpose of this study. Group 1 consisted of patients who underwent PNL under CSEA and Group 2 consisted of patients who underwent PNL under GA. The operative time, stone clearance rate, visual pain analog score, mean analgesic dose and mean hospital stay were compared amongst other parameters. The difference between visual pain analog score after the operation and the dose of analgesic requirement was significant on statistical analysis between both groups. PNL under CSEA is as effective and safe as PNL under GA. Patients who undergo PNL under CESA require lesser analgesic dose and have a shorter hospital stay. Copyright © 2011 S. Karger AG, Basel.

  19. Multi-dose vitamin d supplementation in stable very preterm infants: Prospective randomized trial response to three different vitamin D supplementation doses.

    Science.gov (United States)

    Bozkurt, Ozlem; Uras, Nurdan; Sari, Fatma Nur; Atay, Funda Yavanoglu; Sahin, Suzan; Alkan, Ayse Dogan; Canpolat, Fuat Emre; Oguz, Serife Suna

    2017-09-01

    Preterm newborns are born with lower vitamin D stores. Although vitamin D supplementation is recommended there is no consensus regarding the adequate dose of supplementation for preterm infants. To assess the effect of three different doses of vitamin D supplementation (400, 800 and 1000IU/d) in preterm infants ≤32weeks gestation on the prevalence of vitamin D deficiency and 25(OH) D levels at 36weeks postmenstrual age (PMA). Prospective randomized trial. 121 preterm infants with gestational age of 24-32weeks were randomly allocated to receive 400, 800 or 1000IU/d vitamin D. Serum concentration of 25(OH) D and the prevalence of vitamin D deficiency at 36weeks PMA. Vitamin D deficiency was defined as serum 25(OH) D concentrations vitamin D levels before supplementation. The average 25(OH) vitamin D concentrations at 36weeks PMA were significantly higher in 800IU (40±21.4ng/ml) and 1000IU group (43±18.9ng/ml) when compared to 400IU group (29.4±13ng/ml). The prevalence of vitamin D deficiency (2.5 vs 22.5; RR: 0.09; CI:0.01-0.74) and insufficiency (30 vs 57.5; RR:0.32; CI:0.13-0.80) was significantly lower in 1000IU group when compared to 400IU group at 36weeks PMA. 1000IU/d of vitamin D supplementation in preterm infants ≤32weeks gestation age effectively decreases the prevalence of vitamin D deficiency and leads to higher concentrations of 25(OH) vitamin D at 36weeks PMA TRIAL REGISTRATION: Clinical Trials.gov: NCT02941185. Copyright © 2017. Published by Elsevier B.V.

  20. Bioequivalence and pharmacokinetic evaluation of two formulations of risperidone 2 mg : an open-label, single-dose, fasting, randomized-sequence, two-way crossover study in healthy male Chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Zhang, Meng-qi; Jia, Jing-ying; Liu, Yan-mei; Liu, Gang-yi; Li, Shui-jun; Wang, Wei; Weng, Li-ping; Yu, Chen

    2013-03-01

    Risperidone is a benzisoxazole derivate and is effective in the treatment of schizophrenia and other psychiatric illnesses in adults and children. Although there are a few reports in the literature regarding the pharmacokinetic characteristics of risperidone, insufficient data on its pharmacokinetic properties in a Chinese population are available. To meet the requirements for marketing a new generic product, this study was designed to compare the pharmacokinetic properties and bioequivalence of two 2 mg tablet formulations of risperidone: a newly developed generic formulation (test) and a branded formulation (reference) in healthy adult male Chinese volunteers. A single-dose, open-label, randomized-sequence, 2 × 2 crossover study was conducted in fasted healthy male Chinese volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 1 tablet (2 mg each) of the test formulation (Risperidone tablet; Dr. Reddy's Laboratories Ltd., Hyderabad, India) or the reference formulation (Risperdal(®) tablet; Xian-Janssen Pharmaceutical Ltd., Xi-an, China), followed by a 2-week washout period and subsequent administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Plasma samples were collected over 96 hours. Plasma concentrations of the parent drug, risperidone, and its active metabolite, 9-hydroxy-risperidone, were analyzed by a liquid chromatography-tandem mass spectrometry method. The formulations would be considered bioequivalent if the 90% confidence intervals (CIs) of the natural log-transformed values were within the predetermined 80-125% equivalence range for the maximum plasma drug concentration (Cmax) and the area under the plasma concentration-time curve (AUC), in accordance with guidelines issued by the US Food and Drug Administration. Assessment of tolerability was based on recording of adverse events (AEs), monitoring of vital signs, electrocardiograms, and laboratory tests at baseline

  1. Study on relations between heavy ions single event upset cross sections and γ accumulated doses

    International Nuclear Information System (INIS)

    He Chaohui; Geng Bin; Wang Yanping; Peng Honglun; Yang Hailiang; Chen Xiaohua; Li Guozheng

    2002-01-01

    Experiments were done under 252 Cf and 60 Co γ source to study the relation between heavy ion Single Event Upset (SEU) cross sections and γ accumulated doses. There was no obvious rule and little influence of γ accumulated doses on SEU cross sections when Static Random Access Memories were in power off mode and static power on mode. In active measuring mode, the SEU cross section increased as the accumulated doses increasing when same data were written in memory cells. If reverse data, such as '55' and 'AA', were written in memory cells during the experiment, the SEU cross sections decreased to the level when memories were not irradiated under 60 Co γ source, even more small. It implied that the influence of γ accumulated doses on SEU cross sections can be set off by this method

  2. Bioavailability of two single-dose oral formulations of omeprazole 20 mg: an open-label, randomized sequence, two-period crossover comparison in healthy Mexican adult volunteers.

    Science.gov (United States)

    Poo, Jorge Luis; Galán, Juan Francisco; Rosete, Alejandra; de Lago, Alberto; Oliva, Iván; González-de la Parra, Mario; Jiménez, Patricia; Burke-Fraga, Victoria; Namur, Salvador

    2008-04-01

    Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P disability, or required intervention to prevent permanent impairment or damage. Thirty-four subjects were enrolled and completed the study (25 men and 9

  3. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

    1984-10-01

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  4. Phase I randomized safety study of twice daily dosing of acidform vaginal gel: candidate antimicrobial contraceptive.

    Directory of Open Access Journals (Sweden)

    Marla J Keller

    Full Text Available BACKGROUND: Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. METHODS: Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. RESULTS: The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002. While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra, an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08. CONCLUSIONS: Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than

  5. Phase I Randomized Safety Study of Twice Daily Dosing of Acidform Vaginal Gel: Candidate Antimicrobial Contraceptive

    Science.gov (United States)

    Keller, Marla J.; Carpenter, Colleen A.; Lo, Yungtai; Einstein, Mark H.; Liu, Congzhou; Fredricks, David N.; Herold, Betsy C.

    2012-01-01

    Background Acidform gel, an acid-buffering product that inactivates spermatozoa, may be an effective topical non-hormonal contraceptive. This study was designed to evaluate the safety of vaginal dosing and effects of Acidform on mucosal immune mediators, antimicrobial properties of genital secretions, and vaginal microbiota. Methods Thirty-six sexually abstinent U.S. women were randomized to apply Acidform or hydroxyethylcellulose (HEC) placebo gel twice daily for 14 consecutive days. Safety was assessed by symptoms and pelvic examination. The impact of gel on mucosal immunity was assessed by quantifying cytokines, chemokines, antimicrobial proteins and antimicrobial activity of genital secretions collected by cervicovaginal lavage (CVL) at screening, 2 hours after gel application, and on days 7, 14 and 21. Vaginal microbiota was characterized at enrollment and day 14 using species-specific quantitative PCR assays. Results The median vaginal and cervical pH was significantly lower 2 hours after application of Acidform and was associated with an increase in the bactericidal activity of CVL against E. coli. However, 65% of women who received Acidform had at least one local adverse event compared with 11% who received placebo (p = 0.002). While there was no increase in inflammatory cytokines or chemokines, CVL concentrations of lactoferrin and interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory protein, were significantly lower following Acidform compared to HEC placebo gel application. There were no significant changes in Lactobacillus crispatus or Lactobacillus jensenii in either group but there was a decrease in Gardnerella vaginalis in the Acidform group (p = 0.08). Conclusions Acidform gel may augment mucosal defense as evidenced by an increase in bactericidal activity of genital secretions against E. coli and a decrease in Gardnerella vaginalis colonization. However, Acidform was associated with more irritation than placebo and lower levels

  6. Evaluation of the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Calamita, Simone Aparecida Penimpedo; Biasotto-Gonzalez, Daniela Aparecida; De Melo, Nivea Cristina; dos Santos, Douglas Meira; de Lassa, Roberta; de Mendonça, Fabiana Sarilho; Oliveira, Claudia Santos; Amorim, César Ferreira; Gonzalez, Tabajara Oliveira; Fumagalli, Marco Antônio; de Gomes, Cid André Fidelis Paula; Politti, Fabiano

    2015-03-19

    Nonspecific neck pain can cause considerable suffering, possible disability and reductions in quality of life and productivity. The aim of the proposed study is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. A total of 12 patients with nonspecific neck pain and 12 healthy subjects will be enrolled in a randomized, single-blind crossover study. Each subject will receive two forms of treatment in random order: a single session of traditional acupuncture (acupoints: triple energizer 5, 'Wai-guan' and large intestine 11, 'Qu-chi') and sham acupuncture. To eliminate carry-over treatment effects, a one-week wash-out period will be respected between sessions. Surface electromyography will be used to determine motor control in the upper trapezius muscle before and after treatment. The outcome measures in the group with neck pain will be a numerical pain rating scale (range: 0 (no pain) to 10 (maximum pain)), documentation of the pain area on a body chart and cervical range of motion. Comparisons before and after acupuncture treatment will demonstrate whether acupoints affect the activity of the upper trapezius muscle, pain and cervical range of motion. The purpose of this randomized clinical trial is to evaluate the immediate effect of acupuncture on pain, cervical range of motion and electromyographic activity of the upper trapezius muscle in patients with nonspecific neck pain. Data will be published after the study is completed. The study will support the practice of evidence-based physical therapy for individuals with nonspecific neck pain. This trial was registered with Clinicaltrials.gov (identifier: NCT0984021 ) on 7 November 2013 ( https://clinicaltrials.gov/ct2/show/NCT01984021 ).

  7. Two different doses of supplemental vitamin A did not affect mortality of normal-birth-weight neonates in Guinea-Bissau in a randomized controlled trial

    DEFF Research Database (Denmark)

    Benn, Christine Stabell; Diness, Birgitte R; Balde, Ibraima

    2014-01-01

    Whether neonatal vitamin A supplementation (NVAS) should be policy in areas with vitamin A deficiency is debated. We observed that a smaller dose of vitamin A may decrease mortality more than a larger dose and conducted a randomized, double-blind, placebo-controlled trial in Guinea-Bissau with th...

  8. Georgia fishery study: implications for dose calculations

    International Nuclear Information System (INIS)

    Turcotte, M.D.S.

    1983-01-01

    Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The data indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. A fish consumption value of 11.3 kg/yr should be used to recalculate dose to the average individual from L-Reactor restart. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average fish consumption value of 11.3 kg/yr, and a maximum fish consumption value of 34 kg/yr

  9. Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: A Randomized Double-Blind Study.

    Science.gov (United States)

    Ouchi, Kentaro; Sugiyama, Kazuna

    2016-01-01

    Dexmedetomidine (DEX) dose dependently enhances the local anesthetic action of lidocaine in rats. We hypothesized that the effect might also be dose dependent in humans. We evaluated the effect of various concentrations of DEX with a local anesthetic in humans. Eighteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 4 drug combinations: (1) 1% lidocaine with 2.5 ppm (parts per million) (4.5 μg) DEX, (2) lidocaine with 5.0 ppm (9.0 μg) DEX, (3) lidocaine with 7.5 ppm (13.5μg) DEX, or (4) lidocaine with 1:80,000 (22.5 μg) adrenaline (AD), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 5 minutes for 20 minutes, and every 10 minutes from 20 to 60 minutes. Pulp latency of each tooth increased compared with baseline, from 5 to 15 minutes until 60 minutes. There were no significant intergroup differences at any time point. Anesthesia onset was not different between groups. Anesthesia duration was different between groups (that with DEX 7.5 ppm was significantly longer than that with DEX 2.5 ppm and AD; there was no difference between DEX 2.5 ppm and AD). Blood pressure decreased from baseline in the 5.0 and 7.5 ppm DEX groups at 30 to 60 minutes, although there was no hypotension; moreover, heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in humans. Dexmedetomidine at 2.5 ppm produces similar enhancement of local anesthesia effect as addition of 1:80,000 AD.

  10. The mechanical behavior and reliability prediction of the HTR graphite component at various temperature and neutron dose ranges

    International Nuclear Information System (INIS)

    Fang, Xiang; Yu, Suyuan; Wang, Haitao; Li, Chenfeng

    2014-01-01

    Highlights: • The mechanical behavior of graphite component in HTRs under high temperature and neutron irradiation conditions is simulated. • The computational process of mechanical analysis is introduced. • Deformation, stresses and failure probability of the graphite component are obtained and discussed. • Various temperature and neutron dose ranges are selected in order to investigate the effect of in-core conditions on the results. - Abstract: In a pebble-bed high temperature gas-cooled reactor (HTR), nuclear graphite serves as the main structural material of the side reflectors. The reactor core is made up of a large number of graphite bricks. In the normal operation case of the reactor, the maximum temperature of the helium coolant commonly reaches about 750 °C. After around 30 years’ full power operation, the peak value of in-core fast neutron cumulative dose reaches to 1 × 10 22 n cm −2 (EDN). Such high temperature and neutron irradiation strongly impact the behavior of graphite component, causing obvious deformation. The temperature and neutron dose are unevenly distributed inside a graphite brick, resulting in stress concentrations. The deformation and stress concentration can both greatly affect safety and reliability of the graphite component. In addition, most of the graphite properties (such as Young's modulus and coefficient of thermal expansion) change remarkably under high temperature and neutron irradiations. The irradiation-induced creep also plays a very important role during the whole process, and provides a significant impact on the stress accumulation. In order to simulate the behavior of graphite component under various in-core conditions, all of the above factors must be considered carefully. In this paper, the deformation, stress distribution and failure probability of a side graphite component are studied at various temperature points and neutron dose levels. 400 °C, 500 °C, 600 °C and 750 °C are selected as the

  11. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

    Directory of Open Access Journals (Sweden)

    Sergio Luevano-Gurrola

    2015-09-01

    Full Text Available Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

  12. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.

