[Evaluation of methods to calculate dialysis dose in daily hemodialysis].

Science.gov (United States)

Maduell, F; Gutiérrez, E; Navarro, V; Torregrosa, E; Martínez, A; Rius, A

2003-01-01

Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiological. Different methods have been described to calculate dialysis dose which take into consideration change in frequency. The aim of this study was to calculate all dialysis dose possibilities and evaluate the better and practical options. Eight patients, 6 males and 2 females, on standard 4 to 5 hours thrice weekly on-line hemodiafiltration (S-OL-HDF) were switched to daily on-line hemodiafiltration (D-OL-HDF) 2 to 2.5 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Time average concentration (TAC), time average deviation (TAD), normalized protein catabolic rate (nPCR), Kt/V, equilibrated Kt/V (eKt/V), equivalent renal urea clearance (EKR), standard Kt/V (stdKt/V), urea reduction ratio (URR), hemodialysis product and time off dialysis were measured. Daily on-line hemodiafiltration was well accepted and tolerated. Patients maintained the same TAC although TAD decreased from 9.7 +/- 2 in baseline to a 6.2 +/- 2 mg/dl after six months, p time off dialysis was reduced to half. Dialysis frequency is an important urea kinetic parameter which there are to take in consideration. It's necessary to use EKR, stdKt/V or weekly URR to calculate dialysis dose for an adequate comparison between different frequency dialysis schedules.

Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

LENUS (Irish Health Repository)

Egan, Sean

2012-08-07

BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

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.

A once-daily dose of tadalafil for erectile dysfunction: compliance and efficacy

Directory of Open Access Journals (Sweden)

Samuel L Washington III

2010-08-01

Full Text Available Samuel L Washington III1, Alan W Shindel21School of Medicine, University of California at San Francisco, San Francisco, California, USA; 2Department of Urology, University of California at San Francisco, San Francisco, California, USAAbstract: Selective phosphodiesterase type 5 inhibitors (PDE5Is have revolutionized the ­treatment of erectile dysfunction (ED in men. As an on-demand treatment, PDE5Is have excellent efficacy and safety in the treatment of ED due to a broad spectrum of etiologies. Nevertheless, these drugs do have side-effect profiles that are troublesome to some patients, eg, headache, dyspepsia, myalgia, etc. Furthermore, many patients and their partners dislike the necessity of on-demand treatment for ED, citing a desire for greater spontaneity with sexual interactions. In 2008, approximately 10 years after the release of the first commercially available PDE5I, a paradigm shift in the management of ED occurred with the approval of once-daily dose of tadalafil by the US Food and Drug Administration for the management of ED. The prolonged half-life of tadalafil lends itself well to this dosing regimen and conveys the advantage of separating medication from sexual interactions; lower dose therapy also carries the theoretical benefit of lower incidence of side effects. In this study, we review the current state of the art with respect to this new management strategy for ED, highlighting published reports of the efficacy and tolerability of the daily dose tadalafil regimen.Keywords: PDE5 inhibitor, on-demand therapy, side effects, daily dosing

The effectiveness of reducing the daily dose of finasteride in men with benign prostatic hyperplasia

Directory of Open Access Journals (Sweden)

Geller Jack

2002-01-01

Full Text Available Abstract Background Finasteride, a 5 alpha reductase inhibitor, is an established treatment for benign prostatic hyperplasia. The recommended dosage is 5 mg a day, however case reports have show effectiveness with lower doses. The objective of the current study was to determine in men with benign prostatic hyperplasia, previously treated for at least one year with finasteride 5 mg daily, if they will maintain subjective and objective improvements in urinary obstruction when treated with 2.5 mg of finasteride daily for one year. Methods In an open label, prospective study, 40 men with benign prostatic hyperplasia, previously treated for at least one year with 5 mg of finasteride, took 2.5 mg of finasteride daily for one year. Measurements included AUA symptom score, maximum flow rate, voided volume and PSA. Results There were no significant changes in maximum flow rate, voided volume, or AUA symptom score after one year of finasteride 2.5 mg daily therapy. PSA increased significantly, p Conclusions The daily dose of finasteride can be reduced to 2.5 mg daily without significant effect on subjective and objective measures of urinary obstruction. Although statistically significant increases in PSA are noted when reducing the daily finasteride dose from 5 mg to 2.5 mg, the clinical significance of a mean .6 ng/ml increase in PSA is questionable.

Marijuana’s Dose-Dependent Effects in Daily Marijuana Smokers

OpenAIRE

Ramesh, Divya; Haney, Margaret; Cooper, Ziva D.

2013-01-01

Active marijuana produces significant subjective, psychomotor, and physiological effects relative to inactive marijuana, yet demonstrating that these effects are dose-dependent has proven difficult. This within-subject, double-blind study was designed to develop a smoking procedure to obtain a marijuana dose–response function. In four outpatient laboratory sessions, daily marijuana smokers (N = 17 males, 1 female) smoked six 5-s puffs from 3 marijuana cigarettes (2 puffs/cigarette). The numbe...

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

International Nuclear Information System (INIS)

Rucinski, Antoni; Brons, Stephan; Richter, Daniel; Habl, Gregor; Debus, Jürgen; Bert, Christoph; Haberer, Thomas; Jäkel, Oliver

2015-01-01

Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90 Rectum ), respectively. The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90 Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal

Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19 rapid metabolisers compared with twice-daily omeprazole, rabeprazole or lansoprazole.

Science.gov (United States)

Sahara, S; Sugimoto, M; Uotani, T; Ichikawa, H; Yamade, M; Iwaizumi, M; Yamada, T; Osawa, S; Sugimoto, K; Umemura, K; Miyajima, H; Furuta, T

2013-11-01

Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation to CYP2C19 genotype. We performed 24-h pH monitoring studies on Day 7 of PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers (PMs)] using a randomised four-way crossover design: omeprazole 20 mg, esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily. Although median pH values with esomeprazole, omeprazole, lansoprazole and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5-7.3), respectively (no statistically significant differences), CYP2C19 genotype-dependent differences were smaller for esomeprazole and rabeprazole compared with values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0 independent of the PPI. In intermediate and rapid metabolisers of CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of the four PPIs. Therefore, esomeprazole may be effective in Japanese population when dosed twice daily. © 2013 John Wiley & Sons Ltd.

Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT for prostate cancer

International Nuclear Information System (INIS)

Li, Wen; Vassil, Andrew; Xia, Ping; Zhong, Yahua

2013-01-01

Purpose: To evaluate the feasibility of daily dose monitoring using a patient specific atlas-based autosegmentation method on diagnostic quality verification images.Methods: Seven patients, who were treated for prostate cancer with intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails system, were selected for this study. The prostate, rectum, and bladder were manually contoured on the first six and last seven sets of daily verification images. For each patient, three patient specific atlases were constructed using manual contours from planning CT alone (1-image atlas), planning CT plus first three verification CTs (4-image atlas), and planning CT plus first six verification CTs (7-image atlas). These atlases were subsequently applied to the last seven verification image sets of the same patient to generate the auto-contours. Daily dose was calculated by applying the original treatment plans to the daily beam isocenters. The autocontours and manual contours were compared geometrically using the dice similarity coefficient (DSC), and dosimetrically using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder.Results: The DSC of the autocontours obtained with the 4-image atlases were 87.0%± 3.3%, 84.7%± 8.6%, and 93.6%± 4.3% for the prostate, rectum, and bladder, respectively. These indices were higher than those from the 1-image atlases (p 0.05). Daily prostate D99 of the autocontours was comparable to those of the manual contours (p= 0.55). For the bladder and rectum, the daily D5 were 95.5%± 5.9% and 99.1%± 2.6% of the planned D5 for the autocontours compared to 95.3%± 6.7% (p= 0.58) and 99.8%± 2.3% (p < 0.01) for the manual contours.Conclusions: With patient specific 4-image atlases, atlas-based autosegmentation can adequately facilitate daily dose monitoring for prostate cancer

Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Li, Wen; Vassil, Andrew; Xia, Ping [Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, Ohio 44106 (United States); Zhong, Yahua [Department of Radiation Oncology, Zhongnan Hospital, Wuhan 430071 (China)

2013-11-15

Purpose: To evaluate the feasibility of daily dose monitoring using a patient specific atlas-based autosegmentation method on diagnostic quality verification images.Methods: Seven patients, who were treated for prostate cancer with intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails system, were selected for this study. The prostate, rectum, and bladder were manually contoured on the first six and last seven sets of daily verification images. For each patient, three patient specific atlases were constructed using manual contours from planning CT alone (1-image atlas), planning CT plus first three verification CTs (4-image atlas), and planning CT plus first six verification CTs (7-image atlas). These atlases were subsequently applied to the last seven verification image sets of the same patient to generate the auto-contours. Daily dose was calculated by applying the original treatment plans to the daily beam isocenters. The autocontours and manual contours were compared geometrically using the dice similarity coefficient (DSC), and dosimetrically using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder.Results: The DSC of the autocontours obtained with the 4-image atlases were 87.0%± 3.3%, 84.7%± 8.6%, and 93.6%± 4.3% for the prostate, rectum, and bladder, respectively. These indices were higher than those from the 1-image atlases (p < 0.01) and comparable to those from the 7-image atlases (p > 0.05). Daily prostate D99 of the autocontours was comparable to those of the manual contours (p= 0.55). For the bladder and rectum, the daily D5 were 95.5%± 5.9% and 99.1%± 2.6% of the planned D5 for the autocontours compared to 95.3%± 6.7% (p= 0.58) and 99.8%± 2.3% (p < 0.01) for the manual contours.Conclusions: With patient specific 4-image atlases, atlas-based autosegmentation can adequately facilitate daily dose monitoring for prostate cancer.

Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

Science.gov (United States)

Potel, G; Chau, N P; Pangon, B; Fantin, B; Vallois, J M; Faurisson, F; Carbon, C

1991-10-01

The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

Determination of 210Po concentration in commercially available infant formulae and assessment of daily ingestion dose

Directory of Open Access Journals (Sweden)

Ravi K. Prabhath

2015-07-01

Full Text Available A study has been conducted to estimate the concentration of natural radioactive polonium in commercially available packaged infant food formulae available in Mumbai, India and the corresponding daily dose normalized based on its shelf life. Eleven most popular international brands of infant formulae were sourced from market and three aliquots from each sample were analysed for concordant results. Autodeposition method onto a silver planchet from hot dilute acid solution followed by alpha spectrometry was performed for estimation of polonium. Radiochemical recovery was ascertained by the addition of 209Po tracer. Radiochemical recovery of 209Po tracer was ranged from 14.7 to 98.1 %. The 210Po concentration in the samples was in the range of 0.08–0.23 Bq kg−1 on measured date and the corresponding daily dose, calculated on normalized date which is at mid-point of the shelf life of the sample, was ranged from 0.04 to 0.89 μSv d−1 as per the recommended daily consumption. The annual committed effective dose estimated based on the average of daily dose was found to be 150 μSv.

Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

Directory of Open Access Journals (Sweden)

Inder S Anand

2010-06-01

Full Text Available Inder S Anand1, Anita Deswal2, Dean J Kereiakes3, Das Purkayastha4, Dion H Zappe41Veterans Administration Medical Center, Minneapolis, MN, USA; 2Michael E DeBakey VA Medical Center, Houston, TX, USA; 3The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086Background: The safety of once-daily (qd dosing of valsartan in heart failure (HF patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid.Methods: HF patients (NYHA class II–III receiving diuretics (87%, angiotensin-converting enzyme inhibitors (98%, beta-blockers (92%, aldosterone antagonists (25%, or digoxin (32% were randomized to valsartan 40 mg bid (n = 60 or 80 mg qd (n = 55 and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS. Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%. Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K+, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III heart failure

Patterns of prednisone use during pregnancy in women with rheumatoid arthritis: Daily and cumulative dose.

Science.gov (United States)

Palmsten, Kristin; Rolland, Matthieu; Hebert, Mary F; Clowse, Megan E B; Schatz, Michael; Xu, Ronghui; Chambers, Christina D

2018-04-01

To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length. This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated. Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)). In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose. Copyright © 2018 John Wiley & Sons, Ltd.

Assessment of Parotid Gland Dose Changes During Head and Neck Cancer Radiotherapy Using Daily Megavoltage Computed Tomography and Deformable Image Registration

International Nuclear Information System (INIS)

Lee, Choonik; Langen, Katja M.; Lu Weiguo; Haimerl, Jason; Schnarr, Eric; Ruchala, Kenneth J.; Olivera, Gustavo H.; Meeks, Sanford L.; Kupelian, Patrick A.; Shellenberger, Thomas D.; Manon, Rafael R.

2008-01-01

Purpose: To analyze changes in parotid gland dose resulting from anatomic changes throughout a course of radiotherapy in a cohort of head-and-neck cancer patients. Methods and Materials: The study population consisted of 10 head-and-neck cancer patients treated definitively with intensity-modulated radiotherapy on a helical tomotherapy unit. A total of 330 daily megavoltage computed tomography images were retrospectively processed through a deformable image registration algorithm to be registered to the planning kilovoltage computed tomography images. The process resulted in deformed parotid contours and voxel mappings for both daily and accumulated dose-volume histogram calculations. The daily and cumulative dose deviations from the original treatment plan were analyzed. Correlations between dosimetric variations and anatomic changes were investigated. Results: The daily parotid mean dose of the 10 patients differed from the plan dose by an average of 15%. At the end of the treatment, 3 of the 10 patients were estimated to have received a greater than 10% higher mean parotid dose than in the original plan (range, 13-42%), whereas the remaining 7 patients received doses that differed by less than 10% (range, -6-8%). The dose difference was correlated with a migration of the parotids toward the high-dose region. Conclusions: The use of deformable image registration techniques and daily megavoltage computed tomography imaging makes it possible to calculate daily and accumulated dose-volume histograms. Significant dose variations were observed as result of interfractional anatomic changes. These techniques enable the implementation of dose-adaptive radiotherapy

Daily dose and shielding optimization in work performance at 'Ukrytie' object

International Nuclear Information System (INIS)

Batij, V.G.; Derengovskij, V.V.; Egorov, V.V.; Kuz'menko, V.A.; Rud'ko, V.M.; Sizov, A.A.; Stoyanov, A.I.

2000-01-01

The procedure of daily dose and shielding optimization in work performance at 'Ukryttia' object is offered. The recommendations allowing reducing collective effective doze according to the optimization principle are submitted. The technique of shielding optimization is given at stabilization works realization. The optimum shielding calculation example for the strengthening support is given

A Semiempirical Approach to the Determination of Daily Erythemal Doses.

Science.gov (United States)

Silva, Abel A; Yamamoto, Ana L C; Corrêa, Marcelo P

2018-02-15

The maintenance of ground-based instruments to measure the incidence of ultraviolet radiation (UVR) from the Sun demands strict and well-developed procedures. A piece of equipment can be out of service for a couple of weeks or months for calibration, repair or even the improvement of the facilities where it has been set up. However, the replacement of an instrument in such circumstances can be logistically and financially prohibitive. On the other hand, the lack of data can jeopardize a long-term experiment. In this study, we introduce a semiempirical approach to the determination of the theoretical daily erythemal dose (DED t ) for periods of instrumental absence in a tropical site. The approach is based on 5 years of ground-based measurements of daily erythemal dose (DED) linearly correlated with parameters of total ozone column (TOC) and reflectivity (R PC ) from the Ozone Monitoring Instrument (OMI) and the cosine of solar zenith angle at noon (SZA n ). Seventeen months of missing ground-based data were replaced with DED t , leading to a complete 5-year series of data. The lowest and the highest values of typical DED were 2411 ± 322 J m -2 (1σ) (winter) and 5263 ± 997 J m -2 (summer). The monthly integrated erythemal dose (mED) varied from 59 kJ m -2 (winter) to 162 kJ m -2 (summer). Both of them depended mainly on cos(SZA n ) and R PC . The 12-month integrated erythemal dose (12-ED) ranged from 1350 kJ m -2 to 1546 kJ m -2 , but it can depend significantly on other atmospheric parameter (maybe aerosols) not explicitly considered here. © 2018 The American Society of Photobiology.

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

Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

Energy Technology Data Exchange (ETDEWEB)

Mackova, N; Praslicka, M; Misurova, E [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Prirodovedecka Fakulta

1975-01-01

Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R.

Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

International Nuclear Information System (INIS)

Mackova, N.; Praslicka, M.; Misurova, E.

1975-01-01

Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R. (author)

Bioequivalence and Safety of Twice-Daily Sustained-Release Paracetamol (Acetaminophen) Compared With 3- and 4-Times-Daily Paracetamol: A Repeat-Dose, Crossover Pharmacokinetic Study in Healthy Volunteers.

Science.gov (United States)

Liu, Dongzhou J; Collaku, Agron

2018-01-01

Twice-daily sustained-release (SR) paracetamol (acetaminophen) offers convenient administration to chronic users. This study investigated at steady state (during the last 24 hours of a 3-day dosing period) the pharmacokinetics, bioequivalence, and safety of twice-daily SR paracetamol compared with extended-release (ER) and immediate-release (IR) paracetamol. In this open-label, randomized, multidose, 3-way crossover study, 28 healthy subjects received paracetamol SR (2 × 1000 mg twice daily), ER (2 × 665 mg 3 times daily), and IR (2 × 500 mg 4 times daily). At steady state, twice-daily SR paracetamol was bioequivalent to ER and IR paracetamol. The 90% confidence intervals for the ratios of geometric means were within the acceptance interval for SR/ER paracetamol (AUC 0-t , 0.973-1.033; AUC 0-24 , 0.974-1.034; AUC 0-∞ , 0.948-1.011; C max , 1.082-1.212; C av , 1.011-1.106) and SR/IR paracetamol (AUC 0-t , 0.969-1.029; AUC 0-24 , 0.968-1.027; AUC 0-∞ , 0.963-1.026; C max , 0.902-1.010; C av , 1.004-1.098). Given twice daily, the SR formulation demonstrated SR properties as expected. Mean time at or above a 4 μg/mL plasma concentration of paracetamol from 2 daily doses of the SR formulation was significantly longer than that from 4 daily doses of IR paracetamol. SR formulation also had a greater T max , a longer half-life, and lower C min compared with ER and IR paracetamol. All formulations were well tolerated. © 2017, The American College of Clinical Pharmacology.

Influence of daily setup measurements and corrections on the estimated delivered dose during IMRT treatment of prostate cancer patients

International Nuclear Information System (INIS)

Haaren, Paul M.A. van; Bel, Arjan; Hofman, Pieter; Vulpen, Marco van; Kotte, Alexis N.T.J.; Heide, Uulke A. van der

2009-01-01

Purpose: To evaluate the impact of marker-based position verification, using daily imaging and an off-line correction protocol, by calculating the delivered dose to prostate, rectum and bladder. Methods: Prostate cancer patients (n = 217) were treated with IMRT, receiving 35 daily fractions. Plans with five beams were optimized taking target coverage (CTV, boost) and organs-at-risk (rectum and bladder) into account. PTV margins were 8 mm. Prostate position was verified daily using implanted fiducial gold markers by imaging the first segment of all the five beams on an EPID. Setup deviations were corrected off-line using an adapted shrinking-action-level protocol. The estimated delivered dose, including daily organ movements, was calculated using a version of PLATO's dose engine, enabling batch processing of large numbers of patients. The dose was calculated ± inclusion of setup corrections, and was evaluated relative to the original static plan. The marker-based measurements were considered representative for all organs. Results: Daily organ movements would result in an underdosage of 2-3 Gy to CTV and boost volume relative to the original plan, which was prevented by daily setup corrections. The dose to rectum and bladder was on average unchanged, but a large spread was introduced by organ movements, which was reduced by including setup corrections. Conclusions: Without position verification and setup corrections, margins of 8mm would be insufficient to account for position uncertainties during IMRT of prostate cancer. With the daily off-line correction protocol, the remaining variations are accommodated adequately

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.

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

Science.gov (United States)

Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

2017-01-01

Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

Science.gov (United States)

Yap, Felix Boon-Bin

2017-09-01

Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

SU-E-T-86: Comparison of Two Commercially Available Programs for the Evaluation of Delivered Daily Dose Using Cone Beam CT (CBCT)

International Nuclear Information System (INIS)

Tuohy, R; Bosse, C; Mavroidis, P; Shi, Z; Crownover, R; Papanikolaou, N; Stathakis, S

2014-01-01

Purpose: In this study, two commercially available programs were compared for the evaluation of delivered daily dose using cone beam CT (CBCT). Methods: Thirty (n=30) patients previously treated in our clinic (10 prostate, 10 SBRT lung and 10 abdomen) were used in this study. The patients' plans were optimized and calculated using the Pinnacle treatment planning system. The daily CBCT scans were imported into Velocity and RayStation along with the corresponding planning CTs, structure sets and 3D dose distributions for each patient. The organs at risk (OAR) were contoured on each CBCT by the prescribing physician and were included in the evaluation of the daily delivered dose. Each CBCT was registered to the planning CT, once with rigid registration and then again, separately, with deformable registration. After registering each CBCT, the dose distribution from the planning CT was overlaid and the dose volume histograms (DVH) for the OAR and the planning target volumes (PTV) were calculated. Results: For prostate patients, we observed daily volume changes for the OARs. The DVH analysis for those patients showed variation in the sparing of the OARs while PTV coverage remained virtually unchanged using both Velocity and RayStation systems. Similar results were observed for abdominal patients. In contrast, for SBRT lung patients, the DVH for the OARs and target were comparable to those from the initial treatment plan. Differences in organ volume and organ doses were also observed when comparing the daily fractions using deformable and rigid registrations. Conclusion: By using daily CBCT dose reconstruction, we proved PTV coverage for prostate and abdominal targets is adequate. However, there is significant dosimetric change for the OARs. For lung SBRT patients, the delivered daily dose for both PTV and OAR is comparable to the planned dose with no significant differences

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

Directory of Open Access Journals (Sweden)

Shen J

2017-09-01

Full Text Available Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP, but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans, suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

Science.gov (United States)

Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

1989-12-01

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

An observational study evaluating tacrolimus dose, exposure, and medication adherence after conversion from twice- to once-daily tacrolimus in liver and kidney transplant recipients.

Science.gov (United States)

Bäckman, Lars; Persson, Carl-Axel

2014-03-17

Immunosuppression regimens in transplantation medicine are complex. Drugs with extended release action have simplified medication dosing without affecting efficacy. This prospective, observational, multicenter study, conducted in a routine medical practice setting, evaluated changes in tacrolimus daily dose and trough levels and patient-reported medication adherence at day 90 after 1:1 (mg: mg) conversion to once-daily tacrolimus in adult liver and kidney transplant recipients. Data from 224 recipients of a liver (n=19) or kidney (n=205) transplant, average age 51±14.5 years, were evaluated. The mean change in tacrolimus daily dose was +0.04 mg/day. Dose remained stable after conversion in 62.5%, was lower in 15.6%, and higher in 22% of patients. Trough level after conversion was lower in 62.6% and higher in 36.5%; generally, levels were 12.8% lower than pre-conversion levels. No acute rejection, graft loss, or serious safety events were observed. Two deaths occurred due to myocardial infarction. Conversion helped 19% to less frequently forget medications and 55% reported no difference in remembering to take the once-daily dose after conversion. The change in dosing frequency was identified as "better" for 55%. Tacrolimus daily dose remained stable while trough levels were significantly lower after conversion to once-daily dosing. Safety and efficacy were maintained; reduced dosing frequency had no apparent influence on patient-reported medication adherence.

Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma

International Nuclear Information System (INIS)

Hoebers, Frank J.P.; Heemsbergen, Wilma; Balm, Alfons J.M.; Zanten, Mathilde van; Schornagel, Jan H.; Rasch, Coen R.N.

2007-01-01

Background and purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin. Materials and methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m 2 i.v. x20, daily before RT). After 47 patients, the treatment protocol (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were given to the subsequent 74 patients (Hydr-Ac-RT Group). Results: Mean follow-up was 29 months (range 7-62). More chemotherapy could be administered in the Hydr-Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of patients, p = 0.008), with less renal toxicity (p < 0.001) and less hospital admissions (p < 0.02). However, mucositis was more pronounced and tubefeeding more frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from 74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p = 0.06), although this did not lead to an improvement in loco-regional control. Conclusions: Concurrent chemoradiation with daily low dose cisplatin is feasible and effective for selected patients with advanced HNSCC. Although the addition of accelerated RT resulted in more mucositis and tubefeeding, the introduction of prehydration led to better compliance to therapy with more chemotherapy administered and less hospital admissions

Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

NARCIS (Netherlands)

Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

2012-01-01

Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

Open-Label Single-Sequence Crossover Study Evaluating Pharmacokinetics, Efficacy, and Safety of Once-Daily Dosing of Nitisinone in Patients with Hereditary Tyrosinemia Type 1.

Science.gov (United States)

Guffon, Nathalie; Bröijersén, Anders; Palmgren, Ingrid; Rudebeck, Mattias; Olsson, Birgitta

2018-01-01

Although nitisinone is successfully used to treat hereditary tyrosinemia type 1 (HT-1) with the recommended twice-daily dosing, data describing a long half-life motivate less frequent dosing. Therefore, in agreement with the Pharmacovigilance Risk Assessment Committee at the European Medicines Agency, this study was performed to investigate the switch to once-daily dosing. This open-label, non-randomized, single-sequence crossover study evaluated the pharmacokinetics, efficacy, and safety of once-daily compared to twice-daily dosing of nitisinone in patients with HT-1 (NCT02323529). Well-controlled patients of dry blood spots by tandem mass spectrometry. The primary endpoint was C min of nitisinone after ≥4 weeks of treatment on each dosing regimen. Secondary objectives were evaluation of efficacy and safety during each dosing regimen. In total, 19 patients were enrolled and 17 included in the per-protocol analysis set. The mean (SD) nitisinone C min decreased by 23%, from 26.4 (10.2) to 21.2 (9.9) μmol/L in dry blood spot samples (not equivalent to plasma concentrations), when patients switched from twice- to once-daily dosing. There was no apparent age- or bodyweight-related trend in the degree of C min decrease. No patient had quantifiable succinylacetone levels during the once-daily treatment period, indicating efficacious treatment. All adverse events were mild or moderate and judged unrelated to nitisinone. The switch to once-daily treatment with nitisinone appeared efficacious and safe in the treatment of patients with HT-1.

Treatment of subclinical hypothyroidism in pregnancy using fixed thyroxine daily doses of 75 μg.

Science.gov (United States)

Penin, Manuel; Trigo, Cristina; López, Yolanda; Barragáns, María

2014-01-01

Treatment of hypothyroid pregnant women is usually calculated based on weight (1 μg/kg/day) and TSH levels. This study assessed the usefulness of treating these women with a fixed dose of 75 μg/day. All women with pregnancy diagnosed from January to August 2012 in the Vigo Health Area (Spain) without previous diagnosis of thyroid disease or thyroxine treatment and with TSH levels over 4,5 mUI/ml were enrolled by consecutive sampling. All 116 women in the sample were treated with a fixed daily dose of thyroxine 75 μg-thyroxine levels were measured at two, four, and six months, and thyroxine dose was modified if TSH level was lower than 0.3 or higher than 4.5 mUI/ml. A woman had a TSH level less than 0.3 mUI/ml in a test; reduction of thyroxine dose to 50 μg/day allowed for maintaining TSH level within the desired range until delivery. Six women had TSH levels over 4.5 mUI/ml in one test; in all of them, increase in thyroxine dose to 100 μg/day allowed for maintaining the level within the desired range until delivery. Fixed daily doses of thyroxine 75 μg allowed for achieving goal TSH levels in most of our pregnant women with subclinical hypothyroidism, irrespective of their weight and baseline TSH level. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

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.

A single daily dose enhances the adherence to immunosuppressive treatment in kidney transplant recipients: a cross-sectional study.

Science.gov (United States)

Obi, Yoshitsugu; Ichimaru, Naotsugu; Kato, Taigo; Kaimori, Jun-Ya; Okumi, Masayoshi; Yazawa, Koji; Rakugi, Hiromi; Nonomura, Norio; Isaka, Yoshitaka; Takahara, Shiro

2013-04-01

Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival.

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.

Dynamic interactions between hydrogeological and exposure parameters in daily dose prediction under uncertainty and temporal variability

Energy Technology Data Exchange (ETDEWEB)

Kumar, Vikas, E-mail: vikas.kumar@urv.cat [Department of Chemical Engineering, Rovira i Virgili University, Tarragona 43007 (Spain); Barros, Felipe P.J. de [Sonny Astani Department of Civil and Environmental Engineering, University of Southern California, Los Angeles 90089, CA (United States); Schuhmacher, Marta [Department of Chemical Engineering, Rovira i Virgili University, Tarragona 43007 (Spain); Fernàndez-Garcia, Daniel; Sanchez-Vila, Xavier [Hydrogeology Group, Department of Geotechnical Engineering and Geosciences, University Politècnica de Catalunya-BarcelonaTech, Barcelona 08034 (Spain)

2013-12-15

Highlights: • Dynamic parametric interaction in daily dose prediction under uncertainty. • Importance of temporal dynamics associated with the dose. • Different dose experienced by different population cohorts as a function of time. • Relevance of uncertainty reduction in the input parameters shows temporal dynamism. -- Abstract: We study the time dependent interaction between hydrogeological and exposure parameters in daily dose predictions due to exposure of humans to groundwater contamination. Dose predictions are treated stochastically to account for an incomplete hydrogeological and geochemical field characterization, and an incomplete knowledge of the physiological response. We used a nested Monte Carlo framework to account for uncertainty and variability arising from both hydrogeological and exposure variables. Our interest is in the temporal dynamics of the total dose and their effects on parametric uncertainty reduction. We illustrate the approach to a HCH (lindane) pollution problem at the Ebro River, Spain. The temporal distribution of lindane in the river water can have a strong impact in the evaluation of risk. The total dose displays a non-linear effect on different population cohorts, indicating the need to account for population variability. We then expand the concept of Comparative Information Yield Curves developed earlier (see de Barros et al. [29]) to evaluate parametric uncertainty reduction under temporally variable exposure dose. Results show that the importance of parametric uncertainty reduction varies according to the temporal dynamics of the lindane plume. The approach could be used for any chemical to aid decision makers to better allocate resources towards reducing uncertainty.

Modification of the biologic dose to normal tissue by daily fraction

Energy Technology Data Exchange (ETDEWEB)

Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

1976-12-01

A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

Evaluation of delivered dose for a clinical daily adaptive plan selection strategy for bladder cancer radiotherapy

International Nuclear Information System (INIS)

Lutkenhaus, Lotte J.; Visser, Jorrit; Jong, Rianne de; Hulshof, Maarten C.C.M.; Bel, Arjan

2015-01-01

Purpose: To account for variable bladder size during bladder cancer radiotherapy, a daily plan selection strategy was implemented. The aim of this study was to calculate the actually delivered dose using an adaptive strategy, compared to a non-adaptive approach. Material and methods: Ten patients were treated to the bladder and lymph nodes with an adaptive full bladder strategy. Interpolated delineations of bladder and tumor on a full and empty bladder CT scan resulted in five PTVs for which VMAT plans were created. Daily cone beam CT (CBCT) scans were used for plan selection. Bowel, rectum and target volumes were delineated on these CBCTs, and delivered dose for these was calculated using both the adaptive plan, and a non-adaptive plan. Results: Target coverage for lymph nodes improved using an adaptive strategy. The full bladder strategy spared the healthy part of the bladder from a high dose. Average bowel cavity V30Gy and V40Gy significantly reduced with 60 and 69 ml, respectively (p < 0.01). Other parameters for bowel and rectum remained unchanged. Conclusions: Daily plan selection compared to a non-adaptive strategy yielded similar bladder coverage and improved coverage for lymph nodes, with a significant reduction in bowel cavity V30Gy and V40Gy only, while other sparing was limited

Is Daily Low-Dose Aspirin Safe to Take Following Laparoscopic Roux-en-Y Gastric Bypass for Obesity Surgery?

Science.gov (United States)

Kang, Xian; Hong, Dennis; Anvari, Mehran; Tiboni, Maria; Amin, Nalin; Gmora, Scott

2017-05-01

Laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery is a safe and effective procedure for patients with severe obesity. One potential complication of LRYGB is the development of marginal ulcers (MUs). Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to significantly increase the likelihood of developing marginal ulcers after surgery. However, the risk associated with low-dose aspirin consumption is not well defined. We examined the impact of daily low-dose aspirin (81 mg) on the development of marginal ulcers following LRYGB. A retrospective cohort design studied patients undergoing LRYGB surgery, between January 2009 and January 2013, at a single, high-volume bariatric center in Ontario, Canada. The marginal ulcer rate of patients taking low-dose aspirin after surgery was compared to that of the control patients who did not take any NSAID. Diagnosis of MU was confirmed by upper endoscopy in patients presenting with symptoms and a history indicative of marginal ulceration. A chi-square test of independence was performed to examine the difference in marginal ulcer rates. A total of 1016 patients underwent LRYGB. Patients taking aspirin were more likely to be male, older, and have diabetes than patients not taking NSAIDs. Of the 1016 patients, 145 (14.3%) took low-dose aspirin following LRYGB and the rest did not (n = 871, 85.7%). The incidence of marginal ulceration was not significantly different between the two treatment groups (12/145, 8.3% versus 90/871, 10.3%; p = 0.45). Patients treated with LRYGB at our institution were not at increased risk of marginal ulcer formation when taking low-dose aspirin after surgery.

Adaptive Liver Stereotactic Body Radiation Therapy: Automated Daily Plan Reoptimization Prevents Dose Delivery Degradation Caused by Anatomy Deformations

Energy Technology Data Exchange (ETDEWEB)

Leinders, Suzanne M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Delft University of Technology, Delft (Netherlands); Breedveld, Sebastiaan; Méndez Romero, Alejandra [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Schaart, Dennis [Delft University of Technology, Delft (Netherlands); Seppenwoolde, Yvette, E-mail: y.seppenwoolde@erasmusmc.nl [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands); Heijmen, Ben J.M. [Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam (Netherlands)

2013-12-01

Purpose: To investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery.

Digital Drug Dosing: Dosing in Drug Assays by Light-Defined Volumes of Hydrogels with Embedded Drug-Loaded Nanoparticles

DEFF Research Database (Denmark)

Faralli, Adele; Melander, Fredrik; Larsen, Esben Kjær Unmack

2014-01-01

Polyethylene glycol (PEG)-based hydrogels are widely used for biomedical applications, including matrices for controlled drug release. We present a method for defining drug dosing in screening assays by light-activated cross-linking of PEG-diacrylate hydrogels with embedded drug-loaded liposome...

SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

International Nuclear Information System (INIS)

Zhao, J; Hu, W; Xing, Y; Wu, X; Li, Y

2016-01-01

Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, position and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.

SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

Energy Technology Data Exchange (ETDEWEB)

Zhao, J; Hu, W [Fudan University Shanghai Cancer Center, Shanghai, Shanghai (China); Xing, Y [Fudan univercity shanghai proton and heavy ion center, Shanghai (China); Wu, X [Fudan university shanghai proton and heavy ion center, Shanghai, shagnhai (China); Li, Y [Department of Medical physics at Shanghai Proton and Heavy Ion Center, Shanghai, Shanghai (China)

2016-06-15

Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, position and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.

Influence of the number of daily pills and doses on adherence to antiretroviral treatment: a 7-year study.

Science.gov (United States)

Hernández Arroyo, M J; Cabrera Figueroa, S E; Sepúlveda Correa, R; Valverde Merino, M P; Luna Rodrigo, G; Domínguez-Gil Hurlé, A

2016-02-01

Antiretroviral treatment (ART) is hampered by complicated regimens, high pill burden, drug-drug interactions, and frequent short- and long-term adverse effects, leading to decreased adherence. Over recent years, considerable effort has been directed at developing regimens that are less burdening. We undertook a 7-year retrospective study of the records of 264 HIV-infected subjects enrolled in a pharmaceutical care programme to document the progress made and to study the influence of the number of ART pills and doses on the level of treatment adherence. Antiretroviral dispensing records were analysed for the number of pills and doses administered and the ART adherence rate estimated. In 2005, the patients took a mean of 6·2 pills daily (CI 95%: 5·9-6·6), and 92·9% of them were on a twice-a-day (BID) dosage regimen. By 2012, the mean number of pills was reduced to 4·1 (CI 95%: 3·8-4·4), and only 50·9% were on a BID regimen. No statistically significant relation was observed between number of daily pills and doses and ART adherence reached by the patients in any of the analyses performed. There has been a continuous reduction in the number of pills and doses of antiretrovirals taken by individual patients over the last 7 years due largely to the introduction of improved treatments and regimens. More daily pills or doses was not associated with worse ART adherence in our pharmaceutical care programme. © 2015 John Wiley & Sons Ltd.

Comparison of therapy augmentation and deviation rates from the recommended once-daily dosing regimen between LDX and commonly prescribed long-acting stimulants for the treatment of ADHD in youth and adults.

Science.gov (United States)

Setyawan, Juliana; Hodgkins, Paul; Guérin, Annie; Gauthier, Geneviève; Cloutier, Martin; Wu, Eric; Erder, M Haim

2013-10-01

To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically

Radiotherapy combined with daily administration of low dose cisplatin for head and neck cancer

International Nuclear Information System (INIS)

Fujita, Masahiro; Murayama, Shigeyuki; Matayoshi, Yoshinobu; Ikeda, Hiroshi; Shimizutani, Kimishige; Inoue, Toshihiko; Kozuka, Takahiro; Masaki, Norie.

1990-01-01

Serum concentrations of cisplatin (CDDP) and acute complications were studied in patients treated for head and neck cancer by radiotherapy combined with daily administration of low doses of CDDP (5 mg/m 2 or 6 mg/body) at Osaka University Hospital between March 1988 and December 1989. Serum concentrations of total-CDDP (6 patients) and free-CDDP (2 patients) were studied in cases injected intravenously with 5 mg/m 2 daily. Total-CDDP determined just before daily administration of CDDP was increased gradually (0.35 to 0.64 μg/ml by the 7th day, 0.42 to 0.91 μg/ml by the 14th day and 0.60 to 0.82 μg/ml by the 20th or 21st day) and still observed in the serum for more than two weeks after cessation of the chemotherapy. Serum concentrations of free-CDDP were about 0.35 μg/ml at 5 minutes and 0.15 μg/ml at 30 minutes after the intravenous injection of CDDP. Incidence of the acute complications more severe than grade 2 were nausea and vomiting: 4/52 (8%), leukopenia: 11/52 (21%) and thrombocytopenia: 4/52 (8%). Incidence of myelosuppression (leukopenia and/or thrombocytopenia) was 11/26(42%) when the total dose of CDDP exceeded 120 mg, and 3/26 (12%) when it was less than 120 mg. Transient renal dysfunction (increase of serum creatinine) of grade 1 was seen in only 3 patients. (author)

Rationale and design of the worldwide prospective multicenter registry on radiation dose estimates of cardiac CT angiography in daily practice in 2017 (PROTECTION VI)

DEFF Research Database (Denmark)

Stocker, Thomas J; Deseive, Simon; Chen, Marcus

2018-01-01

-randomized and randomized studies have been performed to reduce the associated radiation exposure. Currently, it is unclear if the advances in technology and knowledge about radiation reduction translated into reduced levels of cardiac CTA radiation dose in daily clinical practice as well as a wide utilization of dose......-saving strategies. METHODS: The PROTECTION VI study is a multicenter, prospective, worldwide registry designed to evaluate radiation dose exposure, utilization of dose-saving strategies and diagnostic image quality during cardiac CTA in current daily practice. Assessment of image quality will be addressed...... median radiation dose levels, image quality, frequency of use and efficacy of algorithms for dose reduction, and patient and study-related predictors associated with radiation dose. CONCLUSIONS: The PROTECTION VI study is designed to provide a reliable estimate of current radiation dose for cardiac CTA...

Radiation therapy in cancer patients with psoriasis. The fractionated daily dose and the Koebner phenomenon

International Nuclear Information System (INIS)

Ben-Yosef, Rami; Soyfer, Vyacheslav; Vexler, Akiva

2005-01-01

Skin side effects following XRT take place more often in patients with skin disorders. In this study six patients with psoriatic lesions were evaluated. The total/daily XRT dose to the tumor site was 50-70/1.8-2.0 Gy. No debilitating effect of XRT was observed in both the psoriatic lesions and in the surrounding normal skin

Hematopoietic tissue repair under chronic low daily dose irradiation

International Nuclear Information System (INIS)

Seed, T.M.

1994-01-01

The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

Nonrandomized study comparing the effects of preoperative radiotherapy and daily administration of low-dose cisplatin with those radiotherapy alone for oral cancer

International Nuclear Information System (INIS)

Kurita, Hiroshi; Azegami, Takuya; Kobayashi, Hirokazu; Kurashina, Kenji; Tanaka, Kouichi; Kotani, Akira; Oguchi, Masahiko; Tamura, Minoru.

1997-01-01

The purpose of this study was to compare the effect of preoperative radiotherapy and daily administration of low-dose cisplatin with those of radiotherapy alone for oral cancer. Ten patients underwent preoperative radiotherapy of 30 to 40 Gy with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten patients received external radiotherapy alone. The locoregional response rates (complete response and partial response) did not differ significantly between the two groups (80% for combined therapy and 60% for radiotherapy alone). On histopathologic evaluation of surgical specimens, however, the combined-therapy group (80%) had a higher response rate than did the radiotherapy-alone group (10%; p<0.01). We conclude that daily administration of low-dose cisplatin enhances the efficacy of radiotherapy against primary tumors. We also suggested that combined therapy may be beneficial as an initial treatment for oral cancer before a planned operation. (author)

Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

International Nuclear Information System (INIS)

Bauer, G

2011-01-01

Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

Estimation of the effectivity of gamma teletherapy with fractionated daily doses in inoperable malignant tumors

International Nuclear Information System (INIS)

Mardynskij, Yu.S.; Leskov, V.P.

1982-01-01

131 patients with lung, esophagus, rectum and mandibulofacial tumors, most of them being inoperable, were treated with fractionated gamma teletherapy. The daily focus dose of 2-2.2 Gy was applied in 2 fractions with an interval of 4-6 h. The total focus dose of one course of treatment was 40-70 Gy. In 56 patients (42.7%) a complete regression of the tumors and of the increased regional lymph nodes was obtained. The irradiation by the mentioned technique showed the highest effectivity for tumors of the lung and the esophagus. The diminished frequency and an easier progress of the radiation reactions are important because they often prevent to carry out a radical therapy. (author)

Development of evaluation method of collective dose of general public considering the daily life activity and time use

International Nuclear Information System (INIS)

Nagaoka, Toshi; Saito, Kimiaki; Sakamoto, Ryuichi; Tsutsumi, Masahiro; Moriuchi, Shigeru

1994-11-01

A code for evaluation of collective dose of general public to natural radiation has been developed, in which the variation of dose rate due to place of stay is taken into consideration. Only external exposure to natural radiation is subject to discussion in this report. Strict manner of dose evaluation requires the dose rate and the time period of stay for each place and for each person. It is possible to know (measure) them all, but not practicable. In this code, dose rate information was obtained from actually measured data by the authors and estimation based on the environmental conditions. Information on the time period of stay was obtained from a Survey Data on Time Use and Leisure Activities by Management and Coordination Agency, and from Statistical Yearbook of Tokyo with some realistic assumptions. By using them, collective dose was evaluated taking both the daily life style and dose rate varying place by place into consideration. In this report, the dose evaluation code and the results about doses for Tokyo citizens are mentioned. (author)

Reducing dosing frequency of carbidopa/levodopa: double-blind crossover study comparing twice-daily bilayer formulation of carbidopa/levodopa (IPX054) versus 4 daily doses of standard carbidopa/levodopa in stable Parkinson disease patients.

