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.

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

Equivalence of a single dose (1200 mg) compared to a three-time a day dose (400 mg) of chondroitin 4&6 sulfate in patients with knee osteoarthritis. Results of a randomized double blind placebo controlled study.

Science.gov (United States)

Zegels, B; Crozes, P; Uebelhart, D; Bruyère, O; Reginster, J Y

2013-01-01

Evaluation of the efficacy and safety of a single oral dose of a 1200 mg sachet of chondroitin 4&6 sulfate (CS 1200) vs three daily capsules of chondroitin 4&6 sulfate 400 mg (CS 3*400) (equivalence study) and vs placebo (superiority study) during 3 months, in patients with knee osteoarthritis (OA). Comparative, double-blind, randomized, multicenter study, including 353 patients of both genders over 45 years with knee OA. Minimum inclusion criteria were a Lequesne index (LI) ≥ 7 and pain ≥ 40 mm on a visual analogue scale (VAS). LI and VAS were assessed at baseline and after 1-3 months. Equivalence between CS was tested using the per-protocol procedure and superiority of CS vs placebo was tested using an intent-to-treat procedure. After 3 months of follow-up, no significant difference was demonstrated between the oral daily single dose of CS 1200 formulation and the three daily capsules of CS 400. Patients treated with CS 1200 or CS 3*400 were significantly improved compared to placebo after 3 months of follow-up in terms of LI (security and tolerability was observed between the three groups. This study suggests that a daily administration of an oral sachet of 1200 mg of chondroitin 4&6 sulfate allows a significant clinical improvement compared to a placebo, and a similar improvement when compared to a regimen of three daily capsules of 400 mg of the same active ingredient. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study

DEFF Research Database (Denmark)

Baccarani, Michele; Rosti, Gianantonio; Castagnetti, Fausto

2009-01-01

Imatinib mesylate (IM), 400 mg daily, is the standard treatment of Philadelphia-positive (Ph(+)) chronic myeloid leukemia (CML). Preclinical data and results of single-arm studies raised the suggestion that better results could be achieved with a higher dose. To investigate whether the systematic...

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.

[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.

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.

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)

Bioequivalence of a single 400-mg dose of imatinib 100-mg oral tablets and a 400-mg tablet in healthy adult Korean volunteers.

Science.gov (United States)

Lee, Hae Won; Seong, Sook Jin; Park, Sung Min; Lee, Joomi; Gwon, Mi-Ri; Kim, Hyun-Ju; Lim, Sung Mook; Lim, Mi-Sun; Kim, Woomi; Yang, Dong Heon; Yoon, Young-Ran

2015-06-01

Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. A new once-daily 400-mg film-coated tablet of imatinib has been developed by a pharmaceutical company in Korea. The present study was designed to assess and compare the PK parameters, bioavailability, and bioequivalence of the new imatinib 400-mg formulation (test) versus the conventional 100-mg formulation (reference) administered as a single 400-mg dose in healthy adult male volunteers. This randomized, open-label, single-dose, two-way crossover study was conducted in healthy Korean male volunteers. Eligible subjects were randomly assigned in a 1 : 1 ratio to receive 400 mg of the test (one 400-mg tablet) or reference (four 100-mg tablets) formulation, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hours after administration. Plasma imatinib concentrations were determined using liquid chromatography coupled with tandem mass spectrometry. The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) of the adjusted geometric mean ratios for Cmax, AUC(0-t), and AUC(0-∞)ž were within the predetermined range of 0.80 - 1.25. In total, 35 subjects completed the study. No serious adverse event was reported during the study. The 90% CIs of the adjusted geometric mean ratios of the test formulation to the reference formulation for C(max), AUC(0-t) and AUC(0-∞)ž of imatinib were all within the bioequivalence criteria range of 0.8 - 1.25. The test formulation of imatinib met the Korean regulatory requirements for bioequivalence. Both imatinib formulations were well-tolerated in all subjects.

High daily doses of benzodiazepines among Quebec seniors: prevalence and correlates

Directory of Open Access Journals (Sweden)

Moride Yola

2001-11-01

Full Text Available Abstract Background Use of high daily doses of benzodiazepines is generally contraindicated for seniors. While both patient and physician factors may influence the use of high daily doses, previous research on the effect of patient factors has been extremely limited. The objectives of this study were to determine the one year prevalence of use of high daily doses of benzodiazepines, and examine physician and patient correlates of such use among Quebec community-dwelling seniors. Methods Patient information for 1423 community-dwelling Quebec seniors who participated in the Canadian Study of Health and Aging was linked to provincial health insurance administrative data bases containing detailed information on prescriptions received and prescribers. Results The standardized one year period prevalence of use of high daily doses of benzodiazepines was 7.9%. Use of high daily doses was more frequent among younger seniors and those who had reported anxiety during the previous year. Patients without cognitive impairment were more likely to receive high dose prescriptions from general practitioners, while those with cognitive impairment were more likely to receive high dose prescriptions from specialists. Conclusion High dose prescribing appears to be related to both patient and physician factors.

The comparison of the effects of standard 20 mg atorvastatin daily and 20 mg atorvastatin every other day on serum LDL-cholesterol and high sensitive C-reactive protein levels.

Science.gov (United States)

Keleş, Telat; Akar Bayram, Nihal; Kayhan, Tuğba; Canbay, Alper; Sahin, Deniz; Durmaz, Tahir; Ozdemir, Ozcan; Aydoğdu, Sinan; Diker, Erdem

2008-12-01

In this study, we aimed at comparing the effects of standard once daily 20 mg atorvastatin treatment with that of atorvastatin 20 mg administered every other day on serum lipids and high sensitive C-reactive protein (hs-CRP) levels. Sixty-one patients with serum total cholesterol levels of above 200 mg/dl and low density lipoprotein (LDL)--cholesterol levels of above 130 mg/dl were included in this prospective, randomized study. The patients were randomized into daily treatment of 20 mg atorvastatin (standard treatment) and 20 mg atorvastatin every other day (every other day treatment) groups. Before the treatment and at each visit, serum lipids and hs-CRP levels of all the patients were measured. Statistical analyses were performed Chi-square, unpaired t and two-way repeated measurements ANOVA tests. In the every other day treatment group, there was a 36.1% reduction in LDL-cholesterol levels by the end of first month (p0.05). The LDL cholesterol levels of the group receiving 20 mg atorvastatin every day was reduced by %41 by the end of 1 month (pevery other day, there was a 21% decrease in hs-CRP levels compared to the basal measurements at the end of first month (pevery day the decrease in hs-CRP levels at the end of one month was more striking (37%, p0.05). Alternate-day dosing of atorvastatin causes a significant lipid-lowering and antiinflammatory effects similar to that of daily administration and yet may provide some cost savings.

Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
.

Science.gov (United States)

Meeves, Suzanne; Leyva, Rina; Richardson, Clark; Wilson, Brenda; Savastano, David M

2017-07-01

Evaluate adherence of US consumers to proposed label directions for a new 400 mg ibuprofen formulation. In this single-arm, open-label, multicenter, 30-day study simulating an over-the-counter (OTC)-like environment, US analgesic consumers reviewed proposed product packaging for a new 400 mg ibuprofen formulation and made a purchase decision. Purchasers used the product as needed and recorded use over 30 days. Outcomes included the percentage of participants who exhibited correct or acceptable product use for the primary endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to the labeled dosing interval of 6 - 8 hours. Primary endpoint success was met if the lower bound of the 95% confidence interval (CI) was ≥ 85%. Of 685 purchasers providing use data, correct or acceptable use behavior occurred in 95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI: 81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%). Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~ 82% re-dosed between the 4- and 6-hour time intervals. Adverse events were consistent with prior ibuprofen 200 mg experience. This study provides evidence that a majority of US consumers would be able to use OTC ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse rates were low and unlikely to generate an excess risk of clinically important adverse events.
.

Pathological consequences of chronic low daily dose gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Seed, T.M.; Miller, A.C.; Ramakrishnan, N. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States); Fritz, T.E.

2000-07-01

The quantitative relationships between the chronic radiation exposure parameters of dose-rate and total dose in relation to associated health risks was examined in dogs. At a dose-rate of 75, 128, and 263 mGy/d the incidence of acute lymphohematopoietic suppression (aplastic anemia) and associated septic complications was 73%, 87%, and 100%, respectively, and it increased in dose-dependent manner. By contrast, at dose-rates below 75 mGy/d, late cancers contributed significantly to the death of relatively long-lived animals, whose mean survival time was 1800 days. Myeloproliferative disease (MPD), mainly myeloid leukemia, was the dominant pathology seen at the higher daily dose-rates (18.8-75 mGy/d). When daily exposure was carried out continuously, the incidence of MPD was quite high. It should be noted that the induction radiation-induced MPD in this study was highly significant, because spontaneous MPD is exceedingly rare in the dog. However, when the daily dose-rate was reduced further or exposure was discontinued, the incidence of MPD declined significantly. At these lower dose-rates, solid tumors contributed heavily to the life-shortening effects of chronic irradiation. The induction and progression of these survival-compromising, late forms of pathology appeared to be driven by the degree of hematopoietic suppression that occurred early during the exposure phase, and in turn by the capacity of hematopoietic system to repair itself, recover, and to accommodate under chronic radiation stress. (K.H.)

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...

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

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.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

Science.gov (United States)

Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

2015-06-01

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

Directory of Open Access Journals (Sweden)

André Daher

2015-06-01

Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Daily fraction dose recalculation based on rigid registration using Cone Beam CT

Directory of Open Access Journals (Sweden)

Courtney Bosse

2014-03-01

Full Text Available Purpose: To calculate the daily fraction dose for CBCT recalculations based on rigid registration and compare it to the planned CT doses.Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. Pinnacle was used to re-contour the regions of interest (ROI for the specific CBCT by copying the contours from the original CT plan, planned by the prescribing physician, onto each daily CBCT and then manually reshaping contours to match the ROIs. A new plan is then created with the re-contoured CBCT as primary image in order to calculate the daily dose delivered to each ROI. The DVH values are then exported into Excel and overlaid onto the original CT DVH to produce a graph.Results: For the SBRT lung patients, we found that there were small daily volume changes in the lungs, trachea and esophagus. For almost all regions of interest we found that the dose received each day was less than the predicted dose of the planned CT while the PTV dose was relatively the same each day. The results for the prostate patients were similar, showing slight differences in the DVH values for different days in the rectum and bladder but similar PTV.Conclusion: By comparing daily fraction dose between the re-contoured CBCT images and the original planned CT show that PTV coverage for both prostate and SBRT, it has been shown that for PTV coverage, a planned CT is adequate. However, there are differences between the dose for the organs surrounding the PTV. The dose difference is less than the planned in most instances.-----------------------Cite this article as: Bosse C, Tuohy R, Mavroidis P, Shi Z, Crownover R, Gutierrez A, Papanikolaou N, Stathakis S. Daily fraction dose recalculation based on rigid registration using Cone Beam CT. Int J Cancer Ther Oncol 2014; 2(2:020217. DOI: 10.14319/ijcto.0202.17

Clinical efficacy of levofloxacin 500 mg once daily for 7 days for patients with non-gonococcal urethritis.

Science.gov (United States)

Takahashi, Satoshi; Ichihara, Kohji; Hashimoto, Jiro; Kurimura, Yuichiro; Iwasawa, Akihiko; Hayashi, Kenji; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Satoh, Takashi; Tsukamoto, Taiji

2011-06-01

To confirm the efficacy of the treatment regimen with oral levofloxacin (LVFX) 500 mg once daily for 7 days for patients with non-gonococcal urethritis (NGU), we evaluated the microbiological and clinical outcomes of the regimen in those patients. We finally evaluated 53 patients with symptomatic NGU and 5 patients with asymptomatic NGU. As a result of microbiological examinations, 19 of the symptomatic patients were diagnosed as having non-gonococcal chlamydial urethritis (NGCU); 13 had non-gonococcal non-chlamydial urethritis (NGNCU), and 21 had urethritis without any microbial detection. Five of the asymptomatic patients were diagnosed as having NGCU. Microbiological cure was achieved in 91% of the 32 patients with symptomatic NGU and in 80% of the 5 patients with asymptomatic NGCU. Clinical cure was obtained in 92% of the 53 patients with symptomatic NGU. The microbiological eradication rate for Chlamydia trachomatis was 92% in 24 patients. As for other organisms, the microbiological eradication rate for Mycoplasma genitalium was 60% in 5 patients and that for Ureaplasma urealyticum was 100% in 10. The microbiological and clinical efficacy of oral LVFX 500 mg once daily for 7 days for the patients with NGU was the same for the azithromycin (AZM) 1,000 mg single dose that we previously reported. The eradication rates of C. trachomatis and U. urealyticum in the treatment regimen with LVFX 500 mg were high enough in the clinical setting; however, for M. genitalium, the rate was relatively inferior to that with AZM.

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.

Steady-State pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol) in healthy human subjects.

Science.gov (United States)

la Porte, Charles; Voduc, Nha; Zhang, Guijun; Seguin, Isabelle; Tardiff, Danielle; Singhal, Neera; Cameron, D William

2010-07-01

Trans-resveratrol is a polyphenol, which is found in red wine and has cancer chemo-preventive properties and disease-preventive properties. The pharmacokinetics of trans-resveratrol have been investigated in single-dose studies and in studies with relatively low dosages. The present study aimed to investigate the steady-state pharmacokinetics and tolerability of trans-resveratrol 2000 mg twice daily with food, quercetin and alcohol (ethanol). This was a two-period, open-label, single-arm, within-subject control study in eight healthy subjects. The steady-state 12-hour pharmacokinetics of trans-resveratrol 2000 mg twice daily were studied with a standard breakfast, a high-fat breakfast, quercetin 500 mg twice daily and 5% alcohol 100 mL. Trans-resveratrol plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. The mean (SD) area under the plasma concentration-time curve from 0 to 12 hours (AUC(12)) and maximum plasma concentration (C(max)) of trans-resveratrol were 3558 (2195) ng * h/mL and 1274 (790) ng/mL, respectively, after the standard breakfast. The high-fat breakfast significantly decreased the AUC(12) and C(max) by 45% and 46%, respectively, when compared with the standard breakfast. Quercetin 500 mg twice daily or 5% alcohol 100 mL did not influence trans-resveratrol pharmacokinetics. Diarrhoea was reported in six of the eight subjects. Significant but not clinically relevant changes from baseline were observed in serum potassium and total bilirubin levels. Trans-resveratrol 2000 mg twice daily resulted in adequate exposure and was well tolerated by healthy subjects, although diarrhoea was frequently observed. In order to maximize trans-resveratrol exposure, it should be taken with a standard breakfast and not with a high-fat meal. Furthermore, combined intake with quercetin or alcohol did not influence trans-resveratrol exposure.

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.

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...

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.

Influence of Daily Set-Up Errors on Dose Distribution During Pelvis Radiotherapy

International Nuclear Information System (INIS)

Kasabasic, M.; Ivkovic, A.; Faj, D.; Rajevac, V.; Sobat, H.; Jurkovic, S.

2011-01-01

An external beam radiotherapy (EBRT) using megavoltage beam of linear accelerator is usually the treatment of choice for the cancer patients. The goal of EBRT is to deliver the prescribed dose to the target volume, with as low as possible dose to the surrounding healthy tissue. A large number of procedures and different professions involved in radiotherapy process, uncertainty of equipment and daily patient set-up errors can cause a difference between the planned and delivered dose. We investigated a part of this difference caused by daily patient set-up errors. Daily set-up errors for 35 patients were measured. These set-up errors were simulated on 5 patients, using 3D treatment planning software XiO (CMS Inc., St. Louis, MO). The differences in dose distributions between the planned and shifted ''geometry'' were investigated. Additionally, an influence of the error on treatment plan selection was checked by analyzing the change in dose volume histograms, planning target volume conformity index (CI P TV) and homogeneity index (HI). Simulations showed that patient daily set-up errors can cause significant differences between the planned and actual dose distributions. Moreover, for some patients those errors could influence the choice of treatment plan since CI P TV fell under 97 %. Surprisingly, HI was not as sensitive as CI P TV on set-up errors. The results showed the need for minimizing daily set-up errors by quality assurance programme. (author)

Dose Estimation from Daily and Weekly Dosimetry Data

International Nuclear Information System (INIS)

Ostrouchov, G.

2001-01-01

Statistical analyses of data from epidemiologic studies of workers exposed to radiation have been based on recorded annual radiation doses (yearly dose of record). It is usually assumed that the dose values are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. In our previous work with weekly data, a probability distribution was used to describe an individual's dose during a specific period of time and statistical methods were developed for estimating it from weekly film dosimetry data. This study showed that the yearly dose of record systematically underestimates doses for Oak Ridge National Laboratory (ORNL) workers. This could result in biased estimates of dose-response coefficients and their standard errors. The results of this evaluation raise serious questions about the suitability of the yearly dose of record for direct use in low-dose studies of nuclear industry workers. Here, we extend our previous work to use full information in Pocket meter data and develop the Data Synthesis for Individual Dose Estimation (DSIDE) methodology. Although the DSIDE methodology in this study is developed in the context of daily and weekly data to produce a cumulative yearly dose estimate, in principle it is completely general and can be extended to other time period and measurement combinations. The new methodology takes into account the ''measurement error'' that is produced by the film and pocket-meter dosimetry systems, the biases introduced by policies that lead to recording left-censored doses as zeros, and other measurement and recording practices. The DSIDE method is applied to a sample of dose histories obtained from hard copy dosimetry records at ORNL for the years 1945 to 1955. First, the rigorous addition of daily pocket-meter information shows that the negative bias is generally more severe than was reported in our work based on weekly film data only, however, the amount of bias also varies

Dose Estimation from Daily and Weekly Dosimetry Data

Energy Technology Data Exchange (ETDEWEB)

Ostrouchov, G.

2001-11-16

Statistical analyses of data from epidemiologic studies of workers exposed to radiation have been based on recorded annual radiation doses (yearly dose of record). It is usually assumed that the dose values are known exactly, although it is generally recognized that the data contain uncertainty due to measurement error and bias. In our previous work with weekly data, a probability distribution was used to describe an individual's dose during a specific period of time and statistical methods were developed for estimating it from weekly film dosimetry data. This study showed that the yearly dose of record systematically underestimates doses for Oak Ridge National Laboratory (ORNL) workers. This could result in biased estimates of dose-response coefficients and their standard errors. The results of this evaluation raise serious questions about the suitability of the yearly dose of record for direct use in low-dose studies of nuclear industry workers. Here, we extend our previous work to use full information in Pocket meter data and develop the Data Synthesis for Individual Dose Estimation (DSIDE) methodology. Although the DSIDE methodology in this study is developed in the context of daily and weekly data to produce a cumulative yearly dose estimate, in principle it is completely general and can be extended to other time period and measurement combinations. The new methodology takes into account the ''measurement error'' that is produced by the film and pocket-meter dosimetry systems, the biases introduced by policies that lead to recording left-censored doses as zeros, and other measurement and recording practices. The DSIDE method is applied to a sample of dose histories obtained from hard copy dosimetry records at ORNL for the years 1945 to 1955. First, the rigorous addition of daily pocket-meter information shows that the negative bias is generally more severe than was reported in our work based on weekly film data only, however, the

FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

Science.gov (United States)

Horn, Kevin P; Yap, Jeffrey T; Agarwal, Neeraj; Morton, Kathryn A; Kadrmas, Dan J; Beardmore, Britney; Butterfield, Regan I; Boucher, Kenneth; Hoffman, John M

2015-09-03

Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed

A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

Science.gov (United States)

Dupoiron, D; Stachowiak, A; Loewenstein, O; Ellery, A; Kremers, W; Bosse, B; Hopp, M

2017-10-01

Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients. © 2017 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

Efficacy and persistence of low-dose mirabegron (25 mg) in patients with overactive bladder: analysis in a real-world urological practice.