    Science.gov (United States)

    Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

    2015-09-30

    Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

  13. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

    Science.gov (United States)

    Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

    2015-01-01

    Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize. PMID:26437425

  14. Benign painful shoulder syndrome. Initial results of a single-center prospective randomized radiotherapy dose-optimization trial

    International Nuclear Information System (INIS)

    Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

    2012-01-01

    Background and purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Patients and methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

  15. Comparative efficacy of continuous and pulse dose terbinafine regimes in toenail dermatophytosis: A randomized double-blind trial.

    Science.gov (United States)

    Yadav, Pravesh; Singal, Archana; Pandhi, Deepika; Das, Shukla

    2015-01-01

    Dermatophytes are the most frequently implicated agents in toenail onychomycosis and oral terbinafine has shown the best cure rates in this condition. The pharmacokinetics of terbinafine favors its efficacy in pulse dosing. To compare the efficacy of terbinafine in continuous and pulse dosing schedules in the treatment of toenail dermatophytosis. Seventy-six patients of potassium hydroxide (KOH) and culture positive dermatophyte toenail onychomycosis were randomly allocated to two treatment groups receiving either continuous terbinafine 250 mg daily for 12 weeks or 3 pulses of terbinafine (each of 500 mg daily for a week) repeated every 4 weeks. Patients were followed up at 4, 8 and 12 weeks during treatment and post-treatment at 24 weeks. At each visit, a KOH mount and culture were performed. In each patient, improvement in a target nail was assessed using a clinical score; total scores for all nails and global assessments by physician and patient were also recorded. Mycological, clinical and complete cure rates, clinical effectivity and treatment failure rates were then compared. The declines in target nail and total scores from baseline were significant at each follow-up visit in both the treatment groups. However, the inter-group difference was statistically insignificant. The same was true for global assessment indices, clinical effectivity as well as clinical, mycological, and complete cure rates. The short follow-up in our study may have led to lower cure rates being recorded. Terbinafine in pulse dosing is as effective as continuous dosing in the treatment of dermatophyte toenail onychomycosis.

  16. Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

    Science.gov (United States)

    Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

    2013-10-01

    To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP

  17. A Study of Adaptive Detection of Range-Distributed Targets

    National Research Council Canada - National Science Library

    Gerlach, Karl R

    2000-01-01

    ... to be characterized as complex zero-mean correlated Gaussian random variables. The target's or targets' complex amplitudes are assumed to be distributed across the entire input data block (sensor x range...

  18. Reliability of single aliquot regenerative protocol (SAR) for dose estimation in quartz at different burial temperatures: A simulation study

    International Nuclear Information System (INIS)

    Koul, D.K.; Pagonis, V.; Patil, P.

    2016-01-01

    The single aliquot regenerative protocol (SAR) is a well-established technique for estimating naturally acquired radiation doses in quartz. This simulation work examines the reliability of SAR protocol for samples which experienced different ambient temperatures in nature in the range of −10 to 40 °C. The contribution of various experimental variables used in SAR protocols to the accuracy and precision of the method is simulated for different ambient temperatures. Specifically the effects of paleo-dose, test dose, pre-heating temperature and cut-heat temperature on the accuracy of equivalent dose (ED) estimation are simulated by using random combinations of the concentrations of traps and centers using a previously published comprehensive quartz model. The findings suggest that the ambient temperature has a significant bearing on the reliability of natural dose estimation using SAR protocol, especially for ambient temperatures above 0 °C. The main source of these inaccuracies seems to be thermal sensitization of the quartz samples caused by the well-known thermal transfer of holes between luminescence centers in quartz. The simulations suggest that most of this inaccuracy in the dose estimation can be removed by delivering the laboratory doses in pulses (pulsed irradiation procedures). - Highlights: • Ambient temperatures affect the reliability of SAR. • It overestimates the dose with increase in burial temperature and burial time periods. • Elevated temperature irradiation does not correct for these overestimations. • Inaccuracies in dose estimation can be removed by incorporating pulsed irradiation procedures.

  19. A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Salah H. Al Janaby

    2017-02-01

    Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

  20. [Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

    Science.gov (United States)

    Martín, M; Díaz-Rubio, E

    1989-06-10

    Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

  1. Ultra-low dose abdominal MDCT: Using a knowledge-based Iterative Model Reconstruction technique for substantial dose reduction in a prospective clinical study

    International Nuclear Information System (INIS)

    Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmangulu, Ali; Padole, Atul; Do, Synho; Brown, Kevin; Thompson, Richard; Morton, Thomas; Raihani, Nilgoun; Koehler, Thomas; Kalra, Mannudeep K.

    2015-01-01

    Highlights: • Limited abdominal CT indications can be performed at a size specific dose estimate of (SSDE) 1.5 mGy (∼0.9 mSv) in smaller patients (BMI less than or equal to 25 kg/m 2 ) using a knowledge based Iterative Model Reconstruction (IMR) technique. • Evaluation of liver tumors and pathologies is unacceptable at this reduced dose with IMR technique especially in patients with a BMI greater than 25 kg/m 2 . • IMR body soft tissue and routine settings perform substantially better than IMR sharp plus setting in reduced dose CT images. • At SSDE of 1.5 mGy, objective image noise in reduced dose IMR images is 8–56% less than compared to standard dose FBP images, with lowest image noise in IMR body-soft tissue images. - Abstract: Purpose: To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. Materials and methods: This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 ± 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy ± 0.4 [∼0.9 mSv] at 120 kV with 17–20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy ± 3 [∼6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1 = image quality better than SD CT to 5 = image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves to

  2. Ultra-low dose abdominal MDCT: Using a knowledge-based Iterative Model Reconstruction technique for substantial dose reduction in a prospective clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Khawaja, Ranish Deedar Ali, E-mail: rkhawaja@mgh.harvard.edu [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Singh, Sarabjeet; Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmangulu, Ali; Padole, Atul; Do, Synho [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Brown, Kevin; Thompson, Richard; Morton, Thomas; Raihani, Nilgoun [CT Research and Advanced Development, Philips Healthcare, Cleveland, OH (United States); Koehler, Thomas [Philips Technologie GmbH, Innovative Technologies, Hamburg (Germany); Kalra, Mannudeep K. [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2015-01-15

    Highlights: • Limited abdominal CT indications can be performed at a size specific dose estimate of (SSDE) 1.5 mGy (∼0.9 mSv) in smaller patients (BMI less than or equal to 25 kg/m{sup 2}) using a knowledge based Iterative Model Reconstruction (IMR) technique. • Evaluation of liver tumors and pathologies is unacceptable at this reduced dose with IMR technique especially in patients with a BMI greater than 25 kg/m{sup 2}. • IMR body soft tissue and routine settings perform substantially better than IMR sharp plus setting in reduced dose CT images. • At SSDE of 1.5 mGy, objective image noise in reduced dose IMR images is 8–56% less than compared to standard dose FBP images, with lowest image noise in IMR body-soft tissue images. - Abstract: Purpose: To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. Materials and methods: This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 ± 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy ± 0.4 [∼0.9 mSv] at 120 kV with 17–20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy ± 3 [∼6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1 = image quality better than SD CT to 5 = image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves

  3. The effect of continuous low dose methylprednisolone infusion on inflammatory parameters in patients undergoing coronary artery bypass graft surgery: a randomized-controlled clinical trial.

    Directory of Open Access Journals (Sweden)

    Abbas Ghiasi

    2015-02-01

    Full Text Available This trial was performed to determine if a continuous low-dose infusion of methylprednisolone is as effective as its bolus of high-dose in reducing inflammatory response. The study was single-center, double-blinded randomized clinical trial and performed in a surgical intensive care unit of an academic hospital. In this study, 72 consecutive patients undergoing elective coronary artery bypass grafting (CABG were assigned to receive either a methylprednisolone loading dose (1mg/kg followed by continuous infusion (2mg/Kg/24 hours for 1 day (low-dose regime or a single dose of methylprednisolone (15 mg/kg before cardiopulmonary bypass (high dose regime. Serum concentrations of IL-6 and C- reactive protein (CRP were measured preoperatively and 6, 24 and 48 hours after surgery, and serum creatinine was measured before the operation and 24, 48 and 72 hours postoperatively. The measurements were then compared between the groups to evaluate the efficacy of each regimen. The basic characteristics and measurements were not different between the study groups. There was no significant difference in IL-6 and CRP elevation (P=0.52 and P=0.46, respectively. Early outcomes such as the length of stay in the intensive care unit, intubation time, changes in serum creatinine and blood glucose levels, inotropic support, insulin requirements, and rate of infection were also similar in both groups. A continuous low dose infusion of methylprednisolone was as effective as a single high dose methylprednisolone in reducing the inflammatory response after CABG with extracorporeal circulation with no significant difference in the postoperative measurements and outcomes.

  4. Simulating threshold voltage shift of MOS devices due to radiation in the low-dose range

    CERN Document Server

    Wan Xin Heng; Gao Wen Yu; Huang Ru; Wang Yang Yuan

    2002-01-01

    An analytical MOSFET threshold voltage shift model due to radiation in the low-dose range has been developed for circuit simulations. Experimental data in the literature shows that the model predictions are in good agreement. It is simple in functional form and hence computationally efficient. It can be used as a basic circuit simulation tool for analysing MOSFET exposed to a nuclear environment up to about 1 Mrad(Si). In accordance with common believe, radiation induced absolute change of threshold voltage was found to be larger in irradiated PMOS devices. However, if the radiation sensitivity is defined in the way authors did it, the results indicated NMOS rather than PMOS devices are more sensitive, specially at low doses. This is important from the standpoint of their possible application in dosimetry

  5. A model for dose estimation in therapy of liver with intraarterial microspheres

    International Nuclear Information System (INIS)

    Zavgorodni, S.F.

    1996-01-01

    Therapy with intraarterial microspheres is a technique which involves incorporation of radioisotope-labelled microspheres into a capillary bed of tumour and normal tissue. Beta-emitters such as 90 Y and 166 Ho are used for this purpose. This technique provides tumour to normal tissue (TNT) dose ratios in the range of 2-10 and demonstrates significant clinical benefit, which could potentially be increased with more accurate dose predictions and delivery. However, dose calculations in this modality face the difficulties associated with nonuniform and inhomogeneous activity distribution. Most of the dose calculations used clinically do not account for the nonuniformity and assume uniform activity distribution. This paper is devoted to the development of a model which would allow more accurate prediction of dose distributions from microspheres. The model calculates dose assuming that microspheres are aggregated into randomly distributed clusters, and using precomputed dose kernels for the clusters. The dose kernel due to a microsphere cluster was found by numerical integration of a point source dose kernel over the volume of the cluster. It is shown that a random distribution of clusters produces an intercluster distance distribution which agrees well with the one measured by Pillai et al in liver. Dose volume histograms (DVHs) predicted by the model agree closely with the results of Roberson et al for normal tissue and tumour. Dose distributions for different concentrations and types of radioisotope, as well as for tumours of different radii, have been calculated to demonstrate the model's possible applications. (author)

  6. Estimation of Electron Dose Delivered by a 0.4 MeV Accelerator from Bremsstrahlung Dose Measurements

    DEFF Research Database (Denmark)

    Karadjov, A. G.; Hansen, Jørgen-Walther

    1980-01-01

    Determination of a 0.4 MeV electron dose from a bremsstrahlung dose measurement using a converter-detector system is considered. The detector used is a Frickle dosimeter, and the converters are aluminum, copper and lead foils. Optimal converter thickness is ascertained experimentally for each mat...... materials within a Z-range of 13–82. A linear relation is found between bremsstrahlung dose and electron dose ranging from 2 to 20 Mrad. Finally the effect of converter area on detector response is studied....

  7. Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset following spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study.

    Science.gov (United States)

    Roth, Thomas; Krystal, Andrew; Steinberg, Frank J; Singh, Nikhilesh N; Moline, Margaret

    2013-02-01

    To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the-night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings. Multicenter randomized, double-blind, placebo-controlled, parallel-group. Outpatient. There were 295 adults (median age 43 y; 68.1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTN awakenings/wk during screening). After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as-needed MOTN dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures. ZST significantly (P Zolpidem Tartrate Tablet in Adult Patients with Insomnia" http://www.clinicaltrials.gov/ct2/show/NCT00466193?spons=%22Transcept+Pharmaceuticals%22&spons_ex=Y&rank=2

  8. Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise - a randomized controlled trial in overweight sedentary males

    DEFF Research Database (Denmark)

    Larsen, Mads Rosenkilde; Auerbach, Pernille Landrock; Reichkendler, Michala Holm

    2012-01-01

    The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g. lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise...... is limited. A randomized controlled trial was performed in healthy sedentary moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition, accumulated energy balance, and the degree of compensation. Eighteen participants were randomized to a continuous...... sedentary control group, 21 to a moderate (MOD; 300 kcal/day) and 22 to a high dose (HIGH; 600 kcal/day) exercise group for 13 weeks, corresponding to approximately 30 and 60 minutes of daily aerobic exercise, respectively. Body weight (MOD: -3.6kg, P...

  9. Gabapentin in traumatic nerve injury pain: A randomized, double-blind, placebo-controlled, cross-over, multi-center study

    DEFF Research Database (Denmark)

    Gordh, Torsten E; Stubhaug, Audun; Jensen, Troels S

    2008-01-01

    A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400mg/day. The study comprised a run...

  10. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.