Science.gov (United States)

Hinson, Vanessa K; Goetz, Christopher G; Leurgans, Sue; Fan, Wenqing; Nguyen, Tiffany; Hsu, Ann

2009-01-01

We compared IPX054, a bilayer tablet of immediate- and extended-release carbidopa/levodopa (CD/LD) given twice daily to standard CD/LD given 4 times daily in patients with stable Parkinson disease (PD). Twelve PD patients with no or mild fluctuations on CD/LD 25/100 mg 4 times daily were randomized to a double-blind crossover comparison with IPX054 (50/200 mg) twice daily. At the end of each 2-week treatment, patients were video recorded while performing a modified Unified Parkinson's Disease Rating Scale motor examination and Rush Dyskinesia Rating Scale at 30-minute intervals over 8.5 hours. The primary outcome measure was the number of videotape epochs rated as "ON" without troublesome dyskinesia by a blinded observer (Wilcoxon signed rank tests). The 9 men and 3 women had a mean age of 69 years and mean PD duration of 6 years. IPX054 and CD/LD showed no significant differences in the primary outcome measure (mean number of video epochs rated as ON without troublesome dyskinesia; P = 0.14). The mean time to ON was improved with IPX054 (P = 0.014), and the mean modified Unified Parkinson's Disease Rating Scale scores slightly favored IPX054 (14.4 vs 16.9; P = 0.052). Mean Rush Dyskinesia Rating Scale scores were not significantly different between IPX054 and CD/LD (0.45 vs 0.69; P = 0.25). No patient developed troublesome dyskinesias. In stable PD patients, no difference was detected between twice-daily treatment with IPX054 and CD/LD given 4 times daily. In this group, substitution with IPX054 reduced dosing frequency while maintaining CD/LD efficacy. In clinical practice, this ease of administration may offer improved treatment compliance.

Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli

2014-01-01

BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

Influence of intravenous opioid dose on postoperative ileus.

Science.gov (United States)

Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

2011-07-01

Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.

Phase I dose escalation clinical trial of phenylbutyrate sodium administered twice daily to patients with advanced solid tumors.

Science.gov (United States)

Camacho, Luis H; Olson, Jon; Tong, William P; Young, Charles W; Spriggs, David R; Malkin, Mark G

2007-04-01

Phenylbutyrate (PBA), and its metabolite phenylacetate (PAA), induce growth inhibition and cellular differentiation in multiple tumor models. However, despite their potential anti-cancer properties, several pharmacodynamic aspects remain unknown. We conducted a dose escalating trial to evaluate twice-daily intravenous PBA infusions for two consecutive weeks (Monday through Friday) every month at five dose levels (60-360 mg/kg/day). Twenty-one patients with the following malignancies were treated: colon carcinoma 4, non-small cell lung carcinoma 4; anaplastic astrocytoma 3, glioblastoma multiforme 3, bladder carcinoma 2, sarcoma 2, and ovarian carcinoma, rectal hemangiopericytoma, and pancreatic carcinoma 1 each. Conversion of PBA to PAA and phenylacetylglutamine (PAG) was documented without catabolic saturation. Plasma content of PBA > or =1 mM was documented for only 3 h following each dose at the top two dosages. The therapy was well tolerated overall. Common adverse effects included grade 1 nausea/vomiting, fatigue, and lightheadedness. Dose limiting toxicities were short-term memory loss, sedation, confusion, nausea, and vomiting. Two patients with anaplastic astrocytoma and a patient with glioblastoma remained stable without tumor progression for 5, 7, and 4 months respectively. Administration of PBA in a twice-daily infusion schedule is safe. The maximum tolerated dose is 300 mg/kg/day. Study designs with more convenient treatment schedules and specific molecular correlates may help to further delineate the mechanism of action of this compound. Future studies evaluating PBA's ability to induce histone acetylation and cell differentiation alone or in combination with other anti-neoplastics are recommended.

Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers

NARCIS (Netherlands)

Aarnoutse, Rob E; Kleinnijenhuis, Johanneke; Koopmans, Peter P; Touw, Daan J; Wieling, Jaap; Hekster, Yechiel A; Burger, David M

2005-01-01

OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers.

NARCIS (Netherlands)

Aarnoutse, R.E.; Kleinnijenhuis, J.; Koopmans †, P.P.; Touw, D.J.; Wieling, J.; Hekster, Y.A.; Burger, D.M.

2005-01-01

OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

Energy Technology Data Exchange (ETDEWEB)

Narayana, V; McLaughlin, P [Providence Cancer Center, Southfield, MI (United States); University of Michigan, Ann Arbor, MI (United States); Ealbaj, J [University of Michigan, Ann Arbor, MI (United States)

2015-06-15

Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma

Directory of Open Access Journals (Sweden)

Woodcock Ashley

2011-12-01

Full Text Available Abstract Background Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD evening and twice-daily (BD regimens of the novel inhaled corticosteroid fluticasone furoate (FF in asthma patients. Methods Patients with moderate asthma (age ≥ 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1 40-85% predicted; FEV1 reversibility of ≥ 12% and ≥ 200 ml were randomized to FF or fluticasone propionate (FP regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ≥ 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 μg OD, FF or FP 100 μg BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough FEV1; non-inferiority of FF 200 μg OD and FF 100 μg BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs and 24-hour urinary cortisol excretion were assessed. Results The intent-to-treat population comprised 147 (FF and 43 (FP patients. On Day 28, pre-dose FEV1 showed FF 200 μg OD to be non-inferior (pre-defined limit -110 ml to FF 100 μg BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml; all FF and FP regimens were significantly superior to placebo (p ≤ 0.02. AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 μg OD, 0.75; 100 μg BD, 0.84; p ≤ 0.02. Conclusions FF 200 μg OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose. Trial registration Clinicaltrials.gov; NCT00766090.

[Study of personal best value of peak expiratory flow in patients with asthma--comparison of the highest value of daily PEF under good control and the highest value of daily PEF obtained after using repeated inhaled beta2-agonist during high-dose inhaled steroid treatment].

Science.gov (United States)

Watanabe, Naoto; Makino, Sohei; Kihara, Norio; Fukuda, Takeshi

2008-12-01

In the guideline for asthma management, it is important to find the personal best value of peak expiratory flow (best PEF). Recently, we have substituted the highest value of PEF in daily life under good control (daily highest PEF) for the best PEF. In the present study, we considered whether the daily highest PEF could be used as the best PEF or not. Subjects were 30 asthmatics who were well controlled but whose baseline PEF values were less than 80 percent of predicted values. We compared the daily highest PEF and the highest of PEF obtained after repeated inhaled beta2-agonist (salbutamol MDI every 20 minutes three times). All subjects then received 1600 microg/day of beclomethasone dipropionate (BDP) for 4 to 8 weeks. We studied the effect of high-dose inhaled steroid treatment on each PEF value and compared the daily highest PEF and the highest PEF obtained after using repeated salbutamol MDI during high dose inhaled steroid therapy on the examination day again. The baseline PEF, daily highest PEF and the highest PEF obtained after salbutamol MDI were significantly less than the each values obtained after high-dose BDP. The best PEF value of them was the value obtained after repeated salbutamol MDI during high dose BDP. We suggest that the daily highest PEF under good control is not a substitute for best PEF because it changes according to the degree of improvement of airway inflammation. We recommend that a course of high dose inhaled steroid is effective in finding the best value of PEF for each individual with moderate asthma.

Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better?

International Nuclear Information System (INIS)

Vicini, Frank A.; Abner, Anthony; Baglan, Kathy L.; Kestin, Larry L.; Martinez, Alvaro A.

2001-01-01

Purpose: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship. Methods and Materials: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded. Results: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] ≥10, Gleason score [GS] ≥7, or tumor stage ≥T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified. Conclusions: Although RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefiting most, and the optimal dose remain to be defined

OMI/Aura Surface UVB Irradiance and Erythemal Dose Daily L2 Global 0.25 deg Lat/Lon Grid V003

Data.gov (United States)

National Aeronautics and Space Administration — The Version 003 of Aura-OMI Spectral Surface UVB Irradiance and Erythemal Dose Level-2G data product (Daily level-2 data binned into global 0.25 deg Lat/Lon grids)...

Determination of 210Po concentration in commercially available infant formulae and assessment of daily ingestion dose

OpenAIRE

Prabhath, Ravi K.; Sreejith, Sathyapriya R.; Nair, Madhu G.; Rao, D.D.; Pradeepkumar, K.S.

2015-01-01

A study has been conducted to estimate the concentration of natural radioactive polonium in commercially available packaged infant food formulae available in Mumbai, India and the corresponding daily dose normalized based on its shelf life. Eleven most popular international brands of infant formulae were sourced from market and three aliquots from each sample were analysed for concordant results. Autodeposition method onto a silver planchet from hot dilute acid solution followed by alpha spec...

Evaluating organ delineation, dose calculation and daily localization in an open-MRI simulation workflow for prostate cancer patients

International Nuclear Information System (INIS)

Doemer, Anthony; Chetty, Indrin J; Glide-Hurst, Carri; Nurushev, Teamour; Hearshen, David; Pantelic, Milan; Traughber, Melanie; Kim, Joshua; Levin, Kenneth; Elshaikh, Mohamed A; Walker, Eleanor; Movsas, Benjamin

2015-01-01

This study describes initial testing and evaluation of a vertical-field open Magnetic Resonance Imaging (MRI) scanner for the purpose of simulation in radiation therapy for prostate cancer. We have evaluated the clinical workflow of using open MRI as a sole modality for simulation and planning. Relevant results related to MRI alignment (vs. CT) reference dataset with Cone-Beam CT (CBCT) for daily localization are presented. Ten patients participated in an IRB approved study utilizing MRI along with CT simulation with the intent of evaluating the MRI-simulation process. Differences in prostate gland volume, seminal vesicles, and penile bulb were assessed with MRI and compared to CT. To evaluate dose calculation accuracy, bulk-density-assignments were mapped onto respective MRI datasets and treated IMRT plans were re-calculated. For image localization purposes, 400 CBCTs were re-evaluated with MRI as the reference dataset and daily shifts compared against CBCT-to-CT registration. Planning margins based on MRI/CBCT shifts were computed using the van Herk formalism. Significant organ contour differences were noted between MRI and CT. Prostate volumes were on average 39.7% (p = 0.002) larger on CT than MRI. No significant difference was found in seminal vesicle volumes (p = 0.454). Penile bulb volumes were 61.1% higher on CT, without statistical significance (p = 0.074). MRI-based dose calculations with assigned bulk densities produced agreement within 1% with heterogeneity corrected CT calculations. The differences in shift positions for the cohort between CBCT-to-CT registration and CBCT-to-MRI registration are −0.15 ± 0.25 cm (anterior-posterior), 0.05 ± 0.19 cm (superior-inferior), and −0.01 ± 0.14 cm (left-right). This study confirms the potential of using an open-field MRI scanner as primary imaging modality for prostate cancer treatment planning simulation, dose calculations and daily image localization

Twelve-hour brain lithium concentration in lithium maintenance treatment of manic-depressive disorder: daily versus alternate-day dosing schedule

DEFF Research Database (Denmark)

Jensen, H.V.; Plenge, P; Stensgaard, A

1996-01-01

The 12-h brain lithium concentration was measured by lithium-7 magnetic resonance spectroscopy in ten manic-depressive patients receiving daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 800 mg in the daily treatment group and 1200 mg in the alternate......-day group. Median 12-h serum lithium concentration in the two groups was 0.86 mmol l-1 and 0.55 mmol l-1, respectively, while the corresponding concentration in brain was 0.67 mmol l-1 and 0.52 mmol l-1, respectively. The 12-h brain lithium concentration was independent of lithium dosing schedule (multiple...... linear regression), but correlated significantly with the 12-h serum lithium concentration (P = 0.003; B = 0.53, 95% c.l. 0.24-0.82; beta = 0.83). Thus at identical 12-h serum lithium concentrations the 12-h brain lithium concentration is similar with both treatment regimes. As the risk of manic...

Effect of daily low dose gamma irradiation on growth and differentiation of human myeloid leukaemic bone marrow in diffusion chambers

Energy Technology Data Exchange (ETDEWEB)

Greenberger, J S [Joint Center for Radiation Therapy, Department of Radiation and Sidney Farber Cancer Institute; Chang, J M; King, V; Fulmer, S; Balzuno, S; Moloney, W C [Division of Hematology, Department of Medicine, Brigham and Women' s Hospital Harvard Medical School, Boston, USA

1981-01-01

Bone marrow from each of 8 untreated patients with myeloproliferative disorders was grown in diffusion chambers in 760 rad total body irradiated rats. Rats were exposed to 11.5, 57.5, or 108.5 rad daily for 14-21 and cell growth compared to that detected in unirradiated chambers. Cells from acute myelogenous leukaemia patients exposed to 11.5 rad per d grew for 11-21 d and there was no consistent stimulation of differentiation of immature granulocytic cells to mature granulocytes that was attributable to irradiation. Cells from a chronic myeloid leukaemia patient in chronic phase or blast crisis, and a polycythaemia vera patient with myeloid metaplasia showed signigicant morphologic differentiation from immature to mature granulocytes in control chambers with no additional effect of daily irradiation. Marrow specimens from 2 AML patients exposed to each of 3 daily dose fractions over 14 d revealed a dose-dependent decrease in immature granulocytes with no persistent increase in mature granulocytes. In both irradiated and control chambers, macrophages increased over 21 d. Thus, cells from patients with myeloprofilerative disorders may not necessarily differentiate to mature granulocytes following in vivo exposure to ionizing irradiation.

Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

Directory of Open Access Journals (Sweden)

Iyoke CA

2017-05-01

Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

Estimation of rectal dose using daily megavoltage cone-beam computed tomography and deformable image registration.

Science.gov (United States)

Akino, Yuichi; Yoshioka, Yasuo; Fukuda, Shoichi; Maruoka, Shintaroh; Takahashi, Yutaka; Yagi, Masashi; Mizuno, Hirokazu; Isohashi, Fumiaki; Ogawa, Kazuhiko

2013-11-01

The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CT value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R(2)=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R(2)=0.61±0.16). We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume. Copyright © 2013 Elsevier Inc. All rights reserved.

Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

Energy Technology Data Exchange (ETDEWEB)

Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Department of Radiology, Osaka University Hospital, Suita, Osaka (Japan); Yoshioka, Yasuo [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Fukuda, Shoichi [Department of Radiation Oncology, Osaka General Medical Center, Osaka (Japan); Maruoka, Shintaroh [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Takahashi, Yutaka [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota (United States); Yagi, Masashi [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan); Mizuno, Hirokazu [Department of Radiology, Osaka University Hospital, Suita, Osaka (Japan); Isohashi, Fumiaki [Oncology Center, Osaka University Hospital, Suita, Osaka (Japan); Ogawa, Kazuhiko [Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

2013-11-01

Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CT value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.

Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

Science.gov (United States)

Gaber, A. Osama; Alloway, Rita R.; Bodziak, Kenneth; Kaplan, Bruce; Bunnapradist, Suphamai

2013-01-01

Background LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations. PMID:23715050

Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

Science.gov (United States)

Orbelo, Diana M; Enders, Felicity T; Romero, Yvonne; Francis, Dawn L; Achem, Sami R; Dabade, Tushar S; Crowell, Michael D; Geno, Debra M; DeJesus, Ramona S; Namasivayam, Vikneswaran; Adamson, Steven C; Arora, Amindra S; Majka, Andrew J; Alexander, Jeffrey A; Murray, Joseph A; Lohse, Matthew; Diehl, Nancy N; Fredericksen, Mary; Jung, Kee Wook; Houston, Margaret S; O'Neil, Angela E; Katzka, David A

2015-01-01

Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

Daily organ tracking in intensity-modulated radiotherapy of prostate cancer using an electronic portal imaging device with a dose saving acquisition mode

International Nuclear Information System (INIS)

Vetterli, Daniel; Thalmann, Sandrine; Behrensmeier, Frank; Kemmerling, Ludger; Born, Ernst J.; Mini, Roberto; Greiner, Richard H.; Aebersold, Daniel M.

2006-01-01

Background and purpose: Daily use of conventional electronic portal imaging devices (EPID) for organ tracking is limited due to the relatively high dose required for high quality image acquisition. We studied the use of a novel dose saving acquisition mode (RadMode) allowing to take images with one monitor unit per image in prostate cancer patients undergoing intensity-modulated radiotherapy (IMRT) and tracking of implanted fiducial gold markers. Patients and methods: Twenty five patients underwent implantation of three fiducial gold markers prior to the planning CT. Before each treatment of a course of 37 fractions, orthogonal localization images from the antero-posterior and from the lateral direction were acquired. Portal images of both the setup procedure and the five IMRT treatment beams were analyzed. Results: On average, four localization images were needed for a correct patient setup, resulting in four monitor units extra dose per fraction. The mean extra dose delivered to the patient was thereby increased by 1.2%. The procedure was precise enough to reduce the mean displacements prior to treatment to ≤0.3 mm. Conclusions: The use of a new dose saving acquisition mode enables to perform daily EPID-based prostate tracking with a cumulative extra dose of below 1 Gy. This concept is efficiently used in IMRT-treated patients, where separation of setup beams from treatment beams is mandatory

Detemir as a once-daily basal insulin in type 2 diabetes

Directory of Open Access Journals (Sweden)

Nelson SE

2011-08-01

Full Text Available Scott E NelsonCleveland Family Medicine, Cleveland, Mississippi, USABackground: Insulin detemir, a long-acting basal insulin analog, is labeled for once-daily or twice-daily dosing in patients with type 1 (T1DM or type 2 (T2DM diabetes mellitus. Protocols for some earlier clinical studies of detemir evaluated twice-daily dosing, which may have generated the misperception that detemir should be prescribed twice daily for most patients. This review examines pharmacokinetic and pharmacodynamic (PK/PD, observational, and controlled studies that have evaluated once-daily and twice-daily detemir in patients with T2DM to determine the efficacy and safety of once-daily dosing.Methods: PubMed was searched using the keywords “detemir,” “once daily,” “twice daily,” and “type 2 diabetes” with the limits of clinical trial, human, and English.Results: Detemir has a relatively flat time–action profile and duration of action of up to 24 hours for patients with T2DM. Once-daily dosing is the most commonly used detemir regimen reported in observational studies, and controlled clinical studies indicate that once-daily dosing controls glycosylated hemoglobin when detemir is administered alone or in combination with a prandial insulin or oral antidiabetes drugs. In comparative clinical trials, detemir had a similar time–action profile and duration of action to another long-acting insulin analog, glargine, with less within-subject variability. Once-daily detemir was associated with no weight gain or less weight gain than comparator regimens. For patients who had not achieved glycemic control with a basal dose of once-daily detemir, adding a prandial insulin provided better glycemic control, less postprandial hypoglycemia, and a lower total daily dose of detemir than twice-daily detemir. Involvement of a multidisciplinary team and the use of a holistic approach for the treatment of T2DM patients are recommended to achieve and maintain the best

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

International Nuclear Information System (INIS)

Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K.

2004-01-01

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 ∼ 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 ∼ 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively (ρ = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively (ρ = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively (ρ = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively (ρ = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia (≥ 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively (ρ = 0.02). There were no statistical differences

Comparison of the result of radiation alone and radiation with daily low dose cisplatin in management of locally advanced cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Kim, Hun Jung; Kim, Woo Chul; Lee, Mee Jo; Kim, Chul Su; Song, Eun Seop; Loh, John J. K. [Inha University Medical College, Inchon (Korea, Republic of)

2004-09-15

An analysis was to compare the results of radiation alone with those of radiation with daily low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was performed. Thirty one patients received radiation alone and 28 patients received daily low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900 {approx} 1,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000 {approx} 3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4%) and 8 (13.6%) stages IIB and stage IIIB, respectively. The overall 5 year survival rate was 65.65% and according to treatment modality were 56.75% and 73.42% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.180). The 5 year disease-free survival rates were 49.39% and 63.34% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.053). The 5 year locoregional control rates were 52.34% and 73.58% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.013). The 5 year distant disease-free survival rates were 59.29% and 81.46% in the radiation alone and chemoradiation groups, respectively ({rho} = 0.477). Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia ({>=} 3 grade) occurred in 3.2% and 28.5% of the radiation alone and chemoradiation groups, respectively ({rho} = 0.02). There were

The daily radon dose in body organs caused by drinking milk and water

International Nuclear Information System (INIS)

Mansoureh Mansour Bahmani; Mohammad Reza Rezaie; Elham Rezvan Nejad; Hassan Reza Dehghan

2014-01-01

Milk is considered as the richest nutrition, being used by people. When drinking milk or water the radon gas will transfer from air to them rapidly. Since milk is majorly composed of water, probably radon existence in livestock consumable water could be the main cause of its presence in milk. Different portion of milk changed by radon gamma ray and consumption of radon included water or milk has its effects on the human body. For investigation the effect of radon in water or milk on human organs, this study has been done in two phases with MCNPX software. In the first phase, the dose rate of absorbed gamma ray by different portion of milk which is indoctrinated by 1 Bq/m 3 of radon during a day is calculated. Moreover, the effects shown by milk and its components in radon gamma spectrum, which is demonstrator of milk absorption spectrum, are also surveyed. In the second phase as well, according to the human body phantom, the absorbed gamma dose caused by daily consumption of indoctrinated water or milk with 1 Bq/m 3 radon is calculated. The production rate of free radicals in milk and its different components are derived according to escape data of MCNPX code. (author)

Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer

International Nuclear Information System (INIS)

Zuur, Charlotte L.; Simis, Yvonne J.W.; Verkaik, Roxanna S.; Schornagel, Jan H.; Balm, Alfons J.M.; Dreschler, Wouter A.; Rasch, Coen R.N.

2008-01-01

Background and purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort. Materials and methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients. Patients received low-dose cisplatin (6 mg/m 2 , daily infusions, 20-25 days) with concomitant accelerated radiotherapy (70 Gy). Results: Audiometry up to 16 kHz was performed before therapy and 31 days (median) post-treatment. The total incidence of ototoxicity in CTCAEv3.0 was 31% in audiograms up to 8 kHz, and 5% of ears tested qualified for HAs due to treatment. The mean hearing loss at speech frequencies was 2.6 dB (SD 5.7) and 2.3 dB (SD 9.2) at PTA 1-2-4 kHz air-conduction and bone-conduction, respectively. The mean hearing loss at ultra-high frequencies (PTA AC 8-10-12.5 kHz) was 9.0 dB (SD 8.1). Low-dose cisplatin CRT caused less acute hearing loss (CTCAE 31%), compared to high-dose cisplatin CRT (CTCAE 78%). Conclusions: Low-dose cisplatin chemo-irradiation for HNSCC is a relatively safe treatment protocol with respect to ototoxicity

Analysis of thermal-dose response to heat

International Nuclear Information System (INIS)

Storm, F.; Roe, D.; Drury, B.

1987-01-01

The authors reasoned that if hyperthermia alone has a clinical anti-tumor effect, response should have a thermal dose relationship. The authors analyzed 100 patients with advanced cancer treated with magnetic-induction. Three methods of determining thermal dose were used: (A) t1x10, the lowest temperature sustained throughout the tumor for 30-60min during the first of ten daily treatments, which represents one usual course of ten hourly sessions; (B) t43 (equivalent minutes at 43C) which accounts for non-linear tumor heating by combining serially measured temperatures during the first treatment with a mathematical description of the time-temperature relationship for thermal inactivation or damage; (C) Ct43 (cumulative t43), which represents the t43 value multiplied by the actual number of subsequent daily treatments received. Response was defined as CR+PR+MR. The results show a statistically significant effect of heat alone for t1x10, t43, and Ct43. These analyses demonstrate a thermal-dose relationship between hyperthermia therapy and tumor response as a sole independent variable, which indicates that heat therapy has clinical anti-cancer activity

Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial

NARCIS (Netherlands)

Eron, Joseph J.; Rockstroh, Jürgen K.; Reynes, Jacques; Andrade-Villanueva, Jaime; Ramalho-Madruga, Jose Valdez; Bekker, Linda-Gail; Young, Benjamin; Katlama, Christine; Gatell-Artigas, Jose Maria; Arribas, Jose R.; Nelson, Mark; Campbell, Havilland; Zhao, Jing; Rodgers, Anthony J.; Rizk, Matthew L.; Wenning, Larissa; Miller, Michael D.; Hazuda, Daria; DiNubile, Mark J.; Leavitt, Randi; Isaacs, Robin; Robertson, Michael N.; Sklar, Peter; Nguyen, Bach-Yen; Bloch, M. T.; Hoy, J.; Workman, C.; Madruga, J. V.; Souza, T.; Telles, F. Q.; Zajdenverg, R.; Angel, J.; Montaner, J. S.; Smith, G. H. R.; Trottier, B.; Tamara, J. R.; Velez, J. D.; Gerstoft, J.; Laursen, A. L.; Mathiesen, L.; Katlama, C.; Molina, J. M.; Raffi, F.; Reynes, J.; Yazdanpanah, Y.; Bogner, J. R.; Fatkenheuer, G.; Hartl, H.; Jaeger, H.; Geerlings, S. E.

2011-01-01

Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to

High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS

Directory of Open Access Journals (Sweden)

Hui-Min Chang

2016-06-01

Conclusion: We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

SU-F-T-224: Importance of Timely Review of Daily Cone-Beam CTs: Dosimetric Evaluation of Rejected CBCTs for Head and Neck Patients

Energy Technology Data Exchange (ETDEWEB)

Andrews, M; Yu, N; Joshi, N; Koyfman, S; Xia, P [Cleveland Clinic, Cleveland, OH (United States); Lin, S [Cleveland State University, Cleveland, OH (United States)

2016-06-15

Purpose: To dosimetrically evaluate the importance of timely reviewing daily CBCTs for patients with head and neck cancer. Methods: After each fraction daily cone-beam CT (CBCT) for head and neck patients are reviewed by physicians prior to next treatment. Physician rejected image registrations of CBCT were identified and analyzed for 17 patients. These CBCT images were rigidly fused with planning CT images and the contours from the planning CT were transferred to CBCTs. Because of limited extension in the superior-inferior dimension contours with partial volumes in CBCTs were discarded. The treatment isocenter was placed by applying the clinically recorded shifts to the volume isocenter of the CBCT. Dose was recalculated at the shifted isocenter using a homogeneous dose calculation algorithm. Dosimetrically relevant changes defined as greater than 5% deviation from the clinically accepted plans but with homogeneous dose calculation were evaluated for the high dose (HD), intermediate dose (ID), and low dose (LD) CTVs, spinal cord, larynx, oropharynx, parotids, and submandibular glands. Results: Among seventeen rejected CBCTS, HD-CTVs, ID-CTVs, and LD-CTVs were completely included in the CBCTs for 17, 1, and 15 patients, respectively. The prescription doses to the HD-CTV, ID-CTV, and LD-CTV were received by < 95% of the CTV volumes in 5/17, 1/1, and 5/15 patients respectively. For the spinal cord, the maximum doses (D0.03cc) were increased > 5% in 13 of 17 patients. For the oropharynx, larynx, parotid, and submandibular glands, the mean dose of these organs at risk was increased > 5% in 7/17, 8/12, 11/16 and 6/16 patients, respectively. Conclusion: Timely review daily CBCTs for head and neck patients under daily CBCT guidance is important, and uncorrected setup errors can translate to dosimetrically relevant dose increases in organsat- risk and dose decreases in the clinical target volumes.

A model to incorporate organ deformation in the evaluation of dose/volume relationship

International Nuclear Information System (INIS)

Yan, D.; Jaffray, D.; Wong, J.; Brabbins, D.; Martinez, A. A.

1997-01-01

treatment have been collected prospectively during their course of treatment. The data was used retrospectively to examine the model, and to evaluate the cumulative dose/volume relationships of the prostate, rectum and bladder in comparison with those in the initial treatment plan. Results: Characteristics of daily organ deformation were specific to the individual patient and could not be easily represented by a global description. Daily deformation of the prostate secondary to local filling of rectum and bladder could not be simply modeled using the linear transformation of rigid body motion. The cumulative dose distribution in the prostate was either overestimated or underestimated using the linear model. Deformation of the rectum due to rectal filling occurred at different positions on different days. Consequently, daily hot spots occurred on different locations of the rectal wall. Therefore, the direct combination of the daily dose volume histograms would overestimate the actual dose/volume relation. Furthermore, the shapes and positions of the prostate, rectum, and bladder defined in the initial planning CT scan were not representative of the mean shape and position as assumed in the linear model for rigid organ motion. As such, the linear convolution method based upon rigid motion of the initial CT volumes led to misleading results in the planning evaluation and optimization for the individual patient. Conclusion: Our proposed model provides a more realistic description of the viscoelastic nature of daily organ deformation than the current rigid body models. It provides a systematic framework to incorporate the daily organ motion in the calculation of cumulative dose/volume relationships throughout the course of treatment. This information may play an important role in the treatment evaluation and reoptimization for the individual patient

Once- versus twice-daily aspirin treatment in patients with essential thrombocytosis

DEFF Research Database (Denmark)

Larsen, Mads Lamm; Pedersen, Oliver Heidmann; Hvas, Anne-Mette

2018-01-01

Insufficient platelet inhibition has been reported in up to 40% of aspirin-treated patients, including patients with essential thrombocytosis. To maintain sufficient platelet inhibition, a shorter dosing interval with aspirin has been suggested. We aimed to investigate the antiplatelet effect...... of low-dose aspirin given twice-daily compared to standard once-daily dosing in patients with essential thrombocytosis. We included 22 patients, who were treated for 7 days with standard once-daily aspirin (75 mg once-daily) followed by 7 days treatment of twice-daily aspirin (37.5 mg twice......-daily). The two regimens were separated by 14 days aspirin washout. Blood samples were obtained 1h and 24h/12h after the last pill intake in each regimen. The effect of aspirin was evaluated by: (1) platelet aggregation measured by whole blood impedance aggregometry (Multiplate® Analyser) using arachidonic acid...

Estimating the real world daily usage and cost for exenatide twice daily and liraglutide in Germany, the Netherlands, and the UK based on volumes dispensed by pharmacies

Directory of Open Access Journals (Sweden)

McDonell AL

2015-01-01

Full Text Available Amanda L McDonell,1 Urpo Kiiskinen,2 Danielle C Zammit,3 Robert W Kotchie,1 Per-Olof Thuresson,3 Claudia Nicolay,4 Thomas Haslam,1 Michiel Bruinsma,5 Anne-Jeanine Janszen-Van Oosterhout,6 Thorsten Otto41IMS Health, London, UK; 2Eli Lilly and Company, Helsinki, Finland; 3IMS Health, Basel, Switzerland; 4Eli Lilly and Company, Bad Homburg, Germany; 5IMS Health, Rotterdam, the Netherlands; 6Eli Lilly Nederland, Houten, the NetherlandsBackground: Glucagon-like peptide-1 (GLP-1 receptor agonists are indicated for improvement of glycemic control in adults with type 2 diabetes. Cost is one aspect of treatment to be considered, in addition to clinical benefits, when selecting optimal therapy for a patient. The objective of this study was to estimate the average dose usage and real world daily cost of the GLP-1 receptor agonists, exenatide twice daily and liraglutide once daily, in Germany, the Netherlands, and the UK.Methods: Administrative databases were used to source the data from longitudinal records of dispensed prescriptions. Data were extracted from the IMS Longitudinal Prescription database which captures details of prescriptions dispensed in pharmacies. Information on the dispensed quantity of each product was used to estimate average daily usage per patient. Daily dose usage was multiplied by the public price per unit to estimate daily cost.Results: The dispensed volume in Germany corresponded to a mean dispensed daily dose of 16.81 µg for exenatide twice daily and 1.37 mg for liraglutide (mean daily cost €4.02 and €4.54, respectively. In the Netherlands, average dispensed daily doses of 17.07 µg and 1.49 mg were observed for exenatide twice daily and liraglutide (mean daily cost €3.05 and €3.97, respectively. In the UK, the mean dispensed volume corresponded to a daily usage of 20.49 µg for exenatide twice daily and 1.50 mg for liraglutide (mean daily cost £2.53 and £3.28, respectively.Conclusion: Estimates of average daily

TU-H-CAMPUS-JeP3-02: Automated Dose Accumulation and Dose Accuracy Assessment for Online Or Offline Adaptive Replanning

International Nuclear Information System (INIS)

Chen, G; Ahunbay, E; Li, X

2016-01-01

Purpose: With introduction of high-quality treatment imaging during radiation therapy (RT) delivery, e.g., MR-Linac, adaptive replanning of either online or offline becomes appealing. Dose accumulation of delivered fractions, a prerequisite for the adaptive replanning, can be cumbersome and inaccurate. The purpose of this work is to develop an automated process to accumulate daily doses and to assess the dose accumulation accuracy voxel-by-voxel for adaptive replanning. Methods: The process includes the following main steps: 1) reconstructing daily dose for each delivered fraction with a treatment planning system (Monaco, Elekta) based on the daily images using machine delivery log file and considering patient repositioning if applicable, 2) overlaying the daily dose to the planning image based on deformable image registering (DIR) (ADMIRE, Elekta), 3) assessing voxel dose deformation accuracy based on deformation field using predetermined criteria, and 4) outputting accumulated dose and dose-accuracy volume histograms and parameters. Daily CTs acquired using a CT-on-rails during routine CT-guided RT for sample patients with head and neck and prostate cancers were used to test the process. Results: Daily and accumulated doses (dose-volume histograms, etc) along with their accuracies (dose-accuracy volume histogram) can be robustly generated using the proposed process. The test data for a head and neck cancer case shows that the gross tumor volume decreased by 20% towards the end of treatment course, and the parotid gland mean dose increased by 10%. Such information would trigger adaptive replanning for the subsequent fractions. The voxel-based accuracy in the accumulated dose showed that errors in accumulated dose near rigid structures were small. Conclusion: A procedure as well as necessary tools to automatically accumulate daily dose and assess dose accumulation accuracy is developed and is useful for adaptive replanning. Partially supported by Elekta, Inc.

Population dose-response analysis of daily seizure count following vigabatrin therapy in adult and pediatric patients with refractory complex partial seizures.

Science.gov (United States)

Nielsen, Jace C; Hutmacher, Matthew M; Wesche, David L; Tolbert, Dwain; Patel, Mahlaqa; Kowalski, Kenneth G

2015-01-01

Vigabatrin is an irreversible inhibitor of γ-aminobutyric acid transaminase (GABA-T) and is used as an adjunctive therapy for adult patients with refractory complex partial seizures (rCPS). The purpose of this investigation was to describe the relationship between vigabatrin dosage and daily seizure rate for adults and children with rCPS and identify relevant covariates that might impact seizure frequency. This population dose-response analysis used seizure-count data from three pediatric and two adult randomized controlled studies of rCPS patients. A negative binomial distribution model adequately described daily seizure data. Mean seizure rate decreased with time after first dose and was described using an asymptotic model. Vigabatrin drug effects were best characterized by a quadratic model using normalized dosage as the exposure metric. Normalized dosage was an estimated parameter that allowed for individualized changes in vigabatrin exposure based on body weight. Baseline seizure rate increased with decreasing age, but age had no impact on vigabatrin drug effects after dosage was normalized for body weight differences. Posterior predictive checks indicated the final model was capable of simulating data consistent with observed daily seizure counts. Total normalized vigabatrin dosages of 1, 3, and 6 g/day were predicted to reduce seizure rates 23.2%, 45.6%, and 48.5%, respectively. © 2014, The American College of Clinical Pharmacology.

Urinary steroid hormone patterns: III. Effect of continuous daily administration of low dose megestrol acetate.

Science.gov (United States)

Kumari, G L; Roy, S; Allag, I S; Ghosal, J

1975-12-01

The effect of megestrol acetate, administered in daily doses of .5 mg, on urinary steroid levels was studied before, during, and after therapy in 4 women volunteers. In each case, pregnanediol levels were reduced, though ovulatory biphasic patterns, as reflected in basal body temperature patterns, were apparent in the majority of the cycles, which suggests that corpus luteum function, but not ovulation, was impaired. 17-ketosteroid levels were significantly (p less than .001) increased either during or after treatment, while 17-hydroxycorticoid levels were reduced in 3 of the women. 2 subjects showed a marked reduction in levels of 17-ketogenic steroids and corticoid levels. Total estrogen levels seemed to correlate with the levels of corticoid excretion.

Twice-daily versus once-daily applications of pimecrolimus cream 1% for the prevention of disease relapse in pediatric patients with atopic dermatitis.

Science.gov (United States)

Ruer-Mulard, Mireille; Aberer, Werner; Gunstone, Anthony; Kekki, Outi-Maria; López Estebaranz, Jose Luis; Vertruyen, André; Guettner, Achim; Hultsch, Thomas

2009-01-01

The aim of this study is to compare twice-daily and once-daily applications of pimecrolimus cream 1% for prevention of atopic dermatitis relapses in pediatric patients. This multicenter trial enrolled 300 outpatients aged 2 to 17 years, with mild-to-severe atopic dermatitis. The patients were initially treated with twice-daily topical pimecrolimus until complete clearance or for up to 6 weeks (open-label period). Those who achieved a decrease of at least 1 point in the Investigator's Global Assessment score were then randomized to double-blind treatment with pimecrolimus cream 1% either twice daily or once daily for up to 16 weeks. Study medication was discontinued during periods of disease remission (Investigator's Global Assessment = 0). The primary efficacy end point of the double-blind phase was disease relapse (worsening requiring topical corticosteroids or additional/alternative therapy and confirmed by Investigator's Global Assessment score > or = 3 and pruritus score > or = 2). Of the 300 patients enrolled in the study, 268 were randomized to treatment with pimecrolimus cream 1% either twice daily or once daily (n = 134 in each group). The relapse rate was lower in the twice-daily dose group (9.9%) than that in the once-daily dose group (14.7%), but analysis of the time to disease relapse, using a Cox proportional model to adjust for confounding variables, did not show a statistically significant difference between treatment arms (hazard ratio: 0.64; 95% CI: 0.31-1.30). Treatment of active atopic dermatitis lesions with pimecrolimus cream 1% twice daily, followed by the once-daily dosing regimen, was sufficient to prevent subsequent atopic dermatitis relapses over 16 weeks in pediatric patients.

Near real-time automated dose restoration in IMPT to compensate for daily tissue density variations in prostate cancer

Science.gov (United States)

Jagt, Thyrza; Breedveld, Sebastiaan; van de Water, Steven; Heijmen, Ben; Hoogeman, Mischa

2017-06-01

Proton therapy is very sensitive to daily density changes along the pencil beam paths. The purpose of this study is to develop and evaluate an automated method for adaptation of IMPT plans to compensate for these daily tissue density variations. A two-step restoration method for ‘densities-of-the-day’ was created: (1) restoration of spot positions (Bragg peaks) by adapting the energy of each pencil beam to the new water equivalent path length; and (2) re-optimization of pencil beam weights by minimizing the dosimetric difference with the planned dose distribution, using a fast and exact quadratic solver. The method was developed and evaluated using 8-10 repeat CT scans of 10 prostate cancer patients. Experiments demonstrated that giving a high weight to the PTV in the re-optimization resulted in clinically acceptable restorations. For all scans we obtained V 95%  ⩾  98% and V 107%  ⩽  2%. For the bladder, the differences between the restored and the intended treatment plan were below  +2 Gy and  +2%-point. The rectum differences were below  +2 Gy and  +2%-point for 90% of the scans. In the remaining scans the rectum was filled with air, which partly overlapped with the PTV. The air cavity distorted the Bragg peak resulting in less favorable rectum doses.

Non-daily pre-exposure prophylaxis for HIV prevention

Science.gov (United States)

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Observability of market daily volatility

Science.gov (United States)

Petroni, Filippo; Serva, Maurizio

2016-02-01

We study the price dynamics of 65 stocks from the Dow Jones Composite Average from 1973 to 2014. We show that it is possible to define a Daily Market Volatility σ(t) which is directly observable from data. This quantity is usually indirectly defined by r(t) = σ(t) ω(t) where the r(t) are the daily returns of the market index and the ω(t) are i.i.d. random variables with vanishing average and unitary variance. The relation r(t) = σ(t) ω(t) alone is unable to give an operative definition of the index volatility, which remains unobservable. On the contrary, we show that using the whole information available in the market, the index volatility can be operatively defined and detected.

SU-F-J-203: Retrospective Assessment of Delivered Proton Dose in Prostate Cancer Patients Based On Daily In-Room CT Imaging

Energy Technology Data Exchange (ETDEWEB)

Stuetzer, K; Paessler, T [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Valentini, C; Thiele, J; Hoelscher, T [Department of Radiation Oncology, University Hospital Carl Gustav Carus, Techenische Universitaet Dresden (Germany); Exner, F [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); now with: University of Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Krause, M; Richter, C [OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universitaet Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Techenische Universitaet Dresden (Germany); Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology, Dresden (Germany); German Cancer Consortium (DKTK), Dresden, Germany and German Cancer Research Center (DKFZ), Heidelberg (Germany)

2016-06-15

Purpose: Retrospective calculation of the delivered proton dose in prostate cancer patients based on a unique dataset of daily CT images. Methods: Inter-fractional motion in prostate cancer patients treated at our proton facility is counteracted by water-filled endorectal ballon and bladder filling protocol. Typical plans (XiO, Elekta Instruments AB, Stockholm) for 74 Gy(RBE) sequential boost treatment in 37 fractions include two series of opposing lateral double-scattered proton beams covering the respective iCTV. Stability of fiducial markers and anatomy were checked in 12 patients by daily scheduled in-room control CT (cCT) after immobilization and positioning according to bony anatomy utilizing orthogonal X-ray. In RayStation 4.6 (RaySearch Laboritories AB, Stockholm), all cCTs are delineated retrospectively and the treatment plans were recalculated on the planning CT and the registered cCTs. All fraction doses were accumulated on the planning CT after deformable registration. Parameters of delivered dose to iCTV (D98%>95%, D2%<107%), bladder (V75Gy<15%, V70Gy<25%, V65Gy<30%), rectum (V70Gy<10%, V50Gy<40%) and femoral heads (V50Gy<5%) are compared to those in the treatment plan. Intra-therapy variation is represented in DVH bands. Results: No alarming differences were observed between planned and retrospectively accumulated dose: iCTV constraints were met, except for one patient (D98%=94.6% in non-boosted iCTV). Considered bladder and femoral head values were below the limits. Rectum V70Gy was slightly exceeded (<11.3%) in two patients. First intra-therapy variability analysis in 4 patients showed no timedependent parameter drift, revealed strongest variability for bladder dose. In some fractions, iCTV coverage (D98%) and rectum V70Gy was missed. Conclusion: Double scattered proton plans are accurately delivered to prostate cancer patients due to fractionation effects and the applied precise positioning and immobilization protocols. As a result of rare

Comparison of health care resource utilization and costs among patients with GERD on once-daily or twice-daily proton pump inhibitor therapy

Directory of Open Access Journals (Sweden)

Mody R

2013-04-01

Full Text Available Reema Mody,1 Debra Eisenberg,2 Likun Hou,2 Siddhesh Kamat,2 Joseph Singer,2 Lauren B Gerson3 1Takeda Pharmaceuticals International Inc, Deerfield, IL, 2HealthCore Inc, Wilmington, DE, 3Stanford University School of Medicine, Stanford, CA, USA Background: The purpose of this study was to assess differences in health care resource utilization and costs associated with once-daily and twice-daily proton pump inhibitor (PPI therapy. Most patients with gastroesophageal reflux disease (GERD achieve symptom control on once-daily PPI therapy, but approximately 20%–30% require twice-daily dosing. Methods: Patients were ≥18 years of age with at least one medical claim for GERD and at least two PPI claims from HealthCore's Integrated Research Database (HIRDSM during 2004–2009. Patients were continuously eligible for 12 months before and after the index date (date of first PPI claim. Based on PPI dosing throughout the post-index period (quantity of medication dispensed/number of days supply, patients were classified as once-daily (dose ≤ 1.5 pills per day or twice-daily (≥1.5 PPI users. Results: The study cohort included 248,386 patients with GERD (mean age 52.8 ± 13.93 years, 56% females of whom 90% were once-daily and 10% were twice-daily PPI users. The Deyo-Charlson Comorbidity Index for once-daily and twice-daily PPI users was 0.70 ± 1.37 and 0.89 ± 1.54, respectively (P < 0.05. More once-daily patients had claims for Barrett's esophagus (5% versus 2%, P < 0.0001 than twice-daily patients. Post-index, higher proportions of twice-daily patients had at least one GERD-related inpatient visit (7% versus 5%, outpatient visit (60% versus 49%, and office visit (48% versus 38% versus once-daily patients (P < 0.0001. Mean total GERD-related health care costs were $2065 ± $6636 versus $3749 ± $11,081 for once-daily and twice-daily PPI users, respectively (P < 0.0001. Conclusion: Patients receiving twice-daily PPI therapy were likely to have more

Changes of some serum proteins in rats continuously irradiated with daily dose rate of 0. 0258 C/kg

Energy Technology Data Exchange (ETDEWEB)

Chlebovska, K; Chlebovsky, O; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

1976-01-01

Changes of serum albumin, haptoglobin, hemopexin and IgG in rats during chronic /sup 60/Co gamma irradiation with a daily dose rate of 0.0258 C/kg within 44 days were investigated by the method of two-dimensional quantitative immunoelectrophoresis. In comparison with normal levels, the values of albumin and IgG in rats during irradiation decreased until the death of animals to 50%, the values of haptoglobin increased till the 39th day of irradiation to 250% and hemopexin values increased to 150%.

Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for AAA and Acuros XB algorithms.

Science.gov (United States)

Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca

2016-10-01

Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (AAA) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for AAA and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by AAA and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for AAA, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

Science.gov (United States)

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (Cmax), and plasma concentrations at the end of the dosing interval (Cτ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80

Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

Science.gov (United States)

Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

2018-01-01

Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

International Nuclear Information System (INIS)

Kumarasiri, A; Siddiqui, F; Liu, C; Kamal, M; Fraser, C; Chetty, I; Kim, J

2015-01-01

Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-mass mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to

SU-E-J-66: Significant Anatomical and Dosimetric Changes Observed with the Pharyngeal Constrictor During Head and Neck Radiotherapy Elicited From Daily Deformable Image Registration and Dose Accumulation

Energy Technology Data Exchange (ETDEWEB)

Kumarasiri, A; Siddiqui, F; Liu, C; Kamal, M; Fraser, C; Chetty, I; Kim, J [Henry Ford Health System, Detroit, MI (United States)

2015-06-15

Purpose: To evaluate the anatomical changes and associated dosimetric consequences to the pharyngeal constrictor (PC) that occurs during head and neck radiotherapy (H&N RT). Methods: A cohort of 13 oro-pharyngeal cancer patients, who had daily CBCT’s for localization, was retrospectively studied. On every 5th CBCT, PC was manually delineated by a radiation oncologist. The anterior-posterior PC thickness was measured at the C3 level. Delivered dose to PC was estimated by calculating daily doses on CBCT’s, and accumulating to corresponding planning CT images. For accumulation, a parameter-optimized B- spline-based deformable image registration algorithm (Elastix) was used, in conjunction with an energy-mass mapping dose transfer algorithm. Mean and maximum dose (Dmean, Dmax) to PC was determined and compared with corresponding planned quantities. Results: The mean (±standard deviation) volume increase (ΔV) and thickness increase (Δt) over the course of 35 total fractions were 54±33% (11.9±7.6 cc), and 63±39% (2.9±1.9 mm), respectively. The resultant cumulative mean dose increase from planned dose to PC (ΔDmean) was 1.4±1.3% (0.9±0.8 Gy), while the maximum dose increase (ΔDmax) was 0.0±1.6% (0.0±1.1 Gy). Patients with adaptive replanning (n=6) showed a smaller mean dose increase than those without (n=7); 0.5±0.2% (0.3±0.1 Gy) vs. 2.2±1.4% (1.4±0.9 Gy). There was a statistically significant (p<0.0001) strong correlation between ΔDmean and Δt (Pearson coefficient r=0.78), and a moderate-to-strong correlation (r=0.52) between ΔDmean and ΔV. Correlation between ΔDmean and weight loss ΔW (r=0.1), as well as ΔV and ΔW (r=0.2) were negligible. Conclusion: Patients were found to undergo considerable anatomical changes to pharyngeal constrictor during H&N RT, resulting in non-negligible dose deviations from intended dose. Results are indicative that pharyngeal constrictor thickness, measured at C3 level, is a good predictor for the dose change to

A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

Science.gov (United States)

Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

2014-03-01

The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Blood responses under chronic low daily dose gamma irradiation: Pt.1

International Nuclear Information System (INIS)

Seed, T.M.; Carnes, B.A.; Tolle, D.V.; Fritz, T.E.

1989-01-01

Male beagles chronically exposed to low daily doses of 60 Co γ rays show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival ( -S -AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders ( + R-MPD group); or (3) high radioresistance with other nonMPD syndromes ( + R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked - S-AA >> + R-MPD > + R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked + R-MPD > + R-nonMPD >>> - S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the + R-nonMPD subgroup consistently exhibited stronger responses than the + R-MPD subgroup. These results support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression. (author)

Development of chronic daily headache : A clinical study

NARCIS (Netherlands)

Spierings, E.L.H.; Schroevers, M.; Honkoop, P.C.; Sorbi, M.

1998-01-01

We studied the development of chronic daily headache in 258 headache practice patients, 50 men and 208 women. Chronic daily headache was defined as headaches occurring at least 5 days per week for at least 1 year. Twenty-two percent of the patients had daily headaches from the onset, and 78%

Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Przemyslaw Kardas

2007-05-01

Full Text Available Przemyslaw KardasThe First Department of Family Medicine, Medical University of LodzBackground: A randomized, controlled trial was conducted in an outpatient setting to examine the effect of beta-blocker dosing frequency on patient compliance, clinical outcome, and health-related quality of life in patients with stable angina pectoris.Methods: One hundred and twelve beta-blockers-naive outpatients with stable angina pectoris were randomized to receive betaxolol, 20 mg once daily or metoprolol tartrate, 50 mg twice daily for 8 weeks. The principal outcome measure was overall compliance measured electronically, whereas secondary outcome measures were drug effectiveness and health-related quality of life.Results: The overall compliance was 86.5 ± 21.3% in the betaxolol group versus 76.1 ± 26.3% in the metoprolol group (p < 0.01, and the correct number of doses was taken on 84.4 ± 21.6% and 64.0 ± 31.7% of treatment days, respectively (p < 0.0001. The percentage of missed doses was 14.5 ± 21.5% in the once-daily group and 24.8 ± 26.4% in the twice-daily group (p < 0.01. The percentage of doses taken in the correct time window (58.6% vs 42.0%, p = 0.01, correct interdose intervals (77.4% v 53.1%, p < 0.0001, and therapeutic coverage (85.6% vs 73.7%, p < 0.001 were significantly higher in the once-daily group. Both studied drugs had similar antianginal effectiveness. Health-related quality of life improved in both groups, but this increase was more pronounced in the betaxolol arm in some dimensions.Conclusions: The study demonstrates that patient compliance with once-daily betaxolol is significantly better than with twice daily metoprolol. Similarly, this treatment provides better quality of life. These results demonstrate possible therapeutic advantages of once-daily over twice-daily beta-blockers in the treatment of stable angina pectoris.Keywords: patient compliance, quality of life, stable angina pectoris, randomized controlled trial

Carbohydrate-to-insulin ratio is estimated from 300-400 divided by total daily insulin dose in type 1 diabetes patients who use the insulin pump.

Science.gov (United States)

Kuroda, Akio; Yasuda, Tetsuyuki; Takahara, Mitsuyoshi; Sakamoto, Fumie; Kasami, Ryuichi; Miyashita, Kazuyuki; Yoshida, Sumiko; Kondo, Eri; Aihara, Ken-ichi; Endo, Itsuro; Matsuoka, Taka-aki; Kaneto, Hideaki; Matsumoto, Toshio; Shimomura, Iichiro; Matsuhisa, Munehide

2012-11-01

To optimize insulin dose using insulin pump, basal and bolus insulin doses are widely calculated from total daily insulin dose (TDD). It is recommended that total daily basal insulin dose (TBD) is 50% of TDD and that the carbohydrate-to-insulin ratio (CIR) equals 500 divided by TDD. We recently reported that basal insulin requirement is approximately 30% of TDD. We therefore investigated CIR after adjustment of the proper basal insulin rate. Forty-five Japanese patients with type 1 diabetes were investigated during several weeks of hospitalization. The patients were served standard diabetes meals (25-30 kcal/kg of ideal body weight). Each meal omission was done to confirm basal insulin rate. Target blood glucose level was set at 100 and 150 mg/dL before and 2 h after each meal, respectively. After the basal insulin rate was fixed and target blood glucose levels were achieved, TBD, CIR, TDD, and their products were determined. Mean (±SD) blood glucose levels before and 2 h after meals were 121±47 and 150±61 mg/dL, respectively. TDD was 31.5±9.0 U, and TBD was 27.0±6.5% of TDD. CIR×TDD of breakfast was significantly lower than those of lunch and supper (288±73 vs. 408±92 and 387±83, respectively; Plunch and supper in type 1 diabetes patients. These results indicate that the insulin dose has been underestimated by using previously established calculations.

Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

Science.gov (United States)

Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

2013-10-01

To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

Dose escalation of cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma

International Nuclear Information System (INIS)

Lin Qiang; Gao Xianshu; Qiao Xueying; Zhou Zhiguo; Zhang Jun; Yang Xiangran; Wan Xin

2006-01-01

Objective: To define the maximum-tolerated dose (MTD) and observe the side effect of escalating cisplatin with 5-fluorouracil in concurrent chemoradiotherapy for esophageal carcinoma in Chinese, with toxicity studied. Methods: Previously untreated fifteen Chinese patients suffering from esophageal carcinoma received conventional fractionation radiotherapy, with 5 daily fractions of 2.0 Gy per week. The total radiation dose was 60 Gy. Concurrent chemotherapy dose escalation was given by the relatively safe and kidney-sparing modified Fibonacci sequence. The starting dose was cisplatin 37.5 mg/m 2 D1 and 5-fluorouracil 500 mg/m 2 D1-5, respectively. This regimen was repeated 4 times every 28 days. Escalation dose was cisplatin 7.5 mg/m 2 and 5- fluorouracil 100 mg/m 2 . Every. cohort contained at least 3 patients. If no dose-limiting toxicity(DLT) was observed, the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: DLT was defined as grade 3 radiation-induced esophagitis at the level of cisplatin 60 mg/m2, 5-fluorouracil 700 mg/m 2 . MTD was defined as cisplatin 52.5 mg/m 2 , 5- fiuorouracil 700 mg/m 2 . The major side effect were radiation-induced esophagitis, leucopenia, nausea, vomiting and anorexia. Conclusion: Maximun tolerated dose of cisplatin with 5-fiuorouracil in concurrent ehemoradiotherapy in the Chinese people with esophageal carcinoma were eisplatin 52.5 mg/m2 D1,5-fluorouracil 700 mg/m 2 D1-5, repeated 4 times every 28 days. (authors)

Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy

International Nuclear Information System (INIS)

Hong, Theodore S.; Tome, Wolfgang A.; Jaradat, Hazim; Raisbeck, Bridget M.; Ritter, Mark A.

2006-01-01

The management of prostate cancer patients with a significant risk of pelvic lymph node involvement is controversial. Both whole pelvis radiotherapy and dose escalation to the prostate have been linked to improved outcome in such patients, but it is unclear whether conventional whole pelvis doses of only 45-50 Gy are optimal for ultimate nodal control. The purpose of this study is to examine the dosimetric and clinical feasibility of combining prostate dose escalation via hypofractionation with conformal avoidance-based IMRT (H-CAD) dose escalation to the pelvic lymph nodes. One conformal avoidance and one conventional plan were generated for each of eight patients. Conformal avoidance-based IMRT plans were generated that specifically excluded bowel, rectum, and bladder. The prostate and lower seminal vesicles (PTV 70) were planned to receive 70 Gy in 2.5 Gy/fraction while the pelvic lymph nodes (PTV 56) were to concurrently receive 56 Gy in 2 Gy/fraction. The volume of small bowel receiving >45 Gy was restricted to 300 ml or less. These conformal avoidance plans were delivered using helical tomotherapy or LINAC-based IMRT with daily imaging localization. All patients received neoadjuvant and concurrent androgen deprivation with a planned total of two years. The conventional, sequential plans created for comparison purposes for all patients consisted of a conventional 4-field pelvic box prescribed to 50.4 Gy (1.8 Gy/fraction) followed by an IMRT boost to the prostate of 25.2 Gy (1.8 Gy/fraction) yielding a final prostate dose of 75.6 Gy. For all plans, the prescription dose was to cover the target structure. Equivalent uniform dose (EUD) analyses were performed on all targets and dose-volume histograms (DVH) were displayed in terms of both physical and normalized total dose (NTD), i.e. dose in 2 Gy fraction equivalents. H-CAD IMRT plans were created for and delivered to all eight patients. Analysis of the H-CAD plans demonstrates prescription dose coverage of >95

Pharmacological doses of daily ascorbate protect tumours from radiation damage after a single dose of radiation in an intracranial mouse glioma model

Directory of Open Access Journals (Sweden)

Carole eGrasso

2014-12-01

Full Text Available Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumour environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionising radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumour, glioblastoma multiforme (GBM, is very resistant to radiation; radiosensitising GBM cells will improve survival of GBM patients. Here we demonstrate that a single fraction (6 Gy of radiation combined with a one hour exposure to ascorbate (5 mM sensitised murine glioma GL261cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy of whole brain radiation combined with daily intra-peritoneal injections of ascorbate (1 mg/kg in an intra-cranial GL261 glioma mouse model. Tumour-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain eight days after tumour implantation, a second group received daily intra-peritoneal injections of ascorbate (day 8-45 after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumour progression, intra-peritoneal ascorbate alone had no effect on tumour progression. Tumour progression was faster in tumour-bearing mice treated with radiation and daily ascorbate than those treated with radiation alone. Histological analysis showed less necrosis in tumours treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumour micro-environment which determines whether ascorbate remains outside the cell, acting as a pro-oxidant or whether it enters the cells and acts as an anti-oxidant.

Pharmacological doses of daily ascorbate protect tumors from radiation damage after a single dose of radiation in an intracranial mouse glioma model.

Science.gov (United States)

Grasso, Carole; Fabre, Marie-Sophie; Collis, Sarah V; Castro, M Leticia; Field, Cameron S; Schleich, Nanette; McConnell, Melanie J; Herst, Patries M

2014-01-01

Pharmacological ascorbate is currently used as an anti-cancer treatment, potentially in combination with radiation therapy, by integrative medicine practitioners. In the acidic, metal-rich tumor environment, ascorbate acts as a pro-oxidant, with a mode of action similar to that of ionizing radiation; both treatments kill cells predominantly by free radical-mediated DNA damage. The brain tumor, glioblastoma multiforme (GBM), is very resistant to radiation; radiosensitizing GBM cells will improve survival of GBM patients. Here, we demonstrate that a single fraction (6 Gy) of radiation combined with a 1 h exposure to ascorbate (5 mM) sensitized murine glioma GL261 cells to radiation in survival and colony-forming assays in vitro. In addition, we report the effect of a single fraction (4.5 Gy) of whole brain radiation combined with daily intraperitoneal injections of ascorbate (1 mg/kg) in an intracranial GL261 glioma mouse model. Tumor-bearing C57BL/6 mice were divided into four groups: one group received a single dose of 4.5 Gy to the brain 8 days after tumor implantation, a second group received daily intraperitoneal injections of ascorbate (day 8-45) after implantation, a third group received both treatments and a fourth control group received no treatment. While radiation delayed tumor progression, intraperitoneal ascorbate alone had no effect on tumor progression. Tumor progression was faster in tumor-bearing mice treated with radiation and daily ascorbate than in those treated with radiation alone. Histological analysis showed less necrosis in tumors treated with both radiation and ascorbate, consistent with a radio-protective effect of ascorbate in vivo. Discrepancies between our in vitro and in vivo results may be explained by differences in the tumor microenvironment, which determines whether ascorbate remains outside the cell, acting as a pro-oxidant, or whether it enters the cells and acts as an anti-oxidant.

SU-F-J-81: Evaluation of Automated Deformable Registration Between Planning Computed Tomography (CT) and Daily Cone Beam CT Images Over the Course of Prostate Cancer Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Matney, J; Hammers, J; Kaidar-Person, O; Wang, A; Chen, R; Das, S; Marks, L; Mavroidis, P [University North Carolina, Chapel Hill, NC (United States)

2016-06-15

Purpose: To compute daily dose delivered during radiotherapy, deformable registration needs to be relatively fast, automated, and accurate. The aim of this study was to evaluate the performance of commercial deformable registration software for deforming between two modalities: planning computed tomography (pCT) images acquired for treatment planning and cone beam (CB) CT images acquired prior to each fraction of prostate cancer radiotherapy. Methods: A workflow was designed using MIM Software™ that aligned and deformed pCT into daily CBCT images in two steps: (1) rigid shifts applied after daily CBCT imaging to align patient anatomy to the pCT and (2) normalized intensity-based deformable registration to account for interfractional anatomical variations. The physician-approved CTV and organ and risk (OAR) contours were deformed from the pCT to daily CBCT over the course of treatment. The same structures were delineated on each daily CBCT by a radiation oncologist. Dice similarity coefficient (DSC) mean and standard deviations were calculated to quantify the deformable registration quality for prostate, bladder, rectum and femoral heads. Results: To date, contour comparisons have been analyzed for 31 daily fractions of 2 of 10 of the cohort. Interim analysis shows that right and left femoral head contours demonstrate the highest agreement (DSC: 0.96±0.02) with physician contours. Additionally, deformed bladder (DSC: 0.81±0.09) and prostate (DSC: 0.80±0.07) have good agreement with physician-defined daily contours. Rectum contours have the highest variations (DSC: 0.66±0.10) between the deformed and physician-defined contours on daily CBCT imaging. Conclusion: For structures with relatively high contrast boundaries on CBCT, the MIM automated deformable registration provided accurate representations of the daily contours during treatment delivery. These findings will permit subsequent investigations to automate daily dose computation from CBCT. However

Comparison of measured and calculated doses for narrow MLC defined fields

International Nuclear Information System (INIS)

Lydon, J.; Rozenfeld, A.; Lerch, M.

2002-01-01

Full text: The introduction of Intensity Modulated Radiotherapy (IMRT) has led to the use of narrow fields in the delivery of radiation doses to patients. Such fields are not well characterized by calculation methods commonly used in radiotherapy treatment planning systems. The accuracy of the dose calculation algorithm must therefore be investigated prior to clinical use. This study looked at symmetrical and asymmetrical 0.1 to 3cm wide fields delivered with a Varian CL2100C 6MV photon beam. Measured doses were compared to doses calculated using Pinnacle, the ADAC radiotherapy treatment planning system. Two high resolution methods of measuring dose were used. A MOSFET detector in a water phantom and radiographic film in a solid water phantom with spatial resolutions of 10 and 89μm respectively. Dose calculations were performed using the collapsed cone convolution algorithm in Pinnacle with a 0.1cm dose calculation grid in the MLC direction. The effect of Pinnacle not taking into account the rounded leaf ends was simulated by offsetting the leaves by 0.1cm in the dose calculation. Agreement between measurement and calculation is good for fields of 1cm and wider. However, fields of less than 1cm width can show a significant difference between measurement and calculation

A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization

DEFF Research Database (Denmark)

Loft, A; Egeberg, Anne Noes; Smitz, J

2012-01-01

Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses...... has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when...

Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer. Effects on local control, control of metastases, and overall survival

International Nuclear Information System (INIS)

Kurita, Hiroshi; Ohtsuka, Akiko; Kobayashi, Hiroichi; Kurashina, Kenji; Shikama, Naoto; Oguchi, Masahiko

2000-01-01

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m 2 ). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer. (author)

Aerosol delivery from spacers in wheezy infants: a daily life study

NARCIS (Netherlands)

H.M. Janssens (Hettie); E.M. Heijnen; V.M. de Jong; W.C.J. Hop (Wim); W.P. Holland (Wim); J.C. de Jongste (Johan); H.A.W.M. Tiddens (Harm)

2000-01-01

textabstractThe aims of this study were to assess and compare dose delivery and dose variability of pressurized metered dose inhalers (pMDI)/spacers in wheezy infants in daily life and to investigate factors influencing aerosol delivery. In an open randomized

The real-world dose-relativity of sevelamer hydrochloride and lanthanum carbonate monotherapy in patients with end-stage renal disease.

Science.gov (United States)

Wilson, Rosamund J; Keith, Michael S; Preston, Peter; Copley, J Brian

2013-12-01

Organization-defined daily dose and previous studies of the relative phosphate binding capacity of the two drugs. Patients requiring SH doses >7,200 mg/day had higher SH:LC dose-relativities of 3.1-4.2 (median individual patient ratios 3.1-4.0). These findings have implications for the tablet burden and cost-effectiveness of SH and LC in the treatment of hyperphosphatemia.

Impact of a daily exercise dose on knee joint cartilage

DEFF Research Database (Denmark)

Bricca, A; Juhl, C B; Grodzinsky, A J

2017-01-01

-analysis of 14 studies investigating cartilage thickness showed no effect in the low dose exercise group (SMD -0.02; 95% CI -0.42 to 0.38; I(2) = 0.0%), large but non-significant cartilage thickening in the moderate dose exercise group (SMD 0.95; 95% CI -0.33 to 2.23; I(2) = 72.1%) and non-significant cartilage...... thinning in the high dose exercise group (SMD -0.19; 95% CI -0.49 to 0.12; I(2) = 0.0%). Results were independent of analyzed covariates. The overall quality of the studies was poor because of inadequate reporting of data and high risk of bias. CONCLUSIONS: Our results suggest that the relationship between...

Dose optimization of intra-operative high dose rate interstitial brachytherapy implants for soft tissue sarcoma

Directory of Open Access Journals (Sweden)

Jamema Swamidas

2009-01-01

Full Text Available Objective : A three dimensional (3D image-based dosimetric study to quantitatively compare geometric vs. dose-point optimization in combination with graphical optimization for interstitial brachytherapy of soft tissue sarcoma (STS. Materials and Methods : Fifteen consecutive STS patients, treated with intra-operative, interstitial Brachytherapy, were enrolled in this dosimetric study. Treatment plans were generated using dose points situated at the "central plane between the catheters", "between the catheters throughout the implanted volume", at "distances perpendicular to the implant axis" and "on the surface of the target volume" Geometrically optimized plans had dose points defined between the catheters, while dose-point optimized plans had dose points defined at a plane perpendicular to the implant axis and on the target surface. Each plan was graphically optimized and compared using dose volume indices. Results : Target coverage was suboptimal with coverage index (CI = 0.67 when dose points were defined at the central plane while it was superior when the dose points were defined at the target surface (CI=0.93. The coverage of graphically optimized plans (GrO was similar to non-GrO with dose points defined on surface or perpendicular to the implant axis. A similar pattern was noticed with conformity index (0.61 vs. 0.82. GrO were more conformal and less homogeneous compared to non-GrO. Sum index was superior for dose points defined on the surface of the target and relatively inferior for plans with dose points at other locations (1.35 vs. 1.27. Conclusions : Optimization with dose points defined away from the implant plane and on target results in superior target coverage with optimal values of other indices. GrO offer better target coverage for implants with non-uniform geometry and target volume.

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study

International Nuclear Information System (INIS)

Morganti, Alessio G.; Picardi, Vincenzo; Ippolito, Edy; Massaccesi, Mariangela; Macchia, Gabriella; Deodato, Francesco; Caravatta, Luciana; Tambaro, Rosa; Mignogna, Samantha; Cellini, Numa; Valentini, Vincenzo; Mattiucci, Gian Carlo; Di Lullo, Liberato; Giglio, Gianfranco; Caprino, Paola; Sofo, Luigi; Ingrosso, Marcello

2010-01-01

The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. Material and methods. Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m 2 . Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. Results and discussion. Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m 2 ) in patients with resected pancreatic carcinoma.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Energy Technology Data Exchange (ETDEWEB)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2013-05-15

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

International Nuclear Information System (INIS)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

Science.gov (United States)

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

Dosimetric comparison of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: Evaluation of the impact on daily dose coverage

International Nuclear Information System (INIS)

Wang Lu; Hayes, Shelly; Paskalev, Kamen; Jin Lihui; Buyyounouski, Mark K.; Ma, Charlie C.-M.; Feigenberg, Steve

2009-01-01

Purpose: To investigate the dosimetric impact of using 4D CT and multiphase (helical) CT images for treatment planning target definition and the daily target coverage in hypofractionated stereotactic body radiotherapy (SBRT) of lung cancer. Materials and methods: For 10 consecutive patients treated with SBRT, a set of 4D CT images and three sets of multiphase helical CT scans, taken during free-breathing, end-inspiration and end-expiration breath-hold, were obtained. Three separate planning target volumes (PTVs) were created from these image sets. A PTV 4D was created from the maximum intensity projection (MIP) reconstructed 4D images by adding a 3 mm margin to the internal target volume (ITV). A PTV 3CT was created by generating ITV from gross target volumes (GTVs) contoured from the three multiphase images. Finally, a third conventional PTV (denoted PTV conv ) was created by adding 5 mm in the axial direction and 10 mm in the longitudinal direction to the GTV (in this work, GTV = CTV = clinical target volume) generated from free-breathing helical CT scans. Treatment planning was performed based on PTV 4D (denoted as Plan-1), and the plan was adopted for PTV 3CT and PTV conv to form Plan-2 and Plan-3, respectively, by superimposing 'Plan-1' onto the helical free-breathing CT data set using modified beam apertures that conformed to either PTV 3CT or PTV conv . We first studied the impact of PTV design on treatment planning by evaluating the dosimetry of the three PTVs under the three plans, respectively. Then we examined the effect of the PTV designs on the daily target coverage by utilizing pre-treatment localization CT (CT-on-rails) images for daily GTV contouring and dose recalculation. The changes in the dose parameters of D 95 and D 99 (the dose received by 95% and 99% of the target volume, respectively), and the V p (the volume receiving the prescription dose) of the daily GTVs were compared under the three plans before and after setup error correction

Low-dose factor VIII infusion in Chinese adult haemophilia A patients: pharmacokinetics evidence that daily infusion results in higher trough level than with every-other-day infusion with similar factor VIII consumption.

Science.gov (United States)

Hua, B; Lee, A; Fan, L; Li, K; Zhang, Y; Poon, M-C; Zhao, Y

2017-05-01

Pharmacokinetics (PK) modelling suggests improvement of trough levels are achieved by using more frequent infusion strategy. However, no clinical study data exists to confirm or quantify improvement in trough level, particularly for low-dose prophylaxis in patients with haemophilia A. To provide evidence that low dose daily (ED) prophylaxis can increase trough levels without increasing FVIII consumption compared to every-other-day (EOD) infusion. A cross-over study on 5 IU kg -1 FVIII daily vs. 10 IU kg -1 EOD infusions, each for 14 days was conducted at the PUMCH-HTC. On the ED schedule, trough (immediate prior to infusion), and peak FVIII:C levels (30 min after infusion) were measured on days 1-5; and trough levels alone on days 7, 9, 11 and 13. For the EOD schedule, troughs, peaks and 4-h postinfusion were measured on day 1; troughs and peaks on days 3, 5, and 7; troughs alone on days 9, 11 and 13 and 24-h postinfusion on days 2, 4 and 6. FVIII inhibitors were assessed on days 0 and 14 during both infusion schedules. Six patients were enrolled. PK evidence showed that daily prophylaxis achieved higher (~2 times) steady-state FVIII trough levels compared to EOD with the same total factor consumption. The daily prophylaxis had good acceptability among patients and reduced chronic pain in the joints in some patients. Our PK study shows low-dose factor VIII daily infusion results in higher trough level than with EOD infusion with similar factor VIII consumption in Chinese adult haemophilia A patients. © 2017 John Wiley & Sons Ltd.

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

Science.gov (United States)

Saffian, S M; Duffull, S B; Wright, Dfb

2017-08-01

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Estimation of 18FDG doses's cost

International Nuclear Information System (INIS)

Hamza, Fatma; Amouri, W.; Jardak, I.; Kallel, F.; Charfeddine, S.; Guermazi, F.

2013-01-01

The cyclotron facility, essentially for medical use, is far from being a simple establishment of a dedicated device to accelerate particles producing a beta plus emitter radioelement. The cyclotron site encompasses more over all necessary equipments for the production and the quality control of considered radiotracer that 18 FDG is just one example. This facility is subject to strict standards in terms of radiopharmaceutical production, radiation level, pressure level and airflow resulting in the production of a drug submitted to the MA (Marketing Authorization). These multiple factors directly influence the final cost of the dose that remains to be reachable by the patient. The aim of this work is to estimate the cost of a dose of 18 FDG to ensure financial viability of the project while accessible to the patient. The cost of the facility will entail the following: buildings and utilities, equipment and operational cost. This calculation is possible only if we define in advance the type of cyclotron, which is bound to the market needs in particular the number of PET facilities, the number of scans per day and the radioactive decay of radioelement. Our study represents a simulation that considers some hypothesis. We assumed that the cyclotron is installed in Sousse and that the PET facilities number (positon emission tomography) is 6 in which 4 are located 2 hours away. For a PET scan, the average dose per patient is about 350 MBq (5 MBq/kg) and the exam duration is about 45 minutes. Each center performs 10 tests per day. In terms of fees, we considered device and building's cost, facility amortization, consumables (target, marking accessories), maintenance, remuneration expense and the annual electricity consumption. All our calculations have been reported to the number of working days per year. The estimates were made outside the customs duties and technical assistance that may last up to 2 years. Requirements and needs were estimated at 5.4 curies per day. For

Presentation of chronic daily headache : A clinical study

NARCIS (Netherlands)

Spierings, E L H; Schroevers, M.; Honkoop, P.C.; Sorbi, M.

We studied the presentation of chronic daily headache in 258 patients from a private headache practice, 50 men and 208 women. Chronic daily headache was defined as headaches, occurring at least 5 days per week for at least 1 year. Seventy-seven percent of the patients experienced the onset of

Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

International Nuclear Information System (INIS)

Kal, H.B.; Bijman, J.Th.

1981-01-01

Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

Multiple daily fractionation in radiotherapy: biological rationale and preliminary clinical experiences

Energy Technology Data Exchange (ETDEWEB)

Arcangeli, G [Instituto Medico Scientifico, Rome (Italy). Dept. of Oncology; Mauro, F; Morelli, D; Nervi, C

1979-09-01

The biological bases of radiation dose fractionation are reviewed and discussed with special emphasis on reassortment. Experimental data on animal model systems are presented to clarify that reassortment has to be added to sublethal damage repair and reoxygenation in the rationale for an optimized radiotherapy course according to tumor cell kinetics. Clinical results on several human tumors treated with twice or thrice daily fractions are described. These results show that some clinically radioresistant tumors (especially if not characterized by a relatively long clinical doubling line) can be satisfactorily dealt with using multiple daily fractionation. Clinical observations indicate that a relatively high cumulative daily dose (200 + 150 + 150 rad) can be safely administered.

Relative efficacy of weekly and two differing doses of daily iron-folate supplementation in improving hemoglobin in mild and moderately anemic children between 3 and 5 years of age: a cluster randomized trial.

Science.gov (United States)

Kapil, U; Sachdev, H P S; Dwivedi, S N; Pandey, R M; Upadhyay, A D; Sareen, N

2013-04-01

In India, 75% of children hemoglobin response with two dosages of daily (20 mg iron and 100 μg folic acid, or 40 mg iron and 200 μg folic acid) and weekly (40 mg iron and 200 μg folic acid) IFA supplementation in children of 3-5 years of age with mild or moderate anemia (hemoglobin 7-10 g/dl). Community-based cluster randomized control trial in nine adjoining Anganwadi Centers. Four hundred twenty six enrolled participants received directly supervised IFA tablet supplementation as per the above three groups. After 100 days, the number of available subjects in the NNACP daily dose (A), daily dose doubled (B) and weekly dose (C) groups were 112, 114 and 110, respectively. Hemoglobin was estimated at baseline, 50 and 100 days by the Cynmeth hemoglobin method. At 50 days, there were no differences between the three groups, but at 100 days, adjusted hemoglobin was lowered with weekly supplementation. The mean (95% confidence interval) hemoglobin (g/dl) differences were: (i) A-B: -0.05 (-0.17, 0.05), (ii) A-C: -0.38 (-0.50, -0.27) and (iii) B-C: -0.33, (-0.45, -0.21). Anemia reduction was 18.8%, 18.4% and 10.9%, respectively, in the three groups. Directly supervised IFA supplementation at the NNACP or double dose is equally efficacious but superior to weekly regimen.

A model to accumulate fractionated dose in a deforming organ

International Nuclear Information System (INIS)

Yan Di; Jaffray, D.A.; Wong, J.W.

1999-01-01

Purpose: Measurements of internal organ motion have demonstrated that daily organ deformation exists throughout the course of radiation treatment. However, a method of constructing the resultant dose delivered to the organ volume remains a difficult challenge. In this study, a model to quantify internal organ motion and a method to construct a cumulative dose in a deforming organ are introduced. Methods and Materials: A biomechanical model of an elastic body is used to quantify patient organ motion in the process of radiation therapy. Intertreatment displacements of volume elements in an organ of interest is calculated by applying an finite element method with boundary conditions, obtained from multiple daily computed tomography (CT) measurements. Therefore, by incorporating also the measurements of daily setup error, daily dose delivered to a deforming organ can be accumulated by tracking the position of volume elements in the organ. Furthermore, distribution of patient-specific organ motion is also predicted during the early phase of treatment delivery using the daily measurements, and the cumulative dose distribution in the organ can then be estimated. This dose distribution will be updated whenever a new measurement becomes available, and used to reoptimize the ongoing treatment. Results: An integrated process to accumulate dosage in a daily deforming organ was implemented. In this process, intertreatment organ motion and setup error were systematically quantified, and incorporated in the calculation of the cumulative dose. An example of the rectal wall motion in a prostate treatment was applied to test the model. The displacements of volume elements in the rectal wall, as well as the resultant doses, were calculated. Conclusion: This study is intended to provide a systematic framework to incorporate daily patient-specific organ motion and setup error in the reconstruction of the cumulative dose distribution in an organ of interest. The realistic dose

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Das, Shiva [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States); Gu, Lin [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Dunphy, Frank R.; Ready, Neal E. [Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Marks, Lawrence B. [Department of Radiation Oncology, University of North Carolina School of Medicine, Chapel Hill, North Carolina (United States)

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standard 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.

One and three doses of propranolol a day in hypertension.

Science.gov (United States)

van den Brink, G; Boer, P; van Asten, P; Dorhout Mees, E J; Geyskes, G G

1980-01-01

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

Multiplexed Dosing Assays by Digitally Definable Hydrogel Volumes

DEFF Research Database (Denmark)

Faralli, Adele; Melander, Fredrik; Larsen, Esben Kjær Unmack

2016-01-01

Stable and low-cost multiplexed drug sensitivity assays using small volumes of cells or tissue are in demand for personalized medicine, including patientspecific combination chemotherapy. Spatially defined projected light photopolymerization of hydrogels with embedded active compounds is introduc...

Effective dose equivalent

International Nuclear Information System (INIS)

Huyskens, C.J.; Passchier, W.F.

1988-01-01

The effective dose equivalent is a quantity which is used in the daily practice of radiation protection as well as in the radiation hygienic rules as measure for the health risks. In this contribution it is worked out upon which assumptions this quantity is based and in which cases the effective dose equivalent can be used more or less well. (H.W.)

SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

Energy Technology Data Exchange (ETDEWEB)

Pham, R; Sun, B; Zhao, T; Li, H; Yang, D; Grantham, K; Goddu, S; Santanam, L; Bradley, J; Mutic, S; Kandlakunta, P; Zhang, T [Washington University School of Medicine, Saint Louis, MO (United States)

2016-06-15

Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculated on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.

Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients

International Nuclear Information System (INIS)

Loven, David; B e'Ery, Einat; Yerushalmi, Rinat; Koren, Claude; Sulkes, Aaron; Fenig, Eyal; Lavi, Idit; Shaked, Yuval

2008-01-01

Metronomic low-dose chemotherapy regimen was found to have an antiangiogenic effect in tumors. However, its effect on levels of circulating pro-angiogenic and anti-angiogenic factors is not fully explored. Materials and methods. The levels of both VEGF and PDGF-BB were measured in three time points, in the serum of 32 rectal carcinoma patients receiving daily reduced-dose/continuous capecitabine in combination with preoperative pelvic irradiation. Results. We found a significant decrease in VEGF and PDGF-BB serum levels during the combination treatment (p<0.0001), followed by an increase in the successive rest-period (p<0.0001). In addition, substantial changes in platelets counts were observed during treatment in correlation with the changes of VEGF and PDGF-BB serum levels. Discussion. These results suggest that combined chemo-irradiation affect levels of pro-angiogenic factors during treatment, and may reflect an anti-angiogenic window induced during this treatment. The potential implications of this inducible phenomenon, including a possible clinical benefit from the administration of long lasting metronomic chemotherapy immediately following combined chemo-irradiation, would warrant further investigation

Influence of low-dose daily cisplatin on the distant metastasis-free survival of patients with locally advanced nonmetastatic head and neck cancer treated with radiation therapy

International Nuclear Information System (INIS)

Jeremic, Branislav; Milicic, Biljana

2008-01-01

We investigated the impact of low dose daily cisplatin on distant metastasis-free survival (DMFS) in locally advanced head and neck cancer treated with hyperfractionated radiotherapy (77 Gy in 70 fractions in 35 treatment days). In locally controlled tumors cisplatin led to better DMFS (p = 0.0272); Cisplatin may have acted independently of micrometastasis in locally advanced H and N cancer

Prospective Trial of High-Dose Reirradiation Using Daily Image Guidance With Intensity-Modulated Radiotherapy for Recurrent and Second Primary Head-and-Neck Cancer

International Nuclear Information System (INIS)

Chen, Allen M.; Farwell, D. Gregory; Luu, Quang; Cheng, Suzan; Donald, Paul J.; Purdy, James A.

2011-01-01

Purpose: To report a single-institutional experience using intensity-modulated radiotherapy with daily image-guided radiotherapy for the reirradiation of recurrent and second cancers of the head and neck. Methods and Materials: Twenty-one consecutive patients were prospectively treated with intensity-modulated radiotherapy from February 2006 to March 2009 to a median dose of 66 Gy (range, 60-70 Gy). None of these patients received concurrent chemotherapy. Daily helical megavoltage CT scans were obtained before each fraction as part of an image-guided radiotherapy registration protocol for patient alignment. Results: The 1- and 2-year estimates of in-field control were 72% and 65%, respectively. A total of 651 daily megavoltage CT scans were obtained. The mean systematic shift to account for interfraction motion was 1.38 ± 1.25 mm, 1.79 ± 1.45 mm, and 1.98 ± 1.75 mm for the medial-lateral, superior-inferior, and anterior-posterior directions, respectively. Pretreatment shifts of >3 mm occurred in 19% of setups in the medial-lateral, 27% in the superior-inferior, and 33% in the anterior-posterior directions, respectively. There were no treatment-related fatalities or hospitalizations. Complications included skin desquamation, odynophagia, otitis externa, keratitis, naso-lacrimal duct stenosis, and brachial plexopathy. Conclusions: Intensity-modulated radiotherapy with daily image guidance results in effective disease control with relatively low morbidity and should be considered for selected patients with recurrent and second primary cancers of the head and neck.

A phase I dose-escalation study of lenalidomide in combination with gemcitabine in patients with advanced pancreatic cancer.

Directory of Open Access Journals (Sweden)

Gustav J Ullenhag

Full Text Available Lenalidomide have both immunomodulatory and anti-angiogenic properties which could confer anti-cancer effects. The aim of this study was to assess the feasibility of combining lenalidomide with the standard treatment gemcitabine in pancreatic cancer patients with advanced disease.Eligible patients had locally advanced or metastatic adenocarcinoma of the pancreas. Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 intravenously (days 1, 8 and 15, each 28 day cycle. Three cohorts of lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 25 mg daily. The maximum tolerated dose (MTD of lenalidomide given in combination with gemcitabine was defined as the highest dose level at which no more than one out of four (25% subjects experiences a dose-limiting toxicity (DLT. Patients should also be able to receive daily low molecular weight heparin (LMWH (e.g. dalteparin 5000 IU s.c. daily as a prophylactic anticoagulant for venous thromboembolic events (VTEs. Twelve patients (n = 4, n = 3 and n = 5 in cohort I, II and III, respectively were enrolled in this study.Median duration of treatment was 11 weeks (range 1-66, and median number of treatment cycles were three (range 1-14. The only DLT was a cardiac failure grade 3 in cohort III. Frequent treatment-related adverse events (AEs (all grades included neutropenia, leucopenia and fatigue (83% each, but there was no febrile neutropenia; thrombocytopenia (75%; dermatological toxicity (75%; diarrhea and nausea (42% each; and neuropathy (42%.This phase I study demonstrates the feasibility of the combination of lenalidomide and gemcitabine as first-line treatment in patients with advanced pancreatic cancer. The tolerability profile demonstrated in the dose escalation schedule of lenalidomide suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard dosing of gemcitabine and merits further evaluation in a phase II trial.ClinicalTrials.gov NCT

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

Daily relations among affect, urge, targeted naltrexone, and alcohol use in young adults.

Science.gov (United States)

Bold, Krysten W; Fucito, Lisa M; Corbin, William R; DeMartini, Kelly S; Leeman, Robert F; Kranzler, Henry R; O'Malley, Stephanie S

2016-10-01

Heavy drinking among young adults is a serious public health problem. Naltrexone, an opioid antagonist, has been shown to reduce drinking in young adults compared to placebo and can be taken on a targeted (i.e., as needed) basis. Understanding risk factors for drinking and naltrexone effects within-person in young adults may help to optimize the use of targeted naltrexone. The current study was a secondary analysis of daily diary data from 127 (n = 40 female) young adults (age 18-25) enrolled in a double-blind clinical trial of daily (25 mg) plus targeted (25 mg) naltrexone versus placebo. Hierarchical linear models were used to examine the effects of daily affect, urge, and taking targeted medication on same-day risk of drinking to intoxication (defined as estimated blood-alcohol-concentration, BAC ≥ .08 g%). Results indicated urge significantly mediated within-person positive affect-drinking relations on a daily level. Specifically, positive affect was associated with greater urge to drink, which in turn was associated with greater odds of BAC ≥ .08 g%. Furthermore, days of greater positive affect and urge were associated with taking a targeted dose of medication, which reduced the likelihood of intoxication by nearly 23% in the naltrexone group compared to placebo. Gender and family history of alcohol dependence were examined as moderators of these daily level effects. These results provide further evidence of naltrexone's ability to reduce alcohol consumption in young adults and identify potential within-person risk processes related to heavy drinking that could inform alcohol-related interventions for this population. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

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.