Science.gov (United States)

Shen, Yuan Chi; Wang, Hung Jen; Chuang, Yao Chi

2018-06-07

Mirabegron is a relatively new drug to treat overactive bladder (OAB). The therapeutic doses are between 25 and 100 mg in clinical trials. We aimed to evaluate the efficacy and persistence of low-dose mirabegron (25 mg) in patients with OAB in daily urological practice. The study was a retrospective consecutive cohort of 177 OAB patients (101 male and 76 female) treated with 25 mg of mirabegron mg since January 2016 to November 2016. The therapeutic outcomes were assessed at baseline, 4, 12, and 24 weeks. Mirabegron usage was associated with a statistically significant decrease in Overactive Bladder Symptom Score, Urgency Severity Score, urge urinary incontinence, International Prostate Symptom Score (both storage and voiding symptom) at 4-week follow-up, and the therapeutic effects were further improved at 12- and 24-week follow-up. Among them, 118 patients (66.7%) and 84 patients (47.5%) were maintained on mirabegron therapy for more than 3 and 6 months, respectively. However, 29 patients (16%) had poor response with drug discontinuation within 3 months and 8 patients (4.5%) stopped medication due to adverse effects. The overall side effect was 10.2%, and the most common side effect was elevated blood pressure (2.8%) and increased post-void residual (2.8%). Between male and female patients, there was no statistical difference of symptom improvement and drug persistence rate. Low-dose mirabegron (25 mg) improves clinical outcomes in two-thirds of OAB patients with good safety profile and high persistence in daily urological practice. The therapeutic effect is similar between the genders.

Phototransfered thermoluminescence for dose reassessment in LiF:mg,ti , LiF: mg,Cu,p TL detectors

International Nuclear Information System (INIS)

Rodriguez Otazo, M.; Baly, L.

2001-01-01

Phototransfered Thermoluminescence (PTTL) from LiF:Mg,Ti (TLD-100) and LiF: Mg,Cu,P (GR-200) was studied at different conditions using different sources of UV light for dose reassessment purposes. The TL dosimeters were irradiated with 137Cs in the range 2 mGy to 100 mGy. The convenience of using PTTL for dose reassessment was analyzed

Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily

Science.gov (United States)

2012-01-01

Background Reduced libido is widely considered the most prominent symptomatic reflection of low testosterone (T) levels in men. Testosterone deficiency (TD) afflicts approximately 30% of men aged 40-79 years. This study seeks to evaluate the effect of a new natural compound “tradamixina “in order to improve male sexual function in elderly men, particularly libido and possible erectile dysfunction, versus administration of tadalafil 5 mg daily. Methods Seventy patients (67.3± 3.7 years) with stable marital relations and affected by reduced libido, with or without erectile dysfunction were recruited. They were randomly separated in 2 groups A-B of 35. Group A was administered twice a day a new compound “Tradamixina” (150 mg of Alga Ecklonia Bicyclis, 396 mg of Tribulus Terrestris and 144 mg of D-Glucosamine and N-Acetyl-D-Glucosamine) for two months, while Group B was administered tadalafil 5 mg daily, for two months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical and sexual history, clinical examination, laboratory investigations (Total and Free T), instrumental examination (NPTR- nocturnal penile tumescence and rigidity test- with Rigiscan). Patients completed a self-administered IIEF questionnaire (The international index of erectile function) and SQoLM questionnaire (Sexual quality of life Questionnarie-Male). The results pre and post treatment were compared by Student t test (p<0.005). Results After 2 months of treatment in group A serum TT levels (230±18 ng/dl vs 671±14 ng/dl ) and FT levels(56± 2.4 pg/ml vs 120± 3.9pg/ml) increased, while in group B serum TT levels (245±12 ng/dl vs 247±15 ng/dl ) and FT levels(53± 0.3 pg/ml vs 55± 0.5pg/ml) increased not statistically significant. The patient’s numbers with negative NPTR improved after treatment in group A and B (15 vs 18 and 13 vs 25 respectively). The IIEF total score in group A increased after treatment with tradamixina (15±1.5 vs 29.77±1

Aspirin administered to women at 100 mg every other day produces less platelet inhibition than aspirin administered at 81 mg per day: implications for interpreting the women's health study.

Science.gov (United States)

Swaim, Lisa; Hillman, Robert S

2009-07-01

We aimed to determine the relative level of platelet inhibition achieved with low-dose aspirin (81 mg daily) compared with a very low-dose (100 mg every other day). The Womens Health Study (WHS) found that a dose of 100 mg every other day of aspirin provided protection against stroke as primary prophylaxis, but not myocardial infarction. In the United States, the most commonly prescribed dose of aspirin for primary prophylaxis is 81 mg per day. As a result, it is important to know whether these doses are equivalent before extrapolating the results of the WHS to women in the U.S. To achieve this goal, we have studied the effects of these two dosing regimens on platelet function in healthy women meeting the WHS inclusion criteria using a randomized design. We enrolled 49 healthy female volunteers and used a sequential, crossover design to compare the two regimens. The participants received a 17-day course of each aspirin-dosing regimen separated by a 7-day washout period. The degree of platelet inhibition was measured on days 14-17 of each dosing regimen using a point-of-care platelet function assay utilizing arachidonic acid to activate platelets (VerifyNow-Aspirin). Participants platelet response, expressed as Aspirin Response Unit (ARU) attained a significantly greater level of platelet inhibition on days 14-17 while taking aspirin 81 mg daily compared to aspirin 100 mg every other day (31.3% vs. 12.7%, P or=550 ARU, a value correlated with clinical outcomes in several studies, with the 100 mg every other day regimen (72.0% vs. 6.4% with 81 mg daily, P day regimen also resulted in more day-to-day variability in platelet function (P = 0.0002). We found significantly less inhibition of platelet function with the dose used in the WHS than the usual U.S. dose. We observed that the degree of platelet inhibition was significantly less with aspirin 100 mg every other day compared with aspirin 81 mg daily, suggesting that results of the Women's Health Study may have

Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

Directory of Open Access Journals (Sweden)

Sidnei Lastória

2014-03-01

Full Text Available CONTEXT: The question of what is the best loading dosage of warfarin when starting anticoagulant treatment has been under discussion for ten years. We were unable to find any comparative studies of these characteristics conducted here in Brazil. OBJECTIVE: To compare the safety and efficacy of two initial warfarin dosage regimens for anticoagulant treatment. METHODS: One-hundred and ten consecutive patients of both sexes, with indications for anticoagulation because of venous or arterial thromboembolism, were analyzed prospectively. During the first 3 days of treatment, these patients were given adequate heparin to keep aPTT (activated partial thromboplastin time between 1.5 and 2.5, plus 5 mg of warfarin. From the fourth day onwards, their warfarin doses were adjusted using International Normalized Ratios (INR; target range: 2 to 3. This prospective cohort was compared with a historical series of 110 patients had been given 10 mg of warfarin on the first 2 days and 5 mg on the third day with adjustments based on INR thereafter. Outcomes analyzed were as follows: recurrence of thromboembolism, bleeding events and time taken to enter the therapeutic range. RESULTS: Efficacy, safety and length of hospital stay were similar in both samples. The sample that were given 10 mg entered the therapeutic range earlier (means: 4.5 days vs. 5.8 days, were on lower doses at discharge and had better therapeutic indicators at the first return appointment. CONCLUSIONS: The 10 mg dosage regimen took less time to attain the therapeutic range and was associated with lower warfarin doses at discharge and better INR at first out-patients follow-up visit.

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

Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial.

Science.gov (United States)

Carpentier, Patrick; van Bellen, Bonno; Karetova, Debora; Hanafiah, Harunarashid; Enriquez-Vega, Elizabeth; Kirienko, Alexander; Dzupina, Andrej; Sabovic, Miso; Reina Gutierrez, Lourdes; Subwongcharoen, Somboom; Tüzün, Hasan; Maggioli, Arnaud

2017-10-01

Chronic venous disorders (CVD) is estimated to affect 30% to 50% of women and 10% to 30% of men. The most widely prescribed treatment for CVD worldwide is micronized purified flavonoid fraction 500 mg (MPFF). The aim of this clinical trial was to develop a new once daily 1000-mg oral suspension of MPFF. In an international, randomized, double-blind, parallel-group study, symptomatic individuals classified CEAP C0s to C4s were randomized in either treatment arm and treated for 8 weeks. Lower limb symptoms (discomfort, pain and heaviness) were assessed using Visual Analog Scales (VAS), and quality of life (QoL) was measured with the CIVIQ-20 Questionnaire. A total of 1139 patients were included in the study. Both MPFF treatment regimens were well tolerated and associated with a significant reduction in lower limb symptoms. A non-inferiority of MPFF 1000-mg oral suspension once daily compared to MPFF 500-mg tablet twice daily (P1000 mg and -3.37 cm for MPFF 500 mg), leg pain (-3.27 cm for MPFF 1000 mg and -3.31 cm for MPFF 500 mg) and leg heaviness (-3.41 cm for MPFF 1000 mg and -3.46 cm for MPFF 500 mg). The patients' QoL was improved by about 20 points on the CIVIQ scale in both groups (19.33 points for MPFF 1000 mg and 20.28 points for MPFF 500 mg). MPFF 1000-mg oral suspension and MPFF 500-mg tablets treatments were associated with similar reductions in lower limb symptoms and QoL improvement. The new once daily MPFF1000-mg oral suspension has a similar safety profile to two tablets of MPFF 500 mg, with the advantage of one daily intake, potentially associated with improved patient adherence and easier CVD management.

Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose.

Science.gov (United States)

Kör, Deniz; Yılmaz, Berna Şeker; Bulut, Fatma Derya; Ceylaner, Serdar; Mungan, Neslihan Önenli

2017-07-26

Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction.

Science.gov (United States)

Karabakan, Mehmet; Keskin, Ercument; Akdemir, Serkan; Bozkurt, Aliseydi

2017-01-01

To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS) in patients with erectile dysfunction. A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5), intravaginal ejaculatory latency time (IELT) and international prostate symptoms scores (IPSS). After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol and total cholesterol were measured. The independentsamples t-test was used to compare the pre- and post-treatment scores of the patients. The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360) mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01). A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time. Copyright® by the International Brazilian Journal of Urology.

Once-daily dosing of saquinavir and low-dose ritonavir in HIV-1-infected individuals: a pharmacokinetic pilot study

NARCIS (Netherlands)

van Heeswijk, R. P.; Veldkamp, A. I.; Mulder, J. W.; Meenhorst, P. L.; Lange, J. M.; Beijnen, J. H.; Hoetelmans, R. M.

2000-01-01

To investigate the steady-state pharmacokinetics of a once-daily dosing regimen of saquinavir soft gelatin capsules in combination with a low dose of ritonavir in HIV-1-infected individuals. Open-label, multi-dose, pharmacokinetic pilot study. Seven HIV-1-infected individuals who were treated with

Health effects of daily airborne particle dose in children: Direct association between personal dose and respiratory health effects

International Nuclear Information System (INIS)

Buonanno, Giorgio; Marks, Guy B.; Morawska, Lidia

2013-01-01

Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35 × 10 3 mm 2 . The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child's activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles. -- Highlights: •Particle dose was estimated through personal monitoring on more than 100 children. •We focused on real-time daily dose of particle alveolar deposited surface area. •Spirometry, skin prick and exhaled Nitric Oxide tests were performed. •Negative link was found between changes in pulmonary functions and individual doses. •A child's lifestyle appeared to have a strong impact on health respiratory outcomes. -- The respiratory health effects of daily airborne particle dose on children through personal monitoring

Daily variations in delivered doses in patients treated with radiotherapy for localized prostate cancer

International Nuclear Information System (INIS)

Kupelian, Patrick A.; Langen, Katja M.; Zeidan, Omar A.; Meeks, Sanford L.; Willoughby, Twyla R.; Wagner, Thomas H.; Jeswani, Sam; Ruchala, Kenneth J.; Haimerl, Jason; Olivera, Gustavo H.

2006-01-01

Purpose: The aim of this work was to study the variations in delivered doses to the prostate, rectum, and bladder during a full course of image-guided external beam radiotherapy. Methods and Materials: Ten patients with localized prostate cancer were treated with helical tomotherapy to 78 Gy at 2 Gy per fraction in 39 fractions. Daily target localization was performed using intraprostatic fiducials and daily megavoltage pelvic computed tomography (CT) scans, resulting in a total of 390 CT scans. The prostate, rectum, and bladder were manually contoured on each CT by a single physician. Daily dosimetric analysis was performed with dose recalculation. The study endpoints were D95 (dose to 95% of the prostate), rV2 (absolute rectal volume receiving 2 Gy), and bV2 (absolute bladder volume receiving 2 Gy). Results: For the entire cohort, the average D95 (±SD) was 2.02 ± 0.04 Gy (range, 1.79-2.20 Gy). The average rV2 (±SD) was 7.0 ± 8.1 cc (range, 0.1-67.3 cc). The average bV2 (±SD) was 8.7 ± 6.8 cc (range, 0.3-36.8 cc). Unlike doses for the prostate, there was significant daily variation in rectal and bladder doses, mostly because of variations in volume and shape of these organs. Conclusion: Large variations in delivered doses to the rectum and bladder can be documented with daily megavoltage CT scans. Image guidance for the targeting of the prostate, even with intraprostatic fiducials, does not take into account the variation in actual rectal and bladder doses. The clinical impact of techniques that take into account such dosimetric parameters in daily patient set-ups should be investigated

Comparative study of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis.

Science.gov (United States)

Francesconi, Glaucia; Francesconi do Valle, Antonio Carlos; Passos, Sonia Lambert; de Lima Barros, Mônica Bastos; de Almeida Paes, Rodrigo; Curi, André Luiz Land; Liporage, José; Porto, Cássio Ferreira; Galhardo, Maria Clara Gutierrez

2011-05-01

Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis. To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis. A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n = 4, 7.3%) and itraconazole (n = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

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

Once versus twice daily gentamicin dosing for infective endocarditis

DEFF Research Database (Denmark)

Buchholtz, Kristine; Larsen, Carsten Toftager; Schaadt, Bente

2011-01-01

Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according...

Inhibitory effects of intravenous lansoprazole 30 mg and pantoprazole 40 mg twice daily on intragastric acidity in healthy Chinese volunteers: a randomized, open-labeled, two-way crossover study.

Science.gov (United States)

Zhan, Xian-Bao; Guo, Xiao-Rong; Li, Zhao-Shen; Gong, Yan-Fang; Gao, Jun; Liao, Zhuan; Li, Zhen; Gao, Shen; Liu, Pei

2012-02-01

Until now there has been no study that directly compares the effect of lansoprazole and pantoprazole administered intravenously on intragastric acidity. The aim of this study is to compare the effect of lansoprazole (30 mg) and pantoprazole (40 mg) administered intravenously on gastric acidity. Helicobacter pylori-negative healthy volunteers were recruited in this open-label, randomized, two-way crossover, single centre study. Lansoprazole at 30 mg or pantoprazole at 40 mg was intravenously administered twice daily for 5 consecutive days with at least a 14-day washout interval. Twenty-four-hour intragastric pH was continuously monitored on days 1 and 5 of each dosing period. Twenty-five volunteers completed the 2 dosing periods. The mean intragastric pH values were higher in subjects treated with lansoprazole than those with pantoprazole on both day 1 (6.41 ± 0.14 vs. 5.49 ± 0.13, P=0.0003) and day 5 (7.09 ± 0.07 vs. 6.64 ± 0.07, P=0.0002). Significantly higher percentages of time with intragastric pH >4 and pH >6 were found in the subjects treated with lansoprazole than those with pantoprazole on day 1 (pH >4, 87.12 ± 4.55% vs. 62.28 ± 4.15%, P=0.0012; pH >6, 62.12 ± 4.12% vs. 47.25 ± 3.76%, P=0.0216) and pH >6 on day 5 (76.79 ± 3.77% vs. 58.20 ± 3.77%, P=0.0025). Intravenous lansoprazole produces a longer and more potent inhibitory effect on intragastric acidity than does intravenous pantoprazole.

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

Directory of Open Access Journals (Sweden)

Farrauto Leonardo

2011-06-01

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

Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

Science.gov (United States)

Schuler, Charles F; Baldwin, James L; Baptist, Alan P

2017-03-01

The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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.

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.

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate.

Science.gov (United States)

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

Science.gov (United States)

Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Clinical and microbiological outcomes in treatment of men with non-gonococcal urethritis with a 100-mg twice-daily dose regimen of sitafloxacin.

Science.gov (United States)

Ito, Shin; Yasuda, Mitsuru; Seike, Kensaku; Sugawara, Takashi; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Deguchi, Takashi

2012-06-01

Several microorganisms cause non-gonococcal urethritis (NGU). Failure to eradicate Mycoplasma genitalium from the urethra could be associated with persistent or recurrent urethritis; thus, the choice of antibiotics with activities potent enough to eradicate M. genitalium is crucial in the treatment of NGU. In in vitro studies, sitafloxacin has been shown to be highly active against Chlamydia trachomatis and M. genitalium. We treated 89 males with NGU, including 15 patients with persistent or recurrent NGU and 1 patient with post-gonococcal urethritis, with a 100-mg twice-daily dose regimen of sitafloxacin to assess its efficacy against NGU. We examined first-void urine samples for the presence of C. trachomatis, M. genitalium, Ureaplasma parvum, and Ureaplasma urealyticum. After treatment, we evaluated 73 patients for clinical outcomes and 44 for microbiological outcomes. Symptoms were alleviated in 62 (84.9%) patients, who were judged clinically cured. Microorganisms detected before treatment were eradicated in 42 (95.5%) patients, who were judged microbiologically cured. Regarding microbiological outcomes of specific microorganisms, eradication rates of C. trachomatis (n = 33), M. genitalium (n = 11), and U. urealyticum (n = 10) were 100%, 100%, and 80.0%, respectively. In all 5 patients with M. genitalium-positive persistent or recurrent NGU who had experienced treatment failures with antibiotics, the mycoplasma was eradicated. These results suggested that the sitafloxacin regimen used, which was effective on both M. genitalium and C. trachomatis infections, could be useful as an appropriate option as first- and second-line treatment of NGU.

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...

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)

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

Science.gov (United States)

Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J

2010-01-01

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

Effect of tadalafil 5mg daily treatment on the ejaculatory times, lower urinary tract symptoms and erectile function in patients with erectile dysfunction

Directory of Open Access Journals (Sweden)

Mehmet Karabakan

Full Text Available ABSTRACT Objective To investigate the effect of a 5mg daily tadalafil treatment on the ejaculation time, erectile function and lower urinary tract symptoms (LUTS in patients with erectile dysfunction. Materials and Methods A total of 60 patients diagnosed with erectile dysfunction were retrospectively evaluated using the international index of erectile function questionnaire-5 (IIEF-5, intravaginal ejaculatory latency time (IELT and international prostate symptoms scores (IPSS. After the patients were treated with 5mg tadalafil once a day for three months, their erection, ejaculation and LUTS were assessed again. The fasting levels of blood glucose, total testosterone, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were measured. The independent-samples t-test was used to compare the pre- and post-treatment scores of the patients. Results The mean age of the 60 participants was 50.4±7.9 and the mean baseline serum total testosterone, total cholesterol, and fasting blood sugar were 444.6±178.6ng dL-1, 188.7±29.6mg/dL-1,104 (80-360 mg dL-1, respectively. The mean baseline scores were 2.2±1.4 min for IELT, 9.5±3.7 for IIEF-5 and 14.1±4.5 for IPSS. Following the three-month daily 5mg tadalafil treatment, the scores were found to be 3.4±1.9 min, 16.1±4.7, and 10.4±3.8 for IELT, IIEF and IPSS, respectively. When the baseline and post-treatment scores were compared, a statistically significant increase was observed in the IELTs and IIEF-5 values whereas there was a significant decrease in IPSS (p<0.01. Conclusion A daily dose of 5mg tadalafil can be safely used in the treatment of erectile dysfunction and LUTS, that prolongs the ejaculatory latency time.

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.

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.

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�

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

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

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.

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.

Dose requirements of alfentanil to eliminate autonomic responses during rapid-sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.