    Science.gov (United States)

    Thaçi, Diamant; Simpson, Eric L; Beck, Lisa A; Bieber, Thomas; Blauvelt, Andrew; Papp, Kim; Soong, Weily; Worm, Margitta; Szepietowski, Jacek C; Sofen, Howard; Kawashima, Makoto; Wu, Richard; Weinstein, Steven P; Graham, Neil M H; Pirozzi, Gianluca; Teper, Ariel; Sutherland, E Rand; Mastey, Vera; Stahl, Neil; Yancopoulos, George D; Ardeleanu, Marius

    2016-01-02

    Data from early-stage studies suggested that interleukin (IL)-4 and IL-13 are requisite drivers of atopic dermatitis, evidenced by marked improvement after treatment with dupilumab, a fully-human monoclonal antibody that blocks both pathways. We aimed to assess the efficacy and safety of several dose regimens of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments. In this randomised, placebo-controlled, double-blind study, we enrolled patients aged 18 years or older who had an Eczema Area and Severity Index (EASI) score of 12 or higher at screening (≥16 at baseline) and inadequate response to topical treatments from 91 study centres, including hospitals, clinics, and academic institutions, in Canada, Czech Republic, Germany, Hungary, Japan, Poland, and the USA. Patients were randomly assigned (1:1:1:1:1:1), stratified by severity (moderate or severe, as assessed by Investigator's Global Assessment) and region (Japan vs rest of world) to receive subcutaneous dupilumab: 300 mg once a week, 300 mg every 2 weeks, 200 mg every 2 weeks, 300 mg every 4 weeks, 100 mg every 4 weeks, or placebo once a week for 16 weeks. We used a central randomisation scheme, provided by an interactive voice response system. Drug kits were coded, providing masking to treatment assignment, and allocation was concealed. Patients on treatment every 2 weeks and every 4 weeks received volume-matched placebo every week when dupilumab was not given to ensure double blinding. The primary outcome was efficacy of dupilumab dose regimens based on EASI score least-squares mean percentage change (SE) from baseline to week 16. Analyses included all randomly assigned patients who received one or more doses of study drug. This trial is registered with ClinicalTrials.gov, number NCT01859988. Between May 15, 2013, and Jan 27, 2014, 452 patients were assessed for eligibility, and 380 patients were randomly assigned. 379 patients received one or more

  11. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

    2016-07-01

    It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

    Science.gov (United States)

    Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

    2015-03-01

    Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

  13. Reducing the sensitivity of IMPT treatment plans to setup errors and range uncertainties via probabilistic treatment planning

    International Nuclear Information System (INIS)

    Unkelbach, Jan; Bortfeld, Thomas; Martin, Benjamin C.; Soukup, Martin

    2009-01-01

    Treatment plans optimized for intensity modulated proton therapy (IMPT) may be very sensitive to setup errors and range uncertainties. If these errors are not accounted for during treatment planning, the dose distribution realized in the patient may by strongly degraded compared to the planned dose distribution. The authors implemented the probabilistic approach to incorporate uncertainties directly into the optimization of an intensity modulated treatment plan. Following this approach, the dose distribution depends on a set of random variables which parameterize the uncertainty, as does the objective function used to optimize the treatment plan. The authors optimize the expected value of the objective function. They investigate IMPT treatment planning regarding range uncertainties and setup errors. They demonstrate that incorporating these uncertainties into the optimization yields qualitatively different treatment plans compared to conventional plans which do not account for uncertainty. The sensitivity of an IMPT plan depends on the dose contributions of individual beam directions. Roughly speaking, steep dose gradients in beam direction make treatment plans sensitive to range errors. Steep lateral dose gradients make plans sensitive to setup errors. More robust treatment plans are obtained by redistributing dose among different beam directions. This can be achieved by the probabilistic approach. In contrast, the safety margin approach as widely applied in photon therapy fails in IMPT and is neither suitable for handling range variations nor setup errors.

  14. Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

    Directory of Open Access Journals (Sweden)

    Olivia Taylor

    Full Text Available Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

  15. Estimation of the optimal dosing regimen of escitalopram in dogs: A dose occupancy study with [11C]DASB.

    Science.gov (United States)

    Taylor, Olivia; Van Laeken, Nick; Polis, Ingeborgh; Dockx, Robrecht; Vlerick, Lise; Dobbeleir, Andre; Goethals, Ingeborg; Saunders, Jimmy; Sadones, Nele; Baeken, Chris; De Vos, Filip; Peremans, Kathelijne

    2017-01-01

    Although the favourable characteristics of escitalopram as being the most selective serotonin reuptake inhibitor and having an increased therapeutic efficacy via binding on an additional allosteric binding site of the serotonin transporter, its dosing regimen has not yet been optimized for its use in dogs. This study aimed to estimate the optimal dosing frequency and the required dose for achieving 80% occupancy of the serotonin transporters in the basal ganglia. The dosing frequency was investigated by determining the elimination half-life after a four day oral pre-treatment period with 0.83 mg/kg escitalopram (3 administrations/day) and a subsequent i.v. injection 0.83 mg/kg. Blood samples were taken up to 12 hours after i.v. injection and the concentration of escitalopram in plasma was analysed via LC-MSMS. The dose-occupancy relationship was then determined by performing two PET scans in five adult beagles: a baseline PET scan and a second scan after steady state conditions were achieved following oral treatment with a specific dose of escitalopram ranging from 0.5 to 2.5 mg/kg/day. As the elimination half-life was determined to be 6.7 hours a dosing frequency of three administrations a day was proposed for the second part of the study. Further it was opted for a treatment period of four days, which well exceeded the minimum period to achieve steady state conditions. The optimal dosing regimen to achieve 80% occupancy in the basal ganglia and elicit a therapeutic effect, was calculated to be 1.85 mg/kg/day, divided over three administrations. Under several circumstances, such as insufficient response to other SSRIs, concurrent drug intake or in research studies focused on SERT, the use of escitalopram can be preferred over the use of the already for veterinary use registered fluoxetine, however, in case of long-term treatment with escitalopram, regularly cardiac screening is recommended.

  16. A study of gonad doses in X-ray radiographic examinations of the abdomen

    International Nuclear Information System (INIS)

    Brown, L.D.

    1980-01-01

    A phantom study has been made in an attempt to redetermine gonad dose associated with routine X-ray diagnostic procedures. Over a range of voltages between 60 kVp and 130 kVp, TLD measurements of skin, ovary, a standardised cassette dose of 1 mrad, and testicle doses were obtained for AP, PA and lateral radiographs. Whilst exact numerical results depended greatly on the characteristics of the film-screen combination used, the contrast required in the final radiograph and the efficiency of the Bucky grid, results of this redetermination did not support the view that a reduction in population genetic dose would follow any general increase in the typical operating potential used for abdominal x-ray examinations. (U.K.)

  17. Standard effective doses for proliferative tumours

    International Nuclear Information System (INIS)

    Jones, L.C.; Hoban, P.

    1999-01-01

    This study was undertaken to investigate the treatment schedules used clinically for highly proliferative tumours, particularly with reference to the effects of fraction size, fraction number and treatment duration. The linear quadratic model (with time component) is used here to compare non-standard treatment regimens (e.g. accelerated and hyperfractionated schedules), currently the focus of randomized trials, with each other and some common 'standard regimens'. To ensure easy interpretation of results, two parameters known as proliferative standard effective dose one (PSED 1 ) and proliferative standard effective dose two (PSED 2 ) have been calculated for each regimen. Graphs of PSED 1 and PSED 2 versus potential doubling time (T p ) have been generated for a range of fractionation regimens which are currently under trial in various randomized studies. From these graphs it can be seen that the highly accelerated schedules (such as CHART) only show advantages for tumours with very short potential doubling times. Calculations for most of the schedules considered showed at least equivalent tumour control expected for the trial schedule compared with the control arm used and these values agree quite well with clinical results. These calculations are in good agreement with clinical results available at present. The greater the PSED 1 or PSED 2 for the schedule considered the greater the tumour control, which can be expected. However, as has been seen with clinical trials, this higher cell kill also results in higher acute effects which have proved too great for some accelerated schedules to continue. (author)

  18. A randomized, non-inferiority study comparing efficacy and safety of a single dose of pegfilgrastim versus daily filgrastim in pediatric patients after autologous peripheral blood stem cell transplant.

    Directory of Open Access Journals (Sweden)

    Simone Cesaro

    Full Text Available PURPOSE: To assess the non-inferiority of pegfilgrastim versus filgrastim in speeding the recovery of polymorphonuclear cells (PMN in pediatric patients who underwent autologous peripheral blood stem cell transplant (PBSCT. METHODS: The sample size of this randomized, multicenter, phase III study, was calculated assuming that a single dose of pegfilgrastim of 100 ug/kg was not inferior to 9 doses of filgrastim of 5 ug/kg/day. Randomization was performed by a computer-generated list and stored by sequentially numbered sealed envelopes. RESULTS: Sixty-one patients, with a median age of 11.5 years, were recruited: 29 in the filgrastim arm and 32 in the pegfilgrastim arm. Twenty percent were affected by lymphoma/leukaemia and eighty percent by solid tumors. The mean time to PMN engraftment was 10.48 days (standard deviation [SD] 1.57 and 10.44 days (SD 2.44 in the filgrastim and pegfilgrastim arms, respectively. Having fixed a non-inferiority margin Delta of 3, the primary endpoint of non-inferiority was reached. No differences were observed for other secondary endpoints: platelet engraftment, mean time to platelet recovery (28 days vs. 33 days, fever of unknown origin (79% vs. 78%, proven infection (34% vs. 28%, mucositis (76% vs. 59%. After a median follow-up of 2.3 years (95% C.I.: 1.5, 3.3, 20 deaths were observed due to disease progression. CONCLUSIONS: We conclude that pegfilgrastim was not inferior to daily filgrastim in pediatric patients who underwent PBSCT. EU CLINICAL TRIAL REGISTER NUMBER: 2007-001430-14.

  19. Efficacy of Albis for the Prevention of Gastric Mucosal Injury Concomitant with the Use of Low-Dose Aspirin: A Prospective, Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Sang Gyun Kim

    2017-03-01

    Full Text Available Background/Aims Long-term use of aspirin can be a risk factor of peptic ulcer diseases. The aim of this study was to evaluate the efficacy of Albis (Daewoong Pharmaceutical Co., Ltd. for the prevention of gastric mucosal injury caused by aspirin. Methods Aspirin users were enrolled and randomized into the Albis or placebo group. Screening and follow-up endoscopy were performed for modified Lanza scores (MLSs. Primary outcome was measured by the incidence rate of peptic ulcer, and secondary outcomes were measured by the incidence rate of gastritis, improvement in MLS and subjective symptoms. Results In total, 81 aspirin users were randomized, 43 in the Albis group and 38 in the placebo group. There was no incidence of peptic ulcer in both groups. The incidence of gastritis was significantly higher in the placebo group (44.4% vs. 10.0%, p=0.003; however, the scores of mucosal edema, hyperemia and hemorrhage were not statistically different between the two groups (p>0.05. The frequency of subjective symptoms were more improved in the Albis group than in the placebo group (p=0.023. Conclusions The incidence of gastritis was lower in the group that received low-dose aspirin and Albis. The development of peptic ulcer due to long-term use of aspirin might be prevented with concomitant use of Albis.

  20. Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

    Science.gov (United States)

    Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

    2017-04-01

    A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

  1. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

    Science.gov (United States)

    Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

    2016-01-01

    Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

  2. Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Mojtaba Shafiekhani

    2016-08-01

    Full Text Available Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l, epinephrine (20 μmol/l, collagen(0.19 mg/ ml and arachidonic acid (0.5mg/ ml was measured by Light Transmittance Aggregometry (LTA in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding. No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method.

  3. Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study.

    Science.gov (United States)

    Zegels, B; Crozes, P; Uebelhart, D; Bruyère, O; Reginster, J Y

    2013-01-01

    Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (security and tolerability was observed between the three groups. This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  4. Low-dose ketamine infusion for labor analgesia: A double-blind, randomized, placebo controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Sam Joel

    2014-01-01

    Full Text Available Background: Most primary and secondary level hospitals in developing countries provide inadequate labor analgesia due to various medical, technical and economic reasons. This clinical trial was an effort to study the efficacy, safety and feasibility of intravenous (IV ketamine to provide labor analgesia. Materials and Methods: A total of 70 parturients were consented and randomly assigned to receive either IV ketamine or 0.9% saline. A loading dose of ketamine (0.2 mg/kg was followed-by an infusion (0.2 mg/kg/h until the delivery of the neonate. Similar volume of saline was infused in the placebo-group. Intramuscular meperidine was the rescue analgesic in both groups. The pain score, hemodynamic parameters of mother and fetus and the anticipated side-effects of ketamine were observed for. The newborn was assessed by the Neonatologist. Results: The pain score showed a decreasing trend in the ketamine group and after the 1 st h more than 60% of women in the ketamine group had pain relief, which was statistically significant. There was no significant clinical change in the maternal hemodynamics and fetal heart rate. However, 17 (48.5% of them had transient light headedness in the ketamine group. All the neonates were breast fed and the umbilical cord blood pH was between 7.1 and 7.2. The overall satisfaction was significantly high in the intervention group (P = 0.028. Conclusion: A low-dose ketamine infusion (loading dose of 0.2 mg/kg delivered over 30 min, followed-by an infusion at 0.2 mg/kg/h could provide acceptable analgesia during labor and delivery.

  5. [Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

    Science.gov (United States)

    Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

    2011-12-27

    To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

  6. Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Bria M.; Brady, Samuel L., E-mail: samuel.brady@stjude.org; Kaufman, Robert A. [Department of Radiological Sciences, St Jude Children' s Research Hospital, Memphis, Tennessee 38105 (United States); Mirro, Amy E. [Department of Biomedical Engineering, Washington University, St Louis, Missouri 63130 (United States)

    2014-07-15

    Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (CF{sub SSDE}{sup organ}) were then multiplied by patient-specific SSDE to estimate patient organ dose. The CF{sub SSDE}{sup organ} were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. IndividualCF{sub SSDE}{sup organ} were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and CF{sub SSDE}{sup organ}, was compared to

  7. Role of signal dose preoperative antibiotic in acute nonperforated appendicitics

    International Nuclear Information System (INIS)

    Malik, S.A.; Rasheed, M.; Abbasi, A.S.; Iqbal, R.A.; Mian, M.A.

    2013-01-01

    Objective: To determine the efficacy of a single dose of preoperative antibiotic in preventing post operative infective complications in patients undergoing appendicectomy for non perforated acute appendicitis. Study Design: Randomized controlled trials. Place and Duration of Study: Surgical unit I and II, department of General Surgery, Combined Military Hospital (CMH) Lahore from 1st June to 31st October 2010. Patients and Methods: Seventy patients with acute appendicitis scheduled for appendicectomy were included in the study and randomly divided into two groups of 35 each using random numbers table. Group A received single dose preoperative antibiotic and group B received three-dose regimens of cefuroxime. Postoperative infective complications were the primary endpoint. Results: The rate of postoperative wound infection was not statistically insignificantly different among the groups; (8.57%) group A and (5.71%) group B at 1st post operative week and (5.71%) group A and (5.71%) group B at 2nd post operative week. None of the patients from either group showed any signs of intra abdominal abscess formation. Conclusion: Single dose of preoperative antibiotics is adequate for prevention of postoperative infective complications in patients with non-perforated appendicitis undergoing open appendicectomy. (author)

  8. Bitemporal v. high-dose right unilateral electroconvulsive therapy for depression: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kolshus, E; Jelovac, A; McLoughlin, D M

    2017-02-01

    Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0-2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate. We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms 'electroconvulsive' OR 'electroshock' AND 'trial'. Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = -0.03, 95% confidence interval (CI) -0.17 to 0.11], remission (RR 1.06, 95% CI 0.93-1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90-2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = -8.28, 95% CI -12.86 to -3.70) and retrograde autobiographical memory (Hedges's g = -0.46, 95% CI -0.87 to -0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory. High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

  9. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

    Science.gov (United States)

    Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

    2018-03-01

    There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

  10. Extending the dose range: Probing deep traps in quartz with 3.06 eV photons

    DEFF Research Database (Denmark)

    Jain, Mayank

    2009-01-01

    stimulation. Although, the fast OSL component is measured with similar efficiency by blue and violet lights, the slower OSL components (especially S3) are measured relatively more efficiently with the latter. New insight into the origins of quartz luminescence is presented through a comparison of violet......This article demonstrates that violet (405 nm) stimulated luminescence (VSL) signal from quartz contains contribution from deep traps that are otherwise not accessible with blue light (470 nm). Additionally, it also contains the typical fast and slow components observed with the blue light...... and blue lights stimulation, and thermal stimulations. Finally, it is shown that the deep traps probed through violet light stimulation have potential for increasing the dose measurement/dating range using quartz. The post-blue VSL signal allows easy, precise measurement of dose up to at least 1 kGy in our...