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.

Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study.

Science.gov (United States)

Russell, Charlotte; Wearden, Alison J; Fairclough, Gillian; Emsley, Richard A; Kyle, Simon D

2016-04-01

This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS. © 2016 Associated Professional Sleep Societies, LLC.

Randomized clinical trial to comparing efficacy of daily, weekly and monthly administration of vitamin D3.

Science.gov (United States)

Takács, István; Tóth, Béla E; Szekeres, László; Szabó, Boglárka; Bakos, Bence; Lakatos, Péter

2017-01-01

The comparative efficacy and safety profiles of selected daily 1000 IU, weekly 7000 IU and monthly 30,000 IU vitamin D 3 -not previously investigated-will be evaluated. Here, a prospective, randomized clinical trial, comparing efficacy and safety of a daily single dose of 1000 IU (group A) to a once-weekly 7000 IU dose (group B), or monthly 30,000 IU dose (group C) of vitamin D 3 . The present study is a controlled, randomized, open-label, multicenter clinical trial, 3  months in duration. Sixty-four adult subjects with vitamin D deficiency (25OHD<20 ng/ml), were included according to the inclusion and exclusion criteria. Dose-responses for increases in serum vitamin 25OHD were statistically equivalent for each of the three groups: A, B and C. Outcomes were 13.0 ± 1.5; 12.6 ± 1.1 and 12.9 ± 0.9 ng/ml increases in serum 25OHD per 1000 IU, daily, weekly and monthly, respectively. The treatment of subjects with selected doses restored 25OHD values to levels above 20 ng/ml in all groups. Treatment with distinct administration frequency of vitamin D 3 did not exhibit any differences in safety parameters. The daily, weekly and monthly administrations of daily equivalent of 1000 IU of vitamin D 3 provide equal efficacy and safety profiles.

Defining a dose-response relationship for prostate external beam radiotherapy

International Nuclear Information System (INIS)

Trada, Yuvnik; Plank, Ash; Martin, Jarad

2013-01-01

We aimed to quantify a relationship between radiotherapy dose and freedom from biochemical failure (FFBF) in low- and intermediate-risk prostate cancer. To reduce confounding we used data with a standardised end–point, mature follow-up, low competing risk of metastatic failure, conventional fractionation and separate reporting for outcomes with hormonal therapy (HT). A systematic review of the literature was carried out. Studies that reported the use of radiotherapy alone in 1.8–2Gy fractions in low- and intermediate-risk prostate cancer were included. The primary end–point was Phoenix definition 5-year FFBF. A logistic regression was used to quantify the dose–response relationship. Data from eight studies with 3037 patients met the inclusion criteria. The data from 810 low-risk patients and 2245 intermediate-risk patients were analysed. A strong association between radiotherapy dose and FFBF was found in low- and intermediate-risk patients managed with radiotherapy alone. In low-risk patients not treated with HT the dose required to achieve 50% biochemical tumour control (TCD 50 ) is 52.0 Gy and the slope of the dose–response curve at TCD 50 (γ 50 ) is 2.1%/Gy. At 78Gy this represented a FFBF of 90.3%. In intermediate-risk patients not treated with HT the TCD 50 is 64.7Gy and γ 50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small effect for low-risk patients and an inconsistent effect for intermediate-risk men. A strong association was found between radiation dose and biochemical outcome in both low- and intermediate-risk patients. Standardised reporting of results from future studies will make future analyses more robust.

Modulation of accelerated repopulation in mouse skin during daily irradiation

International Nuclear Information System (INIS)

Trott, K.-R.; Shirazi, A.; Heasman, F.

1999-01-01

Background and purpose: The timing of acceleration of repopulation in the epidermis during daily irradiation is related to the development of skin erythema and epidermal hypoplasia. Therefore, the relationship between impairment of the epidermal barrier function, the dermal inflammatory response and epidermal hypoplasia with the acceleration of repopulation was investigated.Materials and purpose: Skin fields of approximately 1 cm 2 on the thighs of TUC mice were given five daily fractions of 3 Gy in each week followed by top-up doses at the end of the first, the second, or the third week to determine residual epidermal tolerance and to calculate repopulation rates in weeks 1, 2, or 3. Systemic modulation of repopulation was attempted by daily indomethacine during fractionated irradiation whereas tape stripping or UV-B exposure before the start of fractionated irradiation attempted local modulation. In parallel experiments, the water permeability coefficient of the epidermis was determined ex vivo by studying transepidermal transport of tritiated water.Results: Without modulation, no repopulation was found in the first week of daily fractionation but repopulation compensated 30% of the dose given in week two and 70% of the dose given in week three. Only tape stripping before the start of fractionated irradiation accelerated repopulation in week one. UV-B had no effect on repopulation although it stimulated proliferation as much as tape stripping. Indomethacin did not suppress acceleration of repopulation. A significant increase in transepidermal water loss was found but only after repopulation had already accelerated.Conclusions: Acceleration of repopulation in mouse epidermis during daily-fractionated irradiation is not related to the simultaneous development of an inflammatory response. Also, the loss of the epidermal barrier function is not involved in the development of the acceleration response, which rather seems to be triggered directly by the decreased

Separation of the Galactic Cosmic Rays and Inner Earth Radiation Belt Contributions to the Daily Dose Onboard the International Space Station in 2005-2011

Science.gov (United States)

Lishnevskii, A. E.; Benghin, V. V.

2018-03-01

The DB-8 detectors of the ISS radiation monitoring system (RMS) have operated almost continuously onboard the ISS service module since August 2001 till December 2014. The RMS data obtained were used for the daily monitoring of the radiation environment aboard the station. This paper considers the technique of RMS data analysis that allows one to distinguish the contributions of galactic cosmic rays and the Earth's inner radiation belt to the daily dose based on the dosimetry data obtained as a result of the station's passage in areas of the highest geomagnetic latitudes. The paper presents the results of an analysis of the dosimetry data based on this technique for 2005-2011, as well as a comparison with similar results the authors obtained previously using the technique based on an analysis of the dosimetry data obtained during station passages in the area of the South Atlantic Anomaly.

Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.

Science.gov (United States)

Garwood, Candice L; Clemente, Jennifer L; Ibe, George N; Kandula, Vijay A; Curtis, Kristy D; Whittaker, Peter

2010-06-15

Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups 80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (PAfrican ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (PAfrican ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk. Copyright 2010 Elsevier Inc. All rights reserved.

Defining depth of anesthesia.

Science.gov (United States)

Shafer, S L; Stanski, D R

2008-01-01

In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.

Concurrent chemoradiotherapy for esophageal cancer. Comparison between intermittent standard-dose cisplatin with 5-fluorouracil and daily low-dose cisplatin with continuous infusion of 5-fluorouracil

International Nuclear Information System (INIS)

Sai, Heitetsu; Mitsumori, Michihide; Yamauchi, Chikako; Araki, Norio; Okumura, Setsuko; Nagata, Yasushi; Nishimura, Yasumasa; Hiraoka, Masahiro

2004-01-01

Although current standard treatment for advanced esophageal cancer is intermittent standard-dose cisplatin with 5-fluorouracil (5-FU) (ISD-FP), daily low-dose cisplatin with continuous infusion of 5-FU (CLD-FP) is advocated for equivalent effectiveness and lower toxicity. The feasibility of these two concurrent chemoradiotherapeutic protocols was retrospectively reviewed for local control rate, overall survival, toxicity, and compliance in a single institutional situation. Concurrent chemoradiotherapy, using 60 Gy of radiation and ISD-FP or CLD-FP was non-randomly scheduled for 29 patients between June 1994 and March 2001. Complete response in the irradiated volume at the end of primary treatment was shown by 8 of 15 and 9 of 14 patients in the ISD-FP and CLD-FP groups, respectively. The projected overall survival rate at 2 years was 55% for stage III patients and 13% for stage IV. Median survival times were 14 months versus 15 months in the ISD-FP and CLD-FP groups, with no significant difference. Toxicities were similar, including two treatment-related deaths in each group. Chemotherapy was completed for 10 of 15 and 11 of 14 patients in the ISD-FP and CLD-FP groups, respectively. Modification of the planned regimen was more often required for the CLD-FP group. CLD-FP therapy has no apparent advantage over ISD-FP therapy from the perspective of compliance and safety. A randomized phase II clinical trial comparing ISD-FP and CLD-FP, currently being performed, is expected to provide further information. (author)

Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya.

Science.gov (United States)

Mugo, Peter Mwangi; Sanders, Eduard J; Mutua, Gaudensia; van der Elst, Elisabeth; Anzala, Omu; Barin, Burc; Bangsberg, David R; Priddy, Frances H; Haberer, Jessica E

2015-05-01

A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

Correlation Between Radiation Dose to 18F-FDG-PET Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

International Nuclear Information System (INIS)

Rose, Brent S.; Liang Yun; Lau, Steven K.; Jensen, Lindsay G.; Yashar, Catheryn M.; Hoh, Carl K.; Mell, Loren K.

2012-01-01

Purpose: To test the hypothesis that radiation dose to 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)-defined active bone marrow (BM ACT ) subregions is correlated with hematologic toxicity in cervical cancer patients treated with chemoradiotherapy. Methods and Materials: The conditions of 26 women with cervical cancer who underwent 18 F-FDG-PET before treatment with concurrent cisplatin and intensity-modulated radiation therapy were analyzed. BM ACT was defined as the subregion of total bone marrow (BM TOT ) with a standardized uptake value (SUV) equal to or above the mean for that individual. Inactive bone marrow (BM INACT ) was defined as BM TOT − BM ACT . Generalized linear modeling was used to test the correlation between BM ACT and BM INACT dose–volume metrics and hematologic nadirs, particularly white blood cell count (WBC) and absolute neutrophil count (ANC). Results: Increased BM ACT mean dose was significantly associated with decreased log(WBC) nadir (β = −0.04; 95% CI, −0.07to −0.01; p = 0.009), decreased log(ANC) nadir (β = −0.05; 95% CI, −0.08 to −0.02; p = 0.006), decreased hemoglobin nadir (β = −0.16; 95% CI, −0.27 to −0.05; p = 0.010), and decreased platelet nadir (β = −6.16; 95% CI, −9.37 to −2.96; p INACT mean dose and log(WBC) nadir (β = −0.01; 95% CI, −0.06 to 0.05; p = 0.84), log(ANC) nadir (β = −0.03; 95% CI, −0.10 to 0.04; p = 0.40), hemoglobin nadir (β = −0.09; 95% CI, −0.31 to 0.14; p = 0.452), or platelet nadir (β = −3.47; 95% CI, −10.44 to 3.50; p = 0.339). Conclusions: Irradiation of BM subregions with higher 18 F-FDG-PET activity was associated with hematologic toxicity, supporting the hypothesis that reducing dose to BM ACT subregions could mitigate hematologic toxicity. Future investigation should seek to confirm these findings and to identify optimal SUV thresholds to define BM ACT .

SU-F-J-13: Choosing An IMRT Technique in the Treatment of Head and Neck Cancer with Daily Localization Uncertainties

Energy Technology Data Exchange (ETDEWEB)

Lin, T; Wang, L; Galloway, T; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

2016-06-15

Purpose: Head and Neck cancer treatment with IMRT/VMAT has two choices: split-filed IMRT(SFI), in which the LAN is treated with a separate anterior field and the extended whole-field IMRT(WFI) in which LAN is included with the IMRT/VMAT field. This study shows that under the same dose limit criteria, choosing the technique becomes a critical issue if daily localization and immobilization altered the dose distribution. Methods: Nine common head-and-neck cancer cases were chosen to illustrate how the daily localization and immobilization uncertainties affect to choose between SFI and WFI. Both SFI and WFI at upper target coverage were generated with VMAT. For each case, the same planning criteria were applied to the target and critical structures; therefore, similar target coverage and dose falloff can be observed in both techniques. Thirty days of kV cone beam CT(CBCT) images on each case were also delineated with contralateral and ipsilateral target as well as larynx as critical structure. About 300 CBCT images with daily delivered doses were analyzed and compared in a form of dose-volume histograms. Results: While both plans for SFI and WFI with VMAT planning utilized and meet the criteria of D95>prescription dose and for not-involved larynx with mean dose <35Gy and V55<10%, the daily localization and immobilization has a great contribution to the resulted dose delivery. With WFI, the better daily contralateral and ipsilateral neck target coverage can reflect a simpler or shorter localization; however, a much superior avoidance (WFI: mean dose a 42.5Gy; SFI: mean dose a 18.9Gy) of the non-involved larynx from the SFI is preferred. Conclusion: Dosimetrically, SFI and WFI are equally well for head and Neck cancer treatment with VMAT technique; however, if considering the contribution of daily localization(CBCT) method uncertainties, SFI is better with sparing non-involved larynx and WFI has better target coverage.

Acute migraine medication adherence, migraine disability and patient satisfaction: A naturalistic daily diary study.

Science.gov (United States)

Seng, Elizabeth K; Robbins, Matthew S; Nicholson, Robert A

2017-09-01

Objective To examine the influence of acute migraine medication adherence on migraine disability and acute medication satisfaction. Methods Adults with migraine completed three months of daily electronic diaries assessing headache symptoms, acute medication taken, acute medication satisfaction, and daily migraine disability. Repeated measures mixed-effects models examined the effect of initial medication type [migraine-specific medication (MSM) vs. over-the-counter analgesic (OTC) vs. an opiate/barbiturate], the severity of pain at dosing, and their interaction with daily migraine disability and satisfaction with acute medication. Results Participants (N = 337; 92.5% female; 91.1% Caucasian, non-Hispanic; 84.0% with episodic migraine) recorded 29,722 diary days. Participants took acute medication on 96.5% of 8090 migraine days. MSM was most frequently taken first (58%), followed by OTC (29.9%) and an opiate/barbiturate (12.1%). Acute medication was most frequently taken when pain was mild (41.2%), followed by moderate (37.7%) and severe pain (11.4%). Initially dosing with MSM while pain was mild was associated with the lowest daily disability [medication × pain at dosing F (4, 6336.12) = 58.73, p migraine disability and highest acute medication satisfaction.

Dose Recalculation and the Dose-Guided Radiation Therapy (DGRT) Process Using Megavoltage Cone-Beam CT

International Nuclear Information System (INIS)

Cheung, Joey; Aubry, Jean-Francois; Yom, Sue S.; Gottschalk, Alexander R.; Celi, Juan Carlos; Pouliot, Jean

2009-01-01

Purpose: At University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). Materials and Methods: A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. Results: Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D 1 increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D 5 dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. Conclusions: An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.

Whole-abdomen radiotherapy for non-Hodgkin's lymphoma using twice-daily fractionation

International Nuclear Information System (INIS)

Liauw, Stanley L.; Yeh, Alexander M.; Morris, Christopher G.; Olivier, Kenneth R.; Mendenhall, Nancy Price

2006-01-01

Purpose: To report the tolerability and efficacy of twice-daily whole-abdomen irradiation (WAI) for non-Hodgkin's lymphoma (NHL). Methods and Materials: Of 123 patients treated for NHL with WAI, 37% received previous chemotherapy, 28% received WAI as part of comprehensive lymphatic irradiation (CLI), and 32% received WAI for palliation. The median dose to the whole abdomen was 25.0 Gy, followed by a median tumor boost of 9.8 Gy in 58 patients. Fractionation was 1.0 Gy once daily (54%) or 0.8 Gy twice daily (46%). Blood counts were measured weekly. Results: At a median follow-up of 4.3 years, local control was 72% and overall survival was 55% at 5 years. Median time of WAI was 42 days for once-daily treatment and 32 days for twice-daily treatment. Patients receiving twice-daily WAI did not have a significantly higher rate of acute side effects (e.g., nausea, diarrhea, platelet or red blood cell toxicity). Overall, acute thrombocytopenia was the most frequent side effect of treatment; 24 of 96 patients (25%) with available hematologic data had Grade 3+ toxicity. There was no acute Grade 3 gastrointestinal toxicity and no late small bowel obstruction. Multiple regression indicated that patients with four or less involved sites and disease size ≤6 cm had improved local control and overall survival. Conclusions: Twice-daily WAI using 0.8 Gy/fraction does not appear to have any greater toxicity compared with once-daily treatment using 1 Gy/fraction. Small doses per fraction (0.8-1 Gy/fx) are effective, tolerated well in the acute setting, and associated with a low rate of late toxicity

Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin: a noninferiority trial.

Science.gov (United States)

Clegg, Herbert W; Ryan, Amy G; Dallas, Steven D; Kaplan, Edward L; Johnson, Dwight R; Norton, H James; Roddey, Oliver F; Martin, Edward S; Swetenburg, Raymond L; Koonce, Elizabeth W; Felkner, Mary M; Giftos, P Michael

2006-09-01

Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. In a single pediatric practice, from October through May for 2 consecutive years (2001-2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (or=40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], -0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, -4

Can chlorhexidine mouthwash twice daily ameliorate cyclosporine-induced gingival overgrowth?

Directory of Open Access Journals (Sweden)

Ching-Hwa Gau

2013-03-01

Conclusion: These findings suggest that chlorhexidine mouthwash used twice daily may reduce the severity of CsA-induced gingival overgrowth. Further research is warranted to determine the optimal dose and treatment regimen.

Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response.

Science.gov (United States)

Geber, Selmo; Sales, Liana; Sampaio, Marcos A C

2002-07-01

Compare the efficacy and safety of two different GnRHa, used for pituitary suppression in IVF cycles. A total of 292 patients using depot goserelin (Group 1) and 167 using daily leuprolide acetate (Group 2) were compared. Days required to achieve pituitary function suppression, duration of ovarian stimulation, total dose of HMG, number of aspirated follicles, number of oocytes retrieved, and presence of functional ovarian cyst were analyzed. The time taken to achieve downregulation was similar. The mean number of ampoules used for superovulation was higher in Group 1; however, this difference was observed only for patients >40 years old that started GnRHa in the follicular phase. There was no difference between the two groups in the duration of superovulation, in the number of follicles aspirated, and the number of oocytes retrieved. In the group of patients with >40 years the incidence of ovarian cysts was higher in Group 2. Both routes of GnRHa have similar effects for pituitary suppression and ovulation induction in assisted reproductive technology. Therefore the long-acting GnRHa is an excellent option, as only a single subcutaneous dose is necessary, decreasing the risk of the patient to forget its use and, most important, it does not interfere in the patient's quality of life.

Endorectal high dose rate brachytherapy quality assurance

International Nuclear Information System (INIS)

Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

2008-01-01

We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults.

Science.gov (United States)

Gardner, Rebecca A; Finney, Olivia; Annesley, Colleen; Brakke, Hannah; Summers, Corinne; Leger, Kasey; Bleakley, Marie; Brown, Christopher; Mgebroff, Stephanie; Kelly-Spratt, Karen S; Hoglund, Virginia; Lindgren, Catherine; Oron, Assaf P; Li, Daniel; Riddell, Stanley R; Park, Julie R; Jensen, Michael C

2017-06-22

Transitioning CD19-directed chimeric antigen receptor (CAR) T cells from early-phase trials in relapsed patients to a viable therapeutic approach with predictable efficacy and low toxicity for broad application among patients with high unmet need is currently complicated by product heterogeneity resulting from transduction of undefined T-cell mixtures, variability of transgene expression, and terminal differentiation of cells at the end of culture. A phase 1 trial of 45 children and young adults with relapsed or refractory B-lineage acute lymphoblastic leukemia was conducted using a CD19 CAR product of defined CD4/CD8 composition, uniform CAR expression, and limited effector differentiation. Products meeting all defined specifications occurred in 93% of enrolled patients. The maximum tolerated dose was 10 6 CAR T cells per kg, and there were no deaths or instances of cerebral edema attributable to product toxicity. The overall intent-to-treat minimal residual disease-negative (MRD - ) remission rate for this phase 1 study was 89%. The MRD - remission rate was 93% in patients who received a CAR T-cell product and 100% in the subset of patients who received fludarabine and cyclophosphamide lymphodepletion. Twenty-three percent of patients developed reversible severe cytokine release syndrome and/or reversible severe neurotoxicity. These data demonstrate that manufacturing a defined-composition CD19 CAR T cell identifies an optimal cell dose with highly potent antitumor activity and a tolerable adverse effect profile in a cohort of patients with an otherwise poor prognosis. This trial was registered at www.clinicaltrials.gov as #NCT02028455. © 2017 by The American Society of Hematology.

Dose sculpting with generalized equivalent uniform dose

International Nuclear Information System (INIS)

Wu Qiuwen; Djajaputra, David; Liu, Helen H.; Dong Lei; Mohan, Radhe; Wu, Yan

2005-01-01

With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD 0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD 0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD 0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to

Simplified dose calculation method for mantle technique

International Nuclear Information System (INIS)

Scaff, L.A.M.

1984-01-01

A simplified dose calculation method for mantle technique is described. In the routine treatment of lymphom as using this technique, the daily doses at the midpoints at five anatomical regions are different because the thicknesses are not equal. (Author) [pt

The antianginal efficacy and tolerability of controlled-release metoprolol once daily

DEFF Research Database (Denmark)

Egstrup, K; Gundersen, T; Härkönen, R

1988-01-01

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

Daily Isocenter Correction With Electromagnetic-Based Localization Improves Target Coverage and Rectal Sparing During Prostate Radiotherapy

International Nuclear Information System (INIS)

Rajendran, Ramji Ramaswamy; Plastaras, John P.; Mick, Rosemarie; McMichael Kohler, Diane; Kassaee, Alireza; Vapiwala, Neha

2010-01-01

Purpose: To evaluate dosimetric consequences of daily isocenter correction during prostate cancer radiation therapy using the Calypso 4D localization system. Methods and Materials: Data were analyzed from 28 patients with electromagnetic transponders implanted in their prostates for daily target localization and tracking. Treatment planning isocenters were recorded based on the values of the vertical, longitudinal, and lateral axes. Isocenter location obtained via alignment with skin tattoos was compared with that obtained via the electromagnetic localization system. Daily isocenter shifts, based on the isocenter location differences between the two alignment methods in each spatial axis, were calculated for each patient over their entire course. The mean isocenter shifts were used to determine dosimetric consequences of treatment based on skin tattoo alignments alone. Results: The mean += SD of the percentages of treatment days with shifts beyond += 0.5 cm for vertical, longitudinal and lateral shifts were 62% += 28%, 35% += 26%, and 38% +=21%, respectively. If daily electromagnetic localization was not used, the excess in prescribed dose delivered to 70% of the rectum was 10 Gy and the deficit in prescribed dose delivered to 95% of the planning target volume was 10 Gy. The mean isocenter shift was not associated with the volumes of the prostate, rectum, or bladder, or with patient body mass index. Conclusions: Daily isocenter localization can reduce the treatment dose to the rectum. Correcting for this variability could lead to improved dose delivery, reduced side effects, and potentially improved treatment outcomes.

Technical Note: SCUDA: A software platform for cumulative dose assessment

Energy Technology Data Exchange (ETDEWEB)

Park, Seyoun; McNutt, Todd; Quon, Harry; Wong, John; Lee, Junghoon, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 (United States); Plishker, William [IGI Technologies, Inc., College Park, Maryland 20742 (United States); Shekhar, Raj, E-mail: rshekhar@childrensnational.org, E-mail: junghoon@jhu.edu [IGI Technologies, Inc., College Park, Maryland 20742 and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, Washington, DC 20010 (United States)

2016-10-15

Purpose: Accurate tracking of anatomical changes and computation of actually delivered dose to the patient are critical for successful adaptive radiation therapy (ART). Additionally, efficient data management and fast processing are practically important for the adoption in clinic as ART involves a large amount of image and treatment data. The purpose of this study was to develop an accurate and efficient Software platform for CUmulative Dose Assessment (SCUDA) that can be seamlessly integrated into the clinical workflow. Methods: SCUDA consists of deformable image registration (DIR), segmentation, dose computation modules, and a graphical user interface. It is connected to our image PACS and radiotherapy informatics databases from which it automatically queries/retrieves patient images, radiotherapy plan, beam data, and daily treatment information, thus providing an efficient and unified workflow. For accurate registration of the planning CT and daily CBCTs, the authors iteratively correct CBCT intensities by matching local intensity histograms during the DIR process. Contours of the target tumor and critical structures are then propagated from the planning CT to daily CBCTs using the computed deformations. The actual delivered daily dose is computed using the registered CT and patient setup information by a superposition/convolution algorithm, and accumulated using the computed deformation fields. Both DIR and dose computation modules are accelerated by a graphics processing unit. Results: The cumulative dose computation process has been validated on 30 head and neck (HN) cancer cases, showing 3.5 ± 5.0 Gy (mean±STD) absolute mean dose differences between the planned and the actually delivered doses in the parotid glands. On average, DIR, dose computation, and segmentation take 20 s/fraction and 17 min for a 35-fraction treatment including additional computation for dose accumulation. Conclusions: The authors developed a unified software platform that provides

Dose assessment in patients undergoing lung examinations by computed tomography

International Nuclear Information System (INIS)

Gonzaga, Natalia B.; Silva, Teogenes A. da; Magalhaes, Marcos J.

2011-01-01

In the last fifteen years, the use of computed tomography (CT) has increased alongside other radiology technologies technologies. Its contribution has already achieved 34% in terms of doses undergone by patients. Radiation protection of patients submitted to CT examinations is based on the knowledge of internationally defined dosimetric quantities as the CT air kerma-length product (P K,L ) and weighted CT air kerma index (C w ). In Brazil, those dosimetric quantities are not routinely used and the optimization criteria are based only upon the MSAD - the average dose in multislices. In this work, the dosimetric quantities P K,L and C w were assessed by the CT Expo program for seven protocols used daily for lung examinations in adults with the use of Siemens and Philips scanners in Belo Horizonte. Results showed that P K,L values varied from 163 to 558 mGy.cm and the C w from 9.6 to 17.5 mGy. All results were found to be lower than the reference values internationally recommended by ICRP 87 and the European Community 16262 (30 mGy and 650 mGy.cm). The large dose ranges suggest that optimization of patient dose reduction is still possible without losses in the image quality and new reference dose levels could be recommended after a large survey to be carried out in the region. (author)

Daily targeting of intrahepatic tumors for radiotherapy

International Nuclear Information System (INIS)

Balter, James M.; Brock, Kristy K.; Litzenberg, Dale W.; McShan, Daniel L.; Lawrence, Theodore S.; Haken, Randall Ten; McGinn, Cornelius J.; Lam, Kwok L.; Dawson, Laura A.

2002-01-01

Introduction: A system has been developed for daily targeting of intrahepatic tumors using a combination of ventilatory immobilization, in-room diagnostic imaging, and on-line setup adjustment. By reducing geometric position uncertainty, as well as organ movement, this system permits reduction of margins and thus potentially higher treatment doses. This paper reports our initial experience treating 8 patients with focal liver tumors using this system. Methods and Materials: The system includes diagnostic X-ray tubes mounted on the wall and ceiling of a treatment room, an active matrix flat panel imager, in-room control for image acquisition and setup adjustment, and a ventilatory immobilization system via active breathing control (ABC). Eight patients participated in the study, two using an early prototype ABC unit, and the remaining six with a commercial ABC system and improved setup measurement tools. Treatment margins were reduced, and dose consequently increased because of increased confidence in target position under this protocol. After daily setup via skin marks, orthogonal radiographs were acquired at suspended ventilation. The images were aligned to the CT model using the diaphragm for inferior-superior (IS) alignment, and the skeleton for left-right (LR) and anterior-posterior (AP) alignment. Adjustments were made for positioning errors greater than a threshold (3 or 5 mm). After treatment, retrospective analysis determined the final setup accuracy, as well as the error in initial setup measurement performed before setup adjustment. Results: Two hundred sixty-two treatment fractions were delivered on eight patients, with 171 treatments requiring repositioning. Typical treatment times were 25-30 min. Patients were able to tolerate ABC throughout the course of treatment. Breath holds up to 35 s long were used for treatment. The use of on-line imaging and setup adjustment reduced setup errors (σ) from 4.0 mm (LR), 6.7 mm (IS), and 3.8 mm (AP) to 2.1 mm (LR

The dose-response relationship for UV-tumorigenesis

International Nuclear Information System (INIS)

Gruijl, F.R. de.

1982-01-01

The main objective of the investigations was to extend the knowledge on experimental UV-carcinogenesis and to use the experimental results as guidelines for developing a dose-response model for UV-carcinogenesis. The animal experiments carried out were all long-term ones. It was decided that - in anticipation of the data to be obtained - a model for such an assessment should be developed using the experimental results available at the start of the present study (1977). This initial study is presented. The results of two animal experiments are presented, which show that UV radiation is capable of inducing a systemic effect that enhances the de novo formation of UV induced tumors. The results of the main experiment are presented. In this experiment groups of mice were subjected to daily exposure to a certain dose of UV radiation in order to find the dose-response relationship. The relation between the daily dose and the duration of the treatment till the appearance of tumors (for instance, as measured by the yield) was ascertained for tumors of different sizes. It appears that the growth of a tumor is dose-independent, and, therefore, only the initiation of a tumor is dose-dependent. Finally an experiment is presented in which it was measured that, if a mouse is subjected to daily UV exposure, the transmission of the epidermis in the shortwave UV region decreases continuously. This decrease is due to hyperplasia of the epidermis, i.e., thickening of the epidermis by an increase in the number of cells per unit surface area. (Auth.)

Dose limits

International Nuclear Information System (INIS)

Fitoussi, L.

1987-12-01

The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response

Directory of Open Access Journals (Sweden)

Craig J. Hudson

2014-01-01

Full Text Available Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

The daily you : How the new advertising industry is defining your identity and your worth

NARCIS (Netherlands)

Peters, Chris

Joseph Turow’s The Daily You takes us behind the scenes of the advertising industry to get a better sense of not just how its capitalistic rationale is put into practice but its potential impact on individuals in a consumer society. While readers are probably most familiar with his Breaking Up

Antipsychotic dose escalation as a trigger for Neuroleptic Malignant Syndrome (NMS: literature review and case series report

Directory of Open Access Journals (Sweden)

Langan Julie

2012-11-01

Full Text Available Abstract Background “Neuroleptic malignant syndrome” (NMS is a potentially fatal idiosyncratic reaction to any medication which affects the central dopaminergic system. Between 0.5% and 1% of patients exposed to antipsychotics develop the condition. Mortality rates may be as high as 55% and many risk factors have been reported. Although rapid escalation of antipsychotic dose is thought to be an important risk factor, to date it has not been the focus of a published case series or scientifically defined. Description We aimed to identify cases of NMS and review risk factors for its development with a particular focus on rapid dose escalation in the 30 days prior to onset. A review of the literature on rapid dose escalation was undertaken and a pragmatic definition of “rapid dose escalation” was made. NMS cases were defined using DSM-IV criteria and systematically identified within a secondary care mental health service. A ratio of titration rate was calculated for each NMS patient and “rapid escalators” and “non rapid escalators” were compared. 13 cases of NMS were identified. A progressive mean dose increase 15 days prior to the confirmed episode of NMS was observed (241.7 mg/day during days 1–15 to 346.9 mg/day during days 16–30 and the mean ratio of dose escalation for NMS patients was 1.4. Rapid dose escalation was seen in 5/13 cases and non rapid escalators had markedly higher daily cumulative antipsychotic dose compared to rapid escalators. Conclusions Rapid dose escalation occurred in less than half of this case series (n = 5, 38.5%, although there is currently no consensus on the precise definition of rapid dose escalation. Cumulative antipsychotic dose – alongside other known risk factors - may also be important in the development of NMS.

A comparison of the angular dependence of effective dose and effective dose equivalent

International Nuclear Information System (INIS)

Sitek, M.A.; Gierga, D.P.; Xu, X.G.

1996-01-01

In ICRP (International Commission on Radiological Protection) Publication 60, the set of critical organs and their weighing factors were changed, defining the quantity effective dose, E. This quantity replaced the effective dose equivalent, H E , as defined by ICRP 26. Most notably, the esophagus was added to the list of critical organs. The Monte Carlo neutron/photon transport code MCNP was used to determine the effective dose to sex-specific anthropomorphic phantoms. The phantoms, developed in previous research, were modified to include the esophagus. Monte Carlo simulations were performed for monoenergetic photon beams of energies 0.08 MeV, 0.3 MeV, and 1.0 MeV for various azimuthal and polar angles. Separate organ equivalent doses were determined for male and female phantoms. The resulting organ equivalent doses were calculated from arithmetic mean averages. The angular dependence of effective dose was compared with that of effective dose equivalent reported in previous research. The differences between the two definitions and possible implications to regulatory agencies were summarized

Concept for quantifying the dose from image guided radiotherapy

International Nuclear Information System (INIS)

Schneider, Uwe; Hälg, Roger; Besserer, Jürgen

2015-01-01

Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2 % variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. Dose from radiotherapy

Dose fractionated gamma knife radiosurgery for large arteriovenous malformations on daily or alternate day schedule outside the linear quadratic model: Proof of concept and early results. A substitute to volume fractionation.

Science.gov (United States)

Mukherjee, Kanchan Kumar; Kumar, Narendra; Tripathi, Manjul; Oinam, Arun S; Ahuja, Chirag K; Dhandapani, Sivashanmugam; Kapoor, Rakesh; Ghoshal, Sushmita; Kaur, Rupinder; Bhatt, Sandeep

2017-01-01

To evaluate the feasibility, safety and efficacy of dose fractionated gamma knife radiosurgery (DFGKRS) on a daily schedule beyond the linear quadratic (LQ) model, for large volume arteriovenous malformations (AVMs). Between 2012-16, 14 patients of large AVMs (median volume 26.5 cc) unsuitable for surgery or embolization were treated in 2-3 of DFGKRS sessions. The Leksell G frame was kept in situ during the whole procedure. 86% (n = 12) patients had radiologic evidence of bleed, and 43% (n = 6) had presented with a history of seizures. 57% (n = 8) patients received a daily treatment for 3 days and 43% (n = 6) were on an alternate day (2 fractions) regimen. The marginal dose was split into 2 or 3 fractions of the ideal prescription dose of a single fraction of 23-25 Gy. The median follow up period was 35.6 months (8-57 months). In the three-fraction scheme, the marginal dose ranged from 8.9-11.5 Gy, while in the two-fraction scheme, the marginal dose ranged from 11.3-15 Gy at 50% per fraction. Headache (43%, n = 6) was the most common early postoperative complication, which was controlled with short course steroids. Follow up evaluation of at least three years was achieved in seven patients, who have shown complete nidus obliteration in 43% patients while the obliteration has been in the range of 50-99% in rest of the patients. Overall, there was a 67.8% reduction in the AVM volume at 3 years. Nidus obliteration at 3 years showed a significant rank order correlation with the cumulative prescription dose (p 0.95, P value 0.01), with attainment of near-total (more than 95%) obliteration rates beyond 29 Gy of the cumulative prescription dose. No patient receiving a cumulative prescription dose of less than 31 Gy had any severe adverse reaction. In co-variate adjusted ordinal regression, only the cumulative prescription dose had a significant correlation with common terminology criteria for adverse events (CTCAE) severity (P value 0.04), independent of age, AVM volume

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

Energy Technology Data Exchange (ETDEWEB)

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu [U.C. Davis School of Medicine, Department of Radiation Oncology, Sacramento, CA (United States); Ayala, Deandra; Jensen, Courtney [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Case, L. Douglas [Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Bourland, J. Daniel; Ellis, Thomas L. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); McMullen, Kevin P.; Chan, Michael D. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Tatter, Stephen B. [Neurosurgery, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Lesser, Glen J. [Hematology Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States); Shaw, Edward G. [Radiation Oncology, Wake Forest University Health Sciences, Winston-Salem, NC (United States)

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

International Nuclear Information System (INIS)

Monjazeb, Arta M.; Ayala, Deandra; Jensen, Courtney; Case, L. Douglas; Bourland, J. Daniel; Ellis, Thomas L.; McMullen, Kevin P.; Chan, Michael D.; Tatter, Stephen B.; Lesser, Glen J.; Shaw, Edward G.

2012-01-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4–5 acute neurotoxicity attributable to radiotherapy. Results: All patients experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.

Predictors of pulmonary toxicity in limited stage small cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.

Science.gov (United States)

Salama, Joseph K; Pang, Herbert; Bogart, Jeffrey A; Blackstock, A William; Urbanic, James J; Hogson, Lydia; Crawford, Jeffrey; Vokes, Everett E

2013-12-01

Standard therapy for limited stage small cell lung cancer (L-SCLC) is concurrent chemotherapy and radiotherapy followed by prophylactic cranial radiotherapy. Predictors of post chemoradiotherapy pulmonary toxicity in limited stage (LS) small cell lung cancer (SCLC) patients are not well defined. Current guidelines are derived from non-small cell lung cancer regimens, and do not account for the unique biology of this disease. Therefore, we analyzed patients on three consecutive CALGB LS-SCLC trials treated with concurrent chemotherapy and daily high dose radiotherapy (70 Gy) to determine patient and treatment related factors predicting for post-treatment pulmonary toxicity. Patients treated on CALGB protocols 39808, 30002, 30206 investigating two cycles of chemotherapy followed by concurrent chemotherapy and 70 Gy daily thoracic radiation therapy were pooled. Patient, tumor, and treatment related factors were evaluated to determine predictors of grade 3–5 pulmonary toxicities after concurrent chemoradiotherapy. 100 patients were included. No patient experienced grade 4–5 post-treatment pulmonary toxicity. Patients who experienced post-treatment pulmonary toxicity were more likely to be older (median age 69 vs 60, p = 0.09) and have smaller total lung volumes (2565 cc vs 3530 cc, p = 0.05).). Furthermore,exposure of larger volumes of lung to lower (median V5 = 70%, p = 0.09, median V10 = 63%, p = 0.07), inter-mediate (median V20 = 50, p = 0.04) and high (median V60 = 25%, p = 0.01) doses of radiation were all associated with post-treatment grade 3 pulmonary toxicity, as was a larger mean lung radiation dose(median 31 Gy) p = 0.019. Post-treatment pulmonary toxicity following the completion of 2 cycles of chemotherapy followed by concurrent chemotherapy and high dose daily radiation therapy was uncommon. Care should be taken to minimize mean lung radiation exposure, as well as volumes of low, intermediate and high doses of radiation.

Design and performance of daily quality assurance system for carbon ion therapy at NIRS

Science.gov (United States)

Saotome, N.; Furukawa, T.; Hara, Y.; Mizushima, K.; Tansho, R.; Saraya, Y.; Shirai, T.; Noda, K.

2017-09-01

At National Institute of Radiological Sciences (NIRS), we have been commissioning a rotating-gantry system for carbon-ion radiotherapy. This rotating gantry can transport heavy ions at 430 MeV/u to an isocenter with irradiation angles of ±180° that can rotate around the patient so that the tumor can be irradiated from any direction. A three-dimensional pencil-beam scanning irradiation system equipped with the rotating gantry enables the optimal use of physical characteristics of carbon ions to provide accurate treatment. To ensure the treatment quality using such a complex system, the calibration of the primary dose monitor, output check, range check, dose rate check, machine safety check, and some mechanical tests should be performed efficiently. For this purpose, we have developed a measurement system dedicated for quality assurance (QA) of this gantry system: the Daily QA system. The system consists of an ionization chamber system and a scintillator system. The ionization chamber system is used for the calibration of the primary dose monitor, output check, and dose rate check, and the scintillator system is used for the range check, isocenter, and gantry angle. The performance of the Daily QA system was verified by a beam test. The stability of the output was within 0.5%, and the range was within 0.5 mm. The coincidence of the coordinates between the patient-positioning system and the irradiation system was verified using the Daily QA system. Our present findings verified that the new Daily QA system for a rotating gantry is capable of verifying the irradiation system with sufficient accuracy.