Science.gov (United States)

Abou-Arab, Mohammad H; Rostrup, Morten; Heier, Tom

2016-12-01

Opioids are integral part of anesthesia induction, but information on optimal dosing is limited. We aimed to determine doses of alfentanil needed to eliminate increases in 5 autonomic response variables (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial blood pressure [ABP], and heart rate) during rapid-sequence induction of anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Prospective, randomized, observer-blinded, interventional clinical study. Large academic institution. Eighty-four healthy patients, aged 18 to 55 years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40, 50, and 60 μg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg, administered in rapid succession (15 seconds). Laryngoscopy was initiated 40 seconds after rocuronium, and tracheal intubation was concluded within 15 seconds thereafter. An indwelling radial artery catheter was used for hemodynamic monitoring and blood sampling. Relationships between alfentanil dose and response variables were tested with linear regression, and the influence of covariates (sex, body weight, and age) was determined. Alfentanil dose needed to prevent increases in ABP >10% above baseline with 95% probability was estimated with logistic regression. Significant relationships were determined between alfentanil dose and response variables. Clinically interesting influence of covariates was not found. Alfentanil 55 μg/kg was needed to prevent increases in ABP postintubation >10% above baseline with 95% probability. One individual needed a bolus of vasopressor postintubation. Optimal control of autonomic responses during rapid-sequence induction was achieved with clinically relevant doses of alfentanil in healthy patients anesthetized with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. Copyright © 2016 Elsevier Inc. All rights reserved.

Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

Directory of Open Access Journals (Sweden)

Mulhall JP

2013-11-01

Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

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.

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.

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.

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

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.

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

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.

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

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

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.

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.

Tamsulosin 0.4 mg once daily: effect on sexual function in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction

NARCIS (Netherlands)

Höfner, K.; Claes, H.; de Reijke, T. M.; Folkestad, B.; Speakman, M. J.

1999-01-01

To evaluate the effect of tamsulosin, 0.4 mg once daily, on sexual function in comparison with placebo and alfuzosin, 2.5 mg three times daily, in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). Data from 830 patients randomized into three European

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

Sevelamer hydrochloride (SH) and lanthanum carbonate (LC) are calcium-free phosphate binders used for the management of hyperphosphatemia in patients with end-stage renal disease (ESRD). The objective of this analysis was to evaluate the real-world dose-relativity between SH and LC monotherapy in US patients with ESRD. This was a post hoc analysis of a 16-week, real-world study (Vemuri et al. in BMC Nephrol 12:49, 2011) of the efficacy of conversion to LC monotherapy from other phosphate binders. The SH:LC dose-relativity ratio, based on the mean daily dose, was calculated in the subset of patients from the Vemuri study who converted from SH to LC monotherapy and had available SH and LC dose data. A total of 950 patients converted from SH to LC monotherapy and had recorded dose data. The post hoc analysis population comprised 691 patients with available dose data for both SH at baseline and LC at week 16. The mean (SD) serum phosphate level at baseline was 5.91 (1.66) mg/dL. After conversion to LC monotherapy for 16 weeks, the mean (SD) serum phosphate level was 5.93 (1.85) mg/dL. The mean (SD) daily baseline SH dose was 7,703 (3,642) mg and the mean (SD) daily LC dose at week 16 was 2,800 (939) mg (9.6 versus 2.8 tablets, respectively; P relativity ratio of 2.8. The median individual patient SH:LC dose-relativity ratio was 2.6 (95% CI 2.6-2.8). Across baseline SH dose subgroups (2,400-4,800, >4,800-7,200, >7,200-9,600, and >9,600 mg/day), the mean daily SH dose was 4,051, 7,047, 9,253, and 13,150 mg, respectively. In comparison, the mean daily LC dose was 2,445-3,156 mg. Thus, patients requiring baseline SH doses >7,200 mg/day (41% of the analysis population) had higher SH:LC dose-relativity ratios of 3.1-4.2 (median individual patient ratios 3.1-4.0). In this post hoc analysis of real-world dose-relativity, the overall SH:LC dose-relativity ratio was 2.8 (median individual patient ratio 2.6 (95% CI 2.6-2.8). These findings are consistent with the World Health

Effect of a simple dose-escalation schedule on tramadol tolerability : assessment in the clinical setting.

Science.gov (United States)

Tagarro, I; Herrera, J; Barutell, C; Díez, M C; Marín, M; Samper, D; Busquet, C; Rodríguez, M J

2005-01-01

To assess the effect of a very simple dose-escalation schedule on tramadol tolerability in clinical practice. This schedule consists of starting treatment with sustained-release tramadol 50mg twice daily, and escalating the dose around 7 days later to 100mg twice daily. Data from 1925 outpatients with non-malignant chronic pain were collected in this multicentre, prospective, comparative, non-randomised, open, observational study. A total of 1071 patients (55.6%) were included in the dose-escalation group (50mg group) and 854 patients (44.4%) in the control group (sustained-release tramadol 100mg twice daily; 100mg group). The proportion of patients who interrupted tramadol treatment due to the occurrence of adverse reactions was significantly lower in the 50mg group (5.6%) than in the 100mg group (12.6%) [p = 0.001]. In line with this, the proportion of patients who experienced at least one adverse reaction was significantly lower in the 50mg group (18.4%) than in the 100mg group (30.4%) [p = 0.001] and, interestingly, the two most frequently reported adverse reactions, nausea and dizziness, were found with a significantly lower frequency in the 50mg group (p < 0.001). Multivariate analysis showed that the risk of safety-related treatment cessations was 2.3 times higher in the 100mg group than in the 50mg group, and 2.2 times higher in females than in males. The two treatments were equally effective in reducing pain intensity (p = 0.121), measured as a reduction in pain score obtained by means of a visual analogue scale. The instauration of tramadol treatment, starting with sustained-release 50mg capsules twice daily and escalating the dose some days later to 100mg twice daily, was shown to be an effective and easy way to improve tramadol tolerability in clinical practice, whilst maintaining its analgesic efficacy.

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.

Assessment of postoperative changes in antihypertensive drug consumption in patients with primary aldosteronism using the defined daily dose

Directory of Open Access Journals (Sweden)

Takanobu Utsumi

2014-10-01

Conclusion: The defined daily dose is a useful tool for assessing total changes in the consumption of antihypertensive drugs in patients with primary aldosteronism. Using the defined daily dose, clinicians could explain in detail to patients with primary aldosteronism the predicted postoperative change in antihypertensive drug consumption.

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/

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

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.

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.

Study of the response reduction of LiF:Mg, Ti dosimeter for high dose dosimetry

Energy Technology Data Exchange (ETDEWEB)

Torkzadeh, Falamarz [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School; AEOI, Tehran (Iran, Islamic Republic of); Faripour, Heidar [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Laser and Optics Research School; AEOI, Tehran (Iran, Islamic Republic of); Mardashti, Forough; Manouchehri, Farhad [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School

2017-07-15

A single crystal and 5 polycrystalline samples of LiF:Mg, Ti and their pellets were prepared and investigated so as to apply thermoluminescence high gamma dose dosimetry. Three zones of single crystal with dopant concentrations of 200 ppm of Mg and 20 ppm of Ti were also used to prepare the single crystal samples. For polycrystalline samples, dopant concentrations of 0.062 mol% Mg and Ti concentrations in the range of 0.016 and 0.046 mol% were used. All the samples were exposed to gamma doses of 1 kGy to 700 kGy and their response changes were determined by a gamma dose test of about 60 mGy. According to the results obtained, the use of response reduction by curve-fitting up to about 300 kGy can be performed reliably for high dose gamma dosimetry.

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...

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

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.

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)

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.

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

A randomized, controlled trial of 3.0 mg of Liraglutide in weight management

DEFF Research Database (Denmark)

Pi-Sunyer, Xavier; Astrup, Arne; Fujioka, Ken

2015-01-01

Background Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg...... or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were...... with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. Conclusions In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight...

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.

Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

Science.gov (United States)

Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

2015-06-01

To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

Science.gov (United States)

Bodhidatta, L; Taylor, D N; Chitwarakorn, A; Kuvanont, K; Echeverria, P

1988-01-01

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand. PMID:3293526

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

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

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

Economic impact of the use of rifaximin 550 mg twice daily for the treatment of overt hepatic encephalopathy in Italy.

Science.gov (United States)

Roggeri, Daniela Paola; Roggeri, Alessandro

2017-01-01

Hepatic encephalopathy (HE) is associated with a reduced survival, an increased risk of hospitalization for recurrences, and a reduced health-related quality of life. The purpose of the present economic analysis was to evaluate the impact on the Italian National Health Service (INHS) expenditure of the treatment with rifaximin 550 mg twice daily (Tixteller ® /Tixtar ® ) for the reduction of the recurrences of overt HE, with respect to the current treatment approach. Costs associated with patients treated with rifaximin 550 mg twice daily were estimated considering the reduction in hospitalizations for HE recurrences revealed by registrative clinical trial (-50%) applied to the hospitalization rate (42.5%) emerging from an Italian observational real-world study; costs associated with patients not treated with rifaximin were estimated based on the hospitalization rate, resulting from the same Italian observational study. Sensitivity analyses considering possible different discount levels to INHS structures for rifaximin were performed. The INHS perspective for a period of 3 years was considered. The treatment with rifaximin 550 mg twice daily, although increasing drug costs, is associated with a reduction in hospitalizations for HE recurrences that leads to an overall reduction of total costs charged to INHS, which could be estimated, based on the forecasted uptake of the treatment, at about €130,000 in the first year, reaching ~€260,000 in the third year. Considering a possible discount for rifaximin 550 mg to INHS structure of 20%, the total saving at the third year accounts for ~€3,000,000. Moreover, a relevant reduction in the number of hospitalizations and bed days is associated with rifaximin treatment. The treatment with rifaximin 550 mg twice daily, even if associated with an increase in drug expenditure, results in a reduction in total health care costs charged to INHS due to a reduction in hospitalizations for HE recurrences.

Daily concurrent chemoradiotherapy using superselective intra-arterial infusion via superficial temporal artery. Preoperative therapy for stage III, IV oral cancer

International Nuclear Information System (INIS)

Tohnai, Iwai; Mitsudo, Kenji; Nishiguchi, Hiroaki; Fukui, Takafumi; Yamamoto, Noriyuki; Ueda, Minoru; Fuwa, Nobukazu

2005-01-01

Recently, daily concurrent chemoradiotherapy using new superselective intra-arterial infusion via superficial temporal arterial artery is attracting attention. The catheter with curved tip is inserted superselectively to the feeding artery of the tumor via the superficial temporal artery, allowing long-term catheterization. Forty-one patients with stage III, IV oral cancer were treated. Radiotherapy (total dose: 40 Gy/4 weeks) and superselective intra-arterial infusion chemotherapy using docetaxel (total dose: 60 mg/m 2 , 15 mg/m 2 /week) and cisplatin (total dose: 100 mg/m 2 , 5 mg/m 2 /day) were concurrently performed daily, followed by surgery. In 35 patients, intra-arterial infusion was successful (success rate: 85.4%) and no major complication was observed. The clinical effects were complete response (CR) in 29 patients (82.9%), and pathological effects of resected tumor after surgery were pathological CR in 31 (88.6%). This method promises to be a new strategy of choice for the treatment of oral cancer. (author)

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

Science.gov (United States)

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

2017-08-01

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

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

Estimate of annual daily maximum rainfall and intense rain equation for the Formiga municipality, MG, Brazil

Directory of Open Access Journals (Sweden)

Giovana Mara Rodrigues Borges

2016-11-01

Full Text Available Knowledge of the probabilistic behavior of rainfall is extremely important to the design of drainage systems, dam spillways, and other hydraulic projects. This study therefore examined statistical models to predict annual daily maximum rainfall as well as models of heavy rain for the city of Formiga - MG. To do this, annual maximum daily rainfall data were ranked in decreasing order that best describes the statistical distribution by exceedance probability. Daily rainfall disaggregation methodology was used for the intense rain model studies and adjusted with Intensity-Duration-Frequency (IDF and Exponential models. The study found that the Gumbel model better adhered to the data regarding observed frequency as indicated by the Chi-squared test, and that the exponential model best conforms to the observed data to predict intense rains.

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

Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach.

Science.gov (United States)

Li, Xiaoyan; Keshishian, Allison; Hamilton, Melissa; Horblyuk, Ruslan; Gupta, Kiran; Luo, Xuemei; Mardekian, Jack; Friend, Keith; Nadkarni, Anagha; Pan, Xianying; Lip, Gregory Y H; Deitelzweig, Steve

2018-01-01

Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60-0.81) and major bleeding (HR: 0.59, 95% CI: 0.53-0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49-0.81) and major bleeding (HR: 0.59, 95% CI: 0.49-0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice. Clinicaltrials.Gov Identifier: NCT03087487.

Pre-Altitude Serum Ferritin Levels and Daily Oral Iron Supplement Dose Mediate Iron Parameter and Hemoglobin Mass Responses to Altitude Exposure.

Directory of Open Access Journals (Sweden)

Andrew D Govus

Full Text Available To investigate the influence of daily oral iron supplementation on changes in hemoglobin mass (Hbmass and iron parameters after 2-4 weeks of moderate altitude exposure.Hematological data collected from 178 athletes (98 males, 80 females exposed to moderate altitude (1,350-3,000 m were analysed using linear regression to determine how altitude exposure combined with oral iron supplementation influenced Hbmass, total iron incorporation (TII and blood iron parameters [ferritin and transferrin saturation (TSAT].Altitude exposure (mean ± s: 21 ± 3 days increased Hbmass by 1.1% [-0.4, 2.6], 3.3% [1.7, 4.8], and 4.0% [2.0, 6.1] from pre-altitude levels in athletes who ingested nil, 105 mg and 210 mg respectively, of oral iron supplement daily. Serum ferritin levels decreased by -33.2% [-46.9, -15.9] and 13.8% [-32.2, 9.7] from pre-altitude levels in athletes who supplemented with nil and 105 mg of oral iron supplement daily, but increased by 36.8% [1.3, 84.8] in athletes supplemented with 210 mg of oral iron daily. Finally, athletes who ingested either 105 mg or 210 mg of oral iron supplement daily had a greater TII compared with non-supplemented athletes (0 versus 105 mg: effect size (d = -1.88 [-2.56, -1.17]; 0 versus 210 mg: effect size (d = -2.87 [-3.88, -1.66].Oral iron supplementation during 2-4 weeks of moderate altitude exposure may enhance Hbmass production and assist the maintenance of iron balance in some athletes with low pre-altitude iron stores.

Low-dose caffeine discrimination and self-reported mood effects in normal volunteers.

Science.gov (United States)

Silverman, K; Griffiths, R R

1992-01-01

A caffeine versus placebo discrimination procedure was used to determine the lowest caffeine dose that could produce discrimination and self-reported mood effects in normal volunteers. During daily sessions under double-blind conditions, caffeine-abstinent subjects orally ingested a capsule containing 178 mg caffeine or placebo. Before beginning discrimination training, the compounds were identified to subjects by letter codes. Fifteen, 30, and 45 min after capsule ingestion, subjects guessed the capsule's letter code. Correct guesses at 45 min earned money. After each session, subjects received a supplementary capsule containing caffeine or placebo to ensure that, within each phase of the study, subjects received the same daily dose of caffeine equal to the training dose. Five of the 15 subjects acquired the caffeine versus placebo discrimination within the first 20 sessions (greater than or equal to 75% correct); 6 other subjects acquired the discrimination with additional training. Nine subjects who acquired the discrimination were subsequently trained at progressively lower caffeine doses. In general, the lowest dose to produce discrimination (greater than or equal to 75% correct) was also the lowest dose to produce self-reported mood effects: 4 subjects showed discrimination and self-reported mood effects at 100 mg caffeine, 2 at 56 mg, 1 at 32 mg, and 1 at 18 mg. One of these subjects also showed self-reported mood effects at 10 mg. The present study documents discriminative stimulus and self-reported mood effects of caffeine at doses below those previously shown to affect any behavior in normal volunteers. PMID:1548451

Dose and duration dependent of aluminium in the serum liver and ...

African Journals Online (AJOL)

An atomic absorption spectrophotometric analysis on dose and duration dependent aluminum concentration in serum, liver and brain digests of three groups of male Wistar albino rats were investigated after seven and fourteen days of daily 0.38mg/kg, 3.8mg/kg and 38mg/kg aluminum administration respectively.

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

Thermoluminescent characteristics of LiF:Mg, Cu, P and CaSO_4:Dy for low dose measurement

International Nuclear Information System (INIS)

Del Sol Fernández, S.; García-Salcedo, R.; Mendoza, J. Guzmán; Sánchez-Guzmán, D.; Rodríguez, G. Ramírez; Gaona, E.; Montalvo, T. Rivera

2016-01-01

Thermoluminescence (TL) characteristics for LiF:Mg, Cu, P, and CaSO_4:Dy under the homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescence dosimetry are presented. The irradiation were performed utilizing a conventional X-ray equipment installed at the Hospital Juárez Norte of México. Different thermoluminescence characteristics of two material were studied, such as batch homogeneity, glow curve, linearity, detection threshold, reproducibility, relative sensitivity and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and they were positioned in a generic phantom. The dose analysis, verification and comparison with the measurements obtained by the TLD-100 were performed. Results indicate that the dosimetric peak appears at 202 °C and 277.5 °C for LiF:Mg, Cu, P and CaSO_4:Dy, respectively. TL response as a function of X-ray dose showed a linearity behavior in the very low dose range for all materials. However, the TLD-100 is not accurate for measurements below 4 mGy. CaSO_4:Dy is 80% more sensitive than TLD-100 and it show the lowest detection threshold, whereas LiF:Mg, Cu, P is 60% more sensitive than TLD-100. All materials showed very good repeatability. Fading for a period of one month at room temperature showed low fading LiF:Mg, Cu, P, medium and high for TLD-100 and CaSO_4:Dy. The results suggest that CaSO_4:Dy and LiF:Mg, Cu, P are suitable for measurements at low doses used in radiodiagnostic. - Highlights: • Several dosimetric characteristics were evaluated. • TL dose response to very low dose X-rays was studied. • The applications proposed for each material may be useful for diagnostic radiology dosimetry.

Economic impact of the use of rifaximin 550 mg twice daily for the treatment of overt hepatic encephalopathy in Italy

Directory of Open Access Journals (Sweden)

Roggeri DP

2017-09-01

Full Text Available Daniela Paola Roggeri, Alessandro Roggeri ProCure Solutions, Nembro, Bergamo, Italy Purpose: Hepatic encephalopathy (HE is associated with a reduced survival, an increased risk of hospitalization for recurrences, and a reduced health-related quality of life. The purpose of the present economic analysis was to evaluate the impact on the Italian National Health Service (INHS expenditure of the treatment with rifaximin 550 mg twice daily (Tixteller®/Tixtar® for the reduction of the recurrences of overt HE, with respect to the current treatment approach. Patients and methods: Costs associated with patients treated with rifaximin 550 mg twice daily were estimated considering the reduction in hospitalizations for HE recurrences revealed by registrative clinical trial (−50% applied to the hospitalization rate (42.5% emerging from an Italian observational real-world study; costs associated with patients not treated with rifaximin were estimated based on the hospitalization rate, resulting from the same Italian observational study. Sensitivity analyses considering possible different discount levels to INHS structures for rifaximin were performed. The INHS perspective for a period of 3 years was considered. Results: The treatment with rifaximin 550 mg twice daily, although increasing drug costs, is associated with a reduction in hospitalizations for HE recurrences that leads to an overall reduction of total costs charged to INHS, which could be estimated, based on the forecasted uptake of the treatment, at about €130,000 in the first year, reaching ~€260,000 in the third year. Considering a possible discount for rifaximin 550 mg to INHS structure of 20%, the total saving at the third year accounts for ~€3,000,000. Moreover, a relevant reduction in the number of hospitalizations and bed days is associated with rifaximin treatment. Conclusion: The treatment with rifaximin 550 mg twice daily, even if associated with an increase in drug expenditure

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.

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

Science.gov (United States)

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

2009-11-01

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

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

Science.gov (United States)

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

Standardised high dose versus low dose cranberry Proanthocyanidin extracts for the prevention of recurrent urinary tract infection in healthy women [PACCANN]: a double blind randomised controlled trial protocol.