  11. Dose profile study in head CT scans using radiochromic films

    International Nuclear Information System (INIS)

    Ladino G, A. M.; Prata M, A.

    2016-10-01

    Diagnostic images of computed tomography generate higher doses than other methods of diagnostic radiology using X-ray beam attenuation. Clinical applications of CT have been increased by technological advances, what leads to a wide variety of scanner in the Brazilian technological pool. It has been difficult to implement dose reduction strategies because of the lack of proper guidance on computed tomography examinations. However, CT scanners allow adjusting acquisition parameter according to the patients physical profile and diagnostic application for which the scan is intended. The knowledge of the dose distribution is important because changes in image acquisition parameters may provide dose reduction. In this study, it was used a cylindrical head phantom in PMMA with 5 openings, what allows dose measurement in 5 regions. In a GE CT scanner, Discovery model of 64 channels, the central slice of the head phantom was irradiated and the absorbed doses were measured using a pencil ionization chamber. Radiochromic film strips were placed in the peripheral and in the central region of the head phantom and was performed a scan of 10 cm in the phantom central region. The scan was performed using the head scanning protocol of the radiobiology service, with a voltage of 120 kV. After scanning, the radiochromic film strips were digitalized and their digital images were used to have the dose longitudinal profiles. The dose values recorded have variation in a range of 18.66 to 23.57 mGy. In the results it was compared the dose index values obtained by the pencil chamber measurement to the dose longitudinal profiles recorded by the film strips. (Author)

  12. Dose profile study in head CT scans using radiochromic films

    Energy Technology Data Exchange (ETDEWEB)

    Ladino G, A. M.; Prata M, A., E-mail: amlgphys@gmail.com [Universidade Federal de Minas Gerais, Departamento de Engenharia Nuclear, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2016-10-15

    Diagnostic images of computed tomography generate higher doses than other methods of diagnostic radiology using X-ray beam attenuation. Clinical applications of CT have been increased by technological advances, what leads to a wide variety of scanner in the Brazilian technological pool. It has been difficult to implement dose reduction strategies because of the lack of proper guidance on computed tomography examinations. However, CT scanners allow adjusting acquisition parameter according to the patients physical profile and diagnostic application for which the scan is intended. The knowledge of the dose distribution is important because changes in image acquisition parameters may provide dose reduction. In this study, it was used a cylindrical head phantom in PMMA with 5 openings, what allows dose measurement in 5 regions. In a GE CT scanner, Discovery model of 64 channels, the central slice of the head phantom was irradiated and the absorbed doses were measured using a pencil ionization chamber. Radiochromic film strips were placed in the peripheral and in the central region of the head phantom and was performed a scan of 10 cm in the phantom central region. The scan was performed using the head scanning protocol of the radiobiology service, with a voltage of 120 kV. After scanning, the radiochromic film strips were digitalized and their digital images were used to have the dose longitudinal profiles. The dose values recorded have variation in a range of 18.66 to 23.57 mGy. In the results it was compared the dose index values obtained by the pencil chamber measurement to the dose longitudinal profiles recorded by the film strips. (Author)

  13. The effect of increasing doses of saw palmetto fruit extract on serum prostate specific antigen: analysis of the CAMUS randomized trial.

    Science.gov (United States)

    Andriole, Gerald L; McCullum-Hill, Christie; Sandhu, Gurdarshan S; Crawford, E David; Barry, Michael J; Cantor, Alan

    2013-02-01

    Saw palmetto extracts are used to treat lower urinary tract symptoms in men despite level I evidence that saw palmetto is ineffective in reducing these lower urinary tract symptoms. We determined whether higher doses of saw palmetto as studied in the CAMUS (Complementary and Alternative Medicine for Urologic Symptoms) trial affect serum prostate specific antigen levels. The CAMUS trial was a randomized, placebo controlled, double-blind, multicenter, North American trial conducted between June 5, 2008 and October 10, 2012, in which 369 men older than 45 years with an AUA symptom score of 8 to 24 were randomly assigned to placebo or dose escalation of saw palmetto, which consisted of 320 mg for the first 24 weeks, 640 mg for the next 24 weeks and 960 mg for the last 24 weeks of this 72-week trial. Serum prostate specific antigen levels were obtained at baseline and at weeks 24, 48 and 72, and were compared between treatment groups using the pooled t test and Fisher's exact test. Serum prostate specific antigen was similar at baseline for the placebo (mean ± SD 1.93 ± 1.59 ng/ml) and saw palmetto groups (2.20 ± 1.95, p = 0.16). Changes in prostate specific antigen during the study were similar, with a mean change in the placebo group of 0.16 ± 1.08 ng/ml and 0.23 ± 0.83 ng/ml in the saw palmetto group (p = 0.50). In addition, no differential effect on serum prostate specific antigen was observed between treatment arms when the groups were stratified by baseline prostate specific antigen. Saw palmetto extract does not affect serum prostate specific antigen more than placebo, even at relatively high doses. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

    OpenAIRE

    Quintana, D S; Westlye, L T; Hope, S; N?rland, T; Elvs?shagen, T; D?rum, E; Rustan, ?; Valstad, M; Rezvaya, L; Lishaugen, H; Stens?nes, E; Yaqub, S; Smerud, K T; Mahmoud, R A; Djupesland, P G

    2017-01-01

    The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin?s dose?response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequ...

  15. Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

    Science.gov (United States)

    Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

    2017-09-26

    Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0

  16. /sup 210/Po in marine organisms: a wide range of natural radiation dose domains

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, F P

    1988-01-01

    Marine biota is able to concentrate /sup 210/Po to high levels, as 10/sup 3/-10/sup 5/ relative to sea water concentration. /sup 210/Po concentrations in mixed zooplankton reaches 34-51 Bq.kg/sup -1/ (fresh wt), special groups such as copepods reaching even higher concentrations /similar to/ 90 Bq.kg/sup -1/, whereas gelatinous zooplankton display /similar to/ 1 Bq.kg/sup -1/. Epipelagic teleosts feeding on plankton displayed the highest concentrations found in fish muscle, 2-21 Bq.kg/sup -1/. Contrasting with this, demersal teleosts and elasmobranchs display lower /sup 210/Po concentrations, in the ranges 0.5-7 Bq.kg/sup -1/ and 0.2-1.7 Bq.kg/sup -1/, respectively. Much higher concentrations can, however, be measured in fish liver, gonad, bone and piloric caecca, and small mesopelagic fish can reach /similar to/ 800 Bq.kg/sup -1/ on a whole-body basis. Due to these /sup 210/Po activity concentrations, dose equivalent rates delivered to biological tissues in marine organisms can vary widely, from 0.4 mSv.y/sup -1/ in gelatinous plankton up to 5.6 x 10/sup 3/ mSv.y/sup -1/ in the gut wall of sardines. It is concluded that in organisms living in the same ocean layer a wide range of internal radiation doses exists and it is essentially sustained by /sup 210/Po food-chain transfer. (author).

  17. Efficacy comparison of duloxetine and SSRIs at doses approved in Japan

    Directory of Open Access Journals (Sweden)

    Harada E

    2015-01-01

    Full Text Available Eiji Harada,1 Alexander Schacht,2 Tsukasa Koyama,3 Lauren Marangell,4,5 Toshinaga Tsuji,6 Rodrigo Escobar41Medical Science, Eli Lilly Japan K.K, Kobe, Japan; 2Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany; 3Clinical Research Center, Ohyachi Hospital, Sapporo, Japan; 4Eli Lilly and Company, Indianapolis, IN, 5The University of Texas Health Science Center, Houston, TX, USA; 6Medical Affairs, Shionogi & Co Ltd, Osaka, JapanBackground: Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs at the doses approved in Japan.Methods: Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40–60 mg/day with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316. The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17 total and subscale scores.Results: Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19. Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]: all-randomized group, −0.33 [−0.60, −0.07], P=0.015; severe subgroup,

  18. Monte Carlo studies of two-dimensional random-anisotropy magnets

    Science.gov (United States)

    Denholm, D. R.; Sluckin, T. J.

    1993-07-01

    We have carried out a systematic set of Monte Carlo simulations of the Harris-Plischke-Zuckermann lattice model of random magnetic anisotropy on a two-dimensional square lattice, using the classical Metropolis algorithm. We have considered varying temperature T, external magnetic field H (both in the reproducible and irreproducible limits), time scale of the simulation τ in Monte Carlo steps and anisotropy ratio D/J. In the absence of randomness this model reduces to the XY model in two dimensions, which possesses the familiar Kosterlitz-Thouless low-temperature phase with algebraic but no long-range order. In the presence of random anisotropy we find evidence of a low-temperature phase with some disordered features, which might be identified with a spin-glass phase. The low-temperature Kosterlitz-Thouless phase survives at intermediate temperatures for low randomness, but is no longer present for large D/J. We have also studied the high-H approach to perfect order, for which there are theoretical predictions due to Chudnovsky.

  19. Alanine-EPR dosimetry for measurements of ionizing radiation absorbed doses in the range 0.5-10 kGy

    CERN Document Server

    Peimel-Stuglik, Z

    2001-01-01

    The usefulness of two, easy accessible alanine dosimeters (ALANPOL from IChTJ and foil dosimeter from Gamma Service, Radeberg, Germany) to radiation dose measurement in the range of 0.5-10 kGy, were investigated. In both cases, the result of the test was positive. The foil dosemeter from Gamma Service is recommended for dose distribution measurements in fantoms or products, ALANPOL - for routine measurements. The EPR-alanine method based on the described dosimeters can be successfully used, among others, in the technology of radiation protection of food.

  20. Study of effective dose of various protocols in equipment cone beam CT

    International Nuclear Information System (INIS)

    Soares, M. R.; Maia, A. F.; Batista, W. O.; Caldas, L. V. E.; Lara, P. A.

    2014-08-01

    Currently the cone beam computed tomography is widely used in various procedures of dental radiology. Although the doses values associated with the procedures of cone beam CT are low compared to typical values associated with dental radiology procedure in multi slices CT. However can be high compared to typical values of other techniques commonly used in dental radiology. The present scenario is a very wide range of designs of equipment and, consequently, lack of uniformity in all parameters associated with x-ray generation and geometry. In this context, this study aimed to evaluate and calculate the absorbed dose in organs and tissues relevant and estimate effective dose for different protocols with different geometries of exposure in five cone beam CT equipment. For this, a female Alderson anthropomorphic phantom, manufactured by Radiology Support Devices was used. The phantom was irradiated with 26 dosimeters LiF: Mg, Ti (TLD-100), inserted in organs and tissues along the layers forming the head and neck of the phantom. The equipment used, in this present assessment, was: i-CAT Classical, Kodak 9000 3D, Gendex GXCB 500, Sirona Orthophos X G 3D and Planmeca Pro Max 3D. The effective doses were be determined by the ICRP 103 weighting factors. The values were between 7.0 and 111.5 micro Sv, confirming the broad dose range expected due to the diversity of equipment and protocols used in each equipment. The values of effective dose per Fov size were: between 7 and 51.2 micro Sv for located Fov; between 17.6 and 52.0 micro Sv for medium Fov; and between 11.5 and 43.1 micro Sv to large Fov (maxillofacial). In obtaining the effective dose the measurements highlighted a relevance contribution of dose absorbed by the remaining organs (36%), Salivary glands (30%), thyroid (12%) and bone marrow (12%). (Author)

  1. Study of effective dose of various protocols in equipment cone beam CT

    Energy Technology Data Exchange (ETDEWEB)

    Soares, M. R.; Maia, A. F. [Universidade Federale de Sergipe, Departamento de Fisica, Cidade Universitaria Prof. Jose Aloisio de Campos, Marechal Rondon s/n, Jardim Rosa Elze, 49-100000 Sao Cristovao, Sergipe (Brazil); Batista, W. O. [Instituto Federal da Bahia, Rua Emidio dos Santos s/n, Barbalho, Salvador, 40301015 Bahia (Brazil); Caldas, L. V. E.; Lara, P. A., E-mail: mrs2206@gmail.com [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    Currently the cone beam computed tomography is widely used in various procedures of dental radiology. Although the doses values associated with the procedures of cone beam CT are low compared to typical values associated with dental radiology procedure in multi slices CT. However can be high compared to typical values of other techniques commonly used in dental radiology. The present scenario is a very wide range of designs of equipment and, consequently, lack of uniformity in all parameters associated with x-ray generation and geometry. In this context, this study aimed to evaluate and calculate the absorbed dose in organs and tissues relevant and estimate effective dose for different protocols with different geometries of exposure in five cone beam CT equipment. For this, a female Alderson anthropomorphic phantom, manufactured by Radiology Support Devices was used. The phantom was irradiated with 26 dosimeters LiF: Mg, Ti (TLD-100), inserted in organs and tissues along the layers forming the head and neck of the phantom. The equipment used, in this present assessment, was: i-CAT Classical, Kodak 9000 3D, Gendex GXCB 500, Sirona Orthophos X G 3D and Planmeca Pro Max 3D. The effective doses were be determined by the ICRP 103 weighting factors. The values were between 7.0 and 111.5 micro Sv, confirming the broad dose range expected due to the diversity of equipment and protocols used in each equipment. The values of effective dose per Fov size were: between 7 and 51.2 micro Sv for located Fov; between 17.6 and 52.0 micro Sv for medium Fov; and between 11.5 and 43.1 micro Sv to large Fov (maxillofacial). In obtaining the effective dose the measurements highlighted a relevance contribution of dose absorbed by the remaining organs (36%), Salivary glands (30%), thyroid (12%) and bone marrow (12%). (Author)

  2. Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years

    DEFF Research Database (Denmark)

    Björkman, Sven; Folkesson, Anna; Jönsson, Siv

    2009-01-01

    in the sparse clinical data. Model-predicted doses (based on age and body weight) to maintain a recommended 0.01 U/mL trough level of FVIII with administration on alternate days started at around 60 U/kg in the small children, decreasing to 10 U/kg or less in middle age. However, "true" dose requirements......, as estimated from individual PK parameter data, showed a much greater variation. CONCLUSION: Appropriate dosing of FVIII for prophylactic treatment cannot be calculated only from body weight and/or age. However, plausible starting doses for most patients would be 1,000 U every other day. FVIII levels should...... can be calculated according to patient characteristics, and (3) to present dosing recommendations for initiating prophylactic treatment. METHODS: A population PK model was developed using data from four PK studies on patients aged 7-74 years. The model was tested on sparse FVIII data from 42...