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

Directory of Open Access Journals (Sweden)

Guetz S

2017-02-01

Full Text Available Sylvia Guetz,1,* Amanda Tufman,2,* Joachim von Pawel,3 Achim Rittmeyer,4 Astrid Borgmeier,2 Pierre Ferré,5 Birgit Edlich,6 Rudolf Maria Huber2 1Ev. Diakonissenkrankenhaus Leipzig, Leipzig, 2University Hospital Munich and Thoracic Oncology Centre Munich, Member of the German Center for Lung Research, Comprehensive Pneumology Center Munich (DZL CPC-M, Munich, 3Asklepios Fachkliniken Muenchen-Gauting, Gauting, 4Lungenfachklinik Immenhausen, Immenhausen, Germany; 5Pierre Fabre Pharmaceuticals, Oncology Research and Development Center, Toulouse, France; 6Pierre Fabre Pharma GmbH, Freiburg, Germany *These authors contributed equally to this work Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage. Introduction: We present a Phase I dose-finding study investigating metronomic daily oral vinorelbine (Navelbine® Oral, NVBo in advanced non-small-cell lung cancer (NSCLC. Patients and methods: Patients with stage III/IV NSCLC received daily NVBo at fixed dose levels of 20–50 mg/d for 21 days of each 4-week cycle. Primary end point was the maximum tolerated dose. Secondary end points included tumor response, time to progression (TTP, overall survival (OS and tolerability. Results: Twenty-seven patients with advanced NSCLC were enrolled. Most of them were extensively pretreated. Daily NVBo was well tolerated up to 30 mg/d. At 40 mg/d, two of five patients experienced dose-limiting toxicities (DLTs. Three of six patients had DLTs at the 50 mg/d level. The recommended dose was established at 30 mg/d in cycle 1, with escalation to 40 mg/d in cycle 2, if tolerated. Pharmacokinetic analyses showed continuous blood exposure over 21�

Daily intakes of naturally occurring radioisotopes in typical Korean foods

International Nuclear Information System (INIS)

Choi, Min-Seok; Lin Xiujing; Lee, Sun Ah; Kim, Wan; Kang, Hee-Dong; Doh, Sih-Hong; Kim, Do-Sung; Lee, Dong-Myung

2008-01-01

The concentrations of naturally occurring radioisotopes ( 232 Th, 228 Th, 230 Th, 228 Ra, 226 Ra, and 40 K) in typical Korean foods were evaluated. The daily intakes of these radioisotopes were calculated by comparing concentrations in typical Korean foods and the daily consumption rates of these foods. Daily intakes were as follows: 232 Th, 0.00-0.23; 228 Th, 0.00-2.04; 230 Th, 0.00-0.26; 228 Ra, 0.02-2.73; 226 Ra, 0.01-4.37 mBq/day; and 40 K, 0.01-5.71 Bq/day. The total daily intake of the naturally occurring radioisotopes measured in this study from food was 39.46 Bq/day. The total annual internal dose resulting from ingestion of radioisotopes in food was 109.83 μSv/y, and the radioisotope with the highest daily intake was 40 K. These values were same level compiled in other countries

Impact of daily anatomical changes on EPID-based in vivo dosimetry of VMAT treatments of head-and-neck cancer

International Nuclear Information System (INIS)

Rozendaal, Roel A.; Mijnheer, Ben J.; Hamming-Vrieze, Olga; Mans, Anton; Herk, Marcel van

2015-01-01

Background and purpose: Target dose verification for VMAT treatments of head-and-neck (H&N) cancer using 3D in vivo EPID dosimetry is expected to be affected by daily anatomical changes. By including these anatomical changes through cone-beam CT (CBCT) information, the magnitude of this effect is investigated. Materials and methods: For 20 VMAT-treated H&N cancer patients, all plan-CTs (pCTs), 633 CBCTs and 1266 EPID movies were used to compare four dose distributions per fraction: treatment planning system (TPS) calculated dose and EPID reconstructed in vivo dose, both determined using the pCT and using the CBCT. D2, D50 and D98 of the planning target volume (PTV) were determined per dose distribution. Results: When including daily anatomical information, D2, D50 and D98 of the PTV change on average by 0.0 ± 0.4% according to TPS calculations; the standard deviation of the difference between EPID and TPS target dose changes from 2.5% (pCT) to 2.1% (CBCT). Small time trends are seen for both TPS and EPID dose distributions when using the pCT, which disappear when including CBCT information. Conclusions: Daily anatomical changes hardly influence the target dose distribution for H&N VMAT treatments according to TPS recalculations. Including CBCT information in EPID dose reconstructions slightly improves the agreement with TPS calculations

Declines in Outpatient Antimicrobial Use in Canada (1995–2010)

Science.gov (United States)

Finley, Rita; Glass-Kaastra, Shiona K.; Hutchinson, Jim; Patrick, David M.; Weiss, Karl; Conly, John

2013-01-01

Background With rising reports of antimicrobial resistance in outpatient communities, surveillance of antimicrobial use is imperative for supporting stewardship programs. The primary objective of this article is to assess the levels of antimicrobial use in Canada over time. Methods Canadian antimicrobial use data from 1995 to 2010 were acquired and assessed by four metrics: population-adjusted prescriptions, Defined Daily Doses, spending on antimicrobials (inflation-adjusted), and average Defined Daily Doses per prescription. Linear mixed models were built to assess significant differences among years and antimicrobial groups, and to account for repeated measurements over time. Measures were also compared to published reports from European countries. Results Temporal trends in antimicrobial use in Canada vary by metric and antimicrobial grouping. Overall reductions were seen for inflation-adjusted spending, population-adjusted prescription rates and Defined Daily Doses, and increases were observed for the average number of Defined Daily Doses per prescription. The population-adjusted prescription and Defined Daily Doses values for 2009 were comparable to those reported by many European countries, while the average Defined Daily Dose per prescription for Canada ranked high. A significant reduction in the use of broad spectrum penicillins occurred between 1995 and 2004, coupled with increases in macrolide and quinolone use, suggesting that replacement of antimicrobial drugs may occur as new products arrive on the market. Conclusions There have been modest decreases of antimicrobial use in Canada over the past 15 years. However, continued surveillance of antimicrobial use coupled with data detailing antimicrobial resistance within bacterial pathogens affecting human populations is critical for targeting interventions and maintaining the effectiveness of these products for future generations. PMID:24146863

Daily sitting time and all-cause mortality: a meta-analysis

NARCIS (Netherlands)

Chau, J.Y.; Grunseit, A.C.; Chey, T.; Stamatakis, E.; Brown, W.J.; Matthews, C.E.; Bauman, A.E.; van der Ploeg, H.P.

2013-01-01

Objective: To quantify the association between daily total sitting and all-cause mortality risk and to examine dose-response relationships with and without adjustment for moderate-to-vigorous physical activity. Methods: Studies published from 1989 to January 2013 were identified via searches of

Gabapentin for once-daily treatment of post-herpetic neuralgia: a review

Directory of Open Access Journals (Sweden)

Beal B

2012-07-01

Full Text Available Benjamin Beal,1 Tobias Moeller-Bertram,1,2 Jan M Schilling,1 Mark S Wallace11Division of Pain Medicine, Department of Anesthesiology, University of California, 2VA San Diego Healthcare System, San Diego, CA, USAAbstract: Post-herpetic neuralgia is a neuropathic pain syndrome resulting from an insult to the peripheral and central nervous systems caused by the varicella zoster virus. Spontaneous pain may result in the persistent sensation of burning, tingling, or aching and may be associated with thermally or mechanically provoked pain, resulting in hyperalgesia or allodynia. The majority of cases occur in patients over the age of 50 years. Gabapentin is a structural analog of gamma aminobutyric acid that binds to the α2-δ site of voltage-dependent calcium channels and modulates the influx of calcium, with a resulting reduction in excitatory neurotransmitter release. Gabapentin is effective in reducing neuropathic pain due to post-herpetic neuralgia when given at least three times per day, due to its short half-life, resulting in demonstrable fluctuations in plasma levels. Gabapentin has dose-limiting side effects that prevent some patients from achieving therapeutic plasma levels, such as somnolence (27.4%, dizziness (23.9%, and ataxia (7.1%. Gralise™ is a once-daily extended-release formulation of gabapentin that has been developed using AcuForm™ technology. AcuForm is a polymer-based drug delivery system that retains the tablet in the stomach and upper gastrointestinal tract for a sustained period of time. Once-daily dosing has been shown to provide comparable drug exposure with an identical daily dose of the immediate-release formulation when administered three times daily. Participants given Gralise 1800 mg daily had a statistically significant reduction in average daily pain intensity scores compared with placebo, reduced sleep interference due to pain, and a greater percent of participants reporting being much or very much improved on

Failure-probability driven dose painting

DEFF Research Database (Denmark)

Vogelius, Ivan R; Håkansson, Katrin; Due, Anne K

2013-01-01

To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study...

Daily cranberry juice for the prevention of asymptomatic bacteriuria in pregnancy: a randomized, controlled pilot study.

Science.gov (United States)

Wing, Deborah A; Rumney, Pamela J; Preslicka, Christine W; Chung, Judith H

2008-10-01

We compared the effects of daily cranberry juice cocktail to those of placebo during pregnancy on asymptomatic bacteriuria and symptomatic urinary tract infections. A total of 188 women were randomized to cranberry or placebo in 3 treatment arms of A-cranberry 3 times daily (58), B-cranberry at breakfast then placebo at lunch and dinner (67), and C-placebo 3 times daily (63). After 27.7% (52 of 188) of the subjects were enrolled in the study the dosing regimens were changed to twice daily dosing to improve compliance. There were 27 urinary tract infections in 18 subjects in this cohort, with 6 in 4 group A subjects, 10 in 7 group B subjects and 11 in 7 group C subjects (p = 0.71). There was a 57% and 41% reduction in the frequency of asymptomatic bacteriuria and all urinary tract infections, respectively, in the multiple daily dosing group. However, this study was not sufficiently powered at the alpha 0.05 level (CI 0.14-1.39 and 0.22-1.60, respectively, incidence rate ratios). Of 188 subjects 73 (38.8%) withdrew, most for gastrointestinal upset. These data suggest there may be a protective effect of cranberry ingestion against asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. Further studies are planned to evaluate this effect.

Radiation in daily life

International Nuclear Information System (INIS)

Mora Rodriguez, P.

1999-01-01

The medical community benefits on a daily basis from the ionizing radiations used in the diagnosis and treatment of disease. The doses received in the medical field are only a small fraction of the total radiation received in a year. This bibliographic review has several objectives. The first one is to present the different components of natural radiation (background radiation). Secondly, it will introduce many consumer products that contain radioactive sources and expose our bodies. Third, arguments to diminish the radiation phobia will be presented and finally an easy to understand dosimetric magnitude will be introduced for the physician, the technologist and the patient. (author) [es

Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

International Nuclear Information System (INIS)

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

International Nuclear Information System (INIS)

Sohrabi, M.

1997-01-01

The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

Relationship between Individual External Doses, Ambient Dose Rates and Individuals' Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident.

Directory of Open Access Journals (Sweden)

Wataru Naito

Full Text Available The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses

Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

DEFF Research Database (Denmark)

Reddel, H. K.; Busse, W. W.; Pedersen, Søren

2015-01-01

symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years...

A new warfarin dosing algorithm including VKORC1 3730 G > A polymorphism: comparison with results obtained by other published algorithms.

Science.gov (United States)

Cini, Michela; Legnani, Cristina; Cosmi, Benilde; Guazzaloca, Giuliana; Valdrè, Lelia; Frascaro, Mirella; Palareti, Gualtiero

2012-08-01

Warfarin dosing is affected by clinical and genetic variants, but the contribution of the genotype associated with warfarin resistance in pharmacogenetic algorithms has not been well assessed yet. We developed a new dosing algorithm including polymorphisms associated both with warfarin sensitivity and resistance in the Italian population, and its performance was compared with those of eight previously published algorithms. Clinical and genetic data (CYP2C9*2, CYP2C9*3, VKORC1 -1639 G > A, and VKORC1 3730 G > A) were used to elaborate the new algorithm. Derivation and validation groups comprised 55 (58.2% men, mean age 69 years) and 40 (57.5% men, mean age 70 years) patients, respectively, who were on stable anticoagulation therapy for at least 3 months with different oral anticoagulation therapy (OAT) indications. Performance of the new algorithm, evaluated with mean absolute error (MAE) defined as the absolute value of the difference between observed daily maintenance dose and predicted daily dose, correlation with the observed dose and R(2) value, was comparable with or slightly lower than that obtained using the other algorithms. The new algorithm could correctly assign 53.3%, 50.0%, and 57.1% of patients to the low (≤25 mg/week), intermediate (26-44 mg/week) and high (≥ 45 mg/week) dosing range, respectively. Our data showed a significant increase in predictive accuracy among patients requiring high warfarin dose compared with the other algorithms (ranging from 0% to 28.6%). The algorithm including VKORC1 3730 G > A, associated with warfarin resistance, allowed a more accurate identification of resistant patients who require higher warfarin dosage.

Regular and low-dose aspirin, other non-steroidal anti-inflammatory medications and prospective risk of HER2-defined breast cancer: the California Teachers Study.

Science.gov (United States)

Clarke, Christina A; Canchola, Alison J; Moy, Lisa M; Neuhausen, Susan L; Chung, Nadia T; Lacey, James V; Bernstein, Leslie

2017-05-01

Regular users of aspirin may have reduced risk of breast cancer. Few studies have addressed whether risk reduction pertains to specific breast cancer subtypes defined jointly by hormone receptor (estrogen and progesterone receptor) and human epidermal growth factor receptor 2 (HER2) expression. This study assessed the prospective risk of breast cancer (overall and by subtype) according to use of aspirin and other non-steroidal anti-inflammatory medications (NSAIDs) in a cohort of female public school professionals in California. In 1995 - 1996, participants in the California Teachers Study completed a baseline questionnaire on family history of cancer and other conditions, use of NSAIDs, menstrual and reproductive history, self-reported weight and height, living environment, diet, alcohol use, and physical activity. In 2005-2006, 57,164 participants provided some updated information, including use of NSAIDs and 1457 of these participants developed invasive breast cancer before January 2013. Multivariable Cox proportional hazards regression models provided hazard rate ratios (HRR) for the association between NSAID use and risk of invasive breast cancer as well as hormone receptor- and HER2-defined subtypes. Developing breast cancer was associated inversely with taking three or more tablets of low-dose aspirin per week (23% of participants). Among women reporting this exposure, the HRR was 0.84 (95% confidence interval (CI) 0.72-0.98) compared to those not taking NSAIDs and this was particularly evident in women with the hormone receptor-positive/HER2-negative subtype (HRR = 0.80, 95% CI 0.66-0.96). Use of three or more tablets of "other" NSAIDs was marginally associated with lower risk of breast cancer (HRR = 0.79, 95% CI 0.62-1.00). Other associations with NSAIDs were generally null. Our observation of reduced risk of breast cancer, among participants who took three or more tablets of low-dose aspirin weekly, is consistent with other reports looking at

Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(®) in Asthma Using Standardized Sample-Contamination Avoidance

DEFF Research Database (Denmark)

Beeh, Kai-Michael; Kirsten, Anne-Marie; Dusser, Daniel

2016-01-01

BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(®) 5 μg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacoki...

Vitamin D: Daily vs. Monthly Use in Children and Elderly-What Is Going On?

Science.gov (United States)

Dalle Carbonare, Luca; Valenti, Maria Teresa; Del Forno, Francesco; Caneva, Elena; Pietrobelli, Angelo

2017-06-24

Vitamin D deficiency is highly prevalent among children and adults worldwide. Agreement exists that vitamin D deficiency should be corrected. However, the definitions of vitamin deficiency and effective vitamin D replacement therapy are inconsistent in the literature. Not only is the dosing regimen still under debate, but also the time and period of administration (i.e., daily vs. monthly dose). In pediatric as well as elderly subjects, dosing regimens with high vitamin D doses at less frequent intervals were proposed to help increase compliance to treatment: these became widespread in clinical practice, despite mounting evidence that such therapies are not only ineffective but potentially harmful, particularly in elderly subjects. Moreover, in the elderly, high doses of vitamin D seem to increase the risk of functional decline and are associated with a higher risk of falls and fractures. Achieving good adherence to recommended prophylactic regimens is definitely one of the obstacles currently being faced in view of the wide segment of the population liable to the treatment and the very long duration of prophylaxis. The daily intake for extended periods is in fact one of the frequent causes of therapeutic drop-outs, while monthly doses of vitamin D may effectively and safely improve patient compliance to the therapy. The aim of our paper is a quasi-literature review on dosing regimens among children and elderly. These two populations showed a particularly significant beneficial effect on bone metabolism, and there could be different outcomes with different dosing regimens.

Occupational dose constraint

International Nuclear Information System (INIS)

Heilbron Filho, Paulo Fernando Lavalle; Xavier, Ana Maria

2005-01-01

The revision process of the international radiological protection regulations has resulted in the adoption of new concepts, such as practice, intervention, avoidable and restriction of dose (dose constraint). The latter deserving of special mention since it may involve reducing a priori of the dose limits established both for the public and to individuals occupationally exposed, values that can be further reduced, depending on the application of the principle of optimization. This article aims to present, with clarity, from the criteria adopted to define dose constraint values to the public, a methodology to establish the dose constraint values for occupationally exposed individuals, as well as an example of the application of this methodology to the practice of industrial radiography

Daily Physical Activity and Cognitive Function Variability in Older Adults.

Science.gov (United States)

Phillips, Christine B; Edwards, Jerri D; Andel, Ross; Kilpatrick, Marcus

2016-04-01

Physical activity (PA) is believed to preserve cognitive function in older adulthood, though little is known about these relationships within the context of daily life. The present microlongitudinal pilot study explored within- and between-person relationships between daily PA and cognitive function and also examined within-person effect sizes in a sample of community-dwelling older adults. Fifty-one healthy participants (mean age = 70.1 years) wore an accelerometer and completed a cognitive assessment battery for five days. There were no significant associations between cognitive task performance and participants' daily or average PA over the study period. Effect size estimates indicated that PA explained 0-24% of within-person variability in cognitive function, depending on cognitive task and PA dose. Results indicate that PA may have near-term cognitive effects and should be explored as a possible strategy to enhance older adults' ability to perform cognitively complex activities within the context of daily living.

Update on the clinical utility of once-daily tacrolimus in the management of transplantation

Directory of Open Access Journals (Sweden)

Revollo J

2015-05-01

Full Text Available Jane Revollo Department of Pharmacy, Jackson Memorial Hospital, University of Miami Leonard M Miller School of Medicine Miami, FL, USAThe review by Posadas Salas and Srinivas of the clinical utility of once-daily tacrolimus formulations in the management of transplant patients1 was timely and relevant. It is worth noting, however, the data were presented in a way that overlooked several key differences between two distinct once-daily tacrolimus formulations. These formulations differ in bioavailability, Cmax, Tmax, dose required to achieve target trough levels, and time to reach target trough. The specific formulation and dosing information of one product was detailed in this review (described as modified release 4 [MR-4]; Astagraf®, Astellas Pharma Inc., Tokyo, Japan, but no formulation or dosing details were provided for a very different once-daily tacrolimus formulation (LCP-Tacro™; Veloxis Pharmaceuticals A/S, Hørsholm, Denmark for which a thorough review was recently published.2 The latter product is currently approved in Europe and under review by the US Food and Drug Administration in the US. In presenting data in this review, the authors did not identify which product was investigated in each of the studies discussed. This could easily lead to misinterpretation of results or erroneous conclusions, ie, that both once-daily formulations are the same. In fact, a careful parsing of the data clearly demonstrates that they are not equivalent. Misunderstanding of this point could have a potentially serious impact on appropriate dosing, safety, and patient management in the post-transplant setting. Differentiation between the two products is needed to clarify what appear to be conflicting results of the studies presented in this review.View original paper by Posadas Salas and Srinivas

Fast in vivo volume dose reconstruction via reference dose perturbation

International Nuclear Information System (INIS)

Lu, Weiguo; Chen, Mingli; Mo, Xiaohu; Parnell, Donald; Olivera, Gustavo; Galmarini, Daniel

2014-01-01

Purpose: Accurate on-line reconstruction of in-vivo volume dose that accounts for both machine and patient discrepancy is not clinically available. We present a simple reference-dose-perturbation algorithm that reconstructs in-vivo volume dose fast and accurately. Methods: We modelled the volume dose as a function of the fluence map and density image. Machine (output variation, jaw/leaf position errors, etc.) and patient (setup error, weight loss, etc.) discrepancies between the plan and delivery were modelled as perturbation of the fluence map and density image, respectively. Delivered dose is modelled as perturbation of the reference dose due to change of the fluence map and density image. We used both simulated and clinical data to validate the algorithm. The planned dose was used as the reference. The reconstruction was perturbed from the reference and accounted for output-variations and the registered daily image. The reconstruction was compared with the ground truth via isodose lines and the Gamma Index. Results: For various plans and geometries, the volume doses were reconstructed in few seconds. The reconstruction generally matched well with the ground truth. For the 3%/3mm criteria, the Gamma pass rates were 98% for simulations and 95% for clinical data. The differences mainly appeared on the surface of the phantom/patient. Conclusions: A novel reference-dose-perturbation dose reconstruction model is presented. The model accounts for machine and patient discrepancy from planning. The algorithm is simple, fast, yet accurate, which makes online in-vivo 3D dose reconstruction clinically feasible.

Higher glucocorticoid replacement doses are associated with increased mortality in patients with pituitary adenoma.

Science.gov (United States)

Hammarstrand, Casper; Ragnarsson, Oskar; Hallén, Tobias; Andersson, Eva; Skoglund, Thomas; Nilsson, Anna G; Johannsson, Gudmundur; Olsson, Daniel S

2017-09-01

Patients with secondary adrenal insufficiency (AI) have an excess mortality. The objective was to investigate the impact of the daily glucocorticoid replacement dose on mortality in patients with hypopituitarism due to non-functioning pituitary adenoma (NFPA). Patients with NFPA were followed between years 1997 and 2014 and cross-referenced with the National Swedish Death Register. Standardized mortality ratio (SMR) was calculated with the general population as reference and Cox-regression was used to analyse the mortality. The analysis included 392 patients (140 women) with NFPA. Mean ± s.d. age at diagnosis was 58.7 ± 14.6 years and mean follow-up was 12.7 ± 7.2 years. AI was present in 193 patients, receiving a mean daily hydrocortisone equivalent (HCeq) dose of 20 ± 6 mg. SMR (95% confidence interval (CI)) for patients with AI was similar to that for patients without, 0.88 (0.68-1.12) and 0.87 (0.63-1.18) respectively. SMR was higher for patients with a daily HCeq dose of >20 mg (1.42 (0.88-2.17)) than that in patients with a daily HCeq dose of 20 mg (0.71 (0.49-0.99)), P  = 0.017. In a Cox-regression analysis, a daily HCeq dose of >20 mg was independently associated with a higher mortality (HR: 1.88 (1.06-3.33)). Patients with daily HCeq doses of ≤20 mg had a mortality risk comparable to patients without glucocorticoid replacement and to the general population. Patients with NFPA and AI receiving more than 20 mg HCeq per day have an increased mortality. Our data also show that mortality in patients substituted with 20 mg HCeq per day or less is not increased. © 2017 European Society of Endocrinology.

Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project

Directory of Open Access Journals (Sweden)

Stefanie J. Vaccher

2017-12-01

Full Text Available IntroductionThe effectiveness of daily pre-exposure prophylaxis (PrEP is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM. This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project.Materials and methodsIndividuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day, event-driven (pills taken only around specific risk events, or periodic (daily dosing during periods of increased risk.ResultsOverall, 315 GBM (98% of study sample provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR = 4.58, 95% confidence intervals (95% CI: (1.68, 12.49], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76].DiscussionIndividuals’ preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to

A Phase I Dose-Escalation Study (ISIDE-BT-1) of Accelerated IMRT With Temozolomide in Patients With Glioblastoma

International Nuclear Information System (INIS)

Morganti, Alessio G.; Balducci, Mario; Salvati, Maurizio; Esposito, Vincenzo; Romanelli, Pantaleo; Ferro, Marica; Calista, Franco; Digesu, Cinzia; Macchia, Gabriella; Ianiri, Massimo; Deodato, Francesco; Cilla, Savino; Piermattei, Angelo M.P.; Valentini, Vincenzo; Cellini, Numa; Cantore, Gian Paolo

2010-01-01

Purpose: To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. Methods and Materials: A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed ± enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade ≥3 or any hematological toxicity rated as ≥4 by Radiation Therapy Oncology Group (RTOG) criteria. Results: Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. Conclusion: Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.

Level of occupational exposure during daily work in a Nuclear Medicine Department

Energy Technology Data Exchange (ETDEWEB)

Schwarcke, Marcelo, E-mail: mschwarcke@usp.br [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Dept. de Fisica e Matematica; Ferreira, Nadya [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Engenharia Nuclear; Cardoso, Domingos [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2011-07-01

Workers of the Nuclear Medicine Department have a very complex geometric exposition. The source of irradiation is not collimated and irradiated for all direction, the interaction with many structural tissue is inside the body before could be detected outside. The professional who works in a Nuclear Medicine Department is exposed to this condition and different energies. This work proposes a good approach to estimate the mensal dose level according to the dose rate during their daily routine. To measure the dose rate, a Babyline 81 ionization chamber was used, and the most frequent exams using {sup 99m}Tc were chosen. A previous study was conducted to determine the most frequent exams made in the Nuclear Medicine Department at the Central Army Hospital in Rio de Janeiro, and previous environment monitoring determine the places with higher exposure that could interfere in the measurement of this paper. The Renal scintigraphy with diethylenetriaminepentaacetic acid (DTPA) had an average dose rate of (2.50{+-}0.25) {mu}Sv/h; for the Renal scintigraphy with dimercaptosuccinic acid (DMSA), it was of (1.20{+-}0.25) {mu}Sv/h; for Bone scintigraphy using two different protocols, it was (2.63{+-}0.30) {mu}Sv/h and (3.09{+-}0.30) {mu}Sv/h. Exposition during elution, dose preparing and clinical procedure was considered a critical moment in the daily routine of the employee. The dose rate obtained in this study demonstrated that the professional cannot exceed the public dose limit in one day of his work routine. Therefore, for the Radioprotection Department, this is a good approach to make a radioprotection plan in the Nuclear Medicine Department. (author)

Uncertainty on faecal analysis on dose assessment

Energy Technology Data Exchange (ETDEWEB)

Juliao, Ligia M.Q.C.; Melo, Dunstana R.; Sousa, Wanderson de O.; Santos, Maristela S.; Fernandes, Paulo Cesar P. [Instituto de Radioprotecao e Dosimetria, Comissao Nacional de Energia Nuclear, Av. Salvador Allende s/n. Via 9, Recreio, CEP 22780-160, Rio de Janeiro, RJ (Brazil)

2007-07-01

Monitoring programmes for internal dose assessment may need to have a combination of bioassay techniques, e.g. urine and faecal analysis, especially in workplaces where compounds of different solubilities are handled and also in cases of accidental intakes. Faecal analysis may be an important data for assessment of committed effective dose due to exposure to insoluble compounds, since the activity excreted by urine may not be detectable, unless a very sensitive measurement system is available. This paper discusses the variability of the daily faecal excretion based on data from just one daily collection; collection during three consecutive days: samples analysed individually and samples analysed as a pool. The results suggest that just 1 d collection is not appropriate for dose assessment, since the 24 h uranium excretion may vary by a factor of 40. On the basis of this analysis, the recommendation should be faecal collection during three consecutive days, and samples analysed as a pool, it is more economic and faster. (authors)

Implementation to spanish protocol of quality control of accelerators to daily control of electron beams

International Nuclear Information System (INIS)

Adaimi Hernandez, P.; Ramirez Ros, J. C.; Casa de Julian, M. A. de la; Clemente Gutierrez, F.; Cabello Murillo, E.; Diaz Fuente, R.; Ferrando Sanchez, A.

2011-01-01

A revised procedure for daily control of the electron beams to make measurements more meaningful physically, having a better reproducibility and more in line with the recommendations of the Spanish Protocol for Quality Control in Electron Linear Accelerators Clinical Use. The daily quality control beams of high energy electrons that had been done so far was the finding that the record of a series of measures (symmetry, uniformity, stability, energy, beam central dose) were within tolerance values established. The amendment is to check the beam quality by directly measuring changes in absorption depth at which the dose is reduced to half its maximum value, R50.

Early Assessment of Treatment Responses During Radiation Therapy for Lung Cancer Using Quantitative Analysis of Daily Computed Tomography

Energy Technology Data Exchange (ETDEWEB)

Paul, Jijo; Yang, Cungeng [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Wu, Hui [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou (China); Tai, An [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Dalah, Entesar [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Department of Medical Diagnostic Imaging, College of Health Science, University of Sharjah (United Arab Emirates); Zheng, Cheng [Biostatistics, Joseph. J. Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin (United States); Johnstone, Candice [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Kong, Feng-Ming [Department of Radiation Oncology, Indiana University, Indianapolis, Indiana (United States); Gore, Elizabeth [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2017-06-01

Purpose: To investigate early tumor and normal tissue responses during the course of radiation therapy (RT) for lung cancer using quantitative analysis of daily computed tomography (CT) scans. Methods and Materials: Daily diagnostic-quality CT scans acquired using CT-on-rails during CT-guided RT for 20 lung cancer patients were quantitatively analyzed. On each daily CT set, the contours of the gross tumor volume (GTV) and lungs were generated and the radiation dose delivered was reconstructed. The changes in CT image intensity (Hounsfield unit [HU]) features in the GTV and the multiple normal lung tissue shells around the GTV were extracted from the daily CT scans. The associations between the changes in the mean HUs, GTV, accumulated dose during RT delivery, and patient survival rate were analyzed. Results: During the RT course, radiation can induce substantial changes in the HU histogram features on the daily CT scans, with reductions in the GTV mean HUs (dH) observed in the range of 11 to 48 HU (median 30). The dH is statistically related to the accumulated GTV dose (R{sup 2} > 0.99) and correlates weakly with the change in GTV (R{sup 2} = 0.3481). Statistically significant increases in patient survival rates (P=.038) were observed for patients with a higher dH in the GTV. In the normal lung, the 4 regions proximal to the GTV showed statistically significant (P<.001) HU reductions from the first to last fraction. Conclusion: Quantitative analysis of the daily CT scans indicated that the mean HUs in lung tumor and surrounding normal tissue were reduced during RT delivery. This reduction was observed in the early phase of the treatment, is patient specific, and correlated with the delivered dose. A larger HU reduction in the GTV correlated significantly with greater patient survival. The changes in daily CT features, such as the mean HU, can be used for early assessment of the radiation response during RT delivery for lung cancer.

A randomised clinical trial on the efficacy of oxytetracycline dose through water medication of nursery pigs on diarrhoea, faecal shedding of Lawsonia intracellularis and average daily weight gain.

Science.gov (United States)

Larsen, Inge; Hjulsager, Charlotte Kristiane; Holm, Anders; Olsen, John Elmerdahl; Nielsen, Søren Saxmose; Nielsen, Jens Peter

2016-01-01

Oral treatment with antimicrobials is widely used in pig production for the control of gastrointestinal infections. Lawsonia intracellularis (LI) causes enteritis in pigs older than six weeks of age and is commonly treated with antimicrobials. The objective of this study was to evaluate the efficacy of three oral dosage regimens (5, 10 and 20mg/kg body weight) of oxytetracycline (OTC) in drinking water over a five-day period on diarrhoea, faecal shedding of LI and average daily weight gain (ADG). A randomised clinical trial was carried out in four Danish pig herds. In total, 539 animals from 37 batches of nursery pigs were included in the study. The dosage regimens were randomly allocated to each batch and initiated at presence of assumed LI-related diarrhoea. In general, all OTC doses used for the treatment of LI infection resulted in reduced diarrhoea and LI shedding after treatment. Treatment with a low dose of 5mg/kg OTC per kg body weight, however, tended to cause more watery faeces and resulted in higher odds of pigs shedding LI above detection level when compared to medium and high doses (with odds ratios of 5.5 and 8.4, respectively). No association was found between the dose of OTC and the ADG. In conclusion, a dose of 5mg OTC per kg body weight was adequate for reducing the high-level LI shedding associated with enteropathy, but a dose of 10mg OTC per kg body weight was necessary to obtain a maximum reduction in LI shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

Potential benefit of dolutegravir once daily: efficacy and safety

Directory of Open Access Journals (Sweden)

Fantauzzi A

2013-02-01

Full Text Available Alessandra Fantauzzi,1 Ombretta Turriziani,2 Ivano Mezzaroma11Department of Clinical Medicine, 2Department of Molecular Medicine, Sapienza, University of Rome, Rome, ItalyAbstract: The viral integrase enzyme has recently emerged as a primary alternative target to block HIV-1 replication, and integrase inhibitors are considered a pivotal new class of antiretroviral drugs. Dolutegravir is an investigational next-generation integrase inhibitor showing some novel and intriguing characteristics, ie, it has a favorable pharmacokinetic profile with a prolonged intracellular half-life, rendering feasible once-daily dosing without the need for ritonavir boosting and without regard to meals. Moreover, dolutegravir is primarily metabolized via uridine diphosphate glucuronosyltranferase 1A1, with a minor component of the cytochrome P450 3A4 isoform, thereby limiting drug–drug interactions. Furthermore, its metabolic profile enables coadministration with most of the other available antiretroviral agents without dose adjustment. Recent findings also demonstrate that dolutegravir has significant activity against HIV-1 isolates with resistance mutations associated with raltegravir and/or elvitegravir. The attributes of once-daily administration and the potential to treat integrase inhibitor-resistant viruses make dolutegravir an interesting and promising investigational drug. In this review, the main concerns about the efficacy and safety of dolutegravir as well as its resistance profile are explored by analysis of currently available data from preclinical and clinical studies.Keywords: antiretroviral drugs, HIV-1 integrase, integrase inhibitors, dolutegravir, once daily

Associations between daily musicking and health

DEFF Research Database (Denmark)

Ekholm, Ola; Juel, Knud; Bonde, Lars Ole

2016-01-01

musically, while this pattern was not found among men. CONCLUSIONS GENDER SEEMS TO PLAY AN IMPORTANT ROLE IN THE ASSOCIATION BETWEEN MUSICKING AND HEALTH, BUT MORE RESEARCH IS NEEDED TO UNDERSTAND THESE DIFFERENCES AND THE UNDERLYING MECHANISMS IN ADDITION, LONGITUDINAL STUDIES ARE WARRANTED TO EXAMINE......AIMS: To examine the associations between singing/playing musical instruments daily and various outcomes such as health-related quality of life and health behaviour. METHODS: Data originates from the Danish Health and Morbidity Survey 2013. The survey was based on a random sample of 25,000 adult...... Danes (response rate: 57%). Besides standard health-related questions the survey included eight specific music questions, based on a review of the sparse literature on music and health. On the same basis, 'daily musicking' was defined as normally singing/playing musical instruments at least 1 h...

What is correct: equivalent dose or dose equivalent

International Nuclear Information System (INIS)

Franic, Z.

1994-01-01

In Croatian language some physical quantities in radiation protection dosimetry have not precise names. Consequently, in practice either terms in English or mathematical formulas are used. The situation is even worse since the Croatian language only a limited number of textbooks, reference books and other papers are available. This paper compares the concept of ''dose equivalent'' as outlined in International Commission on Radiological Protection (ICRP) recommendations No. 26 and newest, conceptually different concept of ''equivalent dose'' which is introduced in ICRP 60. It was found out that Croatian terminology is both not uniform and unprecise. For the term ''dose equivalent'' was, under influence of Russian and Serbian languages, often used as term ''equivalent dose'' even from the point of view of ICRP 26 recommendations, which was not justified. Unfortunately, even now, in Croatia the legal unit still ''dose equivalent'' defined as in ICRP 26, but the term used for it is ''equivalent dose''. Therefore, in Croatian legislation a modified set of quantities introduced in ICRP 60, should be incorporated as soon as possible

Examining Margin Reduction and Its Impact on Dose Distribution for Prostate Cancer Patients Undergoing Daily Cone-Beam Computed Tomography

International Nuclear Information System (INIS)

Hammoud, Rabih; Patel, Samir H.; Pradhan, Deepak; Kim, Jinkoo; Guan, Harrison; Li Shidong; Movsas, Benjamin

2008-01-01

Purpose: To examine the dosimetric impact of margin reduction and quantify residual error after three-dimensional (3D) image registration using daily cone-beam computed tomography (CBCT) for prostate cancer patients. Methods and Materials: One hundred forty CBCTs from 5 prostate cancer patients were examined. Two intensity-modulated radiotherapy plans were generated on CT simulation on the basis of two planning target volume (PTV) margins: 10 mm all around the prostate and seminal vesicles except 6 mm posteriorly (10/6) and 5 mm all around except 3 mm posteriorly (5/3). Daily CBCT using the Varian On-Board Imaging System was acquired. The 10/6 and 5/3 simulation plans were overlaid onto each CBCT, and each CBCT plan was calculated. To examine residual error, PlanCT/CBCT intensity-based 3D image registration was performed for prostate localization using center of mass and maximal border displacement. Results: Prostate coverage was within 2% between the 10/6 and 5/3 plans. Seminal vesicle coverage was reduced with the 5/3 plan compared with the 10/6 plan, with coverage difference within 7%. The 5/3 plan allowed 30-50% sparing of bladder and rectal high-dose regions. For residual error quantification, center of mass data show that 99%, 93%, and 96% of observations fall within 3 mm in the left-right, anterior-posterior, and superior-inferior directions, respectively. Maximal border displacement observations range from 79% to 99%, within 5 mm for all directions. Conclusion: Cone-beam CT dosimetrically validated a 10/6 margin when soft-tissue localization is not used. Intensity-based 3D image registration has the potential to improve target localization and to provide guidelines for margin definition

Investigating CT to CBCT image registration for head and neck proton therapy as a tool for daily dose recalculation

Energy Technology Data Exchange (ETDEWEB)

Landry, Guillaume, E-mail: g.landry@lmu.de [Department of Medical Physics, Ludwig-Maximilians-University, Munich D85748, Germany and Department of Radiation Oncology, Ludwig-Maximilians-University, Munich D81377 (Germany); Nijhuis, Reinoud; Thieke, Christian; Reiner, Michael; Ganswindt, Ute; Belka, Claus [Department of Radiation Oncology, Ludwig-Maximilians-University, Munich D81377 (Germany); Dedes, George; Handrack, Josefine; Parodi, Katia [Department of Medical Physics, Ludwig-Maximilians-University, Munich D85748 (Germany); Janssens, Guillaume; Orban de Xivry, Jonathan [ICTEAM, Université Catholique de Louvain, Louvain-La-Neuve B1348 (Belgium); Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Munich D81675, Germany and Physik-Department, Technische Universität München, Garching D85748 (Germany); Paganelli, Chiara; Riboldi, Marco; Baroni, Guido [Dipartimento di Elettronica Informazione e Bioingegneria, Politecnico di Milano, Milan 20133 (Italy)

2015-03-15

Purpose: Intensity modulated proton therapy (IMPT) of head and neck (H and N) cancer patients may be improved by plan adaptation. The decision to adapt the treatment plan based on a dose recalculation on the current anatomy requires a diagnostic quality computed tomography (CT) scan of the patient. As gantry-mounted cone beam CT (CBCT) scanners are currently being offered by vendors, they may offer daily or weekly updates of patient anatomy. CBCT image quality may not be sufficient for accurate proton dose calculation and it is likely necessary to perform CBCT CT number correction. In this work, the authors investigated deformable image registration (DIR) of the planning CT (pCT) to the CBCT to generate a virtual CT (vCT) to be used for proton dose recalculation. Methods: Datasets of six H and N cancer patients undergoing photon intensity modulated radiation therapy were used in this study to validate the vCT approach. Each dataset contained a CBCT acquired within 3 days of a replanning CT (rpCT), in addition to a pCT. The pCT and rpCT were delineated by a physician. A Morphons algorithm was employed in this work to perform DIR of the pCT to CBCT following a rigid registration of the two images. The contours from the pCT were deformed using the vector field resulting from DIR to yield a contoured vCT. The DIR accuracy was evaluated with a scale invariant feature transform (SIFT) algorithm comparing automatically identified matching features between vCT and CBCT. The rpCT was used as reference for evaluation of the vCT. The vCT and rpCT CT numbers were converted to stopping power ratio and the water equivalent thickness (WET) was calculated. IMPT dose distributions from treatment plans optimized on the pCT were recalculated with a Monte Carlo algorithm on the rpCT and vCT for comparison in terms of gamma index, dose volume histogram (DVH) statistics as well as proton range. The DIR generated contours on the vCT were compared to physician-drawn contours on the rp

The economics of 4 grams once daily mesalazine dosing compared with 4 grams twice daily in active ulcerative colitis

NARCIS (Netherlands)

Connolly, M.; Kuyvenhoven, J.; Postma, M.; Nielsen, S.

2013-01-01

Background: Dosing frequency is an important treatment consideration that has been shown to influence adherence and outcomes when treating ulcerative colitis (UC). In this analysis we evaluate the economic consequences of outcome differences observed in the study comparing mesalazine 4g per day once

Proxy-based reconstruction of erythemal UV doses over Estonia for 1955–2004

Directory of Open Access Journals (Sweden)

K. Eerme

2006-08-01

Full Text Available A proxy-based reconstruction of the erythemally-weighted UV doses for 1955-2004 has been performed for the Tartu-Tõravere Meteorological Station (58°16' N, 26°28' E, 70 m a.s.l. site. The pyrheliometer-measured daily sum of direct irradiance on partly cloudy and clear days, and the pyranometer-measured daily sum of global irradiance on overcast days were used as the cloudiness influence related proxies. The TOMS ozone data have been used for detecting the daily deviations from the climatic value (averaged annual cycle. In 1998–2004, the biases between the measured and reconstructed daily doses in 55.5% of the cases were within ±10% and in 83.5% of the cases within ±20%, on average. In the summer half-year these amounts were 62% and 88%, respectively. In most years the results for longer intervals did not differ significantly, if no correction was made for the daily deviations of total ozone from its climatic value. The annual and summer half-yearly erythemal doses (contributing, on average, 89% of the annual value agreed within ±2%, except for the years after major volcanic eruptions and one extremely fine weather year (2002. Using the daily relative sunshine duration as a proxy without detailed correction for atmospheric turbidity results in biases of 2–4% in the summer half-yearly dose in the years after major volcanic eruptions and a few other years of high atmospheric turbidity. The year-to-year variations of the summer half-yearly erythemal dose in 1955–2004 were found to be within 92–111% relative to their average value. Exclusion of eight extreme years reduces this range for the remaining to 95–105.5%. Due to the quasi-periodic alternation of wet and dry periods, the interval of cloudy summers 1976–1993 regularly manifests summer half-yearly erythemal dose values lower than the 1955–2004 average. Since 1996/1997 midwinters have been darker than on average.

Proxy-based reconstruction of erythemal UV doses over Estonia for 1955–2004

Directory of Open Access Journals (Sweden)

K. Eerme

2006-08-01

Full Text Available A proxy-based reconstruction of the erythemally-weighted UV doses for 1955-2004 has been performed for the Tartu-Tõravere Meteorological Station (58°16' N, 26°28' E, 70 m a.s.l. site. The pyrheliometer-measured daily sum of direct irradiance on partly cloudy and clear days, and the pyranometer-measured daily sum of global irradiance on overcast days were used as the cloudiness influence related proxies. The TOMS ozone data have been used for detecting the daily deviations from the climatic value (averaged annual cycle. In 1998–2004, the biases between the measured and reconstructed daily doses in 55.5% of the cases were within ±10% and in 83.5% of the cases within ±20%, on average. In the summer half-year these amounts were 62% and 88%, respectively. In most years the results for longer intervals did not differ significantly, if no correction was made for the daily deviations of total ozone from its climatic value. The annual and summer half-yearly erythemal doses (contributing, on average, 89% of the annual value agreed within ±2%, except for the years after major volcanic eruptions and one extremely fine weather year (2002. Using the daily relative sunshine duration as a proxy without detailed correction for atmospheric turbidity results in biases of 2–4% in the summer half-yearly dose in the years after major volcanic eruptions and a few other years of high atmospheric turbidity. The year-to-year variations of the summer half-yearly erythemal dose in 1955–2004 were found to be within 92–111% relative to their average value. Exclusion of eight extreme years reduces this range for the remaining to 95–105.5%. Due to the quasi-periodic alternation of wet and dry periods, the interval of cloudy summers 1976–1993 regularly manifests summer half-yearly erythemal dose values lower than the 1955–2004 average. Since 1996/1997 midwinters have been darker than on average.

New recommendations for dose equivalent

International Nuclear Information System (INIS)

Bengtsson, G.

1985-01-01

In its report 39, the International Commission on Radiation Units and Measurements (ICRU), has defined four new quantities for the determination of dose equivalents from external sources: the ambient dose equivalent, the directional dose equivalent, the individual dose equivalent, penetrating and the individual dose equivalent, superficial. The rationale behind these concepts and their practical application are discussed. Reference is made to numerical values of these quantities which will be the subject of a coming publication from the International Commission on Radiological Protection, ICRP. (Author)

Once daily controlled-release pregabalin in the treatment of patients with fibromyalgia: a phase III, double-blind, randomized withdrawal, placebo-controlled study.

Science.gov (United States)

Arnold, Lesley M; Arsenault, Pierre; Huffman, Cynthia; Patrick, Jeffrey L; Messig, Michael; Chew, Marci L; Sanin, Luis; Scavone, Joseph M; Pauer, Lynne; Clair, Andrew G

2014-10-01

Safety and efficacy of a once daily controlled-released (CR) formulation of pregabalin was evaluated in patients with fibromyalgia using a placebo-controlled, randomized withdrawal design. This multicenter study included 6 week single-blind pregabalin CR treatment followed by 13 week double-blind treatment with placebo or pregabalin CR. The starting dose of 165 mg/day was escalated during the first 3 weeks, up to 495 mg/day based on efficacy and tolerability. Patients with ≥50% reduction in average daily pain score at the end of the single-blind phase were randomized to continue pregabalin CR at the optimized dose (330-495 mg/day) or to placebo. The primary endpoint was time to loss of therapeutic response (LTR), defined as treatment' (Benefit, Satisfaction, and Willingness to Continue Scale) in the pregabalin CR group; no other secondary endpoints were statistically significant. Most AEs were mild to moderate in severity (most frequent: dizziness, somnolence). The percentage of pregabalin CR patients discontinuing because of AEs was 12.2% and 4.8% in the single-blind and double-blind phases, respectively (placebo, 0%). Time to LTR was significantly longer with pregabalin CR versus placebo in fibromyalgia patients who initially showed improvement with pregabalin CR, indicating maintenance of response. Pregabalin CR was well tolerated in most patients. Generalizability may be limited by study duration and selective population.

Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes

Science.gov (United States)

de Castro, Ana; Jones, Hendreé E.; Johnson, Rolley E.; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.

2015-01-01

BACKGROUND Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine- and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = 0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = 0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. PMID:21245372

Rectal dose variation during the course of image-guided radiation therapy of prostate cancer

International Nuclear Information System (INIS)

Chen Lili; Paskalev, Kamen; Xu Xiu; Zhu, Jennifer; Wang Lu; Price, Robert A.; Hu Wei; Feigenberg, Steven J.; Horwitz, Eric M.; Pollack, Alan; Charlie Ma, C.M.

2010-01-01

Background and purpose: To investigate the change in rectal dose during the treatment course for intensity-modulated radiotherapy (IMRT) of prostate cancer with image-guidance. Materials and methods: Twenty prostate cancer patients were recruited for this retrospective study. All patients have been treated with IMRT. For each patient, MR and CT images were fused for target and critical structure delineation. IMRT treatment planning was performed on the simulation CT images. Inter-fractional motion during the course of treatment was corrected using a CT-on-rails system. The rectum was outlined on both the original treatment plan and the subsequent daily CT images from the CT-on-rails by the same investigator. Dose distributions on these daily CT images were recalculated with the isocenter shifts relative to the simulation CT images using the leaf sequences/MUs based on the original treatment plan. The rectal doses from the subsequent daily CTs were compared with the original doses planned on the simulation CT using our clinical acceptance criteria. Results: Based on 20 patients with 139 daily CT sets, 28% of the subsequent treatment dose distributions did not meet our criterion of V 40 65 < 17%. The inter-fractional rectal volume variation is significant for some patients. Conclusions: Due to the large inter-fractional variation of the rectal volume, it is more favorable to plan prostate IMRT based on an empty rectum and deliver treatment to patients with an empty rectum. Over 70% of actual treatments showed better rectal doses than our clinical acceptance criteria. A significant fraction (27%) of the actual treatments would benefit from adaptive image-guided radiotherapy based on daily CT images.

SU-C-202-02: A Comprehensive Evaluation of Adaptive Daily Planning for Cervical Cancer HDR Brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Meerschaert, R; Paul, A; Zhuang, L [Department of Oncology, Radiation Oncology Division, Wayne State University School of Medicine, Detroit, MI (United States); Nalichowski, A [Department of Oncology, Radiation Oncology Division, Karmanos Cancer Institute, Detroit, MI (United States); Burmeister, J; Miller, A [Department of Oncology, Radiation Oncology Division, Wayne State University School of Medicine, Detroit, MI (United States); Department of Oncology, Radiation Oncology Division, Karmanos Cancer Institute, Detroit, MI (United States)

2016-06-15

Purpose: To evaluate adaptive daily planning for cervical cancer patients who underwent high-dose-rate intra-cavitary brachytherapy (HDR-ICBT). Methods: This study included 22 cervical cancer patients who underwent 5 fractions of HDR ICBT. Regions of interest (ROIs) including high-risk clinical tumor volume (HR-CTV) and organs-at-risk (OARs) were manually contoured on daily CT images. All patients were treated with adaptive daily plans, which involved ROI delineation and dose optimization at each treatment fraction. Single treatment plans were retrospectively generated by applying the first treatment fraction’s dwell times adjusted for decay and dwell positions of the applicator to subsequent treatment fractions. Various existing similarity metrics were calculated for the ROIs to quantify interfractional organ variations. A novel similarity score (JRARM) was established, which combined both volumetric overlap metrics (DSC, JSC, and RVD) and distance metrics (ASD, MSD, and RMSD). Linear regression was performed to determine a relationship between inter-fractional organ variations of various similarity metrics and D2cc variations from both plans. Wilcoxon Signed Rank Tests were used to assess adaptive daily plans and single plans by comparing EQD2 D2cc (α/β=3) for OARs. Results: For inter-fractional organ variations, the sigmoid demonstrated the greatest variations based on the JRARM and DSC similarity metrics. Comparisons between paired ROIs showed differences in JRARM scores and DSCs at each treatment fraction. RVD, MSD, and RMSD were found to be significantly correlated to D2cc variations for bladder and sigmoid. The comparison between plans found that adaptive daily planning provided lower EQD2 D2cc of OARs than single planning, specifically for the sigmoid (p=0.015). Conclusion: Substantial inter-fractional organ motion can occur during HDR-BT, which may significantly affect D2cc of OARs. Adaptive daily planning provides improved dose sparing for OARs

Actual Dose Variation of Parotid Glands and Spinal Cord for Nasopharyngeal Cancer Patients During Radiotherapy

International Nuclear Information System (INIS)

Han Chunhui; Chen Yijen; Liu An; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

2008-01-01

Purpose: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). Methods and Materials: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. Results: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm 3 by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. Conclusions: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications

Modelling of Sub-daily Hydrological Processes Using Daily Time-Step Models: A Distribution Function Approach to Temporal Scaling

Science.gov (United States)

Kandel, D. D.; Western, A. W.; Grayson, R. B.

2004-12-01

erosion models. The statistical description of sub-daily variability is thus propagated through the model, allowing the effects of variability to be captured in the simulations. This results in cdfs of various fluxes, the integration of which over a day gives respective daily totals. Using 42-plot-years of surface runoff and soil erosion data from field studies in different environments from Australia and Nepal, simulation results from this cdf approach are compared with the sub-hourly (2-minute for Nepal and 6-minute for Australia) and daily models having similar process descriptions. Significant improvements in the simulation of surface runoff and erosion are achieved, compared with a daily model that uses average daily rainfall intensities. The cdf model compares well with a sub-hourly time-step model. This suggests that the approach captures the important effects of sub-daily variability while utilizing commonly available daily information. It is also found that the model parameters are more robustly defined using the cdf approach compared with the effective values obtained at the daily scale. This suggests that the cdf approach may offer improved model transferability spatially (to other areas) and temporally (to other periods).

Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

Science.gov (United States)

Thervet, Eric; Anglicheau, Dany; King, Barry; Schlageter, Marie-Hélène; Cassinat, Bruno; Beaune, Philippe; Legendre, Christophe; Daly, Ann K

2003-10-27

Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio. The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies.

Directory of Open Access Journals (Sweden)

Eric Laille

Full Text Available CC-486 (oral azacitidine is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK and pharmacodynamic (PD profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS, chronic myelomonocytic leukemia (CMML or acute myeloid leukemia (AML from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05 reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle, with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle.ClinicalTrials.gov NCT00528983.

Alternate day treatment and late effects: The concept of an effective dose per fraction

International Nuclear Information System (INIS)

Courdi, A.; Hery, M.; Gabillat, J.M.

1990-01-01

Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy

Capturing daily urban rhythms: the use of location aware technologies

CSIR Research Space (South Africa)

Krygsman, S

2007-07-01

Full Text Available Daily activities and travel often follow a natural rhythm or flow that is structured by the fixed spatial and temporal constraints. The work and home location act as pegs that define individual’s activity space and it is within these spaces...

Defining the appropriate radiation dose for pretreatment PSA no. <=no. 10 ng/mL prostate cancer

International Nuclear Information System (INIS)

Pinover, Wayne H.; Hanlon, Alexandra L.; Horwitz, Eric M.; Hanks, Gerald E.

2000-01-01

Purpose: To investigate whether a dose response exists for biochemical no evidence of disease (bNED) control in prostate cancer patients with pretreatment prostate-specific antigen (PSA) no. =no. 7600 cGy. Median dose in these three groups was 7067 cGy, 7278 cGy, and 7734 cGy, respectively. Univariate analysis was performed to determine differences in bNED control (American Society for Therapeutic Radiology and Oncology [ASTRO] Consensus Guidelines definition of failure) by dose group for the entire cohort, for 310 good prognosis patients (T1-T2A, Gleason score 2-6, absence of PNI), and for 178 poor prognosis patients (T2B-T3 or Gleason score 7-10 or presence of PNI) . Multivariate analysis (MVA) was performed to determine if dose was an independent predictor of bNED control. Median follow-up was 36 months. Results: A dose response was not demonstrated for the entire group of patients with pretreatment PSA no. =no. 7600 cGy were associated with 5-year bNED control rates of 73%, 86%, and 89%, respectively (p = 0.12). MVA demonstrated prognosis group (p = 0.038) to be the only independent predictor of bNED control. Good prognosis patients had a 5-year bNED of 85% and no dose response was seen. The subgroup of poor prognosis patients demonstrated a 5-year bNED control rate of 81% and a dose response was seen for those receiving no. >=no. 7600 cGy, compared to the two lower dose groups (94% vs. 75% vs. 70%; p = 0.0062). MVA for the poor prognosis subset demonstrated dose (p = 0.01) to be the only independent predictor for improved bNED control. Conclusions: The poor prognosis subset of PSA no. <=no. 10 ng/mL prostate cancer patients benefit from dose escalation. A dose response is not demonstrated for prostate cancer patients with pretreatment PSA no. <=no. 10 ng/mL and other favorable features

On the definition of absorbed dose

International Nuclear Information System (INIS)

Grusell, Erik

2015-01-01

Purpose: The quantity absorbed dose is used extensively in all areas concerning the interaction of ionizing radiation with biological organisms, as well as with matter in general. The most recent and authoritative definition of absorbed dose is given by the International Commission on Radiation Units and Measurements (ICRU) in ICRU Report 85. However, that definition is incomplete. The purpose of the present work is to give a rigorous definition of absorbed dose. Methods: Absorbed dose is defined in terms of the random variable specific energy imparted. A random variable is a mathematical function, and it cannot be defined without specifying its domain of definition which is a probability space. This is not done in report 85 by the ICRU, mentioned above. Results: In the present work a definition of a suitable probability space is given, so that a rigorous definition of absorbed dose is possible. This necessarily includes the specification of the experiment which the probability space describes. In this case this is an irradiation, which is specified by the initial particles released and by the material objects which can interact with the radiation. Some consequences are discussed. Specific energy imparted is defined for a volume, and the definition of absorbed dose as a point function involves the specific energy imparted for a small mass contained in a volume surrounding the point. A possible more precise definition of this volume is suggested and discussed. Conclusions: The importance of absorbed dose motivates a proper definition, and one is given in the present work. No rigorous definition has been presented before. - Highlights: • A stringent definition of absorbed dose is given. • This requires the definition of an irradiation and a suitable probability space. • A stringent definition is important for an understanding of the concept absorbed dose

Confined prostate cancer treated by conformational irradiation with intensity modulation with or without echography repositioning: is the dose received equivalent to the prescribed dose?; Cancer prostatique localise traite par irradiation conformationnelle avec modulation d'intensite avec ou sans repositionnement echographique: la dose recue est-elle equivalente a la dose prescrite?

Energy Technology Data Exchange (ETDEWEB)

Arnaud, A.; Peignaux, K.; Brenier, J.P.; Truc, G.; Naudy, S.; Maingon, P.; Crehange, G. [Centre Georges-Francois Leclerc, Dept. de Radiotherapie, 21 - Dijon (France); Regis, A. [CHU le Bocage, Service de Radiodiagnostic, 21 - Dijon (France); Deville, C.; Bonnetain, F. [Centre Georges-Francois Leclerc, Dept. de Biostatique, 21 - Dijon (France)

2006-11-15

The results suggest it would be possible to dispense a homogenous dose in agreement with the ICRU recommendations, nearer than the forward looking dose when the daily echographic repositioning is applied. This repositioning does not influence significantly the dosimetry for the risk organs. These results will validated in a bigger population. (N.C.)

Doses from pediatric CT examinations in Norway: are pediatric scan protocols developed and in daily use?

International Nuclear Information System (INIS)

Friberg, Eva G.

2008-01-01

Doses to pediatric patients from CT examinations are known to be unnecessarily high if scan protocols developed for adult patients are adopted. This overexposure is most often not recognized by the operating radiographer, due to the digital behavior of the imaging system. Use of optimized size-specific pediatric scan protocols is therefore essential to keep the doses at an appropriate level. The aim of this study was to investigate the doses to pediatric patients from CT examinations and to evaluate the level of optimization of the scan protocols. Patient data, applied scan parameters together with the dose parameters volume computed tomography dose index (CTD vol ) and dose length product (DLP) for examinations of the head, chest and abdomen were collected by means of a questionnaire from five university hospitals. The effective dose was estimated from the total DLP by use of region-specific conversion coefficients (E DLP ). Totally 136, 108 and 82 questionnaires were received for examinations of the head, chest and abdomen, respectively. Large variations in patient doses between the hospitals were observed, addressing the need for optimization of the scan protocols in general. Most of the hospitals applied successive lower mAs with decreasing patient age for all scan areas, while the use of lower tube voltage for small patients and a higher tube voltage for large patients were more rarely. This indicates the presence, to a certain level, of size specific scan protocols at some Norwegian hospitals. Focus on developing size-specific scan protocols for pediatric patients are important to reduce the doses and risks associated with pediatric CT examinations. (author)

Daily sitting time and all-cause mortality: a meta-analysis.

Directory of Open Access Journals (Sweden)

Josephine Y Chau

Full Text Available To quantify the association between daily total sitting and all-cause mortality risk and to examine dose-response relationships with and without adjustment for moderate-to-vigorous physical activity.Studies published from 1989 to January 2013 were identified via searches of multiple databases, reference lists of systematic reviews on sitting and health, and from authors' personal literature databases. We included prospective cohort studies that had total daily sitting time as a quantitative exposure variable, all-cause mortality as the outcome and reported estimates of relative risk, or odds ratios or hazard ratios with 95% confidence intervals. Two authors independently extracted the data and summary estimates of associations were computed using random effects models.Six studies were included, involving data from 595,086 adults and 29,162 deaths over 3,565,569 person-years of follow-up. Study participants were mainly female, middle-aged or older adults from high-income countries; mean study quality score was 12/15 points. Associations between daily total sitting time and all-cause mortality were not linear. With physical activity adjustment, the spline model of best fit had dose-response HRs of 1.00 (95% CI: 0.98-1.03, 1.02 (95% CI: 0.99-1.05 and 1.05 (95% CI: 1.02-1.08 for every 1-hour increase in sitting time in intervals between 0-3, >3-7 and >7 h/day total sitting, respectively. This model estimated a 34% higher mortality risk for adults sitting 10 h/day, after taking physical activity into account. The overall weighted population attributable fraction for all-cause mortality for total daily sitting time was 5.9%, after adjusting for physical activity.Higher amounts of daily total sitting time are associated with greater risk of all-cause mortality and moderate-to-vigorous physical activity appears to attenuate the hazardous association. These findings provide a starting point for identifying a threshold on which to base clinical and public

Student's music exposure: Full-day personal dose measurements.

Science.gov (United States)

Washnik, Nilesh Jeevandas; Phillips, Susan L; Teglas, Sandra

2016-01-01

Previous studies have shown that collegiate level music students are exposed to potentially hazardous sound levels. Compared to professional musicians, collegiate level music students typically do not perform as frequently, but they are exposed to intense sounds during practice and rehearsal sessions. The purpose of the study was to determine the full-day exposure dose including individual practice and ensemble rehearsals for collegiate student musicians. Sixty-seven college students of classical music were recruited representing 17 primary instruments. Of these students, 57 completed 2 days of noise dose measurements using Cirrus doseBadge programed according to the National Institute for Occupational Safety and Health criterion. Sound exposure was measured for 2 days from morning to evening, ranging from 7 to 9 h. Twenty-eight out of 57 (49%) student musicians exceeded a 100% daily noise dose on at least 1 day of the two measurement days. Eleven student musicians (19%) exceeded 100% daily noise dose on both days. Fourteen students exceeded 100% dose during large ensemble rehearsals and eight students exceeded 100% dose during individual practice sessions. Approximately, half of the student musicians exceeded 100% noise dose on a typical college schedule. This finding indicates that a large proportion of collegiate student musicians are at risk of developing noise-induced hearing loss due to hazardous sound levels. Considering the current finding, there is a need to conduct hearing conservation programs in all music schools, and to educate student musicians about the use and importance of hearing protection devices for their hearing.

Efficacy and Safety of Terbinafine 500 mg Once Daily in Patients with Dermatophytosis.

Science.gov (United States)

Babu, P Ravindra; Pravin, A J S; Deshmukh, Gaurav; Dhoot, Dhiraj; Samant, Aniket; Kotak, Bhavesh

2017-01-01

Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A - terbinafine 500 mg for 2 weeks, Group B - terbinafine 500 mg for 4 weeks, and Group C - terbinafine 500 mg for 6 weeks. Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% ( n = 169) patients showed very good response. In Group B, out of 211 patients, 92% ( n = 194) of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% ( n = 30) patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

Science.gov (United States)

Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

2011-01-01

Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

Local control and functional results after twice-daily radiotherapy for Ewing's sarcoma of the extremities

International Nuclear Information System (INIS)

Bolek, Timothy W.; Marcus, Robert B.; Mendenhall, Nancy Price; Scarborough, Mark T.; Graham-Pole, John

1996-01-01

Purpose: Radiotherapy (RT) has been the predominant local treatment for Ewing's sarcoma of bone at the University of Florida. Twice-daily hyperfractionated RT was initiated in 1982 to improve local control and functional outcome. This retrospective review compares the results of once-daily vs. twice-daily RT in patients with primary Ewing's sarcoma of an extremity, with emphasis on functional outcome. Methods and Materials: Between June 1971 and January 1990, 37 patients were treated at the University of Florida for nonmetastatic Ewing's sarcoma of bone with a primary lesion in an extremity. Three patients underwent amputation. Of 34 patients treated with RT, 31 had RT alone and 3 had a combination of RT and local excision. Before 1982, 14 patients received once-daily RT; since 1982, 17 patients have received twice-daily RT. Doses of once-daily RT varied from 47 to 61 Gy at 1.8-2 Gy per fraction. Doses of twice-daily RT varied, depending on the response of the soft-tissue component of the tumor to chemotherapy, and ranged from 50.4 to 60 Gy at 1.2 Gy per fraction. Some patients in the twice-daily RT group also received total body irradiation 1-3 months after local RT as part of a conditioning regimen before marrow-ablative therapy with stem cell rescue. They received either 8 Gy in two once-daily fractions or 12 Gy in six twice-daily fractions. The six patients who received surgery were excluded from local control analysis. Local control rates were calculated using the Kaplan-Meier (actuarial) method. Fifteen patients had a formal functional evaluation. Results: In the 31 patients treated with RT alone, the actuarial local control rate at 5 years was 81% for patients treated twice daily and 77% for those treated once daily (p = NS). No posttreatment pathologic fractures occurred in patients treated twice daily, whereas five fractures occurred in those treated once daily (p = 0.01). On functional evaluation, less loss in range of motion (15 deg. vs. 28 deg. of loss

Extended Efficacy of Once-Daily Atomoxetine in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2004-07-01

Full Text Available The efficacy of atomoxetine administered once daily (final dose 1.3 +/- 0.3 mg/kg; mean 44.5 mg per day; range 10-80 mg per day in the morning was assessed throughout the day, including evening and early morning, in a total of 197 children, 6 to 12 years of age (71% male, diagnosed with attention-deficit/hyperactivity disorder (ADHD (69% had combined subtype ADHD, and 35% had comorbid oppositional defiant disorder.

Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

International Nuclear Information System (INIS)

Fouchardiere, Christelle de la; Negrier, Sylvie; Labrosse, Hugues; Martel Lafay, Isabelle; Desseigne, Francoise; Meeus, Pierre; Tavan, David; Petit-Laurent, Fabien; Rivoire, Michel; Perol, David; Carrie, Christian

2010-01-01

Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m 2 per day and then escalated by increments of 2 mg/m 2 every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m 2 to 20 mg/m 2 per day). The maximum tolerated dose was determined to be 18 mg/m 2 per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m 2 per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.

The limiting dose rate and its importance in radiation protection

International Nuclear Information System (INIS)

Bakkiam, D.; Sonwani, Swetha; Arul Ananthakumar, A.; Mohankumar, Mary N.

2012-01-01

The concept of defining a low dose of ionizing radiation still remains unclear. Before attempting to define a low dose, it is more important to define a low-dose rate since effects at low dose-rates are different from those observed at higher dose-rates. Hence, it follows that low dose-rates rather than a low dose is an important criteria to determine radio-biological effects and risk factors i.e. stochastic health effects. Chromosomal aberrations induced by ionizing radiations are well fitted by quadratic model Y= áD + âD 2 + C with the linear coefficient of dose predominating for high LET radiations and low doses of low LET. At higher doses and dose rates of sparsely ionizing radiation, break pairs produced by inter-track action leads to the formation of exchange type aberrations and is dependent on dose rate. Whereas at lower doses and dose rates, intra-track action produces break pairs and resulting aberrations are in direct proportion to absorbed dose and independent of dose rate. The dose rate at which inter-track ceases to be observable and where intra-track action effectively becomes the sole contributor of lesion-pair formation is referred to as limiting dose rate (LDR). Once the LDR is reached further reduction in dose rates will not affect the slope of DR since breaks produced by independent charged particle tracks are widely separated in time to interact with each other for aberration yield. This linear dependency is also noticed for acute exposures at very low doses. Existing reports emphasizes the existence of LDR likely to be e6.3cGyh -1 . However no systematic studies have been conducted so far to determine LDR. In the present investigation DR curves were constructed for the dose rates 0.002 and 0.003 Gy/min and to define LDR at which a coefficient approaches zero. Extrapolation of limiting low dose rate data can be used to predict low dose effects regardless of dose rate and its definition ought to serve as a useful index for studies pertaining

MO-G-BRE-04: Automatic Verification of Daily Treatment Deliveries and Generation of Daily Treatment Reports for a MR Image-Guided Treatment Machine

International Nuclear Information System (INIS)

Yang, D; Li, X; Li, H; Wooten, H; Green, O; Rodriguez, V; Mutic, S

2014-01-01

Purpose: Two aims of this work were to develop a method to automatically verify treatment delivery accuracy immediately after patient treatment and to develop a comprehensive daily treatment report to provide all required information for daily MR-IGRT review. Methods: After systematically analyzing the requirements for treatment delivery verification and understanding the available information from a novel MR-IGRT treatment machine, we designed a method to use 1) treatment plan files, 2) delivery log files, and 3) dosimetric calibration information to verify the accuracy and completeness of daily treatment deliveries. The method verifies the correctness of delivered treatment plans and beams, beam segments, and for each segment, the beam-on time and MLC leaf positions. Composite primary fluence maps are calculated from the MLC leaf positions and the beam-on time. Error statistics are calculated on the fluence difference maps between the plan and the delivery. We also designed the daily treatment delivery report by including all required information for MR-IGRT and physics weekly review - the plan and treatment fraction information, dose verification information, daily patient setup screen captures, and the treatment delivery verification results. Results: The parameters in the log files (e.g. MLC positions) were independently verified and deemed accurate and trustable. A computer program was developed to implement the automatic delivery verification and daily report generation. The program was tested and clinically commissioned with sufficient IMRT and 3D treatment delivery data. The final version has been integrated into a commercial MR-IGRT treatment delivery system. Conclusion: A method was developed to automatically verify MR-IGRT treatment deliveries and generate daily treatment reports. Already in clinical use since December 2013, the system is able to facilitate delivery error detection, and expedite physician daily IGRT review and physicist weekly chart

Global Historical Climatology Network - Daily (GHCN-Daily), Version 3

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Global Historical Climatology Network - Daily (GHCN-Daily) dataset integrates daily climate observations from approximately 30 different data sources. Version 3...

Dose from radiological examinations

International Nuclear Information System (INIS)

Imamura, Keiko; Uji, Teruyuki; Sakuyama, Keiko; Fujikawa, Mitsuhiro; Fujii, Masamichi

1976-01-01

Relatively high gonad doses, several hundred to one thousand mR, have been observed in case of pelvis, hip-joint, coccyx, lower abdomen and lumber examination. Dose to the ovary is especially high in barium enema and I.V.P. examinations. About 12 per cent of the 4-ray examination are high-dose. The gonad dose is relatively high in examination of abdomen and lower extremities, in infants. The dose to the eyes is especially high, 1.0 to 2.5R per exposure, in temporal bone and nasal sinuses tomography. X-ray doses have been compared with dose limits recommended by ICRP and with the gonad dose from natural radiations. The gonad dose in lumbar examination, barium enema, I.V.P. etc. is as high as the maximum permissible dose per year recommended by ICRP. Several devices have been made for dose reduction in the daily examinations: (1) separating the radiation field from the gonad by one centimeter decreases the gonad dose about one-half. (2) using sensitive screens and films. In pelvimetry and in infant hip-joint examination, the most sensitive screen and film are used. In the I.V.P. examination of adult, use of MS screen in place of FS screen decreases the dose to one-third, in combination with careful setting of radiation field, (3) use of grid increases the dose about 50 percent and the lead rubber protection (0.1mm lead equivalent) decreases the gonad dose to one-thirtieth in the spinal column examination of infant, (4) A lead protector, 1mm thickness and 2.5cm in diameter, on the eyes decreases the dose to about one-eighth in the face and nead examinations. These simple and effective methods for dose reduction. Should be carried out in as many examinations as possible in addition to observing dose limits recommended by ICRP. (Evans, J.)

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

Science.gov (United States)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

The definition of the individual dose equivalent

International Nuclear Information System (INIS)

Ehrlich, Margarete

1986-01-01

A brief note examines the choice of the present definition of the individual dose equivalent, the new operational dosimetry quantity for external exposure. The consequences of the use of the individual dose equivalent and the danger facing the individual dose equivalent, as currently defined, are briefly discussed. (UK)

Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

Directory of Open Access Journals (Sweden)

William A Prescott

2014-01-01

Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

Natural radionuclides in the South Indian foods and their annual dose

International Nuclear Information System (INIS)

Shanthi, G.; Thampi Thanka Kumaran, J.; Gnana Raj, G. Allan; Maniyan, C.G

2010-01-01

The study was carried out to evaluate the radioactivity concentration in the food crops grown in high-level natural radioactive area (HLNRA) in south west India. Food samples collected were analysed by means of a gamma spectroscopy and estimated annual dietary intakes of the radioisotopes 226 Ra, 228 Ra, 228 Th and 40 K. The annual intake of the food stuffs was estimated on the basis of their average annual consumption. Calculations were also made to determine the effective dose to an individual consuming such diets. The intakes of these radionuclides were calculated using the concentrations in south Indian foods and daily consumption rates of these foods. Daily intakes of these radionuclides were as follows: 226 Ra, 0.001-1.87; 228 Ra, 0.0023-1.26, 228 Th, 0.01-14.09 40 K, 0.46-49.39 Bq/day. The daily internal dose resulting from ingestion of radionuclides in food was 4.92 μSv/day and the annual dose was 1.79 mSv/yr. The radionuclides with highest consumption is 40 K.

The Daily Relationship Between Aspects of Food Insecurity and Medication Adherence Among People Living with HIV with Recent Experiences of Hunger.

Science.gov (United States)

Pellowski, Jennifer A; Kalichman, Seth C; Cherry, Sabrina; Conway-Washington, Christopher; Cherry, Chauncey; Grebler, Tamar; Krug, Larissa

2016-12-01

Limited access to resources can significantly impact health behaviors. Previous research on food insecurity and HIV has focused on establishing the relationship between lacking access to nutritious food and antiretroviral (ARV) medication non-adherence in a variety of social contexts. This study aims to determine if several aspects of food insecurity co-occur with missed doses of medication on a daily basis among a sample of people living with HIV who have recently experienced hunger. The current study utilized a prospective, observational design to test the daily relationship between food insecurity and medication non-adherence. Participants were followed for 45 days and completed daily assessments of food insecurity and alcohol use via interactive text message surveys and electronic medication adherence monitoring using the Wisepill. Fifty-nine men and women living with HIV contributed a total of 2,655 days of data. Results showed that severe food insecurity (i.e., hunger), but not less severe food insecurity (i.e., worrying about having food), significantly predicted missed doses of medication on a daily level. Daily alcohol use moderated this relationship in an unexpected way; when individuals were hungry and drank alcohol on a given day, they were less likely to miss a dose of medication. Among people living with HIV with recent experiences of hunger, this study demonstrates that there is a daily relationship between hunger and non-adherence to antiretroviral therapy. Future research is needed to test interventions designed to directly address the daily relationship between food insecurity and medication non-adherence.

Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma.

Science.gov (United States)

Konstas, A G; Stewart, W C; Topouzis, F; Tersis, I; Holmes, K T; Stangos, N T

2001-06-01

To evaluate the efficacy and safety of brimonidine 0.2% two or three times daily versus timolol maleate 0.5% solution twice daily. Patients with primary open-angle glaucoma were randomized by Latin square technique to one of the three treatment sequences in this crossover, prospective double-masked trial. Each treatment period consisted of 6 weeks of chronic dosing followed by a diurnal curve for the intraocular pressure measured at 08:00, 10:00, 16:00, 18:00, 20:00, 22:00, and 24:00 hours. Intraocular pressure was measured by applanation tonometry. Thirty patients completed this trial. The average diurnal intraocular pressures in the trial were measured for timolol maleate (17.7 +/- 2.7 mm Hg), brimonidine given three times daily (18.0 +/- 2.2 mm Hg), and brimonidine given twice daily (19.2 +/- 2.4 mm Hg). There was a statistical difference between groups (P <.005). When groups were compared by pairs, three times daily dosing with brimonidine and timolol maleate both reduced the pressure more than twice daily brimonidine at every time point past 10:00 hours and for the diurnal curve (P <.05). In contrast, three times daily brimonidine and timolol maleate were statistically similar for the diurnal pressure, and each time point, except timolol maleate, decreased the pressure more at 16:00 (P =.042). Safety was similar between groups. This study demonstrated that both timolol maleate twice daily and brimonidine three times daily provide a similar intraocular pressure reduction to each other. Timolol maleate twice daily and brimonidine three times daily provide a greater decrease in pressure in the late afternoon and nighttime hours, compared with brimonidine twice daily.

A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors

Science.gov (United States)

Meta-analyses reached conflicting results regarding vitamin D and fracture reduction. We pooled individual participant-level data from 11 double-blind RCTs of oral vitamin D supplementation (daily, weekly, 4-monthly) with or without calcium compared with placebo or calcium in seniors age 65 and olde...

Defining enthesitis in spondyloarthritis by ultrasound

DEFF Research Database (Denmark)

Terslev, Lene; Naredo, E; Iagnocco, A

2014-01-01

Objective: To standardize ultrasound (US) in enthesitis. Methods: An Initial Delphi exercise was undertaken to define US detected enthesitis and its core components. These definitions were subsequently tested on static images taken from Spondyloarthritis (SpA) patients in order to evaluate...... elementary component. On static images the intra-observer reliability showed a high degree of variability for the detection of elementary lesions with kappa coefficients ranging from 0.14 - 1. The inter-observer kappa value was variable with the lowest kappa for enthesophytes (0.24) and the best for Doppler...... activity at the enthesis (0.63). Conclusion: This is the first consensus based definition of US enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work. Defining Enthesitis...

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 08: Retrospective Dose Accumulation Workflow in Head and Neck Cancer Patients Using RayStation 4.5.2

International Nuclear Information System (INIS)

Wong, Olive; Chan, Biu; Moseley, Joanne; McNiven, Andrea; Lindsay, Patricia; Bissonnette, Jean-Pierre; Waldron, John; Giuliani, Meredith; Zhang, Beibei

2016-01-01

Purpose: We have developed a semi-automated dose accumulation workflow for Head and Neck Cancer (HNC) patients to evaluate volumetric and dosimetric changes that take place during radiotherapy. This work will be used to assess how dosimetric changes affect both toxicity and disease control, hence inform the feasibility and design of a prospective HNC adaptive trial. Methods: RayStation 4.5.2 features deformable image registration (DIR), where structures already defined on the planning CT image set can be deformably mapped onto cone-beam computed tomography (CBCT) images, accounting for daily treatment set-up shifts and changes in patient anatomy. The daily delivered dose can be calculated on each CBCT and mapped back to the planning CT to allow dose accumulation. The process is partially automated using Python scripts developed in collaboration with RaySearch. Results: To date we have performed dose accumulation on 18 HNC patients treated at our institution during 2013–2015 under REB approval. Our semi-automated process establishes clinical feasibility. Generally, dose accumulation for the entire treatment course of one case takes 60–120 minutes: importing all CBCTs requires 20–30 minutes as each patient has 30 to 40 treated fractions; image registration and dose accumulation require 60–90 minutes. This is in contrast to the process without automated scripts where dose accumulation alone would take 3–5 hours. Conclusions: We have developed a reliable workflow for retrospective dose tracking in HNC using RayStation. The process has been validated for HNC patients treated on both Elekta and Varian linacs with CBCTs acquired on XVI and OBI platforms respectively.

Sci-Fri PM: Radiation Therapy, Planning, Imaging, and Special Techniques - 08: Retrospective Dose Accumulation Workflow in Head and Neck Cancer Patients Using RayStation 4.5.2

Energy Technology Data Exchange (ETDEWEB)

Wong, Olive; Chan, Biu; Moseley, Joanne; McNiven, Andrea; Lindsay, Patricia; Bissonnette, Jean-Pierre; Waldron, John; Giuliani, Meredith; Zhang, Beibei [Princess Margaret Cancer Centre-UHN (Canada)

2016-08-15

Purpose: We have developed a semi-automated dose accumulation workflow for Head and Neck Cancer (HNC) patients to evaluate volumetric and dosimetric changes that take place during radiotherapy. This work will be used to assess how dosimetric changes affect both toxicity and disease control, hence inform the feasibility and design of a prospective HNC adaptive trial. Methods: RayStation 4.5.2 features deformable image registration (DIR), where structures already defined on the planning CT image set can be deformably mapped onto cone-beam computed tomography (CBCT) images, accounting for daily treatment set-up shifts and changes in patient anatomy. The daily delivered dose can be calculated on each CBCT and mapped back to the planning CT to allow dose accumulation. The process is partially automated using Python scripts developed in collaboration with RaySearch. Results: To date we have performed dose accumulation on 18 HNC patients treated at our institution during 2013–2015 under REB approval. Our semi-automated process establishes clinical feasibility. Generally, dose accumulation for the entire treatment course of one case takes 60–120 minutes: importing all CBCTs requires 20–30 minutes as each patient has 30 to 40 treated fractions; image registration and dose accumulation require 60–90 minutes. This is in contrast to the process without automated scripts where dose accumulation alone would take 3–5 hours. Conclusions: We have developed a reliable workflow for retrospective dose tracking in HNC using RayStation. The process has been validated for HNC patients treated on both Elekta and Varian linacs with CBCTs acquired on XVI and OBI platforms respectively.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

Science.gov (United States)

Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org [Department of Radiation Oncology, Experimental Therapeutics and Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center, Tampa, Florida (United States); Won, Minhee [Radiation Therapy Oncology Group, Philadelphia, Pennsylvania (United States); Wen, Patrick Y. [Center for Neuro-Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Rojiani, Amyn M. [Department of Pathology, Medical College of Georgia, Augusta, Georgia (United States); Wendland, Merideth [Radiation Oncology, US Oncology-Willamette Valley Cancer Institute, Eugene, Oregon (United States); Dipetrillo, Thomas A. [Department of Radiation Oncology, Rhode Island Hospital, Providence, Rhode Island (United States); Corn, Benjamin W. [Department of Radiation Oncology, Tel Aviv Medical Center, Tel Aviv (Israel); Mehta, Minesh P. [Department of Radiation Oncology, University of Maryland, Baltimore, Maryland (United States)

2013-08-01

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established daily dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.

Daily oral iron supplementation during pregnancy

Science.gov (United States)

Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Dowswell, Therese; Viteri, Fernando E

2014-01-01

). Although the difference between groups did not reach statistical significance, women who received iron supplements were more likely than controls to report side effects (25.3% versus 9.91%) (RR 2.36; 95% CI 0.96 to 5.82, 11 trials, 4418 women), particularly at doses 60 mg of elemental iron or higher. Women receiving iron were on average more likely to have higher haemoglobin (Hb) concentrations at term and in the postpartum period, but were at increased risk of Hb concentrations greater than 130g/L during pregnancy and at term. Twenty-three studies were conducted in countries that in 2011 had some malaria risk in parts of the country. In some of these countries/territories, malaria is present only in certain areas or up to a particular altitude. Only two of these reported malaria outcomes. There is no evidence that iron supplementation increases placental malaria. For some outcomes heterogeneity was higher than 50%. Authors’ conclusions Prenatal supplementation with daily iron are effective to reduce the risk of low birthweight, and to prevent maternal anaemia and iron deficiency in pregnancy. Associated maternal side effects and particularly high Hb concentrations during pregnancy at currently used doses suggest the need to update recommendations on doses and regimens for routine iron supplementation. PMID:23235616

Age-dependent conversion coefficients for organ doses and effective doses for external neutron irradiation

International Nuclear Information System (INIS)

Nishizaki, Chihiro; Endo, Akira; Takahashi, Fumiaki

2006-06-01

To utilize dose assessment of the public for external neutron irradiation, conversion coefficients of absorbed doses of organs and effective doses were calculated using the numerical simulation technique for six different ages (adult, 15, 10, 5 and 1 years and newborn), which represent the member of the public. Calculations were performed using six age-specific anthropomorphic phantoms and a Monte Carlo radiation transport code for two irradiation geometries, anterior-posterior and rotational geometries, for 20 incident energies from thermal to 20 MeV. Effective doses defined by the 1990 Recommendation of ICRP were calculated from the absorbed doses in 21 organs. The calculated results were tabulated in the form of absorbed doses and effective doses per unit neutron fluence. The calculated conversion coefficients are used for dose assessment of the public around nuclear facilities and accelerator facilities. (author)

Particulate air pollution and daily mortality in Detroit.

Science.gov (United States)

Schwartz, J

1991-12-01

Particulate air pollution has been associated with increased mortality during episodes of high pollution concentrations. The relationship at lower concentrations has been more controversial, as has the relative role of particles and sulfur dioxide. Replication has been difficult because suspended particle concentrations are usually measured only every sixth day in the U.S. This study used concurrent measurements of total suspended particulates (TSP) and airport visibility from every sixth day sampling for 10 years to fit a predictive model for TSP. Predicted daily TSP concentrations were then correlated with daily mortality counts in Poisson regression models controlling for season, weather, time trends, overdispersion, and serial correlation. A significant correlation (P less than 0.0001) was found between predicted TSP and daily mortality. This correlation was independent of sulfur dioxide, but not vice versa. The magnitude of the effect was very similar to results recently reported from Steubenville, Ohio (using actual TSP measurements), with each 100 micrograms/m3 increase in TSP resulting in a 6% increase in mortality. Graphical analysis indicated a dose-response relationship with no evidence of a threshold down to concentrations below half of the National Ambient Air Quality Standards for particulate matter.

Effects of Tadalafil 5 mg Dosed Once Daily in Men with Premature Ejaculation.

Science.gov (United States)

Ozcan, Levent; Polat, Emre Can; Onen, Efe; Kocaaslan, Ramazan; Otunctemur, Alper; Cekmen, Mustafa; Eraldemir, Ceyla; Ozbek, Emin

2017-01-01

In this study, we evaluated the effect of 5 mg tadalafil once daily in men with premature ejaculation (PE). Thirty married men with lifelong PE and 30 healthy men as control group were included in this study. All the patients received 5 mg tadalafil once a day for a month. The international index of erectile function questionnaire and intravaginal ejaculatory latency times (IELTs) and PE profile were recorded before and after treatment. Plasma samples were collected before and after treatment. The mean baseline IELTs was 40.8 ± 8.1 s in the PE group and 196.5 ± 26.2 s in the control group. After treatment in the PE group, the mean IELTs values showed a statistically significant improvement from the baseline values. At the end of 4 weeks, in the PE group, the mean IELT values showed a statistically significant improvement from the baseline values. Baseline serum nitric oxide (NO) levels were 27.3 ± 1.7 in the PE group and in the 31.1 ± 1.4 healthy control groups. After treatment, NO levels were increased from baseline. We consider that 5 mg tadalafil once daily is safety and effective for the treatment of PE. © 2016 S. Karger AG, Basel.

Characterization of toxicosis in sheep dosed with blossoms of sacahuiste (Nolina microcarpa).

Science.gov (United States)

Rankins, D L; Smith, G S; Ross, T T; Caton, J S; Kloppenburg, P

1993-09-01

To characterize more fully sacahuiste (Nolina microcarpa Watson) toxicosis in sheep and to evaluate benefits of supplemental Zn, sheep were dosed intraruminally with sacahuiste blossoms. In Trial 1, eight fine-wool sheep (47 +/- 2 kg BW) were fed alfalfa hay at 1% of BW daily and dosed intraruminally with inflorescences amounting to 1% of BW daily, in three portions per day, for 10 d. Four sheep were dosed intraruminally with aqueous ZnSO4 (30 mg of Zn/kg BW) daily for 3 d before initial sacahuiste dosing and on alternate days thereafter, and four sheep were untreated with Zn. Toxicosis was evident within 24 h after initial sacahuiste dosage, involving inappetence, depression, hypokalemia, hypophosphatemia, hyperbilirubinemia, and elevated serum enzymes (alkaline phosphatase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transpeptidase). One sheep (untreated with Zn) died on d 3. Aqueous ZnSO4 alleviated inappetence and suppressed elevation of serum urea N and creatinine but did not suppress other changes in serum clinical profiles. In Trial 2, sacahuiste inflorescences were ruminally dosed into 12 fine-wool wethers (29 +/- 2 kg BW) in amounts equalling 0, .25, .50, .75% of BW per day, and chopped alfalfa hay was provided at 1.75% of BW per day for 14 d. Sacahuiste inflorescenses dosed at .75% of BW elicited severe toxicosis within 24 h, and dosage at .50 or .25% of BW per day increased (P = .12) serum bilirubin. Ruminal fluid pH, mean particle retention time, and particulate passage rate were not affected (P > .10) by sacahuiste, but ruminal fluid passage rate increased 1.6-fold (P < .10) and ruminal fluid volume decreased by 60% (P < .10) in sheep given inflorescenses amounting to .50% of BW daily. Sacahuiste inflorescenses dosed intraruminally at .75% of BW per day elicited ruminal impaction with severe hepatotoxicosis, and dosages amounting to .50% or .25% of BW per day caused similar trends.

Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression

DEFF Research Database (Denmark)

Straasø, Birgit; Lauritzen, Lise; Lunde, Marianne

2014-01-01

OBJECTIVE: To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy. METHODS: A self-treatment set...

Time-dose modifications

International Nuclear Information System (INIS)

Kian Ang, K.

1987-01-01

Changes in fractionation schedule can be made by various approaches. However, from the first principle, it is anticipated that strategies of hyperfractionation and/or accelerated fractionation offer the most promised in improving the therapeutic ratio. Hyperfractionation is defined as a treatment schedule in which a large number of significantly reduced dose fractions (--1.2 Gy/fraction) is used to give a greater total dose in a conventional overall time period. The results of the pilot studies testing the efficacy of hyperfractionation have been encouraging. The most valid clinical trial of pure hyperfractionation, however, is that conducted by the EORTC. This study compared 70 Gy in 35 fractions or 80.5 Gy in 70 fractions over 7 weeks in the treatment of patients with oropharyngeal carcinomas. The local tumor control was significantly improved in the hyperfractionated arm without increasing the morbidity. Accelerated fractionation is defined as a schedule in which the overall time of treatment is reduced without significant changes in the total dose and fraction size. The strategy has been used to treat patients with malignant gliomas, melanomas and Head and Neck cancers. The data in Head and Neck Cancers seem to be promising

A Phase I study of intermittently dosed vorinostat in combination with bortezomib in patients with advanced solid tumors.