Science.gov (United States)

Asma, Babar; Vicky, Leblanc; Stephanie, Dudonne; Yves, Desjardins; Amy, Howell; Sylvie, Dodin

2018-05-02

Urinary tract infections (UTIs) are amongst the most common bacterial infections affecting women. Although antibiotics are the treatment of choice for UTI, cranberry derived products have been used for many years to prevent UTIs, with limited evidence as to their efficacy. Our objective is to assess the efficacy of a cranberry extract capsule standardized in A-type linkage proanthocyanidins (PACs) for the prevention of recurrent urinary tract infection. We will perform a 1:1 randomized, controlled, double blind clinical trial in women aged 18 years or more who present ≥2 UTIs in 6 months or ≥ 3 UTIs in 12 months. One hundred and forty-eight women will be recruited and randomized in two groups to either receive an optimal dose of cranberry extract quantified and standardized in PACs (2 × 18.5 mg PACs per day) or a control dose (2 × 1 mg PACs per day). The primary outcome for the trial is the mean number of new symptomatic UTIs in women during a 6-month intervention period. Secondary outcomes are: (1) To evaluate the mean number of new symptomatic UTIs with pyuria as demonstrated by a positive leucocyte esterase test; (2) To detect the mean number of new symptomatic culture-confirmed UTIs; (3) To quantify urinary PACs metabolites in women who take a daily dose of 37 mg PACs per day compared to women who take a daily dose of 2 mg per day for 6 months; (4) To characterize women who present recurrent UTI based on known risk factors for recurrent UTI; (5) To describe the side effects of daily intake of cranberry extract containing 37 mg PACs compared to 2 mg PACs. This report provides comprehensive methodological data for this randomized controlled trial. The results of this trial will inform urologists, gynaecologists, family physicians and other healthcare professionals caring for healthy women with recurrent UTI, as to the benefits of daily use of an optimal dose of cranberry extract for the prevention of recurrent UTI. Clinicaltrials

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.

Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

Directory of Open Access Journals (Sweden)

Crawford Gordon M

2011-03-01

Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

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.

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.

Efficacy and tolerability of tamsulosin 0.4 mg in Asian patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia refractory to tamsulosin 0.2 mg: a randomized placebo controlled trial.

Science.gov (United States)

Kim, Jung Jun; Han, Deok Hyun; Sung, Hyun Hwan; Choo, Seol Ho; Lee, Sung Won

2014-07-01

To evaluate the efficacy and safety of tamsulosin dose increase to 0.4 mg daily in Asian patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia refractory to tamsulosin 0.2 mg treatment. We carried out a 12-week, single-center, randomized, placebo-controlled trial in 220 patients. Patients treated with 0.2 mg tamsulosin daily without other lower urinary tract symptoms secondary to benign prostatic hyperplasia medication for more than 3 months and refractory to this treatment were enrolled. We defined "refractory" as an International Prostate Symptom Score of 13 or greater and a maximum flow rate of 15 or under despite medication. Patients with a surgical history related to lower urinary tract symptoms secondary to benign prostatic hyperplasia or a postvoid residual of 150 mL or greater were excluded. Eligible patients were randomly assigned to the 0.4 mg group (two tablets of 0.2 mg tamsulosin once daily) or the 0.2 mg group (one tablet of 0.2 mg tamsulosin and one tablet of placebo once daily). International Prostate Symptom Score, maximum flow rate, blood pressure, heart rate, and adverse events were compared between the two groups at 4 weeks and 12 weeks. A total of 220 patients were enrolled and analyzed. There were no differences in baseline characteristics between the two groups. After 12 weeks of medication, the International Prostate Symptom Score was not different between the two groups. However, the improvement in maximum flow rate was greater in the 0.4 mg group than the 0.2 mg group (3.0 ± 0.48 mL/s vs -0.25 ± 0.30 mL/s, P Tamsulosin 0.4 mg appears to be a safe treatment regimen for treating lower urinary tract symptoms secondary to benign prostatic hyperplasia in Asian patients who do not respond to 0.2 mg treatment. Increasing the dose of tamsulosin results in a significant improvement in maximum flow rate without any increase in cardiovascular complications. © 2014 The

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.

Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy.

Science.gov (United States)

Naiker, Suhashni; Connolly, Cathy; Wiesner, Lubbe; Kellerman, Tracey; Reddy, Tarylee; Harries, Anthony; McIlleron, Helen; Lienhardt, Christian; Pym, Alexander

2014-11-19

Pharmacokinetic interactions between rifampicin and protease inhibitors (PIs) complicate the management of HIV-associated tuberculosis. Rifabutin is an alternative rifamycin, for patients requiring PIs. Recently some international guidelines have recommended a higher dose of rifabutin (150 mg daily) in combination with boosted lopinavir (LPV/r), than the previous dose of rifabutin (150 mg three times weekly {tiw}). But there are limited pharmacokinetic data evaluating the higher dose of rifabutin in combination with LPV/r. Sub-optimal dosing can lead to acquired rifamycin resistance (ARR). The plasma concentration of 25-O-desacetylrifabutin (d-RBT), the metabolite of rifabutin, increases in the presence of PIs and may lead to toxicity. Sixteen patients with TB-HIV co-infection received rifabutin 300 mg QD in combination with tuberculosis chemotherapy (initially pyrazinamide, isoniazid and ethambutol then only isoniazid), and were then randomized to receive isoniazid and LPV/r based ART with rifabutin 150 mg tiw or rifabutin 150 mg daily. The rifabutin dose with ART was switched after 1 month. Serial rifabutin and d-RBT concentrations were measured after 4 weeks of each treatment. The median AUC0-48 and Cmax of rifabutin in patients taking 150 mg rifabutin tiw was significantly reduced compared to the other treatment arms. Geometric mean ratio (90% CI) for AUC0-48 and Cmax was 0.6 (0.5-0.7) and 0.5 (0.4-0.6) for RBT 150 mg tiw compared with RBT 300 mg and 0.4 (0.4-0.4) and 0.5 (0.5-0.6) for RBT 150 mg tiw compared with 150 mg daily. 86% of patients on the tiw rifabutin arm had an AUC0-24 ART, and grade 3 neutropenia (asymptomatic) was reported in 4 patients. These events were not associated with increases in rifabutin or metabolite concentrations. A daily 150 mg dose of rifabutin in combination with LPV/r safely maintained rifabutin plasma concentrations in line with those shown to prevent ARR. ClinicalTrials.gov Identifier: NCT00640887.

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.

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

Directory of Open Access Journals (Sweden)

Aloísio Sales da Cunha

1987-10-01

Full Text Available A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ and the quantitative Kato-Katz (K-K methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28% and K-K (80% became significative. When this number dropped to less than 2,000 the percentage of false negative

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.

Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study.

Science.gov (United States)

Weitz, Jeffrey I; Bauersachs, Rupert; Beyer-Westendorf, Jan; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Davidson, Bruce L; Holberg, Gerlind; Kakkar, Ajay; Lensing, Anthonie W A; Prins, Martin; Haskell, Lloyd; van Bellen, Bonno; Verhamme, Peter; Wells, Philip S; Prandoni, Paolo

2015-08-31

Patients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6-12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).

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.

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.

Randomised clinical trial: daily pantoprazole magnesium 40 mg vs. esomeprazole 40 mg for gastro-oesophageal reflux disease, assessed by endoscopy and symptoms.

Science.gov (United States)

Moraes-Filho, J P; Pedroso, M; Quigley, E M M

2014-01-01

Pantoprazole magnesium (pantoprazole-Mg) may display extended inhibition of the proton pump with the potential for improved clinical efficacy in gastro-oesophageal reflux disease (GERD). To compare the efficacy of pantoprazole-Mg and esomeprazole in GERD. Gastro-oesophageal reflux disease (Los Angeles grades A-D) patients were randomised to 4 weeks of treatment with pantoprazole-Mg (n = 290) or esomeprazole (n = 288), both 40 mg once daily, in this multicentre (14 Brazilian sites in 9 cities), double-blind study, with an additional 4 weeks' treatment in nonresponding patients. Severity of oesophagitis (at endoscopy) and GERD-related symptoms (ReQuest-GI) were assessed. The primary end point was the proportion of patients in complete remission (ReQuest-GI score <1.73 plus endoscopic healing) at week 4. Complete remission occurred in 61% of patients in each treatment group at 4 weeks (primary endpoint) and in 81% and 79% of patients in the pantoprazole-Mg and esomeprazole groups at 8 weeks, with no significant differences. Mucosal healing rates were high and not significantly different. At 8 weeks, symptom relief with pantoprazole-Mg was significantly greater than that with esomeprazole (91.6% vs. 86.0%, P = 0.0370) because of continued improvement in symptoms with pantoprazole-Mg from week 4 to week 8 (P = 0.0206). Pantoprazole-Mg 40 mg was at least as effective as esomeprazole 40 mg for complete remission and the mucosal healing rate was high. Symptom relief with pantoprazole-Mg continued to improve from 4 to 8 weeks and was greater than that with esomeprazole at week 8, suggesting an extended period of treatment effect (ClinicalTrials.gov identifier: NCT01132638). © 2013 John Wiley & Sons Ltd.

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.

Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer

International Nuclear Information System (INIS)

Yavuz, A. Aydin; Aydin, Fazil; Yavuz, Melek N.; Ilis, Esra; Ozdemir, Feyyaz

2001-01-01

Purpose: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer. Methods and Materials: Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m 2 (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m 2 (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m 2 increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0. Results: In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m 2 and 90 mg/m 2 . The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m 2 . Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease. Conclusion: A dose of TW-G at a level of 90 mg/m 2 produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m 2 dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma

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.

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

A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.

Science.gov (United States)

Paniz, Clovis; Bertinato, Juliano Felix; Lucena, Maylla Rodrigues; De Carli, Eduardo; Amorim, Patrícia Mendonça da Silva; Gomes, Guilherme Wataru; Palchetti, Cecília Zanin; Figueiredo, Maria Stella; Pfeiffer, Christine M; Fazili, Zia; Green, Ralph; Guerra-Shinohara, Elvira Maria

2017-09-01

Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown. Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase ( DHFR ), methylenetetrahydrofolate reductase ( MTHFR ), interferon γ ( IFNG ), tumor necrosis factor α ( TNFA ), and interleukin 8 ( IL8 ) genes; and concentrations of serum inflammatory markers. Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m 2 ) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells. Results: Serum folate concentrations increased by ∼5-fold after the intervention ( P 1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number ( P < 0.001) and cytotoxicity ( P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d ( P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d ( P = 0.001 for both). Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp. © 2017 American Society for Nutrition.

Dose Measurements in a Phantom Simulating Neonates by Using Different TL Materials: LiF:Mg,Cu,P and LiF:Mg,Ti

International Nuclear Information System (INIS)

Saez-Vergara, J.C.; Romero, A.M.; Fernandez, C.; Gomez, S.; Vazquez, J.; Olivares, M.P.

1999-01-01

A study reproducing usual exposure conditions in a special care baby unit has been performed to measure doses using TL materials in a versatile phantom specially designed for neonates having X ray examinations. The phantom offers the possibilities of reproducing different patient thicknesses and representing either a solid or hollow lung region. The results of the dose measurements using TL materials at the entrance, exit and both laterals of the phantom during different chest radiograph conditions are presented. Test conditions were reproduced in both hollow and solid chest cages simulating patient thicknesses of 5, 6 and 7 cm. The study was completed using two types of TL materials, LiF:Mg,Cu,P and LiF:Mg,Ti, in order to analyse and correct the differences on energy response between the two phosphors. (author)

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

NARCIS (Netherlands)

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

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

Measurements of low photon doses using LiF:Mg,Cu,P and CaF{sub 2}:Cu dosimeters

Energy Technology Data Exchange (ETDEWEB)

Prokert, K [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics; Mann, G [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics

1997-03-01

The new thermoluminophors LiF:Mg, Cu, P and CaF{sub 2}:Cu in form of pellets exhibit a significantly higher TL-response than the well-known dosimeters of the types TLD-100 (LiF:Mg, Ti), TLD-400 (CaF{sub 2}:Mn), TLD-900 (CaSO{sub 4}:Dy), etc. Furthermore, the thermoluminophor LiF:Mg, Cu, P shows besides its high sensitivity a good tissue equivalence and therefore, only a small variation of the dose response with the photon energy. The lower limits of detection of these new materials are about 5 {mu}Gy and 0.2 {mu}Gy resp. Therefore, short term measurements of absorbed dose can be realised in radiation fields at very low dose rates (environmental radiation, scattering radiation at medical equipment`s etc.) with an accuracy of {+-}10%. In the field of environmental monitoring the period of exposure can be limited to about 10 days. Using CaF{sub 2}:Cu detectors an exposure of 24 hours is sufficient for dose measurements with lower accuracy. The reusability of CaF{sub 2}:Cu pellets is guaranteed without loss of sensitivity independently of the application of different reading and annealing procedures. In the case of LiF:Mg, Cu, P detectors special procedures are needed in order to keep constant TL-properties. The results of dose measurements at low dose levels in different radiation fields demonstrate the advantages of these detector types. (orig.)

Gemfibrozil is a strong inactivator of CYP2C8 in very small multiple doses.

Science.gov (United States)

Honkalammi, J; Niemi, M; Neuvonen, P J; Backman, J T

2012-05-01

Therapeutic doses of gemfibrozil cause mechanism-based inactivation of CYP2C8 via formation of gemfibrozil 1-O-β-glucuronide. We investigated the extent of CYP2C8 inactivation caused by three different doses of gemfibrozil twice dailyfor 5 days, using repaglinide as a probe drug, in 10 healthy volunteers. At the end of this 5-day regimen, there were dose-dependent increases in the area under the plasma concentration–time curve from 0 to infinity (AUC0–∞) of repaglinide by3.4-, 5.5-, and 7.0-fold corresponding to 30, 100, and 600 mg of gemfibrozil, respectively, as compared with the control phase (P gemfibrozil 1-O-β-glucuronide, a gemfibrozil dose of 30 mg twice daily was estimated to inhibit CYP2C8 by >70% and 100 mg twice daily was estimated to inhibit it by >90%. Hence, gemfibrozil is a strong inactivator of CYP2C8 even in very small, subtherapeutic, multiple doses. Administration of small gemfibrozil doses may be useful in optimizing the pharmacokinetics of CYP2C8 substrate drugs and in reducing the formation of their potentially toxic metabolites via CYP2C8.

CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.

Science.gov (United States)

Mukonzo, Jackson K; Bisaso, Ronald K; Ogwal-Okeng, Jasper; Gustafsson, Lars L; Owen, Joel S; Aklillu, Eleni

2016-04-01

To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment outcomes and provide genotype-based EFV doses recommendations during for tuberculosis (TB)-HIV-1 cotreatment. EFV concentrations from 158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed using a population PK model. Simulated AUCs for 600 mg EFV dose were 1.2- and 2.4-times greater than the product label for Ugandans in general and CYP2B6*6/*6 genotypes respectively. EFV daily doses of 450 and 250 mg for Ugandans and CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures comparable to the product label. Around 450 and 250 mg daily doses might meet EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6/*6 genotypes, respectively.

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

Fevipiprant, an oral prostaglandin DP2 receptor (CRTh2) antagonist, in allergic asthma uncontrolled on low-dose inhaled corticosteroids.

Science.gov (United States)

Bateman, Eric D; Guerreros, Alfredo G; Brockhaus, Florian; Holzhauer, Björn; Pethe, Abhijit; Kay, Richard A; Townley, Robert G

2017-08-01

Dose-related efficacy and safety of fevipiprant (QAW039), an oral DP 2 (CRTh2) receptor antagonist, was assessed in patients with allergic asthma uncontrolled by low-dose inhaled corticosteroids (ICS).Adult patients were randomised to 12 weeks' treatment with once-daily (1, 3, 10, 30, 50, 75, 150, 300 or 450 mg q.d ) or twice-daily (2, 25, 75 or 150 mg b.i.d ) fevipiprant (n=782), montelukast 10 mg q.d (n=139) or placebo (n=137). All patients received inhaled budesonide 200 μg b.i.d Fevipiprant produced a statistically significant improvement in the primary end-point of change in pre-dose forced expiratory volume in 1 s at week 12 (p=0.0035) with a maximum model-averaged difference to placebo of 0.112 L. The most favourable pairwise comparisons to placebo were for the fevipiprant 150 mg q.d and 75 mg b.i.d groups, with no clinically meaningful differences between q.d and b.i.d Montelukast also demonstrated a significant improvement in this end-point. No impact on other efficacy end-points was observed. Adverse events were generally mild/moderate in severity, and were evenly distributed across doses and treatments.Fevipiprant appears to be efficacious and well-tolerated in this patient population, with an optimum total daily dose of 150 mg. Further investigations into the clinical role of fevipiprant in suitably designed phase III clinical trials are warranted. Copyright ©ERS 2017.

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.

Repeated dose 28-day oral toxicity study in Wistar rats with a mixture of five pesticides often found as residues in food: alphacypermethrin, bromopropylate, carbendazim, chlorpyrifos and mancozeb

DEFF Research Database (Denmark)

Jacobsen, H.; Østergaard, G.; Lam, Henrik Rye

2004-01-01

Six dose groups of 8 male and female rats respectively received a daily dose equivalent to 0, 0.15, 0.006, 0.03, 0.15 or 0.3 mg/kg b.w./day chlorpyrifos (groups 1-6) and the last four dose groups (groups 3-6) received in addition daily doses equivalent to 18 mg/kg b.w./day alphacypermethrin, 30 mg...... of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by coadministration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies...

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

Science.gov (United States)

Jamaludin, A; Mohamad, M; Navaratnam, V; Yeoh, P Y; Wernsdorfer, W H

1990-09-01

A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

Fixed-dose lercanidipine/enalapril for hypertension.

Science.gov (United States)

Menne, Jan; Haller, Hermann

2008-04-01

The dihydropyridine calcium channel blocker lercanidipine and the ACE inhibitor enalapril are frequently used in the treatment of hypertensive patients. In April 2007, a fixed-dose combination of the two drugs was approved in Germany for the treatment of patients not responding to monotherapy. It is expected that the drug will soon be available in the other European Union markets. In this review the present literature is summarized. Two doses will be available with 10 mg lercanidipine each and 10 or 20 mg enalapril. The medication should be taken once daily, optimally =15 minutes before a meal and the consumption of grapefruit juice should be avoided. The fixed-dose combination of the two drugs has a stronger blood pressure-lowering effect than monotherapy with 20 mg enalapril or 10 mg lercanidipine. The combination is well tolerated and few patients stopped the treatment because of side effects. As expected, the most common side effects reported are cough, peripheral edema, flushing, dizziness and vertigo, occurring in 1-5% of patients. This new fixed-dose combination is a useful adjunct to the present treatment and should increase compliance and help reduce hypertension-related costs. 2008 Prous Science, S.A.U. or its licensors

Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

Directory of Open Access Journals (Sweden)

Webster LR

2015-11-01

Full Text Available Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15 of placebo-treated subjects and 47% (7/15 of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001, and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001. Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. Keywords: opioid dependence, withdrawal symptoms, abuse-deterrent, buprenorphine

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.

SU-E-T-139: Automated Daily EPID Exit Dose Analysis Uncovers Treatment Variations

Energy Technology Data Exchange (ETDEWEB)

Olch, A [University of Southern California, Los Angeles, CA (United States)

2015-06-15

Purpose: To evaluate a fully automated EPID exit dose system for its ability to detect daily treatment deviations including patient setup, delivery, and anatomy changes. Methods: PerFRACTION (Sun Nuclear Corporation) software is a system that uses integrated EPID images taken during patient treatment and automatically pulled from the Aria database and analyzed based on user-defined comparisons. This was used to monitor 20 plans consisting of a total of 859 fields for 18 patients, for a total of 251 fractions. Nine VMAT, 5 IMRT, and 6 3D plans were monitored. The Gamma analysis was performed for each field within a plan, comparing the first fraction against each of the other fractions in each treatment course. A 2% dose difference, 1 mm distance-to-agreement, and 10% dose threshold was used. These tight tolerances were chosen to achieve a high sensitivity to treatment variations. The field passed if 93% of the pixels had a Gamma of 1 or less. Results: Twenty-nine percent of the fields failed. The average plan passing rate was 92.5%.The average 3D plan passing rate was less than for VMAT or IMRT, 84%, vs. an average of 96.2%. When fields failed, an investigation revealed changes in patient anatomy or setup variations, often also leading to variations of transmission through immobilization devices. Conclusion: PerFRACTION is a fully automated system for determining daily changes in dose transmission through the patient that requires no effort other than for the imager panel to be deployed during treatment. A surprising number of fields failed the analysis and can be attributed to important treatment variations that would otherwise not be appreciated. Further study of inter-fraction treatment variations is possible and warranted. Sun Nuclear Corporation provided a license to the software described.

Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction.

Science.gov (United States)

Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C

2015-02-01

Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

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.

Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

Science.gov (United States)

Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

2015-01-01

Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily

Successful withdrawal from high-dose benzodiazepine in a young patient through electronic monitoring of polypharmacy: a case report in an ambulatory setting.

Science.gov (United States)

Loscertales, Hèctor R; Wentzky, Valerie; Dürsteler, Kenneth; Strasser, Johannes; Hersberger, Kurt E; Arnet, Isabelle

2017-05-01

Dependence on high-dose benzodiazepines (BZDs) is well known and discontinuation attempts are generally unsuccessful. A well established protocol for high-dose BZD withdrawal management is lacking. We present the case of withdrawal from high-dose lorazepam (>20 mg daily) in an unemployed 35-year-old male outpatient through agonist substitution with long-acting clonazepam and electronic monitoring over 28 weeks. All medicines were repacked into weekly 7 × 4 cavity multidose punch cards with an electronic monitoring system. The prescribed daily dosages of BZDs were translated into an optimal number of daily tablets, divided into up to four units of use. Withdrawal was achieved by individual leftover of a small quantity of BZDs that was placed in a separate compartment. Feedback with visualization of intake over the past week was given during weekly psychosocial sessions. Stepwise reduction was obtained by reducing the mg content of the cavities proportionally to the leftovers, keeping the number of cavities in order to maintain regular intake behavior, and to determine the dosage decrease. At week 28, the primary objectives were achieved, that is, lorazepam reduction to 5 mg daily and cannabis abstinence. Therapy was continued using multidrug punch cards without electronic monitoring to maintain the management system. At week 48, a smaller size weekly pill organizer with detachable daily containers was dispensed. At week 68, the patient's therapy was constant with 1.5 mg clonazepam + 5 mg lorazepam daily for anxiety symptoms and the last steps of withdrawal were started. Several key factors led to successful withdrawal from high-dose BZD in this outpatient, such as the use of weekly punch cards coupled with electronic monitoring, the patient's empowerment over the withdrawal process, and the collaboration of several healthcare professionals. The major implication for clinical care is reduction by following the leftovers, and not a diktat from the healthcare

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.

Effect of low-dose versus higher-dose antenatal iron supplementation on child health outcomes at 36 months of age in Viet Nam: longitudinal follow-up of a cluster randomised controlled trial.

Science.gov (United States)

Hanieh, Sarah; Ha, Tran T; Simpson, Julie A; Braat, Sabine; Thuy, Tran T; Tran, Thach D; King, Janet; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2017-01-01

Intermittent iron-folic acid supplementation (IFA) is currently recommended for pregnant women in populations where anaemia prevalence among pregnant women is Viet Nam among children of 36 months of age, born to women previously enrolled in a cluster randomised controlled trial of antenatal micronutrient supplementation (daily IFA (60 mg elemental iron) vs twice-weekly IFA (60 mg elemental iron) vs twice-weekly multiple micronutrient (MMN) supplementation (60 mg elemental iron)). Primary outcomes were height-for-age z-scores (HAZ), according to WHO growth standards and cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) at 36 months of age. A total of 1017 children born to mothers enrolled in the cluster randomised trial were assessed at 36 months of age. Adjusted mean differences (MDs) in HAZ were -0.14 (95% CI -0.28 to -0.01) and -0.15 (95% CI -0.29 to -0.01) in children born to mothers who received twice-weekly IFA or MMN compared with those who received daily IFA. Children born to mothers who received twice-weekly MMN had lower composite motor scores compared with those who received daily IFA (MD -2.07, 95% CI -4.11 to -0.03). There were no differences in composite cognitive scores in the twice-weekly compared with daily regimens. Low-dose antenatal IFA supplementation (120 mg elemental iron per week) resulted in lower HAZ and motor composite scores in children compared with higher-dose antenatal IFA supplementation (420 mg elemental iron per week). This highlights the importance of adequate iron stores during pregnancy and the need for careful monitoring when lower-dose antenatal iron regimens are used. Australia New Zealand Clinical Trials Registry: 12610000944033.

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

Directory of Open Access Journals (Sweden)

Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Optimal Clinical Doses of Faropenem, Linezolid, and Moxifloxacin in Children With Disseminated Tuberculosis: Goldilocks.

Science.gov (United States)

Srivastava, Shashikant; Deshpande, Devyani; Pasipanodya, Jotam; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

2016-11-01

 When treated with the same antibiotic dose, children achieve different 0- to 24-hour area under the concentration-time curves (AUC 0-24 ) because of maturation and between-child physiological variability on drug clearance. Children are also infected by Mycobacterium tuberculosis isolates with different antibiotic minimum inhibitory concentrations (MICs). Thus, each child will achieve different AUC 0-24 /MIC ratios when treated with the same dose.  We used 10 000-subject Monte Carlo experiments to identify the oral doses of linezolid, moxifloxacin, and faropenem that would achieve optimal target exposures associated with optimal efficacy in children with disseminated tuberculosis. The linezolid and moxifloxacin exposure targets were AUC 0-24 /MIC ratios of 62 and 122, and a faropenem percentage of time above MIC >60%, in combination therapy. A linezolid AUC 0-24 of 93.4 mg × hour/L was target for toxicity. Population pharmacokinetic parameters of each drug and between-child variability, as well as MIC distribution, were used, and the cumulative fraction of response (CFR) was calculated. We also considered drug penetration indices into meninges, bone, and peritoneum.  The linezolid dose of 15 mg/kg in full-term neonates and infants aged up to 3 months and 10 mg/kg in toddlers, administered once daily, achieved CFR ≥ 90%, with linezolid AUC 0-24 associated with toxicity. The moxifloxacin dose of 25 mg/kg/day achieved a CFR > 90% in infants, but the optimal dose was 20 mg/kg/day in older children. The faropenem medoxomil optimal dosage was 30 mg/kg 3-4 times daily.  The regimen and doses of linezolid, moxifloxacin, and faropenem identified are proposed to be adequate for all disseminated tuberculosis syndromes, whether drug-resistant or -susceptible. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Vaginal bleeding following the use of a single dose of 1.5mg ...

African Journals Online (AJOL)

Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

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

The Concomitant Consumption of Cod Liver Oil Causes a Reduction in the Daily Diclofenac Sodium Usage in Rheumatoid Arthritis Patients: A Pilot Study

Science.gov (United States)

Gupta, Vinay Kumar; Khan, Z. Y. Zafer; Ahmad, Mushtaq

2013-01-01

Objective: To evaluate whether the concomitant consumption of Cod liver oil can reduce the daily dose of Diclofenac Sodium and probably the risk of the side effects which are associated with it in Rheumatoid Arthritis patients. Material and Methods: This longitudinal, prospective, open label study was conducted from April to September 2012 at Mahatma Gandhi Medical College and Hospital, Jaipur, India. 30 Rheumatoid Arthritis patients who were aged between 19 to 60 years, who fulfilled the inclusion criteria, were enrolled. Each patient was given five Cod liver oil capsules twice a day, for a period of 24 weeks. Each capsule which contained 300 mg of Cod liver oil had Eicosapentaenoic acid-20 mg and Docosahexaenoic acid-30 mg. The patients who took different Nonsteroidal anti-inflammatory drugs daily were switched over to Diclofenac Sodium 50 mg as a single dose, up to a maximum dose of 200 mg per day. The dose of Diclofenac Sodium which was consumed per day and the average daily requirement at different visits were recorded in each patient and they were compared. The patients were assessed for their pain scores by using the Visual Analogue Scale (VAS) at different weeks. In addition, the ‘Subjective Response’ to the pain was evaluated in each patient at the respective visits. The Student’s “t”-test was applied for the analysis of the VAS pain score and for the evaluation of the reduction in the mean daily dose of the Diclofenac Sodium consumption. A probability value of less than 0.05 (p< 0.05) was considered to be statistically significant. Moreover, the results of the ‘Subjective Response’ to the pain were expressed as percentage. Results: A significant decrease (p< 0.05) in the mean VAS pain score from 80.38 ± 6.4 at week 0 to 67.30 ± 5.3 at week 24 was noted in the patients. There was a significant reduction (p<0.05) in mean dose of Diclofenac Sodium consumed from 115.04 ± 24.56 at week 4 to 98.83 ± 22.32 at week 24. Moreover, the percentage

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.

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

Science.gov (United States)

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

2016-01-01

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

Liraglutide 3.0 mg for Weight Management: A Population Pharmacokinetic Analysis.

Science.gov (United States)

Overgaard, Rune V; Petri, Kristin C; Jacobsen, Lisbeth V; Jensen, Christine B

2016-11-01

This analysis used a population pharmacokinetic approach to identify covariates that influence plasma exposure of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management in overweight and obese individuals. Samples for pharmacokinetic analysis were drawn at weeks 2, 12 and 28 of the phase IIIa SCALE Obesity and Prediabetes (N = 2339) and SCALE Diabetes (N = 584) trials. Dose proportionality of liraglutide in obese subjects was investigated using data from a phase II dose-finding study (N = 331). Dose-proportional exposure of liraglutide up to and including 3.0 mg was confirmed. Body weight and sex influenced exposure of liraglutide 3.0 mg, while age ≥70 years, race, ethnicity and baseline glycaemic status did not. Compared with a reference subject weighing 100 kg, exposure of liraglutide 3.0 mg was 44 % lower for a subject weighing 234 kg (90 % CI 41-47), 41 % higher for a subject weighing 60 kg (90 % CI 37-46), and 32 % higher (90 % CI 28-35) in females than males with the same body weight. Neither injection site nor renal function significantly influenced exposure of liraglutide 3.0 mg (post hoc analysis). Population pharmacokinetics of liraglutide up to and including 3.0 mg daily in overweight and obese adults demonstrated dose-proportional exposure, and limited effect of covariates other than sex and body weight. These findings were similar to those previously observed with liraglutide up to 1.8 mg in subjects with type 2 diabetes mellitus. Further analysis of exposure-response relationship and its effect on dose requirements is addressed in a separate publication.

Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.

Science.gov (United States)

Rangwala, Reshma; Leone, Robert; Chang, Yunyoung C; Fecher, Leslie A; Schuchter, Lynn M; Kramer, Amy; Tan, Kay-See; Heitjan, Daniel F; Rodgers, Glenda; Gallagher, Maryann; Piao, Shengfu; Troxel, Andrea B; Evans, Tracey L; DeMichele, Angela M; Nathanson, Katherine L; O'Dwyer, Peter J; Kaiser, Jonathon; Pontiggia, Laura; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.

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

Science.gov (United States)

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

2018-05-01

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

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)

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...

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.

Optimal dose of losartan for renoprotection in diabetic nephropathy

DEFF Research Database (Denmark)

Andersen, Steen; Rossing, Peter; Juhl, Tina R

2002-01-01

filtration rate (GFR) ([(51)Cr]EDTA plasma clearance) were determined. RESULTS: Baseline values of albuminuria (geometric mean (95% CI)) and GFR (means+/-SEM) were 1138 (904-1432) mg/24 h and 91+/-3 ml/min/1.73 m(2), respectively. The blood pressure at baseline was 155/81+/-3/2 mmHg. All doses of losartan...... consecutive hypertensive type 1 diabetic patients with diabetic nephropathy received increasing doses of losartan, 50, 100, and 150 mg once daily in three periods each lasting 2 months. At baseline and at the end of each treatment period, albuminuria, 24-h blood pressure (TM2420 A&D), and glomerular...

[Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

Science.gov (United States)

Zavadenko, N N; Suvorinova, S Iu

2004-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

Science.gov (United States)

Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

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

Tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed-dose combination in moderate-to-severe acute pain: sustained analgesic effect over a 56-h period in the postoperative setting.

Science.gov (United States)

Montero Matamala, A; Bertolotti, M; Contini, M P; Guerrero Bayón, C; Nizzardo, A; Paredes Lario, I; Pizà Vallespir, B; Scartoni, S; Tonini, G; Capriati, A; Pellacani, A

2017-06-01

Multimodal analgesia constitutes a common strategy in pain management. A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain. This paper provides additional analyses on the results of two phase III clinical trials (DEX-TRA-04 and DEX-TRA-05) on postoperative pain to document its sustained effect. The analysis was applied to a modified intention-to-treat population (mITT, n = 933) of patients undergoing active treatment from the first dose, to assess the sustained effect of TRAM/DKP 75 mg/25 mg on pain intensity (PI-VAS 0-100) over 56 h from first drug intake. The superior analgesic effect of TRAM/DKP 75 mg/25 mg over 56 h in terms of difference in PI-VAS (mean [SE]) was shown for DEX-TRA-04 (-11.0 [0.55] over dexketoprofen 25 mg and -9.1 [0.55] over tramadol 100 mg, P ≤ 0.0001) and for DEX-TRA-05 (-10.4 [0.51] over dexketoprofen 25 mg and -8.3 [0.51] over tramadol 100 mg, P ≤ 0.0001). The statistical analysis performed on data coming from both studies confirms the superior sustained analgesia of TRAM/DKP 75 mg/25 mg over tramadol 100 mg and dexketoprofen 25 mg. These results are consistent with the previously published data obtained on the ITT population and strongly support the role of this oral fixed-dose combination in the treatment of moderate-to-severe acute pain. Copyright 2017 Clarivate Analytics.

Efficacy of 5MG and 10MG rosuvastatin in type-2 diabetes mellitus with hypercholesteroalemia

International Nuclear Information System (INIS)

Ullah, F.; Rahim, F.; Rahman, S.U.; Ashfaq, M.; Afridi, A.K.

2015-01-01

Background: Coronary Heart Disease (CHD) is the most important complication and the leading cause of death in patients with type 2 diabetes mellitus (T2DM). Hypercholesterolemia is an important modifiable risk factor for CHD. Statins are the first line drugs for the treatment of hypercholesterolemia in DM. Comparative studies between different statins are available but different doses of the same statin have not been compared in our population. The objective of this study is to compare mean reduction in serum LDL-C level after using 5mg and 10mg of rosuvastatin among T2DM patients with hypercholesterolemia. This study will help finding lowest effective dose of rosuvastatin to achieve internationally set low density lipoprotein cholesterol (LDL-C) goals. Method: A total of 82 patients with T2DM having fasting LDL-C levels equal or more than 100mg/dl were randomly allocated into two groups with 41 patients in each group. Baseline fasting serum LCL-C levels were obtained in all patients. Group A received 5mg while group B received 10mg of rosuvastatin daily at night. After 6 weeks, fasting LDL-C levels were obtained and analysed to compare the mean±SD reduction of LDL-C levels in both groups. Results: Baseline mean±SD LDL-C levels in group A and group B were 134.12±30.02 and 143.49±32.01 respectively (p 0.176). Follow up mean ± SD LDL-C levels were 81.59±28.47 and 83.24±36.06 respectively (p 0.818). Mean ± SD reduction in LDL-C levels from baseline levels in group A and group B were 52.51±19.49 and 60.20±24.09 (p 0.116). Conclusion: Rosuvastatin 5mg is as effective as 10mg in reducing the LDL-C levels in type 2 diabetic patients with hypercholesterolemia. (author)

Prophylactic single-dose administration of 600 mg clindamycin versus 4-time administration of 600 mg clindamycin in orthognathic surgery: A prospective randomized study in bilateral mandibular sagittal ramus osteotomies

NARCIS (Netherlands)

Lindeboom, Jerôme A. H.; Baas, Eric M.; Kroon, Frans H. M.

2003-01-01

Objective. The purpose of this study was to compare a single 600-mg dose of preoperative intravenously administered clindamycin with a 24-hour 600-mg regimen of clindamycin as prophylaxis for postoperative infections in bilateral sagittal ramus osteotomies. Study design. Seventy patients were

Measurement of extremely low level dose with LiF(Mg,Cu,P) TL chips

International Nuclear Information System (INIS)

Zha Ziying; Wang Shoushan; Wu Fang; Chen Guolong; Li Yuanfang; Zhu Jianhuan

1986-01-01

This paper presents some of the dosimetric characteristics of newly developed LiF(Mg,Cu,P) TL chips with high signal-to-noise ratio for measurement at the 10 -7 to 10 -4 Gy dose level. Measuring techniques and optimum procedures for annealing and readout are also presented. (author)

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

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens.

Science.gov (United States)

Haeseker, Michiel; Stolk, Leo; Nieman, Fred; Hoebe, Christian; Neef, Cees; Bruggeman, Cathrien; Verbon, Annelies

2013-01-01

The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

Science.gov (United States)

Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

2016-01-01

To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

Science.gov (United States)

Talan, David A; Klimberg, Ira W; Nicolle, Lindsay E; Song, James; Kowalsky, Steven F; Church, Deborah A

2004-02-01

We assessed the efficacy and safety of 1,000 mg extended release ciprofloxacin orally once daily vs conventional 500 mg ciprofloxacin orally twice daily, each for 7 to 14 days, in patients with a complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP). In this prospective, randomized, double-blind, North American multicenter clinical trial adults were stratified based on clinical presentation of cUTI or AUP and randomized to extended release ciprofloxacin or ciprofloxacin twice daily. Efficacy valid patients had positive pretherapy urine cultures (105 or greater cFU/ml) and pyuria within 48 hours of study entry. Bacteriological and clinical outcomes were assessed at the test of cure visit (5 to 11 days after therapy) and the late followup visit (28 to 42 days after therapy). The intent to treat population comprised 1,035 patients (extended release ciprofloxacin in 517 and twice daily in 518), of whom 435 were efficacy valid (cUTI in 343 and AUP in 92). For efficacy valid patients (cUTI and AUP combined) bacteriological eradication rates at test of cure were 89% (183 of 206) vs 85% (195 of 229) (95% CI -2.4%, 10.3%) and clinical cure rates were 97% (198 of 205) vs 94% (211 of 225) (95% CI -1.2%, 6.9%) for extended release vs twice daily ciprofloxacin. Late followup outcomes were consistent with test of cure findings. Eradication rates for Escherichia coli, which accounted for 58% of pathogens, were 97% or greater per group. Drug related adverse event rates were similar for extended release and twice daily ciprofloxacin (13% and 14%, respectively). Extended release ciprofloxacin at a dose of 1,000 mg once daily was as safe and effective as conventional treatment with 500 mg ciprofloxacin twice daily, each given orally for 7 to 14 days in adults with cUTI or AUP. It provides a convenient, once daily, empirical treatment option.

Detection of sub micro Gray dose levels using OSL phosphor LiMgPO_4:Tb,B

International Nuclear Information System (INIS)

Rawat, N.S.; Dhabekar, Bhushan; Muthe, K.P.; Koul, D.K.; Datta, D.

2017-01-01

Highlights: • LiMgPO4:Tb,B has been studied and shown to possesses minimum measurable dose (MMD) in sub micro Gray region. • MMD as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm"2 has been achieved. • The OSL measurements for low doses has strengthened and validated this claim. • OSL spectrum shows several emission peaks and the prominent peak around 380 nm. - Abstract: Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO_4:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb"3"+ emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW–) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm"2 has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Science.gov (United States)

Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

Directory of Open Access Journals (Sweden)

Germana Bancone

Full Text Available Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20% in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg to Artemisinin-based Combination Therapies (ACTs without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant approximates 15%.The tolerability and safety of primaquine (single dose 0.25 mg base/kg combined with dihydroartemisinin-piperaquine (DHA-PPQ given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4

Patch test concentrations (doses in mg/cm2 ) for the 12 non-mix fragrance substances regulated by European legislation.