  3. A review of radiology staff doses and dose monitoring requirements

    International Nuclear Information System (INIS)

    Martin, C. J.

    2009-01-01

    Studies of radiation doses received during X-ray procedures by radiology, cardiology and other clinical staff have been reviewed. Data for effective dose (E), and doses to the eyes, thyroid, hands and legs have been analysed. These data have been supplemented with local measurements to determine the most exposed part of the hand for monitoring purposes. There are ranges of 60-100 in doses to individual tissues reported in the literature for similar procedures at different centres. While ranges in the doses per unit dose-area product (DAP) are between 10 and 25, large variations in dose result from differences in the sensitivity of the X-ray equipment, the type of procedure and the operator technique, but protection factors are important in maintaining dose levels as low as possible. The influence of shielding devices is significant for determining the dose to the eyes and thyroid, and the position of the operator, which depends on the procedure, is the most significant factor determining doses to the hands. A second body dosemeter worn at the level of the collar is recommended for operators with high workloads for use in assessment of effective dose and the dose to the eye. It is proposed that the third quartile values from the distributions of dose per unit DAP identified in the review might be employed in predicting the orders of magnitude of doses to the eye, thyroid and hands, based on interventional operator workloads. Such dose estimates could be employed in risk assessments when reviewing protection and monitoring requirements. A dosemeter worn on the little finger of the hand nearest to the X-ray tube is recommended for monitoring the hand. (authors)

  4. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  5. Raman micro-spectroscopy analysis of human lens epithelial cells exposed to a low-dose-range of ionizing radiation

    Science.gov (United States)

    Allen, Christian Harry; Kumar, Achint; Qutob, Sami; Nyiri, Balazs; Chauhan, Vinita; Murugkar, Sangeeta

    2018-01-01

    Recent findings in populations exposed to ionizing radiation (IR) indicate dose-related lens opacification occurs at much lower doses (micro-spectroscopy was used to investigate the effects of varying doses of radiation, ranging from 0.01 Gy to 5 Gy, on human lens epithelial (HLE) cells which were chemically fixed 24 h post-irradiation. Raman spectra were acquired from the nucleus and cytoplasm of the HLE cells. Spectra were collected from points in a 3  ×  3 grid pattern and then averaged. The raw spectra were preprocessed and principal component analysis followed by linear discriminant analysis was used to discriminate between dose and control for 0.25, 0.5, 2, and 5 Gy. Using leave-one-out cross-validation accuracies of greater than 74% were attained for each dose/control combination. The ultra-low doses 0.01 and 0.05 Gy were included in an analysis of band intensities for Raman bands found to be significant in the linear discrimination, and an induced repair model survival curve was fit to a band-difference-ratio plot of this data, suggesting HLE cells undergo a nonlinear response to low-doses of IR. A survival curve was also fit to clonogenic assay data done on the irradiated HLE cells, showing a similar nonlinear response.

  6. Radon Exposure and the Definition of Low Doses-The Problem of Spatial Dose Distribution.

    Science.gov (United States)

    Madas, Balázs G

    2016-07-01

    Investigating the health effects of low doses of ionizing radiation is considered to be one of the most important fields in radiological protection research. Although the definition of low dose given by a dose range seems to be clear, it leaves some open questions. For example, the time frame and the target volume in which absorbed dose is measured have to be defined. While dose rate is considered in the current system of radiological protection, the same cancer risk is associated with all exposures, resulting in a given amount of energy absorbed by a single target cell or distributed among all the target cells of a given organ. However, the biological effects and so the health consequences of these extreme exposure scenarios are unlikely to be the same. Due to the heterogeneous deposition of radon progeny within the lungs, heterogeneous radiation exposure becomes a practical issue in radiological protection. While the macroscopic dose is still within the low dose range, local tissue doses on the order of Grays can be reached in the most exposed parts of the bronchial airways. It can be concluded that progress in low dose research needs not only low dose but also high dose experiments where small parts of a biological sample receive doses on the order of Grays, while the average dose over the whole sample remains low. A narrow interpretation of low dose research might exclude investigations with high relevance to radiological protection. Therefore, studies important to radiological protection should be performed in the frame of low dose research even if the applied doses do not fit in the dose range used for the definition of low doses.

  7. Influence of titration schedule and maintenance dose on the tolerability of adjunctive eslicarbazepine acetate: An integrated analysis of three randomized placebo-controlled trials.

    Science.gov (United States)

    Krauss, Gregory; Biton, Victor; Harvey, Jay H; Elger, Christian; Trinka, Eugen; Soares da Silva, Patrício; Gama, Helena; Cheng, Hailong; Grinnell, Todd; Blum, David

    2018-01-01

    To examine the influence of titration schedule and maintenance dose on the incidence and type of treatment-emergent adverse events (TEAEs) associated with adjunctive eslicarbazepine acetate (ESL). Data from three randomized, double-blind, placebo-controlled trials were analyzed. Patients with refractory partial-onset seizures were randomized to maintenance doses of ESL 400, 800, or 1200mg QD (dosing was initiated at 400 or 800mg QD) or placebo. The incidence of TEAEs was analyzed during the double-blind period (2-week titration phase; 12-week maintenance phase), according to the randomized maintenance dose and the titration schedule. 1447 patients were included in the analysis. During the first week of treatment, 62% of patients taking ESL 800mg QD had ≥1 TEAE, vs 35% of those taking 400mg QD and 32% of the placebo group; dizziness, somnolence, nausea, and headache were numerically more frequent in patients taking ESL 800mg than those taking ESL 400mg QD. During the double-blind period, the incidences of common TEAEs were lower in patients who initiated ESL at 400mg vs 800mg QD. For the 800 and 1200mg QD maintenance doses, rates of TEAEs leading to discontinuation were lower in patients who began treatment with 400mg than in those who began taking ESL 800mg QD. Initiation of ESL at 800mg QD is feasible. However, initiating treatment with ESL 400mg QD for 1 or 2 weeks is recommended, being associated with a lower incidence of TEAEs, and related discontinuations. For some patients, treatment may be initiated at 800mg QD, if the need for more immediate seizure reduction outweighs concerns about increased risk of adverse reactions during initiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

    Directory of Open Access Journals (Sweden)

    Enrique Gómez-Barrena

    2018-01-01

    Full Text Available ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32 to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC treatments versus iliac crest autograft (ICA to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments. The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108 will be randomly assigned to either the experimental low dose (n=36, the experimental high dose (n=36, or the comparator arm (n=36 using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  9. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

    Science.gov (United States)

    Gómez-Barrena, Enrique; Padilla-Eguiluz, Norma G; Avendaño-Solá, Cristina; Payares-Herrera, Concepción; Velasco-Iglesias, Ana; Torres, Ferran; Rosset, Philippe; Gebhard, Florian; Baldini, Nicola; Rubio-Suarez, Juan C; García-Rey, Eduardo; Cordero-Ampuero, José; Vaquero-Martin, Javier; Chana, Francisco; Marco, Fernando; García-Coiradas, Javier; Caba-Dessoux, Pedro; de la Cuadra, Pablo; Hernigou, Philippe; Flouzat-Lachaniette, Charles-Henri; Gouin, François; Mainard, Didier; Laffosse, Jean Michel; Kalbitz, Miriam; Marzi, Ingo; Südkamp, Norbert; Stöckle, Ulrich; Ciapetti, Gabriela; Donati, Davide Maria; Zagra, Luigi; Pazzaglia, Ugo; Zarattini, Guido; Capanna, Rodolfo; Catani, Fabio

    2018-01-01

    ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 10 6 hBM-MSCs is noninferior to that of 200 × 10 6 hBM-MSCs. The participants ( n = 108) will be randomly assigned to either the experimental low dose ( n = 36), the experimental high dose ( n = 36), or the comparator arm ( n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

  10. High dose Senna or Poly Ethylene Glycol (PEG for elective colonoscopy preparation: a prospective randomized investigator-blinded clinical trial

    Directory of Open Access Journals (Sweden)

    Ahmad Shavakhi

    2011-01-01

    Full Text Available Background: The aim of this study was to determine the efficacy of two methods of colon preparation for colon cleansing in a randomized controlled trial. Methods: In this prospective randomized investigator-blinded trial, consecutive outpatients indicated for elective colonoscopy were randomized into two groups. Patients in Senna group took 24 tablets of 11 mg Senna in two divided doses 24 hour before colonoscopy. In Poly Ethylene Glycol (PEG group they solved 4 sachets in 4 liters of water the day before the procedure and were asked to drink 250 ml every 15 minutes. The overall quality of colon cleansing was evaluated using the Aronchick scoring scale. Difficulty of the procedure, patients′ tolerance and compliance and adverse events were also evaluated. Results: 322 patients were enrolled in the study. There was no significant difference in the quality of colon cleansing, patients′ tolerance, compliance and the difficulty of the procedure between two groups (p > 0.05. The incidence of adverse effects was similar between two groups except for abdominal pain that was more severe in Senna group (p < 0.05 and nausea and vomiting that was more common in PEG group (p < 0.05 Conclusions: In conclusion we deduce that Senna has the same efficacy and patient′s acceptance as Polyethylene glycol-electrolyte solution (PEG-ES and it could be prescribed as an alternative method for bowel preparation.

  11. Low dose oral desmopressin for nocturnal polyuria in patients with benign prostatic hyperplasia: a double-blind, placebo controlled, randomized study.

    Science.gov (United States)

    Wang, Chung-Jing; Lin, Yu-Nan; Huang, Shi-Wei; Chang, Chien-Hsing

    2011-01-01

    We evaluated the long-term efficacy and safety of low dose oral desmopressin in elderly patients with benign prostatic hyperplasia with more than nocturnal voids and nocturnal polyuria more than 30% of total daily urine volume. Eligible patients with benign prostatic hyperplasia older than 65 years with nocturia, nocturnal polyuria and International Prostate Symptom Score 14 or greater were included in the study. All patients received placebo or 0.1 mg desmopressin orally at bedtime. Patients were required to visit the outpatient clinic from the first visit, and after 1, 3, 6 and 12 months of treatment. Patients maintained flow volume charts and used diaries to record voiding data throughout the study. During followup urinalysis, urine sodium, urine osmolality, serum electrolytes, prostate specific antigen, International Prostate Symptom Score, quality of life, transrectal ultrasonography of prostate, uroflowmetry and post-void residual urine volume were performed at each visit. A total of 115 patients were enrolled in the study and randomized as 58 in the placebo group and 57 in the desmopressin group. Desmopressin significantly decreased nocturnal urine output and the number of nocturia episodes, and prolonged the first sleep period (p polyuria in the lower urinary tract symptoms of patients with benign prostatic hyperplasia. Long-term desmopressin therapy gradually decreases serum sodium and it might induce hyponatremia even in patients without initial hyponatremia. For long-term desmopressin administration serum sodium should be assessed carefully, at least at 1 week after treatment. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Modern digital plain-radiography of the whole spine in scoliosis patients. Dose reduction and quality criteria

    International Nuclear Information System (INIS)

    Kloth, Jost Karsten; Stiller, W.; Kauczor, H.U.; Weber, M.A.

    2013-01-01

    To reduce the radiation exposure of plain radiographs of the entire spine depending on specific indications, since these are frequently performed examinations of children and young adults with scoliosis and to determine objective quality control criteria to ensure accurate assessment. In this prospective randomized study 323 patients underwent plain-radiography of the entire spine with standard and 50 % reduced dose. In an experimental pilot-study this target-dose was determined using an Alderson-Phantom. The evaluation of the experimental radiographs, as well as, the randomized plain-radiographs was conducted using the following criteria: endplates (Cobb-angle), spinal process and pedicel (rotation), lateral margin of the vertebral body (lateral alignment), identification of C7 / S1 (perpendicular). Two radiologists evaluated these criteria using a score ranging from 1 (definitely assessable) to 4 (not assessable). If one single criteria was evaluated with a score of 3 or more points or more than 2 criteria with 2 points, the radiograph was scored as ''not assessable''. The statistical analysis was conducted as a non-inferiority-trial. Seven (2.4 %) of the 290 examined x-rays were scored as not assessable. There was no statistic inferiority between the examinations with standard or reduced dose, while singular assessment of the defined criteria was likewise dose-independent. Plain-radiography of the total spine in patients with scoliosis can be performed with a dose reduction of 50 % without a loss of validity. The obtained quality control criteria were clinically applicable. (orig.)

  13. Randomized Phase II Trial of High-Dose Melatonin and Radiation Therapy for RPA Class 2 Patients With Brain Metastases (RTOG 0119)

    International Nuclear Information System (INIS)

    Berk, Lawrence; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Blask, David; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-01-01

    Purpose: To determine if high-dose melatonin for Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) Class 2 patients with brain metastases improved survival over historical controls, and to determine if the time of day melatonin was given affected its toxicity or efficacy. RTOG 0119 was a phase II randomized trial for this group of patients. Methods and Materials: RTOG RPA Class 2 patients with brain metastases were randomized to 20 mg of melatonin, given either in the morning (8-9 AM) or in the evening (8-9 PM). All patients received radiation therapy (30 Gy in 10 fractions) in the afternoon. Melatonin was continued until neurologic deterioration or death. The primary endpoint was overall survival time. Neurologic deterioration, as reflected by the Mini-Mental Status Examination, was also measured. Results: Neither of the randomized groups had survival distributions that differed significantly from the historic controls of patients treated with whole-brain radiotherapy. The median survivals of the morning and evening melatonin treatments were 3.4 and 2.8 months, while the RTOG historical control survival was 4.1 months. Conclusions: High-dose melatonin did not show any beneficial effect in this group of patients

  14. Correlation of patient maximum skin doses in cardiac procedures with various dose indicators

    International Nuclear Information System (INIS)

    Domienik, J.; Papierz, S.; Jankowski, J.; Peruga, J.Z.; Werduch, A.; Religa, W.

    2008-01-01

    In most countries of European Union, legislation requires the determination of the total skin dose received by patients during interventional procedures in order to prevent deterministic damages. Various dose indicators like dose-area product (DAP), cumulative dose (CD) and entrance dose at the patient plane (EFD) are used for patient dosimetry purposes in clinical practice. This study aimed at relating those dose indicators with doses ascribed to the most irradiated areas of the patient skin usually expressed in terms of local maximal skin dose (MSD). The study was performed in two different facilities for two most common cardiac procedures coronary angiography (CA) and percutaneous coronary interventions (PCI). For CA procedures, the registered values of fluoroscopy time, total DAP and MSD were in the range (0.7-27.3) min, (16-317) Gy cm 2 and (43-1507) mGy, respectively, and for interventions, accordingly (2.1-43.6) min, (17-425) Gy cm 2 , (71-1555) mGy. Moreover, for CA procedures, CD and EFD were in the ranges (295-4689) mGy and (121-1768) mGy and for PCI (267-6524) mGy and (68-2279) mGy, respectively. No general and satisfactory correlation was found for safe estimation of MSD. However, results show that the best dose indicator which might serve for rough, preliminary estimation is DAP value. In the study, the appropriate trigger levels were proposed for both facilities. (authors)

  15. Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.