Science.gov (United States)

Deming, Dustin A; Ninan, Jacob; Bailey, Howard H; Kolesar, Jill M; Eickhoff, Jens; Reid, Joel M; Ames, Matthew M; McGovern, Renee M; Alberti, Dona; Marnocha, Rebecca; Espinoza-Delgado, Igor; Wright, John; Wilding, George; Schelman, William R

2014-04-01

Accumulating evidence shows evidence of efficacy with the combination of vorinostat and bortezomib in solid tumors. We previously examined a once-daily continuous dosing schedule of vorinostat in combination with bortezomib which was well tolerated in cycles 1 and 2; however, there was concern regarding the tolerability through multiple cycles. This study was conducted to evaluate an intermittent dosing schedule of vorinostat with bortezomib. Vorinostat was initially administered orally twice daily on days 1-14 with bortezomib IV on days 1, 4, 8, and 11 of a 21 day cycle. Two DLTs (elevated ALT and fatigue) were observed at dose level 1, thus the protocol was amended to administer vorinostat intermittently twice daily on days 1-4 and 8-11. 29 patients were enrolled; 13 men and 16 women. Common cancer types included sarcoma, pancreatic, colorectal, GIST, and breast. The most common Grade 3-4 toxicities at any dose level included thrombocytopenia, fatigue, increased ALT, elevated INR, and diarrhea. DLTs in the intermittent dosing scheduled included thrombocytopenia and fatigue. The Cmax and AUC for the intermittent dosing regimen were similar to those observed in the daily dosing. In this heavily pretreated population, stable disease was observed in patients with sarcoma, colorectal adenocarcinoma and GIST. The MTD was established at vorinostat 300 mg BID on days 1-4 and 8-11 and bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, and 11 of a 21 day cycle. Tolerability was not improved with the intermittent dosing schedule of vorinostat when compared to continuous dosing.

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...

The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation.

Science.gov (United States)

Osmonov, Daniar K; Jünemann, Klaus P; Bannowsky, Andreas

2017-07-01

Radical prostatectomy (RP) is the most common definitive invasive treatment option for localized prostate cancer. Although the different surgical procedures-open RP, laparoscopic RP, and robot-assisted laparoscopic RP-do not differ significantly for the results of postoperative erectile dysfunction (ED) and continence, the fear of losing erectile function (EF) is often an important factor for preoperatively sexually active men when deciding for or against a procedure. To review the available literature on rehabilitation of EF after RP and to evaluate the value of the "Kiel concept" against different strategies of phosphodiesterase type 5 inhibitor (PDE5i) low-dose treatments. A review of the available literature up to January 2017 was undertaken using the key terms postsurgical ED, penile rehabilitation," PDE5i rehabilitation, and PDE5i daily dose treatment. As a main outcome measure we chose reviewed different concepts on the rehabilitation of EF after RP, taking into account the clinical background of the Kiel concept. The different therapeutic concepts for rehabilitation of EF after nerve-sparing RP are surprising. The most frequently applied method is application of different PDE5is. Despite different studies on efficacy, the issue of an optimal concept remains unresolved. The reason for this, among others, can be found in the difficulty of comparing different studies, which can vary with respect to the degree of nerve sparing, postoperative preservation of nocturnal erections, concomitant morbidity, and the number and experience of surgeons. In 86% of patients, the Kiel concept has been shown to support rehabilitation of EF after nerve-sparing RP with some form of therapeutic method. The Kiel concept is one therapeutic option among other comparable therapeutic options. Osmonov DK, Jünemann KP, Bannowsky A. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and

Dose gradient curve: A new tool for evaluating dose gradient.

Science.gov (United States)

Sung, KiHoon; Choi, Young Eun

2018-01-01

Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

Intent to Quit among Daily and Non-Daily College Student Smokers

Science.gov (United States)

Pinsker, E. A.; Berg, C. J.; Nehl, E. J.; Prokhorov, A. V.; Buchanan, T. S.; Ahluwalia, J. S.

2013-01-01

Given the high prevalence of young adult smoking, we examined (i) psychosocial factors and substance use among college students representing five smoking patterns and histories [non-smokers, quitters, native non-daily smokers (i.e. never daily smokers), converted non-daily smokers (i.e. former daily smokers) and daily smokers] and (ii) smoking…

Comparison of radiation doses obtained for radiation monitoring of controlled areas with radiation doses obtained for personnel dosimetry in radiodiagnosis centers

International Nuclear Information System (INIS)

Lescano, Roberto; Caspani, Carlos; Universidad Nacional del Litoral, Santa Fe

2001-01-01

In this paper we propose to search an indicator that shows, at an objective way, the quality of the radioprotection actions. The method is about to determine doses, measured in the work area, connecting them with the workload, and finally get the dose for the center. Them we make a comparison with the personal film dosimetry data. We discuss the final results, evaluating the radioprotection conditions in daily work. (author)

Depth dose factors for lymphoma's radiotherapy using a 4 MV linear accelerator

International Nuclear Information System (INIS)

Scaff, L.A.M.

1976-01-01

In the routine treatment of lymphomas using the mantle technique, the daily doses at the midpoints at five anatomical regions are different because their thickness are not equal. A set of tables of depht dose factors with good precision is presented [pt

Variations in daily quality assurance dosimetry from device levelling, feet position and backscatter material

International Nuclear Information System (INIS)

Ceylan, Abdurrahman; Cullen, Ashley; Butson, Martin; Yu, Peter K.N.; Alnawaf, Hani

2012-01-01

Daily quality assurance procedures are an essential part of radiotherapy medical physics. Devices such as the Sun Nuclear, DQA3 are effective tools for analysis of daily dosimetry including flatness, symmetry, energy, field size and central axis radiation dose measurement. The DQA3 can be used on the treatment couch of the linear accelerator or on a dedicated table/bed for superficial and orthovoltage x-ray machines. This device is levelled using its dedicated feet. This work has shown that depending on the quantity of backscatter material behind the DQA3 device, the position of the levelling feet can affect the measured central axis dose by up to 1.8 % (250 kVp and 6 MV) and that the introduction of more backscatter material behind the DQA3 can lead to up to 7.2 % (6 MV) variations in measured central axis dose. In conditions where no backscatter material is present, dose measurements can vary up to 1 %. As such this work has highlighted the need to keep the material behind the DQA3 device constant as well as maintaining the accuracy of the feet position on the device to effectively measure the most accurate daily constancy achievable. Results have also shown that variations in symmetry and energy calculations of up to 1 % can occur if the device is not levelled appropriately. As such, we recommend the position of the levelling feet on the device be as close as possible to the device so that a constant distance is kept between the DQA3 and the treatment couch and thus minimal levelling variations also occur. We would also recommend having no extra backscattering material behind the DQA3 device during use to minimise any variations which might occur from these backscattering effects.

Variation in water disappearance, daily dose, and synovial fluid concentrations of tylvalosin and 3-O-acetyltylosin in commerical pigs during five day water medication with tylvalosin under field conditions.

Science.gov (United States)

Canning, P; Bates, J; Skoland, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Gauger, P; Ramirez, A; Karriker, L

2018-03-23

Tylvalosin (TVN) is a water soluble macrolide used in swine production to treat enteric, respiratory, and arthritic pathogens. There is limited data on its distribution to synovial fluid beyond gavage studies, which do not represent field conditions. This study measured water disappearance, TVN concentration in the medicated water, daily dose, and concentrations of TVN and 3-O-acetyltylosin (3AT) in the synovial fluid and plasma of treated pigs over the administration period. The study emphasized understanding variation in tissue TVN concentrations within the context of a field setting. Sixty finisher pigs were housed individually with individual waterers. Six pigs were randomly allocated to the following time points for sample collection: 0, 48, 60, 72, 84, 96, 102, 108, 114, and 120 hr on medication. TVN was administered daily in the water for 5 days. Water disappearance and medicated water concentration were measured daily. At each time point, six pigs were euthanized and plasma and synovial fluid were collected for analysis. Median TVN synovial fluid concentrations ranged between <1 ng/ml (hour 0) to 3.6 ng/ml (hour 84). There was substantial variation between individual pigs for water disappearance (mean 4.36L and range 0-7.84). Median TVN water concentration was 59 ppm (range 38-75 ppm). © 2018 John Wiley & Sons Ltd.

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

Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships.

Science.gov (United States)

Forbes, P D; Davies, R E; Urbach, F

1978-12-01

Tumors were induced in the skin of SKH hairless mice by exposure to fluorescent FS sun lamps or to a long-arc xenon solar simulator. Tumores developed about equally well with varying amounts of UV-A radiation (lambda greater than 320 nm) given simultaneously. In contrast, incremental changes in the UV-B region (lambda less than 320 nm) led to substantial increases in carcinogenic effectiveness. A tumor-"initiating" dose of UV-B (4-10 wk of daily FS lamp exposures) was rendered less effective by subsequent exposures of the mice to UV-A (6 hr/day, F-40 T12BL lamps). The mechanism for this effect is not known. Most tumors induced by a short course (10 wk) of FS lamp exposure grew slowly or regressed, whereas mice exposed for a longer period (30 wk) developed more tumors, and many of those that appeared early grew aggressively. Effects of daily dose fractionation were less clear, and the subject requires further study. These and other variables are being tested in a program designed to yield useful information on the effects of changing spectrum, dose, and dose delivery rates on sunlight-induced cancer.

Legal, ethical, and economic implications of breaking down once-daily fixed-dose antiretroviral combinations into their single components for cost reduction.

Science.gov (United States)

Ramiro, Miguel A; Llibre, Josep M

2014-11-01

The availability of generic lamivudine in the context of the current economic crisis has raised a new issue in some European countries: breaking up the once-daily fixed-dose antiretroviral combinations (FDAC) of efavirenz/tenofovir/emtricitabine, tenofovir/emtricitabine, or abacavir/lamivudine, in order to administer their components separately, thereby allowing the use of generic lamivudine instead of branded emtricitabine or lamivudine. The legal, ethical, and economic implications of this potential strategy are reviewed, particularly in those patients receiving a once-daily single-tablet regimen. An unfamiliar change in antiretroviral treatment from a successful patient-friendly FDAC into a more complex regimen including separately the components to allow the substitution of one (or some) of them for generic surrogates (in the absence of a generic bioequivalent FDAC) could be discriminatory because it does not guarantee access to equal excellence in healthcare to all citizens. Furthermore, it could violate the principle of non-maleficence by potentially causing harm both at the individual level (hindering adherence and favouring treatment failure and resistance), and at the community level (hampering control of disease transmission and transmission of HIV-1 resistance). Replacing a FDAC with the individual components of that combination should only be permitted when the substituting medication has the same qualitative and quantitative composition of active ingredients, pharmaceutical form, method of administration, dosage and presentation as the medication being replaced, and a randomized study has demonstrated its non-inferiority. Finally, a strict pharma-economic study supporting this change, comparing the effectiveness and the cost of a specific intervention with the best available alternative, should be undertaken before its potential implementation. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiolog

Some aspects of time-dose relationships

International Nuclear Information System (INIS)

Sugawara, Tadashi; Koito, Kazumitsu; Aihara, Toshinori

1985-01-01

One hundred thirty-seven patients with non-small cell lung cancers, 57 with oral cavity cancers and 98 with postoperative breast cancers treated with external radiotherapy from 1974 to 1980 were analyzed to determine optimal trends of time-dose relationships. Superiorities of fractionation factors were examined by comparing the relative local recurrence or expire rates among the subgroups prognostically homogenized in each entities of the diseases. Faborable fractionation factors for the former two diseases were those in which treatment was given in shortened over-all times, and frequently with low fraction dose to the considerably high daily dose. These results indicate the superiority of accelerated fractionation regime to conventional one in the treatment of those diseases. In contrast, any optimal trend was not found with postoperative breast cancers but total dose administered more than 43 Gy. (author)

Efficacy and safety of terbinafine 500 mg once daily in patients with dermatophytosis

Directory of Open Access Journals (Sweden)

P Ravindra Babu

2017-01-01

Full Text Available Introduction: Dermatophytosis are the most common fungal infections globally. Terbinafine is considered to have good potency against dermatophytes, but resistance to terbinafine is on the rise. Objective: The objective of this study was to evaluate the efficacy and safety of terbinafine 500 mg given once daily in treatment of patients with superficial dermatophytosis. Materials and Methods: It was a retrospective questionnaire-based survey. Each doctor was given survey questionnaire booklet containing survey forms. Clinical response was graded according to the improvement in the affected lesion. Mycological cure was defined as negative microscopy under potassium hydroxide examination and a negative culture in Sabouraud's dextrose agar. Patients were divided into three groups depending on the duration of therapy, Group A – terbinafine 500 mg for 2 weeks, Group B – terbinafine 500 mg for 4 weeks, and Group C – terbinafine 500 mg for 6 weeks. Results: Total 50 doctors completed the survey involving 440 patients. In Group A, out of 194 patients, 87% (n = 169 patients showed very good response. In Group B, out of 211 patients, 92% (n = 194 of the patients showed very good response with >75% improvement in their lesion. In Group C, out of 35 patients, 80% (n = 30 patients showed very good response. Adverse drug reactions of mild to moderate intensity related to terbinafine were seen in 57 patients. Conclusion: Our survey indicates that terbinafine in a dose of 500 mg given once daily was efficacious and safe in the treatment of patients with dermatophytosis.

Natural radionuclides in the South Indian foods and their annual dose

Energy Technology Data Exchange (ETDEWEB)

Shanthi, G., E-mail: shanthidickson@gmail.co [Department of Physics, Women' s Christian College, Nagercoil 629001, Tamil Nadu (India); Thampi Thanka Kumaran, J. [Department of Physics, NM Christian College, Marthandam 629165, Tamil Nadu (India); Gnana Raj, G. Allan [Department of Chemistry and Research Centre, Scott Christian College, Nagercoil 629003, Tamil Nadu (India); Maniyan, C.G [Health Physics Unit, Indian Rare Earths, Manavalakurichi 629252, Tamil Nadu (India)

2010-07-21

The study was carried out to evaluate the radioactivity concentration in the food crops grown in high-level natural radioactive area (HLNRA) in south west India. Food samples collected were analysed by means of a gamma spectroscopy and estimated annual dietary intakes of the radioisotopes {sup 226}Ra, {sup 228}Ra, {sup 228}Th and {sup 40}K. The annual intake of the food stuffs was estimated on the basis of their average annual consumption. Calculations were also made to determine the effective dose to an individual consuming such diets. The intakes of these radionuclides were calculated using the concentrations in south Indian foods and daily consumption rates of these foods. Daily intakes of these radionuclides were as follows: {sup 226}Ra, 0.001-1.87; {sup 228}Ra, 0.0023-1.26, {sup 228}Th, 0.01-14.09 {sup 40}K, 0.46-49.39 Bq/day. The daily internal dose resulting from ingestion of radionuclides in food was 4.92 {mu}Sv/day and the annual dose was 1.79 mSv/yr. The radionuclides with highest consumption is {sup 40}K.

High-dose acetylcysteine in idiopathic pulmonary fibrosis

NARCIS (Netherlands)

Demedts, Maurits; Behr, Juergen; Buhl, Roland; Costabel, Ulrich; Dekhuijzen, Richard; Jansen, Henk M.; MacNee, William; Thomeer, Michiel; Wallaert, Benoit; Laurent, François; Nicholson, Andrew G.; Verbeken, Eric K.; Verschakelen, Johny; Flower, Christopher D. R.; Capron, Frédérique; Petruzzelli, Stefano; de Vuyst, Paul; van den Bosch, Jules M. M.; Rodriguez-Becerra, Eulogio; Corvasce, Giuseppina; Lankhorst, Ida; Sardina, Marco; Montanari, Mauro

2005-01-01

BACKGROUND Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added

Relationship between Optimum Mini-doses of Glucagon and Insulin Levels when Treating Mild Hypoglycaemia in Patients with Type 1 Diabetes - A Simulation Study

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Wendt, Sabrina Lyngbye; Schmidt, Signe

2017-01-01

-treated type 1 diabetes. In each simulation, one of ten different and individualized subcutaneous insulin boluses was administered to decrease plasma glucose (PG) from 7.0 to ≤3.9 mmol/l. Insulin levels were estimated as ratio of actual to baseline serum insulin concentration (se/ba-insulin), insulin on board...... (IOB) or percentage of IOB to total daily insulin dose (IOB/TDD). Insulin bolus sizes were chosen to provide pre-defined insulin levels when PG reached 3.9 mmol/l, where one of 17 subcutaneous glucagon boluses was administered. Optimum glucagon bolus to treat mild hypoglycaemia at varying insulin...... levels was the lowest dose that in most patients caused PG peak between 5.0 and 10.0 mmol/l and sustained PG ≥ 3.9 mmol/l for 2 hr after the bolus. PG response to glucagon declined with increasing insulin levels. The glucagon dose to optimally treat mild hypoglycaemia depended exponentially on insulin...

Farm elders define health as the ability to work.

Science.gov (United States)

Reed, Deborah B; Rayens, Mary Kay; Conley, Christina K; Westneat, Susan; Adkins, Sarah M

2012-08-01

Thirty percent of America's 2.2 million farms are operated by individuals older than 65 years. This study examined how older farmers define health and determined whether demographic characteristics, farm work, and physical and mental health status predict health definition. Data were collected via telephone and mailed surveys during the baseline wave of data collection in a longitudinal study of family farmers residing in two southern states (n=1,288). Nearly 42% defined health as the "ability to work" compared to a physical health-related definition. Predictors of defining health as the ability to work included being White, performing more farm tasks in the past week, taking prescription medications daily, and having minimal health-related limitations to farm work. Health behaviors are centered on the individual's perception of health. Understanding the defining attributes of health can support better approaches to health care and health promotion, particularly among rural subcultures such as farmers, whose identity is rooted in their work. Copyright 2012, SLACK Incorporated.

Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats.

Science.gov (United States)

Clark, Robert E; Kuczenski, Ronald; Segal, David S

2007-07-01

Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.

Chronic and Daily Stressors Along With Negative Affect Interact to Predict Daily Tiredness.

Science.gov (United States)

Hartsell, Elizabeth N; Neupert, Shevaun D

2017-11-01

The present study examines the within-person relationship of daily stressors and tiredness and whether this depends on daily negative affect and individual differences in chronic stress. One hundred sixteen older adult participants were recruited via Amazon's Mechanical Turk for a 9-day daily diary study. Daily tiredness, daily stressors, and negative affect were measured each day, and chronic stress was measured at baseline. Daily stressors, daily negative affect, and chronic stress interacted to predict daily tiredness. People with high chronic stress who experienced an increase in daily negative affect were the most reactive to daily stressors in terms of experiencing an increase in daily tiredness. We also found that people with low levels of chronic stress were the most reactive to daily stressors when they experienced low levels of daily negative affect. Our results highlight the need for individualized and contextualized approaches to combating daily tiredness in older adults.

Alternative dosing of prophylactic enoxaparin in the trauma patient: is more the answer?

Science.gov (United States)

Kopelman, Tammy R; O'Neill, Patrick J; Pieri, Paola G; Salomone, Jeffrey P; Hall, Scott T; Quan, Asia; Wells, Jordan R; Pressman, Melissa S

2013-12-01

Inadequate anti-factor Xa levels and increased venous thromboembolic events occur in trauma patients receiving standard prophylactic enoxaparin dosing. The aim of this study was to test the hypothesis that higher dosing (40 mg twice daily) would improve peak anti-Xa levels and decrease venous thromboembolism. A retrospective review was performed of trauma patients who received prophylactic enoxaparin and peak anti-Xa levels over 27 months. Patients were divided on the basis of dose: group A received 30 mg twice daily, and group B received 40 mg twice daily. Demographics and rates of venous thromboembolism were compared between dose groups and patients with inadequate or adequate anti-Xa levels. One hundred twenty-four patients were included, 90 in group A and 34 in group B. Demographics were similar, except that patients in group B had a higher mean body weight. Despite this, only 9% of group B patients had inadequate anti-Xa levels, compared with 33% of those in group A (P = .01). Imaging studies were available in 69 patients and revealed 8 venous thromboembolic events (P = NS, group A vs group B) with significantly more venous thromboembolic events occurring in patients with low anti-Xa levels (P = .02). Although higher dosing of enoxaparin led to improved anti-Xa levels, this did not equate to a statistical decrease in venous thromboembolism. Copyright © 2013 Elsevier Inc. All rights reserved.

Tracheobronchial and Alveolar Particle Surface Area Doses in Smokers

Directory of Open Access Journals (Sweden)

Fernanda Carmen Fuoco

2017-01-01

Full Text Available Cigarette smoke is the main cause of lung cancer events. Mainstream cigarette smoke (MSS is a direct concern for smokers, but also the secondhand smoke (SHS contributes to the smoker exposure. In addition, smoker exposure is affected by the “free-smoke” particle exposure (B, related to the micro-environments where smokers spend time. The aim of this paper is to evaluate the daily alveolar and tracheobronchial deposited fractions of airborne particles for smokers as the sum of these three contributions: MSS, SHS, and B. Measurements of particle surface area distributions in the MSS were performed through a Scanning Mobility Particle Sizer, an Aerodynamic Particle Sizer, and a Thermo-dilution system on five types of conventional cigarettes. A Monte Carlo method was then applied to evaluate the most probable value of dose received during the inhalation of MSS by smokers. Measurements of particle concentrations in SHS and at the “free-smoke” particle background (B were performed through 24-h monitoring at a personal scale of adult smoker through hand-held devices. This paper found that the total daily deposited dose for typical smokers was 1.03 × 105 mm2·day−1. The main contribution of such a huge daily dose was addressable to the MSS (98% while SHS contributed 1.1%, increasing up to 2% for people smoking only while traveling in a car.

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

Energy Technology Data Exchange (ETDEWEB)

Li, Jun; Sun, Kang [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Ni, Lijuan; Wang, Xufang [School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui (China); Wang, Dongxu [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

2012-02-01

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

International Nuclear Information System (INIS)

Li, Jun; Sun, Kang; Ni, Lijuan; Wang, Xufang; Wang, Dongxu; Zhang, Jinsong

2012-01-01

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

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

What Is the Most Effective Way of Increasing the Bioavailability of Dietary Long Chain Omega-3 Fatty Acids—Daily vs. Weekly Administration of Fish Oil?

Directory of Open Access Journals (Sweden)

Samaneh Ghasemifard

2015-07-01

Full Text Available The recommendations on the intake of long chain omega-3 polyunsaturated fatty acids (n-3 LC-PUFA vary from eating oily fish (“once to twice per week” to consuming specified daily amounts of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA (“250–500 mg per day”. It is not known if there is a difference in the uptake/bioavailability between regular daily consumption of supplementsvs. consuming fish once or twice per week. In this study, the bioavailability of a daily dose of n-3 LC-PUFA (Constant treatment, representing supplements, vs. a large weekly dose of n-3 LC-PUFA (Spike treatment, representing consuming once or twice per week, was assessed. Six-week old healthy male Sprague-Dawley rats were fed either a Constant treatment, a Spike treatment or Control treatment (no n-3 LC-PUFA, for six weeks. The whole body, tissues and faeces were analysed for fatty acid content. The results showed that the major metabolic fate of the n-3 LC-PUFA (EPA+docosapentaenoic acid (DPA + DHA was towards catabolism (β-oxidation accounting for over 70% of total dietary intake, whereas deposition accounted less than 25% of total dietary intake. It was found that significantly more n-3 LC-PUFA were β-oxidised when originating from the Constant treatment (84% of dose, compared with the Spike treatment (75% of dose. Conversely, it was found that significantly more n-3 LC-PUFA were deposited when originating from the Spike treatment (23% of dose, than from the Constant treatment (15% of dose. These unexpected findings show that a large dose of n-3 LC-PUFA once per week is more effective in increasing whole body n-3 LC-PUFA content in rats compared with a smaller dose delivered daily.

Intensity of the absorbing dose of the gamma rays in the air of Krusevac during and after nuclear accident in Chernobil

International Nuclear Information System (INIS)

Fortuna, D.

1997-01-01

In this paper are compared overage daily values of the intensity of the absorbing doses of the gamma rays in the air of Krusevac, during and after nuclear accident in Cernobil. Average daily values of intensity of the absorbing doses of gamma rays in the air of Krusevac, immediately after nuclear accident in Cernobil were, three to seven time higher than of the average daily values of the natural rays. (author)

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

Directory of Open Access Journals (Sweden)

J Gerardo García-Lerma

2008-02-01

Full Text Available In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

Efficacy and safety of once daily low molecular weight heparin (tinzaparin sodium) in high risk pregnancy.

LENUS (Irish Health Repository)

Ní Ainle, Fionnuala

2008-10-01

Low molecular weight heparin (LMWH) is widely regarded as the anticoagulant treatment of choice for the prevention and treatment of venous thromboembolism during pregnancy. However, previous studies have demonstrated that the pharmacokinetic profiles of LMWH vary significantly with increasing gestation. Consequently, it remains unclear whether LMWH regimens recommended for use in nonpregnant individuals can be safely extrapolated to pregnant women. The aims of this study were to assess the safety and the efficacy of tinzaparin sodium (Innohep) administered only once daily during pregnancy. A systematic retrospective review identified a cohort of 37 high-risk pregnancies which had been managed using tinzaparin 175 IU\\/kg once daily. In 26 cases, the index pregnancy had been complicated by development of an acute venous thromboembolism (17 deep vein thrombosis and nine pulmonary embolism). For each individual, case notes were examined and data extracted using a predetermined questionnaire. No episodes of recurrent venous thromboembolism were identified amongst this cohort of pregnancies managed using once daily LMWH administration. However, two unusual thrombotic complications were observed, including a parietal infarct in one patient, and a postpartum cerebral venous thrombosis in another. Once daily tinzaparin was well tolerated, with no cases of heparin-induced thrombocytopaenia, symptomatic osteoporosis, or foetal malformations. Tinzaparin dose modification based upon peak anti-Xa levels occurred in 45% of the cases examined. The present study is the largest study to have examined the clinical efficacy of once daily LMWH for use in pregnant women at high risk of venous thromboembolism. Our data support the safety and efficacy of antenatal tinzaparin at a dose of 175 IU\\/kg. In order to determine whether this once daily regimen provides equivalent (or indeed greater) thromboprophylaxis to twice daily LMWH regimens during pregnancy will require highly powered

Intent to quit among daily and non-daily college student smokers

OpenAIRE

Pinsker, E. A.; Berg, C. J.; Nehl, E. J.; Prokhorov, A. V.; Buchanan, T. S.; Ahluwalia, J. S.

2012-01-01

Given the high prevalence of young adult smoking, we examined (i) psychosocial factors and substance use among college students representing five smoking patterns and histories [non-smokers, quitters, native non-daily smokers (i.e. never daily smokers), converted non-daily smokers (i.e. former daily smokers) and daily smokers] and (ii) smoking category as it relates to readiness to quit among current smokers. Of the 4438 students at six Southeast colleges who completed an online survey, 69.7%...

The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study.

Science.gov (United States)

Chasset, François; Arnaud, Laurent; Costedoat-Chalumeau, Nathalie; Zahr, Noel; Bessis, Didier; Francès, Camille

2016-04-01

Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. The main limitations of the study are its open-label design and the limited number of patients included. Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

Energy Technology Data Exchange (ETDEWEB)

Fortan, L; Van Hecke, H; Van Duyse, B; De Neve, W; De Meerleer, B [Ghent Rijksuniversiteit (Belgium). Kliniek voor Radiotherapie en Kerngeneeskunde; Pattyn, P; Van Renthergem, K [Ghent University (Belgium). Dept. of Surgery

1995-12-01

The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible.

In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

International Nuclear Information System (INIS)

Fortan, L.; Van Hecke, H.; Van Duyse, B.; De Neve, W.; De Meerleer, B.; Pattyn, P.; Van Renthergem, K.

1995-01-01

The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible

Recalculation of dose for each fraction of treatment on TomoTherapy.

Science.gov (United States)

Thomas, Simon J; Romanchikova, Marina; Harrison, Karl; Parker, Michael A; Bates, Amy M; Scaife, Jessica E; Sutcliffe, Michael P F; Burnet, Neil G

2016-01-01

The VoxTox study, linking delivered dose to toxicity requires recalculation of typically 20-37 fractions per patient, for nearly 2000 patients. This requires a non-interactive interface permitting batch calculation with multiple computers. Data are extracted from the TomoTherapy(®) archive and processed using the computational task-management system GANGA. Doses are calculated for each fraction of radiotherapy using the daily megavoltage (MV) CT images. The calculated dose cube is saved as a digital imaging and communications in medicine RTDOSE object, which can then be read by utilities that calculate dose-volume histograms or dose surface maps. The rectum is delineated on daily MV images using an implementation of the Chan-Vese algorithm. On a cluster of up to 117 central processing units, dose cubes for all fractions of 151 patients took 12 days to calculate. Outlining the rectum on all slices and fractions on 151 patients took 7 h. We also present results of the Hounsfield unit (HU) calibration of TomoTherapy MV images, measured over an 8-year period, showing that the HU calibration has become less variable over time, with no large changes observed after 2011. We have developed a system for automatic dose recalculation of TomoTherapy dose distributions. This does not tie up the clinically needed planning system but can be run on a cluster of independent machines, enabling recalculation of delivered dose without user intervention. The use of a task management system for automation of dose calculation and outlining enables work to be scaled up to the level required for large studies.

Dose calculations algorithm for narrow heavy charged-particle beams

Energy Technology Data Exchange (ETDEWEB)

Barna, E A; Kappas, C [Department of Medical Physics, School of Medicine, University of Patras (Greece); Scarlat, F [National Institute for Laser and Plasma Physics, Bucharest (Romania)

1999-12-31

The dose distributional advantages of the heavy charged-particles can be fully exploited by using very efficient and accurate dose calculation algorithms, which can generate optimal three-dimensional scanning patterns. An inverse therapy planning algorithm for dynamically scanned, narrow heavy charged-particle beams is presented in this paper. The irradiation `start point` is defined at the distal end of the target volume, right-down, in a beam`s eye view. The peak-dose of the first elementary beam is set to be equal to the prescribed dose in the target volume, and is defined as the reference dose. The weighting factor of any Bragg-peak is determined by the residual dose at the point of irradiation, calculated as the difference between the reference dose and the cumulative dose delivered at that point of irradiation by all the previous Bragg-peaks. The final pattern consists of the weighted Bragg-peaks irradiation density. Dose distributions were computed using two different scanning steps equal to 0.5 mm, and 1 mm respectively. Very accurate and precise localized dose distributions, conform to the target volume, were obtained. (authors) 6 refs., 3 figs.

Randomized Trial of Once-Daily Fluticasone Furoate in Children with Inadequately Controlled Asthma

DEFF Research Database (Denmark)

Oliver, Amanda J.; Covar, Ronina A.; Goldfrad, Caroline H.

2016-01-01

Objective To evaluate the dose-response, efficacy, and safety of fluticasone furoate (FF; 25 µg, 50 µg, and 100 µg), administered once daily in the evening during a 12-week treatment period to children with inadequately controlled asthma. Study design This was a Phase IIb, multicenter, stratified...

Switch from a ZDV/3TC-based regimen to a completely once daily (QD regimen of emtricitabine/tenofovir DF fixed dose combination plus a third QD agent (SONETT

Directory of Open Access Journals (Sweden)

Arasteh K

2009-05-01

Full Text Available Abstract Objectives To assess the efficacy and safety of a treatment switch from a twice-daily (BID regimen containing zidovudine (ZDV and lamivudine (3TC plus a third agent to a once daily (QD regimen containing the fixed-dose combination of tenofovir DF/emtricitabine (TDF/FTC, Truvada® plus a divergent third QD agent in HIV-1 infected patients. Methods Prospective, 48-week, non-randomised, single-group, open-label, study. Fifty-one patients on stable ZDV/3TC-containing HAART, with HIV-1 RNA 50 cells/μl, were switched to TDF/FTC plus a third agent. Plasma HIV-1 RNA, CD4+ and CD8+ T-cell counts were assessed at baseline and weeks 4, 12, 24, 36 and 48 post-switch. Results During the 48-week study, 10 patients discontinued prematurely, including three due to adverse events (AEs. At week 48, plasma HIV-1 RNA was p Conclusions Results from this study support switching from a ZDV/3TC-containing HAART regimen to a completely QD regimen of TDF/FTC plus a third agent. Virologic and immunologic control are maintained, with apparent benefits in haemoglobin.

[Efficacy of low-dose tadalafil on ED assessed by Self-Esteem and Relationship Questionnaire].

Science.gov (United States)

Li, Jing-Ping; Li, Fei; Guo, Wen-Bin; Zhou, Qi-Zhao; Liu, Cun-Dong; Mao, Xiang-Ming; Tan, Wan-Long; Zheng, Shao-Bin

2010-12-01

To explore the effects of low-dose oral tadalafil on self-esteem, confidence and sexual relationship in ED patients. We treated 17 ED patients with oral tadalafil at the low dose of 5 mg once daily for 12 weeks, and used the paired t test to compare their scores on The Self-Esteem and Relationship Questionnaire (SEAR) and IIEF-5 and the results of nocturnal penile tumescence (NPT) obtained by nocturnal electrobioimpedance volumetric assessment (NEVA) before and after the medication. The scores on SEAR and IIEF-5 were significantly increased (P P Low-dose oral tadalafil once daily can significantly improve the self-esteem, confidence, sexual relationship satisfaction and NPT of ED patients.

Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial

DEFF Research Database (Denmark)

de Groot, Kirsten; Harper, Lorraine; Jayne, David R W

2009-01-01

BACKGROUND: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. OBJECTIVE: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. DESIGN: Randomized, controlled trial. Random assignments were...... outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). RESULTS: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87...... regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. PRIMARY FUNDING SOURCE: The European Union....

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

Science.gov (United States)

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Once-Daily Radiation Therapy for Inflammatory Breast Cancer

International Nuclear Information System (INIS)

Brown, Lindsay; Harmsen, William; Blanchard, Miran; Goetz, Matthew; Jakub, James; Mutter, Robert; Petersen, Ivy; Rooney, Jessica; Stauder, Michael; Yan, Elizabeth; Laack, Nadia

2014-01-01

Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

Studies on the reference Korean and estimation of radiation exposure dose

International Nuclear Information System (INIS)

Kim, Y.J.; Lee, K.S.; Chun, K.J.; Kim, J.B.; Chung, G.H.; Kim, S.R.

1982-01-01

For the purpose of establishment of Reference Korean and estimation of internal and external exposure doses in the Reference Korean, we have surveyed reference values for Koreans such as physical standards including height, weight, and body surface area, food consumption rate of daily intake of radioactive substances and exposure dose from natural radiation. (Author)

Daily tritium intakes by people living near a heavy-water research reactor facility: dosimetric significance

International Nuclear Information System (INIS)

Trivedi, A.; Cornett, R.J.; Galeriu, D.; Workman, W.; Brown, R.M.

1997-02-01

We have estimated the relative daily intakes of tritiated water (HTO) and organically bound tritium (OBT), and have measured HTO-in-urine, in an adult population residing in the town of Deep River, Ontario, near a heavy-water research reactor facility at Chalk River. The daily intake of elevated levels of atmospheric tritium has been estimated from its concentration in environmental and biological samples, and various food items from a local tritium-monitoring program. Where the available data were inadequate, we used estimates generated by an environmental tritium-transfer model. From these data and estimates, we calculated a total daily tritium intake of about 55 Bq. Of this amount, 2.5 Bq is obtained from OBT-in-diet. Inhalation of HTO-in-air (15 Bq d -1 ) and HTO-in-drinking water (15 Bq d -1 ) accounts for more than half of the HTO intake. Skin absorption of HTO from air and bathing or swimming (for 30 min d -1 ) accounts for another 9 Bq d -1 and 0.1 Bq d -1 , respectively. The remaining intake of HTO is from food as tissue-free water tritium. The International Commission on Radiological Protection's recommended two-compartment metabolic model for tritium predicts an equilibrium body burden of about 900 Bq from HTO (818 Bq) and OBT (83 Bq) in the body, which corresponds to an annual tritium dose of 0.41 μSv. The model-predicted urinary excretion of HTO (∼18 Bq L -1 ) agrees well with measured HTO-in-urine (range, 10-32 Bq L -1 ). The OBT dose contribution to the total tritium dose is about 16%. We conclude that for the people living near the Chalk River research reactor facility, the bulk of the tritium dose is due to HTO intake. (author)

Efficacy and optimal dose of daily polyethylene glycol 3350 for treatment of constipation and encopresis in children.

Science.gov (United States)

Pashankar, D S; Bishop, W P

2001-09-01

To determine efficacy, safety, and optimal dose of a laxative, polyethylene glycol (PEG) 3350, in children with chronic constipation. Children with chronic constipation (n = 24) were treated with PEG for 8 weeks at an initial dose of 1 g/kg/d. The dose was adjusted every 3 days as required to achieve 2 soft stools per day. A diary was kept to monitor dose, stool frequency and consistency, soiling, and other symptoms. Stool consistency was rated from 1 (hard) to 5 (watery). Subjects were examined for fecal retention. The Student t test and the Fisher exact test were used for data analysis. All 20 children who completed the study found PEG to be palatable and were satisfied with the treatment. There were no significant adverse effects. Weekly stool frequency increased from 2.3 +/- 0.4 to 16.9 +/- 1.6 (P PEG at a mean dose of 0.8 g/kg is an effective, safe, and palatable treatment for constipation.

Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

Directory of Open Access Journals (Sweden)

Deville Curtiland

2012-05-01

Full Text Available Abstract Background Our purpose was to report acute gastrointestinal (GI and genitourinary (GU toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT with a daily endorectal water-filled balloon (ERBH2O, and assess associations with planning parameters and pretreatment clinical characteristics. Methods The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERBH2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0 were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Results Mean age was 68 (range 51–88. Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps  Conclusion Prostate IG-IMRT using a daily ERBH2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities.

Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity

International Nuclear Information System (INIS)

Shun, Wong C.; Yong, Hao; Hill, Richard P.

1995-01-01

Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes ((α(β)) of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to ≤ 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED 50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an (α(β)) of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the (α(β)) value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes ≥ 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments. These results in which top-up doses were given initially are consistent with a large sparing effect of very small fraction sizes in rat spinal cord provided sufficient time is allowed for repair of sublethal damage between fractions, and provide no evidence for a paradoxical increase in radiosensitivity in the rat spinal cord below 1 Gy down to 0.4 Gy per fraction

[Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

Science.gov (United States)

Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

2015-01-01

To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (Pnutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Shefner, Jeremy M; Watson, Mary Lou; Meng, Lisa; Wolff, Andrew A

2013-12-01

Abstract Tirasemtiv is a fast skeletal muscle activator that increases the sensitivity of the sarcomere to calcium, increasing the efficiency of muscle contraction when the muscle is stimulated at submaximal contraction frequencies. A previous study showed single doses of tirasemtiv to be well tolerated and associated with potentially important improvements in a variety of functional outcomes. This study determined safety of tirasemtiv when given at doses up to 500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to 375 mg for two weeks, with and without concomitant riluzole. In a separate cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given in two divided doses. Safety and tolerability were assessed, as well as measures of function, muscle strength and endurance. Results showed that tirasemtiv was well tolerated, with dizziness the most common adverse event. Tirasemtiv approximately doubled the serum concentration of riluzole. Trends were noted for improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely with a reduced dose of riluzole. Positive trends in multiple exploratory outcome measures support the further study of this agent in ALS.

Once-Daily Tacrolimus Extended-Release Formulation: 1 Year after Conversion in Stable Pediatric Kidney Transplant Recipients

Directory of Open Access Journals (Sweden)

Lars Pape

2011-01-01

Full Text Available It is speculated that a once-daily dosage of immunosuppression can increase adherence and thereby graft survival. Until now, there have been no studies on once-daily use of Tacrolimus extended-release formulation (TAC-ER in children following pediatric kidney transplantation. In 11 stable pediatric kidney recipients >10 years, efficacy, safety, and tolerability of a switch to TAC-ER were observed over one year. Adherence was determined by use of the BAASIS-Scale Interview and comparison of individual variability of Tacrolimus trough levels. Over the observation period, two acute rejections were observed in one girl with nonadherence and repeated Tacrolimus trough levels of 0 ng/m. Beside this, there were no acute rejections in this trial. TAC dose was increased in 3/11 patients and decreased in 2/11 patients within the course of the study. Six patients did not require a dose adjustment. All but one patient had a maximum of 1 dose change during therapy. Mean Tacrolimus dose, trough levels, and Glomerular filtration rates were also stable. Adherence, as measured by BAASIS-Scale Interview and coefficient of variation of Tacrolimus trough levels, was good at all times. It is concluded that conversion to Tac-ER is safe in low-risk children following pediatric kidney transplantation.

Limits of dose escalation in lung cancer: a dose-volume histogram analysis comparing coplanar and non-coplanar techniques

Energy Technology Data Exchange (ETDEWEB)

Derycke, S; Van Duyse, B; Schelfhout, J; De Neve, W

1995-12-01

To evaluate the feasibility of dose escalation in radiotherapy of inoperable lung cancer, a dose-volume histogram analysis was performed comparing standard coplanar (2D) with non-coplanar (3D) beam arrangements on a non-selected group of 20 patients planned by Sherouse`s GRATISTM 3D-planning system. Serial CT-scanning was performed and 2 Target Volumes (Tvs) were defined. Gross Tumor Volume (GTV) defined a high-dose Target Volume (TV-1). GTV plus location of node stations with > 10% probability of invasion (Minet et al.) defined an intermediate-dose Target Volume (TV-2). However, nodal regions which are incompatible with cure were excluded from TV-2. These are ATS-regions 1, 8, 9 and 14 all left and right as well as heterolateral regions. For 3D-planning, Beam`s Eye View selected (by an experienced planner) beam arrangements were optimised using Superdot, a method of target dose-gradient annihilation developed by Sherouse. A second 3D-planning was performed using 4 beam incidences with maximal angular separation. The linac`s isocenter for the optimal arrangement was located at the geometrical center of gravity of a tetraheder, the tetraheder`s comers being the consecutive positions of the virtual source. This ideal beam arrangement was approximated as close as possible, taking into account technical limitations (patient-couch-gantry collisions). Criteria for tolerance were met if no points inside the spinal cord exceeded 50 Gy and if at least 50% of the lung volume received less than 20Gy. If dose regions below 50 Gy were judged acceptable at TV-2, 2D- as well as 3D-plans allow safe escalation to 80 Gy at TV-1. When TV-2 needed to be encompassed by isodose surfaces exceeding 50Gy, 3D-plans were necessary to limit dose at the spinal cord below tolerance. For large TVs dose is limited by lung tolerance for 3D-plans. An analysis (including NTCP-TCP as cost functions) of rival 3D-plans is being performed.

Defining safety goals. 2. Basic Consideration on Defining Safety Goals

International Nuclear Information System (INIS)

Hakata, T.