Science.gov (United States)

Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner; Bruynzeel, Derk; Goossens, An; Johansen, Jeanne Duus; Matura, Mihaly; Orton, David; Vigan, Martine

2012-03-01

According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. To establish the optimal patch test doses in mg/cm2 for the 12 fragrance substances that are not included in fragrance mix I or II in the European baseline patch test series. Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual maximum concentration/dose was determined for each fragrance substance. The predetermined maximum patch test concentrations/doses could be tested for all 12 fragrance substances, with no observable adverse reactions being noted. For each fragrance substance investigated, it is recommended that half of the maximum patch test dose (mg/cm2) be used for aimed and screening patch testing. © 2012 John Wiley & Sons A/S.

Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

NARCIS (Netherlands)

Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

1997-01-01

This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

Why did the FDA approve efavirenz 800 mg when co-administered with rifampin?

Science.gov (United States)

Liu, Jiang; Chan-Tack, Kirk M; Jadhav, Pravin; Seo, Shirley; Robertson, Sarah M; Kraft, Jeffrey; Singer, Mary E; Struble, Kimberly A; Arya, Vikram

2014-06-01

Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue. DDI study and supportive semi-mechanistic population PK analyses were provided by BMS. Population PK analysis was based on six studies with intensive EFV PK sampling. An ACTG study with sparse PK sampling was used for model evaluation. Simulations compared EFV exposure at various doses in combination with RIF to EFV exposures at 600 mg once daily (QD). Effects of CYP2B6 genotypes on the magnitude of EFV-RIF interaction were also explored. In DDI study, co-administering EFV 600 mg QD and RIF reduced mean EFV exposure by ~ 30%. Population PK model provided acceptable predictive performance of central tendency and variability for EFV C0, Cmax, and AUC. Simulations predicted that increasing EFV to 800 mg QD with RIF would result in EFV AUC and Cmax similar to EFV 600 mg QD alone. EFV AUC and Cmax were ~ 2 times higher in subjects with reduced function CYP2B6 genotypes. However, the RIF effect was consistent across all genotypes. EFV dose adjustment to 800 mg QD did not increase the risk of overexposure compared to 600 mg EFV QD within each genotype. Dose adjustment based on matching systemic exposure was recommended to mitigate the potential for sub-therapeutic EFV exposures. Our review did not reveal any safety concerns in subjects receiving EFV 800 mg QD with RIF.

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

Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

Directory of Open Access Journals (Sweden)

Farzad Gheshlaghi

2013-03-01

Full Text Available Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patients were divided into three groups according to methadone daily dose (G1: 0-59 mg, G2: 60-109 mg, G3: 110-150 mg. Twelve-lead electrocardiograms (ECG were performed at baseline and two months later, after reaching the maximum daily dose of methadone. The QTc were calculated for each patient. Comparison of mean QTc and mean QTc prolongation between baseline and follow up ECGs were analyzed. Results: In total, mean (SD age was 32.4 (8.5. TdP was not detected in any patients. Mean QTc was 405.2 (17.0 and 418.5 (23.1 msec before and two months after MMT respectively. There was a significant difference between mean QTc in each group before and after treatment (P

Efficacy of sacubitril/valsartan vs. enalapril at lower than target doses in heart failure with reduced ejection fraction: the PARADIGM-HF trial.

Science.gov (United States)

Vardeny, Orly; Claggett, Brian; Packer, Milton; Zile, Michael R; Rouleau, Jean; Swedberg, Karl; Teerlink, John R; Desai, Akshay S; Lefkowitz, Martin; Shi, Victor; McMurray, John J V; Solomon, Scott D

2016-10-01

In this analysis, we utilized data from PARADIGM-HF to test the hypothesis that participants who exhibited any dose reduction during the trial would have similar benefits from lower doses of sacubitril/valsartan relative to lower doses of enalapril. In a post-hoc analysis from PARADIGM-HF, we characterized patients by whether they received the maximal dose (200 mg sacubitril/valsartan or 10 mg enalapril twice daily) throughout the trial or had any dose reduction to lower doses (100/50/0 mg sacubitril/valsartan or 5/2.5/0 mg enalapril twice daily). The treatment effect for the primary outcome was estimated, stratified by dose level using time-updated Cox regression models. In the two treatment arms, participants with a dose reduction (43% of those randomized to enalapril and 42% of those randomized to sacubitril/valsartan) had similar baseline characteristics and similar baseline predictors of the need for dose reduction. In a time-updated analysis, any dose reduction was associated with a higher subsequent risk of the primary event [hazard ratio (HR) 2.5, 95% confidence interval (CI) 2.2-2.7]. However, the treatment benefit of sacubitril/valsartan over enalapril following a dose reduction was similar (HR 0.80, 95% CI 0.70-0.93, P sacubitril/valsartan relative to those on lower doses of enalapril was similar to that of patients who remained on target doses of both drugs. © 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Pharmacokinetic Modeling of Voriconazole To Develop an Alternative Dosing Regimen in Children.

Science.gov (United States)

Gastine, Silke; Lehrnbecher, Thomas; Müller, Carsten; Farowski, Fedja; Bader, Peter; Ullmann-Moskovits, Judith; Cornely, Oliver A; Groll, Andreas H; Hempel, Georg

2018-01-01

The pharmacokinetic variability of voriconazole (VCZ) in immunocompromised children is high, and adequate exposure, particularly in the first days of therapy, is uncertain. A population pharmacokinetic model was developed to explore VCZ exposure in plasma after alternative dosing regimens. Concentration data were obtained from a pediatric phase II study. Nonlinear mixed effects modeling was used to develop the model. Monte Carlo simulations were performed to test an array of three-times-daily (TID) intravenous dosing regimens in children 2 to 12 years of age. A two-compartment model with first-order absorption, nonlinear Michaelis-Menten elimination, and allometric scaling best described the data (maximal kinetic velocity for nonlinear Michaelis-Menten clearance [ V max ] = 51.5 mg/h/70 kg, central volume of distribution [ V 1 ] = 228 liters/70 kg, intercompartmental clearance [ Q ] = 21.9 liters/h/70 kg, peripheral volume of distribution [ V 2 ] = 1,430 liters/70 kg, bioavailability [ F ] = 59.4%, K m = fixed value of 1.15 mg/liter, absorption rate constant = fixed value of 1.19 h -1 ). Interindividual variabilities for V max , V 1 , Q , and F were 63.6%, 45.4%, 67%, and 1.34% on a logit scale, respectively, and residual variability was 37.8% (proportional error) and 0.0049 mg/liter (additive error). Monte Carlo simulations of a regimen of 9 mg/kg of body weight TID simulated for 24, 48, and 72 h followed by 8 mg/kg two times daily (BID) resulted in improved early target attainment relative to that with the currently recommended BID dosing regimen but no increased rate of accumulation thereafter. Pharmacokinetic modeling suggests that intravenous TID dosing at 9 mg/kg per dose for up to 3 days may result in a substantially higher percentage of children 2 to 12 years of age with adequate exposure to VCZ early during treatment. Before implementation of this regimen in patients, however, validation of exposure, safety, and tolerability in a carefully designed

Pharmacokinetics, safety and efficacy of ritonavir-boosted atazanavir (300/100 mg once daily) in HIV-1-infected pregnant women.

Science.gov (United States)

Lê, Minh P; Mandelbrot, Laurent; Descamps, Diane; Soulié, Cathia; Ichou, Houria; Bourgeois-Moine, Agnès; Damond, Florence; Lariven, Sylvie; Valantin, Marc-Antoine; Landman, Roland; Faucher, Philippe; Tubiana, Roland; Duro, Dominique; Meier, Françoise; Legac, Sylvie; Bourse, Patricia; Mortier, Emmanuel; Dommergues, Marc; Calvez, Vincent; Matheron, Sophie; Peytavin, Gilles

2015-01-01

Atazanavir/ritonavir (ATV/r) is a boosted protease inhibitor recommended to minimize the risk of mother-to-child HIV-1 transmission (MTCT). We aimed to assess the pharmacokinetics, safety and efficacy of ATV/r in HIV-1-infected pregnant women and their neonates. A multicentre, cross-sectional, non-interventional cohort of HIV-1-infected pregnant women receiving ATV/r (300/100 mg once daily) who delivered in three Paris hospitals from 2006 to 2013 was designed. We determined antiretroviral trough plasma concentrations using liquid chromatography-mass spectrometry at each of the three trimesters, delivery and post-partum. ATV concentrations at 24 h (C24h) were interpreted by the 150-850 ng/ml efficacy-tolerance thresholds. Safety data and newborn HIV status were recorded. A mother's virological failure was defined as two successive measurements of plasma HIV-1 RNA>50 copies/ml within the 2 months before delivery. 103 pregnant women were included, mostly from sub-Saharan Africa (88%). ATV C24h at each of the three trimesters and delivery remained similar to post-partum values. No dose adjustment was needed during pregnancy. The median plasma ratio of fetal/maternal ATV level was 0.19 (n=28). Only three patients showed two successive detectable viral loads but <400 copies/ml. Among 82 available newborn data, 16 were born preterm. Three in utero deaths occurred. Tolerance was good with one case of maternal grade 3 hyperbilirubinaemia, no cases in neonates at delivery and no clinically relevant adverse event. No case of MTCT was reported. In this population, an ATV/r-containing antiretroviral regimen demonstrated good pharmacokinetics, virological efficacy and safety. No significant impact of pregnancy on ATV C24h was found. No dose adjustment was required.

Patch test concentrations (doses in mg/cm(2) ) for the 12 non-mix fragrance substances regulated by European legislation

DEFF Research Database (Denmark)

Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner

2012-01-01

Background. According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. Objectives. To establish the optimal patch test doses in mg/cm(2) for the 12 fragrance substances......, it is recommended that half of the maximum patch test dose (mg/cm(2) ) be used for aimed and screening patch testing....... that are not included in fragrance mix I or II in the European baseline patch test series. Materials and Methods. Patch testing with the 12 fragrance substances was performed in a stepwise manner encompassing up to five rounds in at least 100 dermatitis patients for each round. Before patch testing, an individual...

Interference of intrinsic UV response of LiF:Mg,Ti (Poland) pellets in dose reassessment

International Nuclear Information System (INIS)

Bhasin, B.D.; Kalyane, G.N.; Kathuria, S.P.; Sunta, C.M.

1987-01-01

The thermoluminescence (TL) behaviour of sintered pellets of LiF:Mg,Ti (Poland) (LiF(P)) is markedly different from that of LiF:Mg,Ti TLD-100 (Harshaw) phosphor as far as their intrinsic responses to ultraviolet (UV) (253.7 nm) radiation are concerned. The intrinsic response of LiF(P) phosphor is very much dependent on the physical form of the phosphor. In addition, it is highly sensitive to any changes in experimental conditions such as the nature of the atmosphere during readout, the pre-heat and the readout history of the phosphor. The high intrinsic UV response (IUVR) of LiF(P) interferes in the dose reassessment by the PTTL (photo-transferred thermoluminescence) technique. Nevertheless, a fortuitous situation exists wherein a PTTL dosimetry peak signal is seen clearly over-riding the IUVR valley at the corresponding point of the glow curve. A procedure to correct for the IUVR interference and to re-estimate the dose by the PTTL technique is described. (author)

Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg.

Science.gov (United States)

Wesnes, Keith A; Edgar, Chris; Tretter, Reiner N; Bolodeoku, John

2009-11-01

To assess the cognitive effects of single doses of solifenacin 10 mg compared with placebo (primary objective) and oxybutynin immediate release (IR) 10 mg (secondary objective) in elderly subjects. Single-centre, randomised, double-blind, placebo-controlled study in 12 healthy elderly volunteers, with three crossover periods separated by two 14-day washout periods. Each sequence consisted of a single dose of solifenacin 10 mg in one period, oxybutynin IR 10 mg in another and placebo in another. Aspects of attention, information processing, working memory, episodic memory and self-rated mood and alertness were tested using the validated Cognitive Drug Research computerised assessment system. There was no evidence from absolute mean values or changes from baseline to suggest that solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no statistically significant cognitive deterioration with solifenacin versus placebo, when measured at a time point closest to the probable C(max) of solifenacin. Oxybutynin was associated with statistically significant impairments in several measures of cognitive function at a time point corresponding with its probable C(max). In this pilot study, single 10 mg doses of solifenacin did not show any clear propensity to impair cognitive function in a healthy elderly population.

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)

Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group.

Science.gov (United States)

Fleischmann, R; Mease, P J; Schwartzman, S; Hwang, L-J; Soma, K; Connell, C A; Takiya, L; Bananis, E

2017-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis investigated the effect of methotrexate (MTX) dose on the efficacy of tofacitinib in patients with RA. ORAL Scan (NCT00847613) was a 2-year, randomized, Phase 3 trial evaluating tofacitinib in MTX-inadequate responder (IR) patients with RA. Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo, with low (≤12.5 mg/week), moderate (>12.5 to tofacitinib 5 mg BID (N = 321), tofacitinib 10 mg BID (N = 316), or placebo (N = 160); 242, 333, and 222 patients received low, moderate, and high MTX doses, respectively. At months 3 and 6, ACR20/50/70 response rates were greater for both tofacitinib doses vs placebo across all MTX doses. At month 3, mean changes from baseline in CDAI and HAQ-DI were significantly greater for both tofacitinib doses vs placebo, irrespective of MTX category; improvements were maintained at month 6. Both tofacitinib doses demonstrated improvements in DAS28-4(ESR), and less structural progression vs placebo, across MTX doses at month 6. Tofacitinib plus MTX showed greater clinical and radiographic efficacy than placebo in MTX-IR patients with RA, regardless of MTX dose.

A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

Science.gov (United States)

Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

2016-11-01

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose

[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.

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)

Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction

Directory of Open Access Journals (Sweden)

Hagen KB

2018-01-01

Full Text Available Kerry B Hagen,1 Raman Bedi,2 Caroline A Blackie,3 Kellie J Christenson-Akagi1 1EyeHealth Northwest, Portland, OR, USA; 2Iris Advanced Eye Centre, Chandigarh, India; 3TearScience, Inc., Morrisville, NC, USA Purpose: The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD.Methods: This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED], meibomian gland (MG function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE, tear breakup time (TBUT and corneal and conjunctival staining.Results: In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53, SPEED score (11.00±3.30 to 5.42±2.15, TBUT (6.26±2.01 to 8.44±1.81, corneal staining (0.38±0.50 to 0.12±0.33 and conjunctival staining (1.69±1.93 to 0.62±0.85. In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91, SPEED score (13.42±4.17 to 9.42±5.47 and conjunctival staining (2.38±1.88 to 1.13±1.51, but the improvement in TBUT (6.90±2.56 to 7.59±2.03 and corneal staining (0.21±0.41 to 0.13±0.34 was not statistically significant (p=0.262 and p=0.414, respectively. At 3 months, SPEED score was significantly better in the VTP group (p<0.05; other parameters were comparable between the two groups.Conclusion: A single 12-minute bilateral VTP procedure was significantly more effective than the 3-month daily course of oral doxycycline at improving the dry eye symptoms secondary to MGD. A single

Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

International Nuclear Information System (INIS)

Ford, Judith M.; Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

2007-01-01

Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide

Whole-body dose and energy measurements in radiotherapy by a combination of LiF:Mg,Cu,P and LiF:Mg,Ti.

Science.gov (United States)

Hauri, Pascal; Schneider, Uwe

2018-04-01

Long-term survivors of cancer who were treated with radiotherapy are at risk of a radiation-induced tumor. Hence, it is important to model the out-of-field dose resulting from a cancer treatment. These models have to be verified with measurements, due to the small size, the high sensitivity to ionizing radiation and the tissue-equivalent composition, LiF thermoluminescence dosimeters (TLD) are well-suited for out-of-field dose measurements. However, the photon energy variation of the stray dose leads to systematic dose errors caused by the variation in response with radiation energy of the TLDs. We present a dosimeter which automatically corrects for the energy variation of the measured photons by combining LiF:Mg,Ti (TLD100) and LiF:Mg,Cu,P (TLD100H) chips. The response with radiation energy of TLD100 and TLD100H compared to 60 Co was taken from the literature. For the measurement, a TLD100H was placed on top of a TLD100 chip. The dose ratio between the TLD100 and TLD100H, combined with the ratio of the response curves was used to determine the mean energy. With the energy, the individual correction factors for TLD100 and TLD100H could be found. The accuracy in determining the in- and out-of-field dose for a nominal beam energy of 6MV using the double-TLD unit was evaluated by an end-to-end measurement. Furthermore, published Monte Carlo (M.C.) simulations of the mean photon energy for brachytherapy sources, stray radiation of a treatment machine and cone beam CT (CBCT) were compared to the measured mean energies. Finally, the photon energy distribution in an Alderson phantom was measured for different treatment techniques applied with a linear accelerator. Additionally, a treatment plan was measured with a cobalt machine combined with an MRI. For external radiotherapy, the presented double-TLD unit showed a relative type A uncertainty in doses of -1%±2% at the two standard deviation level compared to an ionization chamber. The type A uncertainty in dose was in

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...

The effect of pre-dose on thermally and optically stimulated luminescence from α-Al2O3:C,Mg and α-Al2O3:C.

Science.gov (United States)

Kalita, J M; Chithambo, M L

2018-06-15

We report the effect of pre-dose on the thermoluminescence (TL) and optically stimulated luminescence (OSL) dose response of α-Al 2 O 3 :C,Mg and α-Al 2 O 3 :C. Before any luminescence measurement, the samples were irradiated with different doses, namely 100, 500 and 1000 Gy to populate the deep electron traps. This is the pre-dose. The results from TL and OSL studies are compared with results from samples used without any pre-measurement dose. The TL glow curves and OSL decay curves of α-Al 2 O 3 :C,Mg recorded after pre-doses of 100, 500 and 1000 Gy are identical to those from a sample used without any pre-dose. Further, the TL and OSL dose response of all α-Al 2 O 3 :C,Mg samples are similar regardless of pre-dose. In comparison, the TL glow curves and OSL decay curves of α-Al 2 O 3 :C are influenced by pre-dose. We conclude that the differences in the TL and OSL dose response of various pre-dosed samples of α-Al 2 O 3 :C are due to the concentration of charge in the deep traps. On the other hand, owing to the lower concentration of such deep traps in α-Al 2 O 3 :C,Mg, the TL or OSL dose responses are not affected by pre-dose in this material. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics Compared With Immediate-Release Tofacitinib and Impact of Food.

Science.gov (United States)

Lamba, Manisha; Wang, Rong; Fletcher, Tracey; Alvey, Christine; Kushner, Joseph; Stock, Thomas C

2016-11-01

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 (C max ) 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. C max 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. © 2016, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

DEFF Research Database (Denmark)

Dahl, J B; Rosenberg, J; Hansen, B L

1992-01-01

In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

Science.gov (United States)

Wu, C; Zhang, H; Qian, Y; Wang, L; Gu, X; Dai, Z

2013-08-01

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication. © 2013 John Wiley & Sons Ltd.

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.

[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.

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.

Detection of sub micro Gray dose levels using OSL phosphor LiMgPO{sub 4}:Tb,B

Energy Technology Data Exchange (ETDEWEB)

Rawat, N.S., E-mail: naru@barc.gov.in [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Dhabekar, Bhushan [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Muthe, K.P. [Technical Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Koul, D.K.; Datta, D. [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)

2017-04-15

Highlights: • LiMgPO4:Tb,B has been studied and shown to possesses minimum measurable dose (MMD) in sub micro Gray region. • MMD as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved. • The OSL measurements for low doses has strengthened and validated this claim. • OSL spectrum shows several emission peaks and the prominent peak around 380 nm. - Abstract: Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO{sub 4}:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb{sup 3+} emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW–) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

2017-01-01

AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p birth. CONCLUSION: A single high...

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

Science.gov (United States)

Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

2017-01-01

Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

Comparison of a single-dose vectored thermal pulsation procedure with a 3-month course of daily oral doxycycline for moderate-to-severe meibomian gland dysfunction.