    Science.gov (United States)

    Park, Jeong Bae; Shin, Joon-Han; Kim, Dong-Soo; Youn, Ho-Joong; Park, Seung Woo; Shim, Wan Joo; Park, Chang Gyu; Kim, Dong-Woon; Lee, Hae-Young; Choi, Dong-Ju; Rim, Se-Joong; Lee, Sung-Yun; Kim, Ju-Han

    2016-04-01

    Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies. This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic. Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition

  16. Comparative study of dose descriptor in pediatric computed tomography exams

    International Nuclear Information System (INIS)

    Finatto, Jerusa Dalbosco; Silva, Ana Maria Marques da; Froner, Ana Paula Pastre; Pimentel, Juliana

    2014-01-01

    This work aims to investigate the dose descriptor, volumetric Computed Tomography Dose Index (CTDI), a pediatric patients sample undergoing to skull CT, comparing the results with the diagnostic reference levels of the literature. Were collected volumetric CTDI values of all skull CT exams performed retrospectively in children of 0-10 years of age in a period of 12 months in a large hospital size. Patients, in a total of 103, were divided into four groups, where the criterion of separation used was age, trying to use the same division used in international references dose descriptors. In all acquisitions we used the pediatric protocol and the Automatic Exposure Control (AEC) available on the equipment. The CDTI values, with and without the use of AEC for pediatric studies, were compared. There was a reduction of approximately 100% in the absorbed dose value due to the use of the AEC. From the data collected and analyzed in this work, it is concluded that the use of dose reduction systems is relevant, such as the Care Dose, to maintain volumetric CTDI values within the reference levels. Also it is important the observation of range of children age to the appropriate choice of parameters used in the test protocol. The values obtained are according to the diagnostic reference levels from the literature

  17. Renoprotective effects of topiroxostat for hyperuremic patients with overt diabetic nephropathy study (ETUDE Study): A prospective, randomized, multicenter clinical trial.

    Science.gov (United States)

    Mizukoshi, Toshihiro; Kato, Sawako; Ando, Masahiko; Sobajima, Hiroshi; Ohashi, Norimi; Naruse, Tomohiko; Saka, Yosuke; Shimizu, Hideaki; Nagata, Takanobu; Maruyama, Shoichi

    2017-10-09

    We aimed to evaluate the anti-albuminuric effects of topiroxostat in Japanese hyperuricemic patients with diabetic nephropathy. In this 24-week, multicenter, open-label, randomized (1:1) trial, we assigned hyperuricemic patients with diabetic nephropathy (estimated glomerular filtration rate ≥ 20 mL/min/1.73m 2 ) and overt proteinuria (0.3 ≤ urine protein to creatinine ratio (UPCR) <3.5 g/g Cr) to either high dose (160 mg daily) or low dose (40 mg daily) topiroxostat. The primary endpoint was the change in albuminuria indicated by urine albumin-to-creatinine ratio (UACR) from the baseline at the final time point. A total of 80 patients underwent randomization. The changes in UACR after 24 weeks of treatment (or at the final time point if patients failed to reach 24 weeks) relative to the baseline were -122 mg/gCr (95% CI: -5.1 to -240.1, P = 0.041) in patients treated with high dose, while treatment with low dose topiroxostat could not show significant reduction (P = 0.067). In the linear mixed model including baseline albuminuria, eGFR, age, and sex as covariates, the decreases in UACR were still significant from baseline to 12 weeks by 228.7 ± 83.2 mg/gCr (P = 0.0075) in the high dose group. The adverse-event profile during this study was not different between the groups. Topiroxostat 160 mg daily reduced albuminuria in patients with diabetic nephropathy. (Funded by Sanwa Kagaku Kenkyusho; Trial registration, UMIN000015403). This article is protected by copyright. All rights reserved.

  18. Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

    Directory of Open Access Journals (Sweden)

    Leonore Lovis

    Full Text Available BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45 or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45. Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI: 56.6-88.5% and 80.8% (95% CI: 60.6-93.4% for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60. O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4% and 96.6% (95% CI: not defined, respectively (P = 0.009. Egg reduction rates (ERRs against O. viverrini were very high for both doses (>99%, but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1% and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment. Adverse events were common (96%, mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled

  19. Dose-Dependent Effects of the Cimicifuga racemosa Extract Ze 450 in the Treatment of Climacteric Complaints: A Randomized, Placebo-Controlled Study

    Directory of Open Access Journals (Sweden)

    Ruediger Schellenberg

    2012-01-01

    Full Text Available Extracts from Cimicifuga racemosa (CR, synonym Actaea racemosa have shown efficacy in trials in women with menopausal symptoms. Yet, dose dependency remains unclear. Therefore, 180 female outpatients with climacteric complaints were treated for 12 weeks in a randomized, double-blind, placebo-controlled, 3-armed trial (CR extract Ze 450 in 6.5 mg or 13.0 mg, or placebo. Primary outcome was the difference in menopausal symptoms (vasomotor, psychological, and somatic, assessed by the Kupperman Menopausal Index between baseline and week 12. Secondary efficacy variables were patients’ self-assessments of general quality of life (QoL, responder rates, and safety. Compared to placebo, patients receiving Ze 450 showed a significant reduction in the severity of menopausal symptoms in a dose-dependent manner from baseline to endpoint (mean absolute differences 17.0 (95% CI 14.65–19.35 score points, P<0.0001 for 13.0 mg; mean absolute differences 8.47 (95% CI 5.55–11.39 score points, P=0.0003 for 6.5 mg. QoL and responder rates corresponded with the main endpoint. Changes in menopausal symptoms and QoL were inversely correlated. Reported adverse events and clinical laboratory testing did not raise safety concerns. The CR extract Ze 450 is an effective and well-tolerated nonhormonal alternative to hormone treatment for symptom relief in menopausal women.

  20. Comparison of the Effects of Daily Single-Dose Use of Flurbiprofen, Diclofenac Sodium, and Tenoxicam on Postoperative Pain, Swelling, and Trismus: A Randomized Double-Blind Study.

    Science.gov (United States)

    Kaplan, Volkan; Eroğlu, Cennet Neslihan

    2016-10-01

    The aim of the present study was to compare the effects of daily single-dose use of flurbiprofen, diclofenac sodium, and tenoxicam on pain, swelling, and trismus that occur after surgical extraction of impacted wisdom teeth using local anesthesia. The present study included 3 groups with 30 patients in each group. Those volunteering to participate in this double-blind randomized study (n = 90) were selected from a patient population with an indication for extraction of impacted wisdom teeth. Group 1 patients received 200 mg flurbiprofen, group 2 patients received 100 mg diclofenac sodium, and group 3 patients received 20 mg tenoxicam. All doses were once a day, starting preoperatively. Pain was evaluated postoperatively at 1, 2, 3, 6, 8, and 24 hours and at 2 and 7 days using a visual analog scale (VAS). For comparison with the preoperative measurements, the patients were invited to postoperative follow-up visits 2 and 7 days after extraction to evaluate for swelling and trismus. The statistical analysis was performed using descriptive statistics in SAS, version 9.4 (SAS Institute, Cary, NC), software. Statistical analysis of the pain, swelling, and trismus data was performed using the Kruskal-Wallis, Dunn, and Wilcoxon-Mann-Whitney U tests. The statistical level of significance was accepted at P = .05 and power of 0.80. Clinically, tenoxicam showed better analgesic and anti-inflammatory efficacy compared with diclofenac sodium and, in particular, flurbiprofen. Although the VAS scores in the evaluation of pain showed statistically significant differences at 2 days, no statistically significant difference was found for swelling and trismus. Our study evaluated the analgesic and anti-inflammatory effects with a daily single dose of flurbiprofen, diclofenac sodium, and tenoxicam. Daily 20 mg tenoxicam can be accepted as an adequate and safe option for patients after a surgical procedure. Copyright © 2016 American Association of Oral and Maxillofacial

  1. The basic approaches to evaluation of effects of the long-therm radiation exposure in a range of 'low' doses

    International Nuclear Information System (INIS)

    Takhauov, R.M.; Karpov, A.B.; Litvyakov, N.V.

    2010-01-01

    The previously performed research allowed forming the main concepts about deterministic effects of radiation impact and defining the main postulates of radiation medicine with respect to average and high levels of exposure. At the same time the research performed to evaluate stochastic effects caused by 'low' doses of ionizing radiation influence failed to find a single-valued answer relating both to dose impact inducing the effect development and to the spectrum of recorded pathologic processes or diseases. In this connection on our opinion the most prospective decision of present problem are studies in follow directions: 1. The evaluation of radiation productions personal and residents of nearby territories mortality and morbidity structure and dynamics. 2. The estimation of risk main diseases development with long-term radiation exposure and analysis of radiation factor role in its pathogenesis. 3. The study of genetic disturbances of persons and their descendants exposed long-term ionizing radiation in 'low' doses. 4. The study of individual radio sensitivity genetic markers. 5. The evaluation of structural and functional homeostasis disturbances inducing the radiation exposure in 'low' doses. The object of study is the Close administrative territorial formation Seversk population and mainly Siberian Group Chemical Enterprises (SGCE) personal - the largest complex productions of atomic industry in the world. The Regional Medico-Dosimetric Register (RMDR), creating since 2001 is the basis for epidemiological studies. The register database contain the information concerning to about 66 000 SGCE workers (it is a whole number of workers in all years of SGCE existence from 1950 to now day). The 35 000 from 66 000 workers are the workers of so-called main productions. About 96% workers exposed external radiation has cumulative dose less 500 mSv. On the base of laboratory of genomic medicine it was created and constantly enriched the bank DNA and biological material

  2. A Monotonicity Result for the Range of a Perturbed Random Walk

    OpenAIRE

    Chen, Lung-Chi; Sun, Rongfeng

    2012-01-01

    We consider a discrete time simple symmetric random walk on Z^d, d>=1, where the path of the walk is perturbed by inserting deterministic jumps. We show that for any time n and any deterministic jumps that we insert, the expected number of sites visited by the perturbed random walk up to time n is always larger than or equal to that for the unperturbed walk. This intriguing problem arises from the study of a particle among a Poisson system of moving traps with sub-diffusive trap motion. In pa...

  3. Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

    Directory of Open Access Journals (Sweden)

    Moshood O. Omotayo

    2015-11-01

    Full Text Available Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca intake, the World Health Organisation (WHO recommends routine Ca supplementation during antenatal care (ANC. WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients. Design and methods: This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill and IFA (60 mg Fe + 400 μg folic acid taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill with IFA taken as above. Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering. Expected public health impact: If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.

  4. Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

    Science.gov (United States)

    Jacobson, Ira M; Brown, Robert S; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y; Santoro, John; Becker, Scott; Wakil, Adil E; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H; Brass, Clifford A

    2007-10-01

    This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

  5. Dose rate and dose fractionation studies in total body irradiation of dogs

    International Nuclear Information System (INIS)

    Kolb, H.J.; Netzel, B.; Schaffer, E.; Kolb, H.

    1979-01-01

    Total body irradiation (TBI) with 800-900 rads and allogeneic bone marrow transplantation according to the regimen designated by the Seattle group has induced remissions in patients with otherwise refractory acute leukemias. Relapse of leukemia after bone marrow transplantation remains the major problem, when the Seattle set up of two opposing 60 Co-sources and a low dose rate is used in TBI. Studies in dogs with TBI at various dose rates confirmed observations in mice that gastrointestinal toxicity is unlike toxicity against hemopoietic stem cells and possibly also leukemic stem cells depending on the dose rate. However, following very high single doses (2400 R) and marrow infusion acute gastrointestinal toxicity was not prevented by the lowest dose rate studied (0.5 R/min). Fractionated TBI with fractions of 600 R in addition to 1200 R (1000 rads) permitted the application of total doses up to 300 R followed by marrow infusion without irreversible toxicity. 26 dogs given 2400-3000 R have been observed for presently up to 2 years with regard to delayed radiation toxicity. This toxicity was mild in dogs given single doses at a low dose rate or fractionated TBI. Fractionated TBI is presently evaluated with allogeneic transplants in the dog before being applied to leukemic patients

  6. Fundamental studies on miniature dose meter using variable capacitance Si-diode

    International Nuclear Information System (INIS)

    Inoue, Yoshio

    1976-01-01

    The results of fundamental studies on development of a miniature dose meter using a semiconductor applicable for dosimetry in both intracavitary and external radiotherapy are described. Many different instruments have been applied in clinical dosimetry for regional lesions, mostly in phantom studies, e. g. the small sized ionization chamber, the fluoroluminescence glass dose meter and the thermoluminescence dose meter. However, there are considerable problems regarding safety, reproducibility, and simplicity for regional dosimetry of intracavitary lesions, such as genitourinary, gastrointestinal and respiratory malignancies. To overcome these problems, an attempt was made to develop a miniature catheter type detector using a variable capacitance Si-diode for gamma ray dosimetry. The newly developed miniature dose meter using a semiconductor has the following characteristics. As the tip of detector (23mm long and 3mm in diameter) is very small, the apparatus unit is easy to manipulate in the dosimetry of intracavitary lesions. As no voltage is supplied to the detector, there is no danger of electric shock from in vivo studies. A strict linearity existed between the radiation dose rate and the generated voltage even when the range of experimental irradiation dose rate was extremely wide. The sensitivity of the detector was affected by the environmental temperature, but it was easy to correct the sensitivity by applying a special calibration chart to the value derived from a thermister enclosed in the detector. Even with the experimental irradiation of more than 50,000R, no changes in the sensitivity of the detector were observed. Thus, the durability of the apparatus was shown to be excellent. (auth.)

  7. Add-on-Statin Extended Release Nicotinic Acid/Laropiprant but Not the Switch to High-Dose Rosuvastatin Lowers Blood Pressure: An Open-Label Randomized Study

    Directory of Open Access Journals (Sweden)

    Anastazia Kei

    2011-01-01

    Full Text Available Introduction. Nicotinic acid (NA and statins have been associated with reductions in blood pressure (BP. Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day or to add-on current statin treatment with extended release (ER NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 134±12 to 125±10 mmHg, <.001 versus baseline and =.01 versus rosuvastatin group and a 5% reduction of diastolic BP (from 81±9 to 77±6 mmHg, =.009 versus baseline and =.01 versus rosuvastatin group. These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

  8. Dialysis dose in acute kidney injury: no time for therapeutic nihilism--a critical appraisal of the Acute Renal Failure Trial Network study.