2001-01-01

cancer and severe hereditary effects are 10 x 10 -2 /Sv and 1.3 x10 -2 /Sv, respectively. The basic safety goals can be expressed by the complementary accumulative distribution function (CCDF) of dose versus frequencies of events: Pc(C > Cp) 5 (Cp/Co) -α . The aversion factor a is here expressed by the following arbitrary equation, which gives a polynomial curve of the order of m on a logarithmic plane: α = a+b(log(Cp/Co)) m , where: Pc = CCDF frequency for Cp (/yr), Cp = dose (mSv), Co = Cp for Pc =1, a, b, m = constants. Figure 1 shows a typical tolerable risk profile (risk limit curve), which is drawn so that all the points obtained in the previous discussions are above the curve (Co=1, a=1, b=0.0772, and m = 2). Safety criteria by ANS (Ref. 2) and SHE (Ref. 3) are shown in Fig. 1 for comparison. An aversion of a factor of 2 is resulted between 1 mSv and 1 Sv. No ALARA is included, which must be considered in defining specific safety goals. The frequency of a single class of events must be lower than the CCDF profile, and a curve lower by a factor of 10 is drawn in Fig. 1. The doses referenced in the current Japanese safety guidelines and site criteria are shown in Fig. 1. The referenced doses seem reasonable, considering the conservatism in the analysis of design-basis accidents. Specific safety goals for each sort of facility can be defined based on the basic safety goals, reflecting the characteristics of the facilities and considering ALARA. The indexes of engineering terms, such as CMF and LERF, are preferable for nuclear power plants, although interpretation from dose to the engineering terms is needed. Other indexes may be used (such as frequency of criticality accidents, etc.) for facilities except for power plants. The applicability of safety goals will thus be improved. Figure 2 shows the relative risk factors (1, 1%, and 0.1%) versus the severity of radiation effects. This might indicate the adequacy of the risk factors. The absolute risk limits, which

New observations on chronic intoxication by very small doses of sodium fluosilicate

Energy Technology Data Exchange (ETDEWEB)

Cristiani, H; Chausse, P

1927-01-01

It was determined that daily doses of approximately 0.1 of the lethal dose of sodium fluoride produced a fluoric cachexia in guinea pigs which caused the death of the animals in 2 or 3 months. Animals which were given 0.02 of the lethal dose of sodium fluoride were apparently in good health for a period of 10 months. However, after two or three years cachexia was likely to appear.

Low, fixed dose defibrotide in management of hepatic veno-occlusive disease post stem cell transplantation.

Science.gov (United States)

Bagal, Bhausaheb; Chandrasekharan, Arun; Chougle, Aliya; Khattry, Navin

2018-03-01

Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive. We report our experience of using fixed low dose of defibrotide in patients with VOD. We retrospectively evaluated 511 patients who underwent stem cell transplant at our center from November 2007 and December 2015. All patients received ursodeoxycholic acid as VOD prophylaxis. Modified Seattle criterion was used for diagnosis and severity grading of VOD. Patients developing VOD were initially treated with furosemide and adequate analgesia. Defibrotide was started within 12 to 24 hours of diagnosis of VOD. All adult patients received defibrotide at a fixed dose of 200mg twice daily while two children were given dose of 100mg and 50mg twice daily. Nine (1.7%) of our patients developed VOD. Daily dose of defibrotide ranged from 5mg/kg/d to 20mg/kg/d till resolution of VOD. All patients had complete resolution of VOD. None of our patients required ventilator support or dialysis. No episodes of bleeding were observed. No dose response relationship was observed between defibrotide dose and time to resolution of VOD. Low fixed dose defibrotide initiated early seems to be effective and safe in treatment of VOD. This is relevant in a resource limited setting and warrants prospective evaluation. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Psychosocial work conditions, social capital, and daily smoking: a population based study.

Science.gov (United States)

Lindström, M

2004-09-01

To investigate the associations between psychosocial conditions at work, social capital/social participation, and daily smoking. The 2000 public health survey in Scania is a cross sectional postal questionnaire study with a 59% participation rate. A total of 5180 persons aged 18-64 years that belonged to the work force and the unemployed were included in this study. Logistic regression models were used to investigate the associations between psychosocial factors at work/unemployment, social participation, and daily smoking. Psychosocial conditions at work were defined according to the Karasek-Theorell demand-control/decision latitudes into relaxed, active, passive, and jobstrain categories. The multivariate analyses included age, country of origin, education and economic stress. 17.2% proportion of all men and 21.9% of all women were daily smokers. The jobstrain (high demands/low control) and unemployed categories had significantly higher odds ratios of daily smoking among both men and women compared to the relaxed (low demands/high control) reference category. The passive (low demands/low control), jobstrain, and unemployed categories were also significantly associated with low social participation. Low social participation was significantly and positively associated with daily smoking within each of the psychosocial work conditions and unemployed categories. The positive association between low social capital/low social participation and daily smoking is well known. However, both social participation and daily smoking are associated with psychosocial work conditions and unemployment. Psychosocial work conditions and unemployment may affect daily smoking both directly and through a pathway including social participation.

Effect of low-dose radiation on ocular circulation

International Nuclear Information System (INIS)

Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro

1999-01-01

We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

Effect of low-dose radiation on ocular circulation

Energy Technology Data Exchange (ETDEWEB)

Baba, Keiko; Hiroishi, Goro; Honda, Masae; Yoshikawa, Hiroshi; Fujisawa, Kimihiko; Ishibashi, Tatsuro [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1999-05-01

We treated 6 eyes of unilateral age-related macular degeneration by low-dose radiation. Each eye received daily dose of 2 Gy by 4MV lineac totalling 20 Gy over 2 weeks. Color doppler flowmetry was used to determine the mean blood flow velocity (Vmean) and vascular resistive index (RI) in the short posterior ciliary artery, central retinal artery and ophthalmic artery in the treated and fellow eyes before and up to 6 months of treatment. There were no significant differences in Vmean and RI before and after treatment. The findings show the absence of apparent influence of low-dose radiation on the ocular circulation in age-related macular degeneration. (author)

Age-dependent dose coefficients for tritium in Asian populations

Energy Technology Data Exchange (ETDEWEB)

Trivedi, A

1999-10-01

The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10{sup -11} Sv Bq{sup -1} for Asian Man compared to 2.0 x 10{sup -11} Sv Bq{sup -1} for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10{sup -11} Sv Bq{sup -11} compared to 4.6 x 10{sup -11} Sv Bq{sup -1} for Reference Man. (author)

Age-dependent dose coefficients for tritium in Asian populations

International Nuclear Information System (INIS)

Trivedi, A.

1999-10-01

The International Commission on Radiological Protection (ICRP) Publications 56 (1989) and 67 (1993) have prescribed the biokinetic models and age-dependent dose coefficients for tritiated water and organically bound tritium. The dose coefficients are computed from values selected to specify the anatomical, morphological and physiological characteristics of a three-month-old, one-year-old, five-year-old, 10-year-old, 15-year-old and adult (Reference Man) Caucasian living in North America and Western Europe. However, values for Reference Man and other age groups are not directly applicable to Asians, because of differences in race, custom, dietary habits and climatic conditions. An Asian Man model, including five age groups, has been proposed by Tanaka and Kawamura (1996, 1998) for use in internal dosimetry. The basic concept of the ICRP Reference Man and the system describing body composition in ICRP Publication 23 (1975) were used. Reference values for Asians were given for the body weight and height, the mass of soft tissue, the mass of body water and the daily fluid balance, and are used to compute the dose coefficients for tritium. The age-dependent dose coefficients for Asians for tritiated water intakes are smaller by 20 to 30% of the currently prescribed values (Trivedi, 1998). The reduction in the dose coefficient values is caused by the increased daily fluid balance among Asians. The dose coefficient for tritiated water is 1.4 x 10 -11 Sv Bq -1 for Asian Man compared to 2.0 x 10 -11 Sv Bq -1 for Reference Man. The dose coefficients for organically bound tritium are only marginally different from those of the ICRP values. The dose coefficient for organically bound tritium for Asian Man is 4.0 x 10 -11 Sv Bq -11 compared to 4.6 x 10 -11 Sv Bq -1 for Reference Man. (author)

Single toxin dose-response models revisited

Energy Technology Data Exchange (ETDEWEB)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

2017-01-01

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

An automatic dose verification system for adaptive radiotherapy for helical tomotherapy

International Nuclear Information System (INIS)

Mo, Xiaohu; Chen, Mingli; Parnell, Donald; Olivera, Gustavo; Galmarini, Daniel; Lu, Weiguo

2014-01-01

Purpose: During a typical 5-7 week treatment of external beam radiotherapy, there are potential differences between planned patient's anatomy and positioning, such as patient weight loss, or treatment setup. The discrepancies between planned and delivered doses resulting from these differences could be significant, especially in IMRT where dose distributions tightly conforms to target volumes while avoiding organs-at-risk. We developed an automatic system to monitor delivered dose using daily imaging. Methods: For each treatment, a merged image is generated by registering the daily pre-treatment setup image and planning CT using treatment position information extracted from the Tomotherapy archive. The treatment dose is then computed on this merged image using our in-house convolution-superposition based dose calculator implemented on GPU. The deformation field between merged and planning CT is computed using the Morphon algorithm. The planning structures and treatment doses are subsequently warped for analysis and dose accumulation. All results are saved in DICOM format with private tags and organized in a database. Due to the overwhelming amount of information generated, a customizable tolerance system is used to flag potential treatment errors or significant anatomical changes. A web-based system and a DICOM-RT viewer were developed for reporting and reviewing the results. Results: More than 30 patients were analysed retrospectively. Our in-house dose calculator passed 97% gamma test evaluated with 2% dose difference and 2mm distance-to-agreement compared with Tomotherapy calculated dose, which is considered sufficient for adaptive radiotherapy purposes. Evaluation of the deformable registration through visual inspection showed acceptable and consistent results, except for cases with large or unrealistic deformation. Our automatic flagging system was able to catch significant patient setup errors or anatomical changes. Conclusions: We developed an automatic

Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

International Nuclear Information System (INIS)

Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

2015-01-01

Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account

Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: a randomized double-blind study.

Science.gov (United States)

Lundholm, Kent; Gunnebo, Lena; Körner, Ulla; Iresjö, Britt-Marie; Engström, Cecilia; Hyltander, Anders; Smedh, Ulrika; Bosaeus, Ingvar

2010-04-15

The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 microg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 microg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism. (c) 2010 American Cancer Society.

Extended‐Release Once‐Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate‐Release Tofacitinib and Impact of Food

Science.gov (United States)

Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C.

2016-01-01

Abstract Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. An extended‐release (XR) formulation has been designed to provide a once‐daily (QD) dosing option to patients to achieve comparable pharmacokinetic (PK) parameters to the twice‐daily immediate‐release (IR) formulation. We conducted 2 randomized, open‐label, phase 1 studies in healthy volunteers. Study A characterized single‐dose and steady‐state PK of tofacitinib XR 11 mg QD and intended to demonstrate equivalence of exposure under single‐dose and steady‐state conditions to tofacitinib IR 5 mg twice daily. Study B assessed the effect of a high‐fat meal on the bioavailability of tofacitinib from the XR formulation. Safety and tolerability were monitored in both studies. In study A (N = 24), the XR and IR formulations achieved time to maximum plasma concentration at 4 hours and 0.5 hours postdose, respectively; terminal half‐life was 5.9 hours and 3.2 hours, respectively. Area under plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax) after single‐ and multiple‐dose administration were equivalent between the XR and IR formulations. In study B (N = 24), no difference in AUC was observed for fed vs fasted conditions. Cmax increased by 27% under the fed state. On repeat administration, negligible accumulation (Tofacitinib administration as an XR or IR formulation was generally well tolerated in these studies. PMID:26970526

Weekly azathioprine pulse versus daily azathioprine in the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study

Directory of Open Access Journals (Sweden)

Kaushal K Verma

2015-01-01

Full Text Available Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the efficacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92% patients on WAP and 21 (96% on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically significant and comparable (P = 0.366. Patients on WAP had a higher incidence of adverse effects (P = 0.02. Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Pulsed-dosing with oral sodium phenylbutyrate increases hemoglobin F in a patient with sickle cell anemia.

Science.gov (United States)

Hines, Patrick; Dover, George J; Resar, Linda M S

2008-02-01

Increasing hemoglobin F (HbF) appears to be beneficial for patients with sickle cell anemia. We previously demonstrated that daily, oral sodium phenylbutyrate (OSPB) induces HbF synthesis in pediatric and adult patients with hemoglobin SS (HbSS). The high doses and need for daily therapy, however, have limited its use. Here, we report a patient treated with pulsed-dosing of OSPB for over 3 years. This patient developed a modest, but sustained elevation in HbF over the course of therapy without side effects. Although larger studies are needed, this case demonstrates that pulsed-dosing with OSPB enhances HbF synthesis. (c) 2007 Wiley-Liss, Inc.

Computed radiography dose optimization in pediatric patients

International Nuclear Information System (INIS)

Juste, B.; Verdu, G.; Tortosa, R.; Villaescusa, J.I.

2008-01-01

Radiation dose reduction in pediatric X-ray imaging is especially important because of children radiation sensitivity. For any radiographic examination performed at a fixed radiographic tube potential, the patient absorbed dose is directly proportional to the value of milliampere-seconds (mAs) selected by the operator. Nevertheless, reducing X-ray exposure has the unavoidable disadvantage of increasing the quantum noise in the resultant image. The objective of this work is to identify the minimum tube current setting required for maintaining accurate examinations, to modify, if required, the daily protocols applied at La Fe de Valencia Universitary Hospital. To accomplish this goal, a noise addition software has been developed in order to study the diagnostic accuracy as a function of reducing dose by artificially increasing the image noise. The noise addition tool has been applied to several thorax images acquired from pediatric unit to simulate new lower dose radiographies and allow medical researchers to study how lower dose affects the patient pneumonia diagnosis. (author)

SU-F-J-191: Dosimetric Evaluation of a Left Chestwall Patient Treated with a Compact Proton Pencil Beam Gantry Utilizing Daily Setup CBCT

Energy Technology Data Exchange (ETDEWEB)

Maynard, M; Chen, K; Rosen, L; Wu, H [Willis-Knighton Medical Center, Shreveport, LA (United States)

2016-06-15

Purpose: To evaluate the robustness of the gradient technique for treating a multi-isocenter left chest wall patient with a compact proton pencil beam gantry. Both CBCT and stereoscopic imaging are used to facilitate daily treatment setup. Methods: To treat the elongated chest wall planning target volume (PTV) with the compact PBS system, a 28 fraction (5040 CcGE) treatment plan was created using two fields with gradient matching technique. Daily table shifts between treatment field isocenters were obtained from the record and verify system for each treatment fraction. Copies of the initial treatment plan were made for each fraction and the field isocenter coordinates for each plan copy were adjusted to reflect daily table shifts. Doses were re-calculated for each fraction, summed, and compared against the initial plan. Results: The table shifts (average and range) were 2.2 (−5.1–+3.9), 3.0 (−6.0–+4.0) and 3.0 (−10.1–+1.9) millimeters in the anterior-posterior, superior-inferior and right-left directions, respectively. Dose difference to the PTV, heart and ipsilateral lung were evaluated. The percentage of the PTV receiving the prescription dose decreased from 94.6% to 89.1%. The D95 of the PTV increased from 99.6% to 99.9%. The maximum dose in PTV increased from 106.6% to 109.2% and V105 increased from 1.0% to 16.5%. The V20 of the ipsilateral lung increased from 18.5% to 21.0%. The mean heart dose difference was negligible. Conclusion: Observed dose differences to lung and heart tissues due to daily setup variations remained acceptably low while maintaining sufficient dose coverage to the PTV. This initial case study demonstrates the robustness of the gradient technique to treat a large target, multi-isocenter plan with a compact proton pencil beam gantry equipped with CBCT and stereoscopic imaging modalities.

Effect of single dose, fractionated, and hyperfractionated trunk irradiation on weight gain, respiration frequency, and survival in rats

International Nuclear Information System (INIS)

Kimler, B.F.; Giri, P.G.S.; Giri, U.P.; Cox, G.G.

1986-01-01

It is concluded that, in this rat trunk irradiation model, fractionation of a single dose into two equal doses separated by 4-6 h produced a sparing effect of approx. 5Gy as measured by delay in weight gain; approx. 4Gy as measured by increased respiration frequency; and approx. 6Gy as measured by survival. Fractionation into daily doses or hyperfractionation into twice-daily doses permitted an approximate doubling of the dose required for the same suppression of weight gain. For the respiration rates and survival endpoints, fractionation or hyperfractionation produced an even greater sparing effect since there was no increase in the respiration frequency at twice the doses that would produce changes if delivered within a few hours; and since essentially no lethality was observed at twice the doses that would kill 70%-100% of animals if delivered in one day. (UK)

Organ doses and effective doses in some medical and industrial applications

International Nuclear Information System (INIS)

Keshavkumar, Biju

2000-01-01

The ICRP recommends radiation protection standards for the safe use of radiation and also prescribes the radiation protection quantities and periodically reviews them. In this context, the quantities like organ doses and effective doses are defined by ICRP. In this work we calculate these quantities and hence the conversion functions for the industrial radiation sources and those for CT and diagnostic X-ray exposures. Workers who are occupationally exposed to radiation are regularly monitored to evaluate the radiation dose received by them. It is quite possible that in an accident situation, the worker involved in the accident might not have worn a personal monitor, popularly known as the monitoring badge. In addition, even some non radiation workers (who are obviously not monitored) may also have received exposure. Under these circumstances, the persons involved are interviewed, the accident site inspected, and on the basis of realistic assumptions, the likely doses received by the exposed persons are estimated

Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

Directory of Open Access Journals (Sweden)

Laitinen Kirsi

2012-10-01

Full Text Available Abstract Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for

Maternal methadone dosing schedule and fetal neurobehavior

Science.gov (United States)

Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.

2008-01-01

Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. PMID:19085624

From physical dose constraints to equivalent uniform dose constraints in inverse radiotherapy planning

International Nuclear Information System (INIS)

Thieke, Christian; Bortfeld, Thomas; Niemierko, Andrzej; Nill, Simeon

2003-01-01

Optimization algorithms in inverse radiotherapy planning need information about the desired dose distribution. Usually the planner defines physical dose constraints for each structure of the treatment plan, either in form of minimum and maximum doses or as dose-volume constraints. The concept of equivalent uniform dose (EUD) was designed to describe dose distributions with a higher clinical relevance. In this paper, we present a method to consider the EUD as an optimization constraint by using the method of projections onto convex sets (POCS). In each iteration of the optimization loop, for the actual dose distribution of an organ that violates an EUD constraint a new dose distribution is calculated that satisfies the EUD constraint, leading to voxel-based physical dose constraints. The new dose distribution is found by projecting the current one onto the convex set of all dose distributions fulfilling the EUD constraint. The algorithm is easy to integrate into existing inverse planning systems, and it allows the planner to choose between physical and EUD constraints separately for each structure. A clinical case of a head and neck tumor is optimized using three different sets of constraints: physical constraints for all structures, physical constraints for the target and EUD constraints for the organs at risk, and EUD constraints for all structures. The results show that the POCS method converges stable and given EUD constraints are reached closely

Short-term digestive tolerance of different doses of NUTRIOSE FB, a food dextrin, in adult men.

Science.gov (United States)

van den Heuvel, E G H M; Wils, D; Pasman, W J; Bakker, M; Saniez, M-H; Kardinaal, A F M

2004-07-01

To determine the tolerance of increasing dosages of an incompletely hydrolysed and/or incompletely absorbed food dextrin coming from wheat starch, NUTRIOSE FB, at daily levels of 10 and 15 g up to 60 and 80 g, respectively. A randomized, double-blind, multiple dose, placebo-controlled, combined crossover and parallel trial. The metabolic ward of TNO Nutrition and Food Research. A total of 20 healthy men (age 31.7 +/- 9.1 y; BMI 24.5 +/- 2.9 kg/m2). One group of 10 subjects consumed on top of their diet 10, 30 and 60 g of NUTRIOSE FB or maltodextrin (placebo) daily. The other group of 10 subjects consumed 15, 45 and 80 g daily. Each dose was consumed for 7 days. Compared with placebo, flatulence occurred more frequently over the last 6 days on 30, 60 or 80 g/day of NUTRIOSE FB (P FB, the frequency of flatulence was even higher (P FB, the frequency of defecation decreased (P FB (P FB resulted in diarrhoea. Compared to baseline levels, breath H2 excretion, which was only measured after a week with 10 and 15 g of NUTRIOSE FB daily, increased (P FB is a fermentable carbohydrate and is well tolerated up to a dose of 45 g daily. Higher daily dosages (60 and 80 g) may result in flatulence, but does not result in diarrhoea. TNO Nutrition and Food Research was assigned by Roquette Frères to perform the study.

Amikacin Dosing and Monitoring in Spinal Cord Injury Patients: Variation in Clinical Practice Between Spinal Injury Units and Differences in Experts' Recommendations

Directory of Open Access Journals (Sweden)

Subramanian Vaidyanathan

2006-01-01

Full Text Available The objective of this article was to determine the current practice on amikacin dosing and monitoring in spinal cord injury patients from spinal cord physicians and experts. Physicians from spinal units and clinical pharmacologists were asked to provide protocol for dosing and monitoring of amikacin therapy in spinal cord injury patients. In a spinal unit in Poland, amikacin is administered usually 0.5 g twice daily. A once-daily regimen of amikacin is never used and amikacin concentrations are not determined. In Belgium, Southport (U.K., Spain, and the VA McGuire Medical Center (Richmond, Virginia, amikacin is given once daily. Whereas peak and trough concentrations are determined in Belgium, only trough concentration is measured in Southport. In both these spinal units, modification of the dose is not routinely done with a nomogram. In Spain and the VA McGuire Medical Center, monitoring of serum amikacin concentration is not done unless a patient has renal impairment. In contrast, the dose/interval of amikacin is adjusted according to pharmacokinetic parameters at the Edward Hines VA Hospital (Hines, Illinois, where amikacin is administered q24h or q48h, depending on creatinine clearance. Spinal cord physicians from Denmark, Germany, and the Kessler Institute for Rehabilitation (West Orange, New Jersey state that they do not use amikacin in spinal injury patients. An expert from Canada does not recommend determining serum concentrations of amikacin, but emphasizes the value of monitoring ototoxicity and nephrotoxicity. Experts from New Zealand recommend amikacin in conventional twice- or thrice-daily dosing because of the theoretical increased risk of neuromuscular blockade and apnea with larger daily doses in spinal cord injury patients. On the contrary, experts from Greece, Israel, and the U.S. recommend once-daily dosing and determining amikacin pharmacokinetic parameters for each patient. As there is considerable variation in clinical

Mutation process at low or high radiation doses

International Nuclear Information System (INIS)

Abrahamson, S.; Wisconsin Univ., Madison

1976-01-01

A concise review is given of the status of research on the genetic effects of low-level radiation in general. The term ''low dose'' is defined and current theories on low dose are set out. Problems and their solutions are discussed. (author)

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...

Calculation methods for determining dose equivalent

International Nuclear Information System (INIS)

Endres, G.W.R.; Tanner, J.E.; Scherpelz, R.I.; Hadlock, D.E.

1987-11-01

A series of calculations of neutron fluence as a function of energy in an anthropomorphic phantom was performed to develop a system for determining effective dose equivalent for external radiation sources. Critical organ dose equivalents are calculated and effective dose equivalents are determined using ICRP-26 [1] methods. Quality factors based on both present definitions and ICRP-40 definitions are used in the analysis. The results of these calculations are presented and discussed. The effective dose equivalent determined using ICRP-26 methods is significantly smaller than the dose equivalent determined by traditional methods. No existing personnel dosimeter or health physics instrument can determine effective dose equivalent. At the present time, the conversion of dosimeter response to dose equivalent is based on calculations for maximal or ''cap'' values using homogeneous spherical or cylindrical phantoms. The evaluated dose equivalent is, therefore, a poor approximation of the effective dose equivalent as defined by ICRP Publication 26. 3 refs., 2 figs., 1 tab

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

Science.gov (United States)

Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

2011-08-01

Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Contents and daily intakes of gamma-ray emitting nuclides, 90Sr, and 238U using market-basket studies in japan

International Nuclear Information System (INIS)

Sugiyama, Hideo; Terada, Hiroshi; Takahashi, Mitsuko; Iijima, Ikuyo; Isomura, Kimio

2007-01-01

To investigate the contents of radionuclides in foods marketed in Japan and their daily intakes and exposure doses in adults, we performed market-basket studies concerning radionuclide intakes. The study period was 2003-2005, and the studies were performed in 13 cities in Japan. Foods including drinking water were divided into 14 food groups, and samples were prepared by common cooking procedures. γ-ray emitting nuclides (an artificial radionuclide, radioactive Cs, and natural radionuclides, 40 K and U series such as 214 Bi, and 212 Pb, and Th series) were measured in each food group, and artificial radionuclides, 90 Sr and 238 U, were measured in a mixed sample of 13 food groups excluding drinking water. The daily intakes in adults were calculated from the concentrations of the radionuclides and mean daily consumption of foods and drinking water. The daily 137 Cs and 40 K intakes (mBq/person · day) in the 13 cities were 12.5- 90 Sr intake from the food groups excluding drinking water was 20.8-53.6, with a mean of 39.2 (mBq/person · day) (deviation of the mean: 23%). Similarly, the daily 238 U intake was 5.9-31.1, with a mean of 12.6 (mBq/person · day) (deviation: 60%), showing a more than 5-fold difference between the minimum and maximum values, and there were regional differences. Since the contents of the U series, such as 214 Bi and 212 Pb, and Th series were lower than the lower detection limits in many samples, their daily intakes were not calculated. Regarding the daily intake of 137 Cs from each food group, the intakes from fish and shellfish, milk, meat/eggs, and mushrooms/seaweed tended to be higher. The daily 40 K intake from each food group varied among the areas, but the total intake from the 14 food groups was similar in all 13 cities. 40 K from these foods accounted for most of the annual effective dose (μSv/person · year) of γ-ray emitting nuclides, and the doses of 40 K, 90 Sr, and 238 U were 130-217, 0.21-0.55, and 0.10-0.51, respectively

Temozolomide during radiotherapy of glioblastoma multiforme. Daily administration improves survival

Energy Technology Data Exchange (ETDEWEB)

Nachbichler, Silke Birgit; Schupp, Gabi; Ballhausen, Hendrik; Niyazi, Maximilian; Belka, Claus [LMU Munich, Department of Radiation Oncology, Munich (Germany)

2017-11-15

Temozolomide-(TMZ)-based chemoradiotherapy defines the current gold standard for the treatment of newly diagnosed glioblastoma. Data regarding the influence of TMZ dose density during chemoradiotherapy are currently not available. We retrospectively compared outcomes in patients receiving no TMZ, TMZ during radiotherapy on radiotherapy days only, and TMZ constantly 7 days a week. From 2002-2012, a total of 432 patients with newly diagnosed glioblastoma received radiotherapy in our department: 118 patients had radiotherapy alone, 210 had chemoradiotherapy with TMZ (75 mg/m{sup 2}) daily (7/7), and 104 with TMZ only on radiotherapy days (5/7). Radiotherapy was applied to a total dose of 60 Gy. Median survival after radiotherapy alone was 9.1 months, compared to 12.6 months with 5/7-TMZ and to 15.7 months with 7/7-TMZ. The 1-year survival rates were 33, 52, and 64%, respectively. Kaplan-Meier analysis showed a significant improvement of TMZ-7/7 vs. 5/7 (p = 0.01 by the log-rank test), while 5/7-TMZ was still superior to no TMZ at all (p = 0.02). Multivariate Cox regression showed a significant influence of TMZ regimen (p = 0.009) on hazard rate (+58% between groups) even in the presence of confounding factors age, sex, resection status, and radiotherapy dose concept. Our results confirm the findings of the EORTC/NCIC trial. It seems that also a reduced TMZ scheme can at first prolong the survival of glioblastoma patients, but not as much as the daily administration. (orig.) [German] Eine Temozolomid-(TMZ-)basierte Radiochemotherapie ist der gegenwaertige Goldstandard in der Behandlung von neu diagnostizierten Glioblastomen. Daten bezueglich des Einflusses der TMZ-Dosisdichte waehrend der Radiochemotherapie sind derzeit nicht vorhanden. Wir haben retrospektiv die Ergebnisse von Patienten verglichen, die entweder kein TMZ, TMZ zur Strahlentherapie nur an Bestrahlungstagen oder TMZ konstant 7 Tage/Woche erhalten hatten. Von 2002-2012 bekamen insgesamt 432 Patienten mit

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

Science.gov (United States)

Ranganath, Lakshminarayan R; Milan, Anna M; Hughes, Andrew T; Dutton, John J; Fitzgerald, Richard; Briggs, Michael C; Bygott, Helen; Psarelli, Eftychia E; Cox, Trevor F; Gallagher, James A; Jarvis, Jonathan C; van Kan, Christa; Hall, Anthony K; Laan, Dinny; Olsson, Birgitta; Szamosi, Johan; Rudebeck, Mattias; Kullenberg, Torbjörn; Cronlund, Arvid; Svensson, Lennart; Junestrand, Carin; Ayoob, Hana; Timmis, Oliver G; Sireau, Nicolas; Le Quan Sang, Kim-Hanh; Genovese, Federica; Braconi, Daniela; Santucci, Annalisa; Nemethova, Martina; Zatkova, Andrea; McCaffrey, Judith; Christensen, Peter; Ross, Gordon; Imrich, Richard; Rovensky, Jozef

2016-02-01

Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463. 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/

A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose.

Science.gov (United States)

Ero, Michael Penfield; Ng, Connie M; Mihailovski, Tamara; Harvey, Nathaniel R; Lewis, Brad Howard

2013-01-01

Nattokinase is a serine protease and is derived from natto, a traditional Japanese, fermented, soybean food meal. Multiple authors have described the significant fibrinolytic, antithrombotic, and antihypertensive effects of natto. Nattokinase has been growing in popularity for use as a dietary supplement for the benefit of cardiovascular health. Little is known regarding the pharmacokinetic and pharmacodynamic properties of this enzyme, and the bioavailability of nattokinase is currently unknown. This study intended to (1) detect nattokinase directly and immunologically, (2) show that nattokinase and/or its metabolites were detectable in human blood following ingestion of a commercial preparation, and (3) chart a pharmacokinetic dosing effect for nattokinase. The research team designed the pilot study as an in vivo, human clinical trial. Healthy human subjects responded to an advertisement and were screened. Subjects who satisfied both inclusion and exclusion criteria were enrolled into the study. Subjects were then instructed to orally ingest a single capsule containing a known concentration of nattokinase immediately following a baseline blood draw. Subsequent blood draws occurred over a 24-h period. This study was conducted in Oakland, California, at a clinical reference laboratory and was performed with the approval of an institutional review board (IRB) to ensure that appropriate ethical standards were met. Eleven healthy participants (five male, six female, ages 21-65), who met eligibility criteria, were enrolled. Administration of nattokinase occurred orally with the ingestion of a single daily dose (2000 FU) of nattokinase. Capsules, each containing approximately 100 mg of nattokinase, in softgel form (NSK-SD, Japan Bio Science Laboratory, Osaka, Japan), were used in the study. Baseline blood samples were collected, and participants were observed swallowing a single capsule of the nattokinase supplement before returning at 2, 4, 8, 12, 24, and 48 h post

Evaluation of the influence of weather conditions on external dose rate

International Nuclear Information System (INIS)

Knight, A.

1993-01-01

Six time periods in 1989/90, when there were high gamma ray dose rate readings at three or more RIMNET Phase 1 sites, were selected for detailed study. The high dose rates were compared with meteorological data (rainfall, temperatures, windspeeds and atmospheric pressure) at the sites for the time periods studied. The results using daily and hourly data clearly show a correlation between gamma ray dose rate and rainfall but not with the other meteorological parameters studied. The increase in dose rate with increased rainfall is believed to be due to radon decay products being washed down with heavy rain. (author)

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

Directory of Open Access Journals (Sweden)

Ning Ma

Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Contribution of time-activity pattern and microenvironment to black carbon (BC) inhalation exposure and potential internal dose among elementary school children

Science.gov (United States)

Jeong, Hyeran; Park, Donguk

2017-09-01

The aims of this study were to quantify the contributions of activities or microenvironments (MEs) to daily total exposure to and potential dose of black carbon (BC). Daily BC exposures (24-h) were monitored using a micro-aethalometer micoAeth AE51 with forty school-aged children living in an urban area in Korea from August 2015 to January 2016. The children's time-activity patterns and the MEs they visited were investigated by means of a time-activity diary (TAD) and follow-up interviews with the children and their parents. Potential inhaled dose was estimated by multiplying the airborne BC concentrations (μg/m3) we monitored for the time the children spent in a particular ME by the inhalation rate (IR, m3/h) for the time-activity performed. The contribution of activities and MEs to overall daily exposure to and potential dose of BC was quantified. Overall mean daily potential dose was equal to 24.1 ± 10.6 μg/day (range: 6.6-46.3 μg/day). The largest contribution to BC exposure and potential dose (51.9% and 41.7% respectively) occurred in the home thanks to the large amount of time spent there. Transportation was where children received the most intense exposure to (14.8%) and potential dose (20.2%) of BC, while it accounted for 7.6% of daily time. School on weekdays during the semester was responsible for 20.3% of exposure and 22.5% of potential dose. Contribution to BC exposure and potential dose was altered by several time-activity parameters, such as type of day (weekdays vs. weekends; school days vs. holidays), season, and gender. Traveling by motor vehicle and subway showed more elevated exposure or potential dose intensity on weekdays or school days, probably influenced by the increased surrounding traffic volumes on these days compared to on weekends or holidays. This study may be used to prioritize targets for minimizing children's exposure to BC and to indicate outcomes of BC control strategies.

Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

Science.gov (United States)

Sacristán, J A; Gómez, J C; Montejo, A L; Vieta, E; Gregor, K J

2000-05-01

The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

Evaluation of the dose uniformity for double-plane high dose rate interstitial breast implants with the use of dose reference points and dose non-uniformity ratio

International Nuclear Information System (INIS)

MAjor, T.; Polgar, C.; Somogyi, A.; Nemeth, G.

2000-01-01

This study investigated the influence of dwell time optimizations on dose uniformity characterized by dose values in dose points and dose non-uniformity ratio (DNR) and analyzed which implant parameters have influence on the DNR. Double-plane breast implants with catheters arranged in triangular pattern were used for the calculations. At a typical breast implant, dose values in dose reference points inside the target volume and volumes enclosed by given isodose surfaces were calculated and compared for non-optimized and optimized implants. The same 6-cm treatment length was used for the comparisons. Using different optimizations plots of dose non-uniformity ratio as a function of catheter separation, source step size, number of catheters, length of active sections were drawn and the minimum DNR values were determined. Optimization resulted in less variation in dose values over dose points through the whole volume and in the central plane only compared to the non-optimized case. At implant configurations consisting of seven catheters with 15-mm separation, 5-mm source step size and various active lengths adapted according to the type of optimization, the no optimization, geometrical (volume mode) and dose point (on dose points and geometry) optimization resulted in similar treatment volumes, but an increased high dose volume was observed due to the optimization. The dose non-uniformity ratio always had the minimum at average dose over dose normalization points, defined in the midpoints between the catheters through the implant volume. The minimum value of DNR depended on catheter separation, source step size, active length and number of catheters. The optimization had only a small influence on DNR. In addition to the reference points in the central plane only, dose points positioned in the whole implant volume can be used for evaluating the dose uniformity of interstitial implants. The dose optimization increases not only the dose uniformity within the implant but

A RCT Comparing Daily Mindfulness Meditations, Biofeedback Exercises, and Daily Physical Exercise on Attention Control, Executive Functioning, Mindful Awareness, Self-Compassion, and Worrying in Stressed Young Adults.

Science.gov (United States)

de Bruin, Esther I; van der Zwan, J Esi; Bögels, Susan M

2016-01-01

Our Western society is characterized by multitasking, competition, and constant time pressure. Negative effects of stress for the individual (anxiety, depression, somatic complaints) and for organizations and society (costs due to work absence) are very high. Thus, time-efficient self-help interventions to address these issues are necessary. This study assessed the effects of daily mindfulness meditations (MM) versus daily heart rate variability biofeedback (HRV-BF) and daily physical exercise (PE) on attention control, executive functioning, mindful awareness, self-compassion, and worrying. Young adults ( n  = 75, age range 18 to 40) with elevated stress levels were randomized to MM, HRV-BF, or PE, and measurements were taken at pre-test, post-test, and follow-up. Interventions in all three groups were self-guided and lasted for 5 weeks. Generalized estimating equation analyses showed that overall, all three interventions were effective and did not differ from each other. However, practice time differed between groups, with participants in the PE group practicing much more than participants in the other two groups. Therefore, additional analyses were carried out in two subsamples. The optimal dose sample included only those participants who practiced for at least 70 % of the total prescribed time. In the equal dose sample, home practice intensity was equal for all three groups. Again, the effects of the three interventions did not differ. In conclusion, MM, HRV-BF, and PE are all effective self-help methods to improve attention control, executive functioning, mindful awareness, self-compassion, and worrying, and mindfulness meditation was not found to be more effective than HRV-biofeedback or physical exercise for these cognitive processes.

Daily transactional and transformational leadership and daily employee engament

NARCIS (Netherlands)

Breevaart, K.; Bakker, A.B.; Hetland, Jorn; Demerouti, E.; Olsen, O.K.; Espevik, R.

2014-01-01

This diary study adds to the leadership literature by examining the daily influence of transformational leadership, contingent reward, and active management-by-exception (MBE active) on followers' daily work engagement. We compare the unique contribution of these leadership behaviours and focus on

SU-F-J-221: Adjusted Dose and Its Relation to Radiation Induced Liver Disease During Hepatocellular Carcinoma Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Huang, P; Gang, Y; Qin, S; Li, D [Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University (China); Li, H; Chen, J; Ma, C; Yin, Y [Department of Radiation Oncology, Shandong Cancer Hospital and Institute (China)

2016-06-15

Purpose: Many patients with hepatocellular carcinoma (HCC) had hepatic anatomy variations as a result of inter-fraction deformation during fractionated radiotherapy, which may result in difference from the planned dose. This study aimed to investigate the relationship between adjusted dose and radiation induced liver disease (RILD) in HCC patients receiving three dimensional conformal radiotherapy (3DCRT). Methods: Twenty-three HCC patients received conventional fractionated 3DCRT were enrolled in this retrospective investigation. Among them, seven patients had been diagnosed of RILD post-radiotherapy, including 4 cases of grade 2, 3 cases of grade 3 according to the CTCAE Version 3.0. Daily cone-beam CT (CBCT) scans were acquired throughout the whole treatment course for each patient. To reconstruct the daily dose to a patient considering the interfraction anatomy variations, the planned beams from each patient’s treatment plan were firstly applied to each daily modified CBCT (mCBCT). The daily doses were then summed together with the help of deformable image registration (DIR) to obtain the adjusted dose (Dadjusted) of the patient. Finally, the dose changes in normal liver between planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40 and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Results: Among the twenty-three patients, the adjusted liver V20, V30, V40 and MDTNL showed significant changes from the planned ones (p<0.05) and averagely increased by 4.1%, 4.7%, 4.5% and 3.9Gy, respectively. And the adjusted liver dose in twenty-one patients (91%) were higher than planned value, the adjusted dose of patients with RILD (6/7) exceeds to the hepatic radiation tolerance. Conclusion: The adjusted dose of all the studied patients significantly differs from planned dose, and mCBCT-based dose reconstruction can aid in evaluating the robustness of the planning solutions, and adjusted dose

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

TU-PIS-Exhibit Hall-01: CT Dose Optimization Technologies II

International Nuclear Information System (INIS)

Driesser, I; Angel, E

2014-01-01

Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The imaging topic this year is CT scanner dose optimization capabilities. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Siemens‘ Commitment to the Right Dose in Computed Tomography Presentation Time: 11:15 - 11:45 AM Providing sustainable clinical results at highest patient safety: This is the challenge in medical imaging. Especially for Computed Tomography this means applying not simply the lowest, but the right dose for sound diagnostic imaging. Consequently, Siemens is committed to deliver the right dose in CT. In order to reduce radiation to the right dose, the first step is to provide the right dose technology. Through decades of research and development in CT imaging, Siemens CT has constantly introduced new ideas leading to a comprehensive portfolio of unique CARE technologies to deliver the right dose. For example automated kV adjustment based on patient size and the clinical question with CARE kV and three generations of iterative reconstruction. Based on the right dose technology, the next step is to actually scan at the right dose. For this, it is key to know the right dose targets for every examination. Siemens continuously involves CT experts to push developments further and outline how users can best adapt their procedures to the right dose. For users to know whether they met the right dose targets, it is therefore important to understand and monitor the actual absolute dose values. All scanners are delivered with defined default protocols which automatically use the available right dose technologies. Finally, to deliver the right dose not just in singular cases, but ideally to patients everywhere, organizations need then to manage dose across

Pharmacokinetics of a once-daily extended-release formulation of pramipexole in healthy male volunteers: three studies.

Science.gov (United States)

Jenner, Peter; Könen-Bergmann, Michael; Schepers, Cornelia; Haertter, Sebastian

2009-11-01

Pramipexole is a dopamine agonist used in the treatment of Parkinson's disease. The currently available immediate-release (IR) formulation is taken orally 3 times daily. These studies were conducted to evaluate the pharmacokinetic properties of a variety of prototypes for a once-daily extended-release (ER) formulation of pramipexole and to further characterize the prototype whose pharmacokinetics best matched those of the IR formulation. Three Phase I studies were conducted, all in healthy adult men aged food effect. In the third study, steady-state pharmacokinetics of the optimal ER formulation were assessed across a range of pramipexole doses (0.375-4.5 mg/d), including investigation of the food effect at steady state for the highest dose. Tolerability was assessed throughout all studies based on physical examinations, laboratory measurements, and adverse events (AEs). The 3 studies included 18, 15, and 39 subjects, respectively. Among the ER prototypes tested at 0.75 mg once daily in study 1, a matrix tablet had the optimal pharmacokinetic resemblance to IR pramipexole 0.25 mg TID, with a geometric mean AUC(0-24h,ss) of 17.4 ng.h/mL (vs 16.0 ng.h/mL for the IR formulation), C(max,ss) of 0.967 ng/mL (vs 1.09 ng/mL), and C(min,ss) of 0.455 ng/mL (vs 0.383 ng/mL). For single-dose ER 0.375 mg administered in the fasted state in study 2, in vivo bioavailability was predictable from in vitro dissolution data, with internal mean absolute percent prediction errors of 3.18% for AUC(0-30h) and 4.87% for C(max), and external mean absolute prediction errors of 6.61% and 3.34%, respectively, satisfying current guidelines for a level A IVIVC. For single-dose ER 0.375 mg administered in the fed state, the upper bound of the 90% CI for fed:fasted values was 119.8 for AUC(0-30h) (within the bioequivalence limits of 80%-125%) and 134.1 for C(max). At steady state in study 3 (subjects' 5th treatment day), dosing at 0.375 to 4.5 mg in the fasted state was associated with a linear

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC.

Science.gov (United States)

Karschner, Erin L; Schwope, David M; Schwilke, Eugene W; Goodwin, Robert S; Kelly, Deanna L; Gorelick, David A; Huestis, Marilyn A

2012-10-01

Determining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. Ten male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40-120 mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography-mass spectrometry. Maximum whole blood THC occurred 3.0 h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1-5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. Predictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily. Published by Elsevier Ireland Ltd.