Science.gov (United States)

Hagen, Kerry B; Bedi, Raman; Blackie, Caroline A; Christenson-Akagi, Kellie J

2018-01-01

The aim of this study was to compare the efficacy of a single bilateral 12-minute vectored thermal pulsation (VTP) procedure versus daily oral doxycycline for 3 months for moderate-to-severe meibomian gland dysfunction (MGD). This prospective, randomized, parallel-group, single-masked study included 28 subjects who received either a single-dose VTP or 3 months of doxycycline treatment. At baseline and 3 months post treatment, all subjects were evaluated for the following: dry eye symptoms with a standard dry eye questionnaire (the Standard Patient Evaluation for Eye Dryness [SPEED]), meibomian gland (MG) function by counting the number of glands yielding liquid secretion with the MG evaluator (MGE), tear breakup time (TBUT) and corneal and conjunctival staining. In the VTP group, at 3 months, there was a significant improvement in MG function (4.00±1.47 to 7.73±5.53), SPEED score (11.00±3.30 to 5.42±2.15), TBUT (6.26±2.01 to 8.44±1.81), corneal staining (0.38±0.50 to 0.12±0.33) and conjunctival staining (1.69±1.93 to 0.62±0.85). In the doxycycline group, there was a significant improvement in MG function (4.63±1.41 to 10.63±5.91), SPEED score (13.42±4.17 to 9.42±5.47) and conjunctival staining (2.38±1.88 to 1.13±1.51), but the improvement in TBUT (6.90±2.56 to 7.59±2.03) and corneal staining (0.21±0.41 to 0.13±0.34) was not statistically significant ( p =0.262 and p =0.414, respectively). At 3 months, SPEED score was significantly better in the VTP group ( p oral doxycycline at improving the dry eye symptoms secondary to MGD. A single 12-minute VTP treatment was at least as effective as a dose of doxycycline for 3 months, in improving MG function and all measured signs of MGD. Given the minimal risk profile of the single VTP procedure over long-term doxycycline use, a single VTP presents a favorable alternative to long-term antibiotic use.

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

Science.gov (United States)

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

2016-10-01

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

Pharmacokinetically guided sunitinib dosing: a feasibility study in patients with advanced solid tumours

NARCIS (Netherlands)

Lankheet, N.; Kloth, J.S.; Gadellaa-van Hooijdonk, C.G.M.; Cirkel, G.A.; Mathijssen, R.H.; Lolkema, M.P.; Schellens, J.H.; Voest, E.E.; Sleijfer, S.; Jonge, M.J. de; Haanen, J.B.; Beijnen, J.H.; Huitema, A.D.; Steeghs, N.

2014-01-01

Background:Plasma exposure of sunitinib shows large inter-individual variation. Therefore, a pharmacokinetic (PK) study was performed to determine safety and feasibility of sunitinib dosing based on PK levels.Methods:Patients were treated with sunitinib 37.5 mg once daily. At days 15 and 29 of

Reduced protection of stem spermatogonia by WR-2721 at low doses of irradiation

International Nuclear Information System (INIS)

Meistrich, M.; Finch, M.; Hunter, N.; Milas, L.

1984-01-01

The radioprotection of normal cells with WR-2721 at low doses of radiation (about 2 Gy per fraction) was investigated using testicular stem cells. Survival of stem spermatogonia to single doses of irradiation, measured using sperm head counts at 56 days postirradiation, indicated no protection factor (PF = 1.00) at 2 GY by 400 mg/kg WR-2721, but a significant PF = 1.44 at 12 Gy. Stem cell survival was also measured after 5 fractions. When daily fractionation was used with 300 mg/kg WR-2721, given prior to each irradiation, little or no protection was observed at 2 Gy using the sperm head assay (PF = 0.98) or at 2.4 Gy using counts of repopulating tubules at 35 days postirradiation (PF = 1.12). In contrast, there was more significant protection (PF's = 1.22 and 1.27) for these two assays when 300 mg/kg WR-2721 was used with single high doses of radiation. When 4-hour fractionation was used with 300 mg/kg WR-2721, given prior to the first dose and 150 mg/kg prior to subsequent doses, minimal protection was observed at 2 Gy/fraction using the sperm head assay (PF = 0.98) and the repopulating tubule assay (PF = 1.09). Thus, protection of these cells in the clinical dose range is much lower than that observed at doses above 10 Gy. These results may be explained by a decrease in the intrinsic ability of WR-2721 to protect at lower radiation doses plus a cytotoxic effect of WR-2721

Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.

Science.gov (United States)

Krishna Kumar, Dhakchinamoorthi; Shewade, Deepak Gopal; Loriot, Marie-Anne; Beaune, Philippe; Balachander, Jayaraman; Sai Chandran, B V; Adithan, Chandrasekaran

2014-01-01

To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. Patients receiving stabilized warfarin therapy (n=257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) (pmaintenance dose. Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations.

Growth performance and feed utilization of keureling (Tor tambra fingerlings fed a formulated diet with different doses of vitamin E (alpha-tocopherol

Directory of Open Access Journals (Sweden)

Muchlisin Zainal A.

2016-03-01

Full Text Available The objective of the present study was to determine the optimum dosage of vitamin E (alpha-tocopherol in the diet of keureling, Tor tambra (Val. fingerlings for optimal growth performance and feed utilization. Five doses of vitamin E were tested: 0 mg kg−1 feed (control; 150 mg kg−1 feed; 300 mg kg−1 feed; 450 mg kg−1 feed; 600 mg kg−1. The feed ratio was 5% body weight, which was delivered twice daily at 08:00 and 17:00 for 60 days. The results showed that higher growth performance, feeding conversion ratios, feed efficiency, protein retention, and protein digestibility were obtained at 600 mg kg−1 feed, but the value was not significantly different from the other doses. The optimal dose in terms of the hepatosomatic index and survival rate was 300 mg kg−1. Hence, it was concluded that the optimum, most economical dose of vitamin E supplement for keureling (T. tambra was 150 mg kg−1 feed, because this value was not significantly different from the doses of 300 and 600 mg kg−1 feed.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Tofacitinib 5 mg Twice Daily in Patients with Rheumatoid Arthritis and Inadequate Response to Disease-Modifying Antirheumatic Drugs: A Comprehensive Review of Phase 3 Efficacy and Safety.

Science.gov (United States)

Bird, Paul; Bensen, William; El-Zorkany, Bassel; Kaine, Jeffrey; Manapat-Reyes, Bernadette Heizel; Pascual-Ramos, Virginia; Witcombe, David; Soma, Koshika; Zhang, Richard; Thirunavukkarasu, Krishan

2018-05-24

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs. A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed. Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib. Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where

Acetylsalicylic Acid Daily vs Acetylsalicylic Acid Every 3 Days in Healthy Volunteers: Effect on Platelet Aggregation, Gastric Mucosa, and Prostaglandin E2 Synthesis.

Science.gov (United States)

Ferreira, Plinio Minghin Freitas; Gagliano-Jucá, Thiago; Zaminelli, Tiago; Sampaio, Marinalva Ferreira; Blackler, Rory Willian; Trevisan, Miriam da Silva; Novaes Magalhães, Antônio Frederico; De Nucci, Gilberto

2016-07-01

Substantial platelet inhibition was observed 3 days after a single administration of acetylsalicylic acid 81 mg to healthy volunteers. Here we investigate prostaglandin E2 (PGE2 ) antrum concentrations and gastrointestinal symptoms in two treatment groups: one receiving losartan and acetylsalicylic acid every day and the other receiving losartan every day and acetylsalicylic acid every 3 days. Twenty-eight healthy volunteers from both sexes received either 50 mg losartan and acetylsalicylic acid 81 mg daily or 50 mg losartan and acetylsalicylic acid 81 every 3 days with placebo on the other days. Therapy was delivered for 30 days for both groups. Gastric endoscopy was performed before and after treatment period. Biopsies were collected for PGE2 quantification. Platelet function tests were carried out before and during treatment and TXB2 release on platelet rich plasma was measured. The every 3 day low-dose acetylsalicylic acid regimen produced complete inhibition of platelet aggregation compared to the daily treatment. Thromboxane B2 release was substantially abolished for both groups during treatment. There was no significant difference on the endoscopic score of both treatment groups after the 30-day treatment (P = .215). There was over 50% suppression of antrum PGE2 content on volunteers receiving acetylsalicylic acid daily (P = .0016), while for the every 3 day dose regimen there was no significant difference between pre and post-treatment antrum PGE2 dosages (P = .4193). Since PGE2 is involved in gastric healing, we understand that this new approach could be safer and as efficient as the standard daily therapy on a long-term basis. © 2015, The American College of Clinical Pharmacology.

Assessment of daily intake of major and trace elements by inhabitants of potential radiation protection of greater Cairo area, Egypt

International Nuclear Information System (INIS)

Ramadan, A.B.

2005-01-01

Concentrations of K, Ca, U, Th, Cs, Sr, I, Al, Cd, Cu, Mn, Pb, Ni and Cr were determined in vegetables, common foodstuffs and some animal products consumed by adult inhabitants of Greater Cairo Area. Some of these elements have chemical and biological similarity to some of the radionuclides abundantly encountered during nuclear power production and therefore data on these elements could provide important information on their biokinetic behavior. A total of 120 samples were analyzed using Neutron Activation Analysis (NAA) and Atomic Absorption Spectrometry (AAS). Generally, highest contributions for the intake of micro nutrients (Cu, Mn and Ni) arise from broad bean, rice and wheat flour consumption. Meat, milk, eggs and some vegetables are the major sources of K, Ca, U, Th, Cs, Al, Cd and Pb. The medium daily intake for the adult inhabitants of greater Cairo area was found to be 1.98 g of K, 0.54 mg of Ca, 1.14 fig of U, 0.8 μg of Th, 5.2μg of Cs, 1.3 mg of Sr, 105 μg of 1, 3.2 mg of Mn, 0.9 mg of Cu, 5.7 mg of Al, 5, 2 x 10 -2 mg of Pb, 2.1x10 -3 mg of Cd, 7.7x10 -2 mg of Ni and 2.1 x 10 -2 mg of Cr. The lower daily intake of Ca, Th, Cs and I by adult inhabitants of greater Cairo area could be due to the significantly lower consumption of milk and milk products, which are rich in these elements. The significantly lower intake of calcium by adult inhabitants of greater Cairo area may lead to higher uptake of radiostrontium and could result in higher internal radiation dose. The use of highly sensitive and reliable analytical methods resulted in accurate assessment of the values recorded for thorium and uranium suggested that radiation dose from their ingestion at natural background levels, is likely to be lower than those included in ICRP data. Concerning micro nutrients, the recommended values of daily intake of Cu and Mn are conveniently supplied by the common diet; however for Cr is lower than the recommended daily allowance. Due to high metals concentrations

The applicability of the PTTL dose re-analysis method to the Harshaw LiF:Mg,Cu,P material

International Nuclear Information System (INIS)

Moscovitch, M.; Benevides, L.; Romanyukha, A.; Hull, F.; Duffy, M.; Voss, S.; Velbeck, K. J.; Nita, I.; Rotunda, J. E.

2011-01-01

The photo-transferred thermoluminescence (PTTL) technique is applied to the Harshaw LiF:Mg,Cu,P material. It is demonstrated that using 254-nm UV light, dose levels as low as 0.2 mGy can be re-estimated. The PTTL efficiency was found to be ∼6 % in the dose range of 0.2 mGy -1 Gy, and it appears to be dose-independent. This implies that a simple calibration factor could be applied to the PTTL data for the re-estimation of dose levels. It was demonstrated that with a proper choice of the TL readout parameters, and the UV-light irradiation conditions, dose levels that are relevant to personal or environmental dosimetry can be re-estimated. (authors)

Comparison of early treatment with low doses of nilotinib, imatinib and a clinically relevant dose of silymarin in thioacetamide-induced liver fibrosis.

Science.gov (United States)

Shaker, Mohamed E; Shiha, Gamal E; Ibrahim, Tarek M

2011-11-30

Our previous study has already confirmed a promising anti-fibrotic activity especially for nilotinib; when given at a daily dose of 10 mg/kg during the last 4 weeks of thioacetamide (TAA)-induced liver fibrosis for 12 weeks in rats. Therefore, this study was carried out to compare the prophylactic potential of low dose of nilotinib to that of its predecessor, imatinib, and a clinically relevant dose of the standard hepatoprotective treatment, silymarin, in TAA-intoxication. Male Wistar rats received intraperitoneal injections of TAA (150 mg/kg, twice weekly) for 8 weeks, as well as oral treatments with imatinib (5 mg/kg/day), nilotinib (5 mg/kg/day) and silymarin (50 mg/kg/day) from the first day of TAA-intoxication. At the end of the study, chronic hepatic injury was evaluated by analysis of liver function tests in serum. Hepatic oxidative stress was assessed by measuring malondialdehyde, 4-hydroxynonenal, total nitrate/nitrite and reduced glutathione contents, as well as myeloperoxidase and superoxide dismutase activities. Hepatic fibrosis was evaluated by histopathology and collagen content. Our results suggest that the prophylactic potential of nilotinib (5 mg/kg/day), imatinib (5mg/kg/day) and silymarin (50 mg/kg/day) in TAA-intoxication for 8 weeks is lower than the late treatments of nilotinib (10 mg/kg/day), imatinib (10mg/kg/day) and silymarin (100 mg/kg/day) during the last 4 weeks of TAA-intoxication for 12 weeks in rats. Taken together, this study suggests that nilotinib may have higher anti-fibrotic activity when administered at a significant stage of fibrosis as a result of impairment of its metabolism in the fibrotic livers. Copyright © 2011 Elsevier B.V. All rights reserved.

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)...

Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

Directory of Open Access Journals (Sweden)

Jan Susilo

2011-08-01

Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

LENUS (Irish Health Repository)

Behan, L A

2011-06-01

The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer's disease taking cholinesterase inhibitors.

Science.gov (United States)

Grossberg, George T; Manes, Facundo; Allegri, Ricardo F; Gutiérrez-Robledo, Luis Miguel; Gloger, Sergio; Xie, Lei; Jia, X Daniel; Pejović, Vojislav; Miller, Michael L; Perhach, James L; Graham, Stephen M

2013-06-01

Immediate-release memantine (10 mg, twice daily) is approved in the USA for moderate-to-severe Alzheimer's disease (AD). This study evaluated the efficacy, safety, and tolerability of a higher-dose, once-daily, extended-release formulation in patients with moderate-to-severe AD concurrently taking cholinesterase inhibitors. In this 24-week, double-blind, multinational study (NCT00322153), outpatients with AD (Mini-Mental State Examination scores of 3-14) were randomized to receive once-daily, 28-mg, extended-release memantine or placebo. Co-primary efficacy parameters were the baseline-to-endpoint score change on the Severe Impairment Battery (SIB) and the endpoint score on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). The secondary efficacy parameter was the baseline-to-endpoint score change on the 19-item Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL19); additional parameters included the baseline-to-endpoint score changes on the Neuropsychiatric Inventory (NPI) and verbal fluency test. Data were analyzed using a two-way analysis of covariance model, except for CIBIC-Plus (Cochran-Mantel-Haenszel test). Safety and tolerability were assessed through adverse events and physical and laboratory examinations. A total of 677 patients were randomized to receive extended-release memantine (n = 342) or placebo (n = 335); completion rates were 79.8 and 81.2 %, respectively. At endpoint (week 24, last observation carried forward), memantine-treated patients significantly outperformed placebo-treated patients on the SIB (least squares mean difference [95 % CI] 2.6 [1.0, 4.2]; p = 0.001), CIBIC-Plus (p = 0.008), NPI (p = 0.005), and verbal fluency test (p = 0.004); the effect did not achieve significance on ADCS-ADL19 (p = 0.177). Adverse events with a frequency of ≥5.0 % that were more prevalent in the memantine group were headache (5.6 vs. 5.1 %) and diarrhea (5.0 vs. 3.9�

Safety and Pharmacokinetic Profiles of Repeated-Dose Micafungin in Children and Adolescents Treated for Invasive Candidiasis

Science.gov (United States)

Benjamin, Daniel K.; Deville, Jaime G.; Azie, Nkechi; Kovanda, Laura; Roy, Mike; Wu, Chunzhang; Arrieta, Antonio

2013-01-01

Background Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida species. Objective To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable, or suspected invasive candidiasis. Methods Micafungin safety and pharmacokinetics were assessed in two Phase I, open-label, repeat-dose trials. In Study 2101, children aged 2–16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10–14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. Results Safety was analyzed in seventy-eight and nine children in Studies 2101 and 2102, respectively. Although adverse events were experienced by most children (2101: n = 62; 2102: n = 9), micafungin-related adverse events were less common (2101: n = 28; 2102: n = 1), and the number of patients discontinuing due to adverse events was low (2101: n = 4; 2102: n = 1). The most common micafungin-related adverse events were infusion-associated symptoms, pyrexia, and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. Conclusions In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support U.S. dosing recommendations in children. PMID:23958810

Effects of recording time and residue on dose-response by LiMgPO4: Tb, B ceramic disc synthesized via improved sintering process

Science.gov (United States)

Kong, Xirui; Fu, Zhilong; Que, Huiying; Fan, Yanwei; Chen, Zhaoyang; He, Chengfa

2018-05-01

The LiMgPO4: Tb, B ceramic disc is successfully synthesized via improved sintering method which enables the disc sample to have two flat and smooth surfaces. It is worth mentioning that the OSL signal intensity of LiMgPO4: Tb, B disc attenuates much faster than that of commercial Al2O3: C. It costs only 1 s to reduce the intensity to 10%, but the Al2O3:C needs more than 40 s to finish it. Some essential OSL properties related to the dose detection method of this sample also have been systematically investigated. Although the dose-response cure would have better linearity with longer recording time, extended recording time (≥6 s) will not make any contribution to the linearity of the curve. If the bleaching time is more than 35 s, the residue created by previous detection (high dose of 10 Gy) would do almost no influence (with a positive deviation lower than 5.59%) on next lower-dose detection (0.1 Gy). The material would reach its service life when the total-ionizing dose runs up to 30 k Gy. Therefore, the LiMgPO4: Tb, B ceramic material is a potential candidate for real-time dose monitoring with optical fiber telemetering technology.

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

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.

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.

Time of administration important? Morning versus evening dosing of valsartan.

Science.gov (United States)

Zappe, Dion H; Crikelair, Nora; Kandra, Albert; Palatini, Paolo

2015-02-01

Studies suggest that bedtime dosing of an angiotensin-converting enzyme (ACE)-inhibitor or angiotensin receptor blocker shows a more sustained and consistent 24-h antihypertensive profile, including greater night-time blood pressure (BP) reduction. We compared the antihypertensive effects of morning (a.m.) and evening (p.m.) dosing of valsartan on 24-h BP. This 26-week, multicentre, randomized, double-blind study evaluated the efficacy and safety of valsartan 320 mg, dosed a.m. or p.m., versus lisinopril 40 mg (a.m.), a long-acting ACE-inhibitor, in patients with grade 1-2 hypertension and at least one additional cardiovascular risk factor. Patients (n = 1093; BP = 156 ± 11/91 ± 8 mmHg; 62 years, 56% male, 99% white) received (1 : 1 : 1) valsartan 160 mg a.m. or p.m. or lisinopril 20 mg a.m. for 4 weeks, then force-titrated to double the initial dose for 8 weeks. At Week 12, hydrochlorothiazide (HCTZ) 12.5 mg was added for 14 weeks if office BP was more than 140/90 mmHg and/or ambulatory BP more than 130/80 mmHg. Mean 24-h ambulatory SBP change from baseline to Weeks 12 and 26 was comparable between valsartan a.m. (-10.6 and -13.3 mmHg) and p.m. (-9.8 and -12.3 mmHg) and lisinopril (-10.7 and -13.7 mmHg). There was no benefit of valsartan p.m. versus a.m. on night-time BP, early morning BP and morning BP surge. Evening dosing also did not improve BP lowering in patients requiring add-on HCTZ or in nondippers at baseline. All treatments were well tolerated. Once-daily dosing of valsartan 320 mg results in equally effective 24-h BP efficacy, regardless of dosing time. ClinicalTrials.gov Identifier: NCT00241124.