    Science.gov (United States)

    Ronco, Claudio; Cruz, Dinna; Oudemans van Straaten, Helen; Honore, Patrick; House, Andrew; Bin, Du; Gibney, Noel

    2008-01-01

    The optimal dialysis dose for acute kidney injury is a matter of great controversy. Clinical trials, predominantly single-center studies, have shown conflicting results. The Acute Renal Failure Trial Network (ATN) Study was designed to compare clinical outcomes between patients allocated to an intensive dose versus a less-intensive dose of renal replacement therapy. Recently, the results of this large randomized controlled multicenter study were published. The present article will discuss certain aspects of this trial: the overall design, the baseline patient characteristics, and comparison of the results with earlier studies. Finally, the article will address the implications of the ATN Study results for clinical practice.

  9. Studies on external gamma dose rates in air around Hassan city, Karnataka

    International Nuclear Information System (INIS)

    Shashikumar, T.S.; Gowda, Shivalinge; Chandrashekar; Shivakumar, B.C.

    2017-01-01

    Gamma-ray dose rates in air have been measured in the environment of Hassan City. The measurements were done from 15 locations in and around Hassan city at 1m above from the ground surface using a light weight portable radiation survey meter (Scintillometer) which is suited for radiometric, and environmental surveys. The meter reading fluctuates around a mean value and is proportional to the count rate detected by the unit. This is because of the random nature of radioactivity. The detailed results of the study will be presented. (author)

  10. Oral sumatriptan for migraine in children and adolescents: a randomized, multicenter, placebo-controlled, parallel group study.

    Science.gov (United States)

    Fujita, Mitsue; Sato, Katsuaki; Nishioka, Hiroshi; Sakai, Fumihiko

    2014-04-01

    The objective of this article is to evaluate the efficacy and tolerability of two doses of oral sumatriptan vs placebo in the acute treatment of migraine in children and adolescents. Currently, there is no approved prescription medication in Japan for the treatment of migraine in children and adolescents. This was a multicenter, outpatient, single-attack, double-blind, randomized, placebo-controlled, parallel-group study. Eligible patients were children and adolescents aged 10 to 17 years diagnosed with migraine with or without aura (ICHD-II criteria 1.1 or 1.2) from 17 centers. They were randomized to receive sumatriptan 25 mg, 50 mg or placebo (1:1:2). The primary efficacy endpoint was headache relief by two grades on a five-grade scale at two hours post-dose. A total of 178 patients from 17 centers in Japan were enrolled and randomized to an investigational product in double-blind fashion. Of these, 144 patients self-treated a single migraine attack, and all provided a post-dose efficacy assessment and completed the study. The percentage of patients in the full analysis set (FAS) population who report pain relief at two hours post-treatment for the primary endpoint was higher in the placebo group than in the pooled sumatriptan group (38.6% vs 31.1%, 95% CI: -23.02 to 8.04, P  = 0.345). The percentage of patients in the FAS population who reported pain relief at four hours post-dose was higher in the pooled sumatriptan group (63.5%) than in the placebo group (51.4%) but failed to achieve statistical significance ( P  = 0.142). At four hours post-dose, percentages of patients who were pain free or had complete relief of photophobia or phonophobia were numerically higher in the sumatriptan pooled group compared to placebo. Both doses of oral sumatriptan were well tolerated. No adverse events (AEs) were serious or led to study withdrawal. The most common AEs were somnolence in 6% (two patients) in the sumatriptan 25 mg treatment group and chest

  11. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points - An international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

    DEFF Research Database (Denmark)

    Puhringer, F.K.; Rex, C.; Sielenkamper, A.W.

    2008-01-01

    Background: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade...... was evaluated. Methods: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.......9. Neuromuscular monitoring was performed using acceleromyography. Results: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg...

  12. MO-FG-303-03: Demonstration of Universal Knowledge-Based 3D Dose Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Shiraishi, S; Moore, K L [University of California, San Diego, La Jolla, CA (United States)

    2015-06-15

    Purpose: To demonstrate a knowledge-based 3D dose prediction methodology that can accurately predict achievable radiotherapy distributions. Methods: Using previously treated plans as input, an artificial neural network (ANN) was trained to predict 3D dose distributions based on 14 patient-specific anatomical parameters including the distance (r) to planning target volume (PTV) boundary, organ-at-risk (OAR) boundary distances, and angular position ( θ,φ). 23 prostate and 49 stereotactic radiosurgery (SRS) cases with ≥1 nearby OARs were studied. All were planned with volumetric-modulated arc therapy (VMAT) to prescription doses of 81Gy for prostate and 12–30Gy for SRS. Site-specific ANNs were trained using all prostate 23 plans and using a 24 randomly-selected subset for the SRS model. The remaining 25 SRS plans were used to validate the model. To quantify predictive accuracy, the dose difference between the clinical plan and prediction were calculated on a voxel-by-voxel basis δD(r,θ,φ)=Dclin(r,θ,φ)-Dpred(r, θ,φ). Grouping voxels by boundary distance, the mean <δ Dr>=(1/N)Σ -θ,φ D(r,θ,φ) and inter-quartile range (IQR) quantified the accuracy of this method for deriving DVH estimations. The standard deviation (σ) of δ D quantified the 3D dose prediction error on a voxel-by-voxel basis. Results: The ANNs were highly accurate in predictive ability for both prostate and SRS plans. For prostate, <δDr> ranged from −0.8% to +0.6% (max IQR=3.8%) over r=0–32mm, while 3D dose prediction accuracy averaged from σ=5–8% across the same range. For SRS, from r=0–34mm the training set <δDr> ranged from −3.7% to +1.5% (max IQR=4.4%) while the validation set <δDr> ranged from −2.2% to +5.8% (max IQR=5.3%). 3D dose prediction accuracy averaged σ=2.5% for the training set and σ=4.0% over the same interval. Conclusion: The study demonstrates this technique’s ability to predict achievable 3D dose distributions for VMAT SRS and prostate. Future

  13. MO-FG-303-03: Demonstration of Universal Knowledge-Based 3D Dose Prediction

    International Nuclear Information System (INIS)

    Shiraishi, S; Moore, K L

    2015-01-01

    Purpose: To demonstrate a knowledge-based 3D dose prediction methodology that can accurately predict achievable radiotherapy distributions. Methods: Using previously treated plans as input, an artificial neural network (ANN) was trained to predict 3D dose distributions based on 14 patient-specific anatomical parameters including the distance (r) to planning target volume (PTV) boundary, organ-at-risk (OAR) boundary distances, and angular position ( θ,φ). 23 prostate and 49 stereotactic radiosurgery (SRS) cases with ≥1 nearby OARs were studied. All were planned with volumetric-modulated arc therapy (VMAT) to prescription doses of 81Gy for prostate and 12–30Gy for SRS. Site-specific ANNs were trained using all prostate 23 plans and using a 24 randomly-selected subset for the SRS model. The remaining 25 SRS plans were used to validate the model. To quantify predictive accuracy, the dose difference between the clinical plan and prediction were calculated on a voxel-by-voxel basis δD(r,θ,φ)=Dclin(r,θ,φ)-Dpred(r, θ,φ). Grouping voxels by boundary distance, the mean =(1/N)Σ -θ,φ D(r,θ,φ) and inter-quartile range (IQR) quantified the accuracy of this method for deriving DVH estimations. The standard deviation (σ) of δ D quantified the 3D dose prediction error on a voxel-by-voxel basis. Results: The ANNs were highly accurate in predictive ability for both prostate and SRS plans. For prostate, ranged from −0.8% to +0.6% (max IQR=3.8%) over r=0–32mm, while 3D dose prediction accuracy averaged from σ=5–8% across the same range. For SRS, from r=0–34mm the training set ranged from −3.7% to +1.5% (max IQR=4.4%) while the validation set ranged from −2.2% to +5.8% (max IQR=5.3%). 3D dose prediction accuracy averaged σ=2.5% for the training set and σ=4.0% over the same interval. Conclusion: The study demonstrates this technique’s ability to predict achievable 3D dose distributions for VMAT SRS and prostate. Future investigations will attempt to

  14. Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized, double-blinded, placebo-controlled study.

    Science.gov (United States)

    Choi, Sun Young; Hong, Ji Yeon; Ko, Eun Jung; Kim, Beom Joon; Hong, Sung-Woon; Lim, Mi Hyoung; Yeon, Sung Hum; Son, Rak Ho

    2018-02-01

    Oxidative stress and photodamage resulting from ultraviolet radiation exposure play key roles in skin aging. Fermented Cyclopia intermedia, which is used to brew honeybush tea, exerts antioxidant and anti-wrinkle effects by inhibiting reactive oxygen species production and downregulating matrix metalloproteinase activity. This randomized, double-blinded, placebo-controlled study aimed to evaluate the efficacy and safety of fermented honeybush (Cyclopia intermedia) extract (HU-018) for skin rejuvenation. 120 Korean subjects with crow's feet wrinkles were randomized to receive either low-dose extract (400 mg/day), high-dose extract (800 mg/day), or placebo (negative control, only dextran) for 12 weeks. Wrinkles were evaluated using JANUS ® and PRIMO pico ® . Skin elasticity, hydration and transepidermal water loss were measured. Global skin wrinkle grade was significantly improved in both low-dose and high-dose groups compared to placebo group, as well as for skin hydration and elasticity. Both the low- and high-dose groups showed significantly decreased TEWL compared to the placebo group. There were no adverse effects during the entire study period. Our data indicate that HU-018 is effective for improving skin wrinkles, elasticity, and hydration. Therefore, daily supplementation with fermented honeybush could be helpful for protecting against skin aging.

  15. Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

    Science.gov (United States)

    Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

    2012-09-01

    A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study

  16. LD-aminopterin in the canine homologue of human atopic dermatitis: a randomized, controlled trial reveals dosing factors affecting optimal therapy.

    Science.gov (United States)

    Zebala, John A; Mundell, Alan; Messinger, Linda; Griffin, Craig E; Schuler, Aaron D; Kahn, Stuart J

    2014-01-01

    Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD.

  17. LD-aminopterin in the canine homologue of human atopic dermatitis: a randomized, controlled trial reveals dosing factors affecting optimal therapy.

    Directory of Open Access Journals (Sweden)

    John A Zebala

    Full Text Available Options are limited for patients with atopic dermatitis (AD who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR. However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD.This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg or twice-weekly (0.007 mg/kg LD-aminopterin. The primary efficacy outcome was the Global Score (GS, a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01. The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo.Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD.

  18. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Martin-Martin LS

    2017-03-01

    Full Text Available LS Martin-Martin,1 F Giovannangeli,2 E Bizzi,2 U Massafra,2 E Ballanti,2 M Cassol,3 A Migliore2 1Department of Internal Medicine, Regina Apostolorum Hospital, 2Operative Unit of Rheumatology, 3Department of Internal Medicine, San Pietro Fatebenefratelli Hospital, Rome, Italy Background: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA. One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA. The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28, clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA

  19. Prospective, randomized, double-blind, Phase 2 dose-ranging study comparing efficacy and safety of imipenem/cilastatin plus relebactam with imipenem/cilastatin alone in patients with complicated urinary tract infections.

    Science.gov (United States)

    Sims, Matthew; Mariyanovski, Valeri; McLeroth, Patrick; Akers, Wayne; Lee, Yu-Chieh; Brown, Michelle L; Du, Jiejun; Pedley, Alison; Kartsonis, Nicholas A; Paschke, Amanda

    2017-09-01

    The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem non-susceptible pathogens. To explore relebactam's safety, tolerability and efficacy, we conducted a randomized (1:1:1), controlled, Phase 2 trial comparing imipenem/cilastatin+relebactam 250 mg, imipenem/cilastatin+relebactam 125 mg and imipenem/cilastatin alone in adults with complicated urinary tract infections (cUTI) or acute pyelonephritis, regardless of baseline pathogen susceptibility. Treatment was administered intravenously every 6 h for 4-14 days, with optional step-down to oral ciprofloxacin. The primary endpoint was favourable microbiological response rate (pathogen eradication) at discontinuation of intravenous therapy (DCIV) in the microbiologically evaluable (ME) population. Non-inferiority of imipenem/cilastatin+relebactam over imipenem/cilastatin alone was defined as lower bounds of the 95% CI for treatment differences being above -15%. At DCIV, 71 patients in the imipenem/cilastatin + 250 mg relebactam, 79 in the imipenem/cilastatin + 125 mg relebactam and 80 in the imipenem/cilastatin-only group were ME; 51.7% had cUTI and 48.3% acute pyelonephritis. Microbiological response rates were 95.5%, 98.6% and 98.7%, respectively, confirming non-inferiority of both imipenem/cilastatin + relebactam doses to imipenem/cilastatin alone. Clinical response rates were 97.1%, 98.7% and 98.8%, respectively. All 23 ME patients with imipenem non-susceptible pathogens had favourable DCIV microbiological responses (100% in each group). Among all 298 patients treated, 28.3%, 29.3% and 30.0% of patients, respectively, had treatment-emergent adverse events. The most common treatment-related adverse events across groups (1.0%-4.0%) were diarrhoea, nausea and headache. Imipenem/cilastatin + relebactam (250 or 125 mg) was as effective as imipenem/cilastatin alone for treatment of cUTI. Both relebactam-containing regimens were well tolerated. (NCT01505634).

  20. Higher dose of palonosetron versus lower dose of palonosetron plus droperidol to prevent postoperative nausea and vomiting after eye enucleation and orbital hydroxyapatite implant surgery: a randomized, double-blind trial

    Directory of Open Access Journals (Sweden)

    Hu X

    2017-05-01

    Full Text Available Xiao Hu, Fang Tan, Lan Gong Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai Medical College of Fudan University, Shanghai, China Objective: Postoperative nausea and vomiting (PONV is commonly observed after eye enucleation and orbital hydroxyapatite implant surgery. This prospective, randomized, double-blind trial was conducted to investigate the hypothesis that compared with monotherapy using a higher dose of palonosetron, using a lower dose of palonosetron in combination with droperidol could reduce the incidence of PONV and achieve similar prophylaxis against PONV after the aforementioned surgery.Patients and methods: A total of 129 patients who were in the American Society of Anesthesiologists Classes I and II, aged between 18 and 70 years, and scheduled for eye enucleation and orbital hydroxyapatite implant surgery, were enrolled in this study. They were randomized into three groups: Group P2.5 (2.5 µg/kg palonosetron, Group P7.5 (7.5 µg/kg palonosetron, and Group P+D (2.5 µg/kg palonosetron and 15 µg/kg droperidol. Patients received the different antiemetic regimens intravenously 5 min before surgery. The severity of nausea and vomiting and the complete response (CR rate during a 72-h postoperative period were assessed.Results: All patients completed the trial. The nausea score of Group P2.5 was significantly higher than those of the other two groups at 0–4 h and 24–48 h (P<0.05. Vomiting scores among all groups were similar during all intervals (P>0.05. Compared with Group P2.5, the CR rate was significantly improved at all intervals in Group P+D, except at 4–72 h, and was also elevated at 24–72 h in Group P7.5 (P<0.05. Fewer patients in Group P2.5 did not experience any nausea or vomiting throughout the study (49% compared with those in Group P7.5 (67% and Group P+D (81%; P<0.01.Conclusion: Combining low-dose palonosetron with droperidol potentiated prophylaxis

  1. Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

    Science.gov (United States)

    Wu, L; Sun, D; He, Y

    2016-10-01

    The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

  2. Optical haze of randomly arranged silver nanowire transparent conductive films with wide range of nanowire diameters

    Directory of Open Access Journals (Sweden)

    M. Marus

    2018-03-01

    Full Text Available The effect of the diameter of randomly arranged silver nanowires on the optical haze of silver nanowire transparent conductive films was studied. Proposed simulation model behaved similarly with the experimental results, and was used to theoretically study the optical haze of silver nanowires with diameters in the broad range from 30 nm and above. Our results show that a thickening of silver nanowires from 30 to 100 nm results in the increase of the optical haze up to 8 times, while from 100 to 500 nm the optical haze increases only up to 1.38. Moreover, silver nanowires with diameter of 500 nm possess up to 5% lower optical haze and 5% higher transmittance than 100 nm thick silver nanowires for the same 10-100 Ohm/sq sheet resistance range. Further thickening of AgNWs can match the low haze of 30 nm thick AgNWs, but at higher transmittance. The results obtained from this work allow deeper analysis of the silver nanowire transparent conductive films from the perspective of the diameter of nanowires for various optoelectronic devices.

  3. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

    Science.gov (United States)

    Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S

    2017-09-01

    Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH

  4. 
Intrathecal analgesia by bupivacaine is not enhanced by coadministration of morphine in patients with severe cancer-related pain: a randomized double-blind cross-over study.

    Science.gov (United States)

    Reif, Ingalill; Wincent, Anders; Stiller, Carl-Olav

    2017-06-01

    The objective of this randomized double blind cross-over trial was to determine if patients with severe cancer-related pain and inadequate response to systemic opioids prefer intrathecal (IT) pain relief with a combination of bupivacaine and morphine or bupivacaine only. Adult patients with cancer-related pain (n = 23) scheduled for IT analgesia at the Pain Center at the Karo-linska University Hospital Solna, Stockholm, Sweden, were included. The optimal individual flow rate of IT bupivacaine (2 mg/mL) in addition to bolus doses was titrated and maintained for 4 days. Morphine (1 mg/mL) was added to bupivacaine either on day 2 or 4 according to a randomization protocol. Expression of pain relief preference for morphine instead of control (bupivacaine only) was the primary outcome. Secondary outcomes were difference in pain intensity, pain relief, total use of bupivacaine per 24 hours and number of requested bolus doses. Eight patients dropped out during the 4-day study period for reasons not related to the trial. IT bupivacaine significantly decreased median (interquartile range) pain intensity from 5 (3 - 7) at baseline (before catheter insertion) to 1 (0 - 1) (p = 0.0001; Wilcoxon test). Only 1 patient of 15 with 4-day data expressed any preference for morphine. The addition of IT morphine did not result in any significant change of pain intensity, pain relief score, total use of bupivacaine per 24 hours, or number of requested bolus doses. These results suggest that patients with cancer-related pain treated with high doses of systemic opioids, may start IT treatment with an optimal dose of IT bupivacaine without morphine.
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  5. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: results of a randomized, double-blind, clinical trial.

    Science.gov (United States)

    Beaudoin, Francesca L; Lin, Charlie; Guan, Wentao; Merchant, Roland C

    2014-11-01

    Low-dose ketamine has been used perioperatively for pain control and may be a useful adjunct to intravenous (IV) opioids in the control of acute pain in the emergency department (ED). The aim of this study was to determine the effectiveness of low-dose ketamine as an adjunct to morphine versus standard care with morphine alone for the treatment of acute moderate to severe pain among ED patients. A double-blind, randomized, placebo-controlled trial with three study groups was conducted at a large, urban academic ED over a 10-month period. Eligible patients were 18 to 65 years old with acute moderate to severe pain (score of at least 5 out of 10 on the numerical pain rating scale [NRS] and pain duration ketamine (group 1), or 3) morphine and 0.3 mg/kg ketamine (group 2). Participants were assessed at 30, 60, and 120 minutes after study medication administration and received rescue analgesia as needed to target a 50% reduction in pain. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the NRS and calculated as the summed pain-intensity (SPID) difference over 2 hours. The amount and timing of rescue opioid analgesia was evaluated as a secondary outcome. The occurrence of adverse events was also measured. Sixty patients were enrolled (n = 20 in each group). There were no differences between study groups with respect to age, sex, race/ethnicity, preenrollment analgesia, or baseline NRS. Over the 2-hour poststudy medication administration period, the SPIDs were higher (greater pain relief) for the ketamine study groups than the control group (standard care 4.0, interquartile range [IQR] = 1.8 to 6.5; group 1 7.0, IQR = 4.3 to 10.8; and group 2 7.8, IQR = 4.8 to 12.8; p ketamine groups were similar (p pain intensity up to 2 hours, whereas group 1 was similar to standard care by 2 hours. Similar numbers of patients received rescue analgesia: standard care group, seven of 20, 35%; group 1, four of 20, 20%; and group 2, four of 20, 20

  6. Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment

    International Nuclear Information System (INIS)

    Saini, Amarjit S.; Zhang, Geoffrey G.; Finkelstein, Steven E.; Biagioli, Matthew C.

    2011-01-01

    Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken with each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 ± 0.002 for contrast/saline solution and 0.808 ± 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 ± 0.010 and 0.781 ± 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.

  7. Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

    Science.gov (United States)

    Riviere, A.

    1994-01-01

    The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

  8. Cytogenetic effect of low dose gamma-radiation in Hordeum vulgare seedlings: non-linear dose-effect relationship.

    Science.gov (United States)

    Geras'kin, Stanislav A; Oudalova, Alla A; Kim, Jin Kyu; Dikarev, Vladimir G; Dikareva, Nina S

    2007-03-01

    The induction of chromosome aberrations in Hordeum vulgare germinated seeds was studied after ionizing irradiation with doses in the range of 10-1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose was found to be nonlinear. A dose-independent plateau in the dose range from about 50 to 500 mGy was observed, where the level of cytogenetic damage was significantly different from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexity, using the most common quantitative criteria, demonstrated the advantage of a piecewise linear model over linear and polynomial models in approximating the frequency of cytogenetical disturbances. The results of the study support the hypothesis of indirect mechanisms of mutagenesis induced by low doses. Fundamental and applied implications of these findings are discussed.

  9. Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

    Science.gov (United States)

    Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

    2014-04-01

    The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

  10. Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

    Science.gov (United States)

    Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C

    2016-03-01

    Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing. The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days. Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry. Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose. PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped. © 2015 The British Pharmacological Society.

  11. Monte Carlo simulation study on dose enhancement by gold nanoparticles in brachytherapy

    International Nuclear Information System (INIS)

    Cho, Sungkoo; Jeong, Jonghwi; Kim, Chanhyeong; Yoon, Myonggeun

    2010-01-01

    Radiation dose enhancement by injection of a high atomic number (Z) material into tumor volumes has been studied for various radiation sources and different concentrations of gold nanoparticles. Brachytherapy employs low energy photons of less than ∼0.5 MeV, which indeed is the optimal energy range for radiation dose enhancement by introduction of high-Z material. The present study uses the MCNPX TM code to estimate the dose enhancement by gold nanoparticles for the four common brachytherapy sources ( 137 Cs, 192 Ir, 125 I, and 103 Pd). Additionally, cisplatin (H 6 Cl 2 N 2 Pt), a platinum-based chemotherapeutic drug, was used to evaluate the dose enhancement. The simulated source models were evaluated with reference to the calculated TG-43 parameter values. The dose enhancement in the tumor region due to the gold nanoparticles and cisplatin was evaluated according to the dose enhancement factor (DEF). The maximum values of the average DEFs were found to be 1.03, 1.11, 3.43, and 2.17 for the 137 Cs, 192 Ir, 125 I, and 103 Pd sources, respectively. The dose enhancement values for the low-energy sources were significantly higher than those for the high-energy sources. The dose enhancement due to cisplatin was calculated by using the same approach and was found to be comparable to that of the gold nanoparticles. The maximum value of the average DEF for cisplatin was 1.12 for the 5% concentration level in water and a 192 Ir source. We confirmed that cisplatin could be applied to cancer therapy that combines chemotherapeutic drugs with radiation therapy. The results presented herein will be used to study dose enhancement in tumor regions using various radiation modalities with high atomic number materials.

  12. Single-center open-label randomized study of anemia management improvement in ESRD patients with secondary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    Bellasi Antonio

    2016-04-01

    Full Text Available Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD] are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs to correct hemoglobin (Hb may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD (Optimal ESRD Treatment study will assess whether lowering of parathyroid hormone (PTH is associated with a reduction in ESA consumption. The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH 300-540 pg/mL and Hb 10-11.5 g/dL will be randomized 1:1 to strict PTH control (150-300 pg/mL versus standard care (PTH range 300-540 pg/mL. Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation and Hb (10-11.5 g/dL. Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

  13. Male gonadal dose of ionizing radiation delivered during X-ray examinations and monthly probability of pregnancy: a population-based retrospective study

    Directory of Open Access Journals (Sweden)

    Slama Remy

    2006-03-01

    Full Text Available Abstract Background Male gonadal exposure to ionizing radiation may disrupt spermatogenesis, but its influence on the fecundity of couples has been rarely studied. We aimed to characterize the influence of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy. Methods We recruited a random sample of women who retrospectively described 1110 periods of unprotected intercourse beginning between 1985 and 1999 and leading either to a live birth or to no pregnancy; their duration was censored after 13 months. The male partner answered a telephone questionnaire on radiodiagnostic examinations. We assigned a mean gonadal dose to each type of radiodiagnostic examination. We defined male dose for each period of unprotected intercourse as the sum of the gonadal doses of the X-ray examinations experienced between 18 years of age and the date of discontinuation of contraception. Time to pregnancy was analysed using a discrete Cox model with random effect allowing to estimate hazard ratios of pregnancy. Results After adjustment for female factors likely to influence fecundity, there was no evidence of an association between male dose and the probability of pregnancy (test of homogeneity, p = 0.55. When compared to couples with a male gonadal dose between 0.01 and 0.20 milligrays (n = 321 periods of unprotected intercourse, couples with a gonadal dose above 10 milligrays had a hazard ratio of pregnancy of 1.44 (95% confidence interval, 0.73–2.86, n = 31. Conclusion Our study provides no evidence of a long-term detrimental effect of male gonadal dose of ionizing radiation delivered during radiodiagnostic on the monthly probability of pregnancy during the year following discontinuation of contraceptive use. Classification errors due to the retrospective assessment of male gonadal exposure may have limited the statistical power of our study.

  14. A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: Hormonal and clinical effects

    NARCIS (Netherlands)

    Valerio, Paolo G.; van Wassenaer, Aleid G.; de Vijlder, Jan J. M.; Kok, Joke H.

    2004-01-01

    A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T-3) 24 h after birth, followed by a daily dose of thyroxine (T-4) during 6 wk to infants <28 wk gestational age.

  15. Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

    Science.gov (United States)

    Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

    2011-01-01

    Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

  16. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    International Nuclear Information System (INIS)

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.

    2010-01-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  17. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice.

    Science.gov (United States)

    Ware, J H; Sanzari, J; Avery, S; Sayers, C; Krigsfeld, G; Nuth, M; Wan, X S; Rusek, A; Kennedy, A R

    2010-09-01

    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  18. Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study

    Directory of Open Access Journals (Sweden)

    Massimo Allegri

    2017-01-01

    Full Text Available Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05. Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P>0.05. Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

  19. Research staff training in a multisite randomized clinical trial: Methods and recommendations from the Stimulant Reduction Intervention using Dosed Exercise (STRIDE) trial.

    Science.gov (United States)

    Walker, Robrina; Morris, David W; Greer, Tracy L; Trivedi, Madhukar H

    2014-01-01

    Descriptions of and recommendations for meeting the challenges of training research staff for multisite studies are limited despite the recognized importance of training on trial outcomes. The STRIDE (STimulant Reduction Intervention using Dosed Exercise) study is a multisite randomized clinical trial that was conducted at nine addiction treatment programs across the United States within the National Drug Abuse Treatment Clinical Trials Network (CTN) and evaluated the addition of exercise to addiction treatment as usual (TAU), compared to health education added to TAU, for individuals with stimulant abuse or dependence. Research staff administered a variety of measures that required a range of interviewing, technical, and clinical skills. In order to address the absence of information on how research staff are trained for multisite clinical studies, the current manuscript describes the conceptual process of training and certifying research assistants for STRIDE. Training was conducted using a three-stage process to allow staff sufficient time for distributive learning, practice, and calibration leading up to implementation of this complex study. Training was successfully implemented with staff across nine sites. Staff demonstrated evidence of study and procedural knowledge via quizzes and skill demonstration on six measures requiring certification. Overall, while the majority of staff had little to no experience in the six measures, all research assistants demonstrated ability to correctly and reliably administer the measures throughout the study. Practical recommendations are provided for training research staff and are particularly applicable to the challenges encountered with large, multisite trials.

  20. Hyperuniformity, quasi-long-range correlations, and void-space constraints in maximally random jammed particle packings. I. Polydisperse spheres.

    Science.gov (United States)

    Zachary, Chase E; Jiao, Yang; Torquato, Salvatore

    2011-05-01

    Hyperuniform many-particle distributions possess a local number variance that grows more slowly than the volume of an observation window, implying that the local density is effectively homogeneous beyond a few characteristic length scales. Previous work on maximally random strictly jammed sphere packings in three dimensions has shown that these systems are hyperuniform and possess unusual quasi-long-range pair correlations decaying as r(-4), resulting in anomalous logarithmic growth in the number variance. However, recent work on maximally random jammed sphere packings with a size distribution has suggested that such quasi-long-range correlations and hyperuniformity are not universal among jammed hard-particle systems. In this paper, we show that such systems are indeed hyperuniform with signature quasi-long-range correlations by characterizing the more general local-volume-fraction fluctuations. We argue that the regularity of the void space induced by the constraints of saturation and strict jamming overcomes the local inhomogeneity of the disk centers to induce hyperuniformity in the medium with a linear small-wave-number nonanalytic behavior in the spectral density, resulting in quasi-long-range spatial correlations scaling with r(-(d+1)) in d Euclidean space dimensions. A numerical and analytical analysis of the pore-size distribution for a binary maximally random jammed system in addition to a local characterization of the n-particle loops governing the void space surrounding the inclusions is presented in support of our argument. This paper is the first part of a series of two papers considering the relationships among hyperuniformity, jamming, and regularity of the void space in hard-particle packings.