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

High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

Science.gov (United States)

Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

2006-09-01

The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

Thermoluminescence kinetic analysis and dosimetry features of MgSO4:Dy and MgSO4:Cu nano-rods

International Nuclear Information System (INIS)

Zahedifar, M.; Almasifard, F.; Sadeghi, E.; Biroon, M. Kashefi; Ramazani- Moghaddam-Arani, A.

2016-01-01

MgSO 4 :Dy and MgSO 4 :Cu nano-rods (NRs) were synthesized for the first time by semi co- precipitation method. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive spectrometry (EDS) were utilized for sample characterization. The optimum amount of dysprosium and copper concentrations were obtained both at 0.1 mol% in MgSO 4 :Dy and MgSO 4 :Cu NRs. T m -T stop and computerized glow curve deconvolution (CGCD) methods were used for identifying the number of component glow peaks and kinetic parameters of the synthesized NRs. Initial rise and variable heating rate methods were also used to ensure the reliability of obtained kinetic parameters. Results show that the TL sensitivity of MgSO 4 :Dy is about 7 times more than that of magnesium sulfate doped with Cu. The TL dose response of MgSO 4 :Dy and MgSO 4 :Cu NRs are linear up to absorbed dose of 10 KGy. Other TL dosimetry characteristics of the produced NRs are also presented and discussed. - Highlights: • MgSO4:Dy and MgSO4:Cu nano-rods were synthesized for the first time. • Thermoluminescence dosimetry properties were studied. • The nano-phosphors showed linear dose response up to very high dose levels. • The synthesized nano-rods have potential application for high dose dosimetry.

Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

DEFF Research Database (Denmark)

Andersen, O; Nielsen, M K; Eriksen, P B

1983-01-01

Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

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

Method of thermoluminescent measurement of radiation doses from micrograys up to a megagray with a single LiF: Mg,Cu,P detector

International Nuclear Information System (INIS)

Obryk, B.; Bilski, P.; Olko, P.

2011-01-01

On the basis of the newly discovered behaviour of LiF:Mg,Cu,P detectors at high and ultra-high doses, a new method of thermoluminescence (TL) measurement of radiation doses ranging from micrograys up to a megagray, has been recently developed at the Inst. of Nuclear Physics (IFJ). The method is based on the relationship between the TL signal, integrated in the given temperature range and dose. It is quantified by a parameter called the 'ultra-high temperature ratio'. It has been demonstrated that this new method can measure radiation doses in the range of about 1 μGy to 1 MGy, using a single LiF:Mg,Cu,P detector. This method was recently successfully blindly tested for 10 MeV electrons up to doses of 200 kGy. It can be used for dosimetry in high-energy accelerators, especially in the Large Hadron Collider at CERN, and has great potential for accident dosimetry in particular. (authors)

High dose methylphenidate treatment in adult attention deficit hyperactivity disorder: a case report

Directory of Open Access Journals (Sweden)

Liebrenz Michael

2012-05-01

Full Text Available Abstract Introduction Stimulant medication improves hyperactivity, inattention, and impulsivity in both pediatric and adult populations with Attention Deficit Hyperactivity Disorder (ADHD. However, data regarding the optimal dosage in adults is still limited. Case presentation We report the case of a 38-year-old Caucasian patient who was diagnosed with Attention Deficit Hyperactivity Disorder when he was nine years old. He then received up to 10 mg methylphenidate (Ritalin® and 20 mg sustained-release methylphenidate (Ritalin SR® daily. When he was 13, his medication was changed to desipramine (Norpramin®, and both Ritalin® and Ritalin SR® were discontinued; and at age 18, when he developed obsessive-compulsive symptoms, his medication was changed to clomipramine (Anafranil® 75 mg daily. Still suffering from inattention and hyperactivity, the patient began college when he was 19, but did not receive stimulant medication until three years later, when Ritalin® 60 mg daily was re-established. During the 14 months that followed, he began to use Ritalin® excessively, both orally and rectally, in dosages from 4800-6000 mg daily. Four years ago, he was referred to our outpatient service, where his Attention Deficit Hyperactivity Disorder was re-evaluated. At that point, the patient’s daily Ritalin® dosage was reduced to 200 mg daily orally, but he still experienced pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage was raised again. The patient’s plasma levels consistently remained between 60–187 nmol/l—within the recommended range—and signs of his obsessive-compulsive symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378 mg extended-release methylphenidate (Concerta®, his symptoms of Attention Deficit Hyperactivity Disorder have improved dramatically and no further use of methylphenidate has been recorded during the 24 months preceding this report. Conclusions Symptoms of

High and low doses of antimony (Sb v in American cutaneous leishmaniasis: a five years follow-up study of 15 patients

Directory of Open Access Journals (Sweden)

MP Oliveira-Neto

1996-04-01

Full Text Available Seventeen patients proceeding from the municipality of Rio de Janeiro, Brazil presenting with the cutaneous ulcerative form of American leishmaniasis were treated with one ampoule of pentavalent antimony daily for 30 days. With this regimen the individuals doses varies greatly: from 3.8 mg/kg of body weight to 22.3 mg/kg. After five years, patients receiving either a smaller dose or a bigger one, showed the same therapeutic result: cutaneous scars and no mucosal lesions.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

Directory of Open Access Journals (Sweden)

Jose Muñoz

2018-01-01

Full Text Available Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax of the reference product (WA-ref with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax was not

High doses of systemic corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease. A cohort study.

Science.gov (United States)

Rueda-Camino, J A; Bernal-Bello, D; Canora-Lebrato, J; Velázquez-Ríos, L; García de Viedma-García, V; Guerrero-Santillán, M; Duarte-Millán, M A; Cristóbal-Bilbao, R; Zapatero-Gaviria, A

2017-12-01

To assess the effect of high doses of corticosteroids in patients hospitalised for exacerbation of chronic obstructive pulmonary disease (COPD). A prospective cohort study was conducted on patients hospitalized with COPD between January and March 2015, grouped according to the glucocorticoid dosage administered (cutoff, 40mg of prednisone/day). We compared the results of hospital stay, readmission and mortality at 3 months of discharge. We analysed 87 patients. The median daily dose was 60mg of prednisone (interquartile range, 46.67-82.33mg/day), and the administration route was intravenous in 96.6% of the cases. We established a relative risk (RR) for hospital stays longer than 8 days of 1.095 (95% CI 0.597-2.007; P=.765) when steroid dosages greater than 40mg/day were employed. In these patients, the hazard ratio (HR) for readmission in the 3 months after discharge was 0.903 (95% CI 0.392-2.082; P=.811), and the mortality was 1.832 (95% CI 0.229-16.645; P=.568). Neither the RR nor the HR varied in a statistically significant manner after adjusting for confounding factors. A daily dose greater than 40mg of prednisone in patients hospitalised for COPD exacerbation was not associated with a shorter hospital stay or a reduction in readmissions or mortality at 3 months. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Dose-dependent efficacy of the Vitex agnus castus extract Ze 440 in patients suffering from premenstrual syndrome.

Science.gov (United States)

Schellenberg, Ruediger; Zimmermann, Christian; Drewe, Jürgen; Hoexter, Godehard; Zahner, Catherine

2012-11-15

Preparations of Vitex agnus castus L. (VAC) have been shown to be effective to treat irregular menstrual cycles, cyclical mastalgia and symptoms of the premenstrual syndrome (PMS). However, the dose-effect relationship for the treatment of PMS has not yet been established. This study aimed to investigate the clinical effects of three different doses of the VAC extract Ze 440 in comparison to placebo in patients suffering from PMS. In a multicenter, double-blind, placebo-controlled, parallel-group study, 162 female patients with PMS (18-45 years) were randomized to either placebo or different doses of Ze 440 (8, 20 and 30 mg) over three menstrual cycles. PMS symptoms' severity was assessed by patients using visual analog scales (VAS) for the symptoms irritability, mood alteration, anger, headache, bloating and breast fullness. Each of the treatments was well tolerated. Improvement in the total symptom score (TSS) in the 20mg group was significantly higher than in the placebo and 8 mg treatment group. The higher dose of 30 mg, on the other hand, did not significantly decrease symptom severity compared to the 20mg treatment, providing a rational for the usage of 20mg. Corresponding results were observed with the single PMS symptom scores. This study demonstrated that the VAC extract Ze 440 was effective in relieving symptoms of PMS, when applied in a dose of 20mg. Therefore, for patients suffering from PMS, 20mg Ze 440 should be the preferred daily dose. Copyright © 2012 Elsevier GmbH. All rights reserved.

Lansoprazole 15 mg once daily for 14 days is effective for treatment of frequent heartburn: results of 2 randomized, placebo-controlled, double-blind studies.

Science.gov (United States)

Kushner, Pamela R; Snoddy, Andrew M; Gilderman, Larry; Peura, David A

2009-07-01

To investigate the efficacy and safety of a 14-day treatment period with lansoprazole 15 mg for frequent heartburn in patients who are likely to select a nonprescription medication before consulting a prescriber. Adults with untreated frequent heartburn > or = 2 days a week over the past month were recruited for 2 identical multicenter, double-blind studies conducted with a 1-week screening and heartburn medication washout, a 1-week placebo run-in, a 2-week placebo-controlled treatment, and a 1-week placebo follow-up. After the washout and placebo run-in, subjects were randomly assigned to receive lansoprazole 15 mg or placebo once daily for 14 days in a double-blind fashion. Antacid tablets were permitted as rescue medication. Endpoints included percentage of 24-hour days without heartburn (primary), percentage of night-times without heartburn, and percentage of subjects without heartburn during day 1 of treatment (secondary endpoints). Data were collected daily via an interactive voice response system. In studies 1 and 2, 282 and 288 subjects, respectively, were randomly assigned to lansoprazole, and 282 in each study received placebo. The mean percentage of days without heartburn was greater among lansoprazole recipients compared with placebo recipients (P heartburn and no heartburn during day 1 of the 14-day treatment. Adverse events were infrequent and were similar for lansoprazole and placebo groups. During the 14-day treatment period in a population with frequent heartburn who were likely to select a medication without consulting a prescriber, lansoprazole 15 mg once daily showed rapid and sustained effectiveness throughout a 24-hour period and was well tolerated.

Measurement of low-LET radiation dose aboard the chinese scientific experiment satellite (1988) by highly sensitive LiF (Mg, Cu, P) TL chips

International Nuclear Information System (INIS)

Zhang Zhonglun; Zheng Yanzhen.

1989-01-01

Low-LET radiation dose is an important portion of spaceflight dose. It is a new application that highly sensitive LiF(Mg, Cu, P) TL chips are used in measurement of low-LET dose aboard the chinese scientific experiment satellite. Avarage dose rate in satellite is 9.2 mrad/day and on the ground is about 0.32 mrad/day

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.

Science.gov (United States)

Choueiri, Toni K; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David; Robbins, Paul B; Chism, David D; Cho, Daniel; Atkins, Michael B; Gordon, Michael S; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; di Pietro, Alessandra; Rini, Brian I

2018-04-01

The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the

Influence of different doses of octenidine hexafluorosilicate on parodontotium state of rat, which received cariesogenic ration

Directory of Open Access Journals (Sweden)

V. Yu. Anisimov

2017-06-01

Full Text Available Aim: To determine of parodontium state of rat, which received cariesogenic ration and different doses of octenidine hexafluorosilicate (O-HFS. Methods: The octenidine hexafluorosilicate was synthesized by us and was used into mucoso-adgesive gels (Na-CMC in next concentrations: 1 mg/ml, 2 mg/ml and 4 mg/ml. The rats received high-sugar cariesogenic ration and oral applications of gels with O-HFS in doses of 0,3 ml (daily doses of O-HFS were 1,4 mg/kg, 2,8 mg/kg and 5,6 mg/kg. The duration of experiment was 35 days. The activities of urease, lysozyme and elastase were determined into gum. The activities of urease, lysozyme, ALT and alkaline phosphatase (APh were determined into serum. The degree of dysbiosis calculated by ration urease and lysozyme. The degree of atrophy of parodontale bone was determined by Nicolaeva method. Results: The activities of elastase and urease, the degree of atrophy and dysbiosis were raised into gum of rat, which received cariesogenic ration. The activities of ALT and APh, the degree of dysbiosis were raised into serum. The oral application of O-HFS-gels decreased the all these indices. The maximal action made O-HFS-gel in dose 2,8 mg/kg. Conclusion: The oral application of O-HFS-gel make parodontoprotective action.

A double-blind study comparing ibuprofen 1800 mg or 2400 mg daily and placebo in sports injuries.

Science.gov (United States)

Hutson, M A

1986-01-01

In a double-blind, placebo-controlled study of forty-six patients with acute ligamentous damage of the knee, ibuprofen in dosages 1800 mg and 2400 mg produced significant improvements in joint mobility, weight bearing ability and match fitness. Joint effusion, pain on stress and pain severity was significantly improved by all three treatments. Only two patients reported side-effects (one while taking placebo and one taking ibuprofen 2400 mg). The study confirmed the efficacy and excellent tolerance to ibuprofen in patients with sports injuries to the knee.

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

Science.gov (United States)

Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

2011-07-01

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

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

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

Dose-Related Effects of Acetylsalicylic acid (ASA) on Gamma Radiation-Induced Teratogenicity in Pregnant Albino Rats

International Nuclear Information System (INIS)

Ibrahim, M.F.

2013-01-01

Reviews of acetylsalicylic acid (ASA), a widely used nonsteroidal anti- inflammatory drug, has consistently suggested a possible association between prenatal ASA ingestion and adverse effects in the pregnant mothers and their developing fetuses. The objective of the current study was to comprehensively define the effect of relatively low and high doses of ASA (25 mg/kg body wt. and 200 mg/kg body wt. respectively) on gestating rats and their possible impact on the irradiated ones. Therefore 36 pregnant rats were randomly divided into 6 equal groups. Three rat groups were daily orally gavaged from the 7th to the 18th gestational days with: distilled water (Group 1), 25 mg/kg body wt. ASA (Group 2) and 200 mg/kg body wt. ASA (Group 3). The other three groups similarly received the same previous treatments besides 2 Gy whole body gamma irradiation of each, to serve as: Group 4 (distilled water + irradiation), Group 5 (25 mg/kg body wt. ASA + irradiation) and Group 6 (200 mg/kg body wt. ASA + irradiation). All rat groups were sacrificed on the 20th day of pregnancy and the uterine contents were examined. The lower ASA dose (25 mg/kg body wt.) treated group (Group 2) displayed healthy mothers and fetuses whereas that of the higher dose (200 mg/kg body wt.) (Group 3) despite not showing significant maternal or fetal mortalities, yet the intrauterine contents presented fetal developmental disorders including stunted growth and resorption together with some head and limb anomalies including plagiocephaly, marked acampsia and acrocontracture. Meanwhile, results have unexpectedly shown a radioprotective role of the lower ASA dose (25 mg/kg. body wt.) (Group 5) to pregnant rats and their fetuses as inspected by its efficacy in retrieving the radiation induced maternal weight loss together with its noticeable ameliorating effects on the intrauterine lethality of the affected fetuses and their externally detected abnormalities in addition toits effectiveness in retaining some

Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study.

Science.gov (United States)

Ito, Yoshinori; Suenaga, Mitsukuni; Hatake, Kiyohiko; Takahashi, Shunji; Yokoyama, Masahiro; Onozawa, Yusuke; Yamazaki, Kentaro; Hironaka, Shuichi; Hashigami, Kiyoshi; Hasegawa, Hirotaka; Takenaka, Nobuko; Boku, Narikazu

2012-04-01

Neratinib (HKI-272), a potent, irreversible, small-molecule, orally administered, pan-ErbB inhibitor that blocks signal transduction via inhibition of three epidermal growth factor receptors [ErbB1, ErbB2 (Her2) and ErbB4], is being developed for the treatment of solid tumors, including breast cancer. This Phase 1 dose-escalation study assessed the safety, tolerability, maximum-tolerated dose, antitumor activity and pharmacokinetics of neratinib in Japanese patients with advanced solid tumors. Patients received neratinib 80, 160, 240 or 320 mg orally; each patient enrolled in only one dose cohort. Patients received a single dose in week 1, followed by daily continuous doses. Blood samples collected were on days 1 and 21 for pharmacokinetic analyses. Twenty-one patients were enrolled (3 breast cancer; 17 colorectal cancer; 1 gastric cancer). Neratinib-related adverse events (all grades) included diarrhea (20 patients), fatigue (14 patients), nausea and abdominal pain (9 patients each) and anorexia (8 patients). Grade ≥3 neratinib-related adverse events in two or more patients were diarrhea and anorexia (two patients each). Dose-limiting toxicities were diarrhea and anorexia (two patients, 320 mg dose). The maximum-tolerated dose and recommended dose was neratinib 240 mg once daily. Of 21 evaluable patients, 2 with breast cancer had partial response, 3 had stable disease ≥24 weeks, 7 had stable disease ≥16 weeks and 9 had progressive disease. Pharmacokinetic analyses indicated that neratinib exposures increased with dose. The safety, efficacy and pharmacokinetic profiles of neratinib are consistent with those reported for non-Japanese patients and warrant further investigation of neratinib in Japanese patients with solid tumors.

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

Science.gov (United States)

Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

2015-07-01

Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

International Nuclear Information System (INIS)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.; Enker, W.E.; Kelsen, D.P.; Schwartz, G.; Saltz, L.; Dougherty, J.; Frankel, J.; Wiseberg, J.

1993-01-01

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs

Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial.

Science.gov (United States)

Younes, Anas; Berdeja, Jesus G; Patel, Manish R; Flinn, Ian; Gerecitano, John F; Neelapu, Sattva S; Kelly, Kevin R; Copeland, Amanda R; Akins, Amy; Clancy, Myles S; Gong, Lucy; Wang, Jing; Ma, Anna; Viner, Jaye L; Oki, Yasuhiro

2016-05-01

Treatment options for patients with relapsed or refractory lymphoma and multiple myeloma are limited. CUDC-907 is an oral, first-in-class, small molecule that is designed to inhibit both histone deacetylase (HDAC) and PI3K enzymes, which are members of common oncogenic pathways in haematological malignancies. We aimed to assess overall safety and preliminary activity in this dose-escalation study of CUDC-907 monotherapy in patients with relapsed or refractory lymphoma and multiple myeloma. This open-label, first-in-man, phase 1 trial recruited adult patients (aged ≥18 years) with lymphoma or multiple myeloma who were refractory to or had relapsed after two or more previous regimens, from four US cancer centres. CUDC-907 was orally administered in a standard 3 + 3 dose-escalation design at four different dosing schedules, to which participants were sequentially assigned as follows: once daily, intermittently (twice or three times weekly; simultaneous enrolment), and daily for 5 days followed by a 2-day break (5/2), in 21-day cycles. Dosing started at 30 mg for the once-daily schedule and 60 mg for other schedules, escalating in 30 mg increments. Patients continued to receive CUDC-907 until disease progression or until other treatment discontinuation criteria were met. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose, assessed in patients who received at least 66% of cycle 1 doses without modification and those who had a dose-limiting toxicity (DLT) in cycle 1 irrespective of dose modification. We assessed safety in all patients who received at least one dose of study drug. This ongoing trial is registered at ClinicalTrials.gov, number NCT01742988. Between Jan 23, 2013, and July 27, 2015, we enrolled 44 patients, of whom ten were sequentially assigned to CUDC-907 once-daily (MTD 60 mg), 12 to twice-weekly (MTD 150 mg), 15 to three-times-weekly (MTD 150 mg), and seven to the 5/2 dosing schedule (MTD 60 mg). 37

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

Science.gov (United States)

Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

Science.gov (United States)

Soman, A; Honeybourne, D; Andrews, J; Jevons, G; Wise, R

1999-12-01

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

Directory of Open Access Journals (Sweden)

Abhijna Chandan Chattopadhyay

2016-01-01

Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

Around-the-clock oral THC effects on sleep in male chronic daily cannabis smokers.

Science.gov (United States)

Gorelick, David A; Goodwin, Robert S; Schwilke, Eugene; Schroeder, Jennifer R; Schwope, David M; Kelly, Deanna L; Ortemann-Renon, Catherine; Bonnet, Denis; Huestis, Marilyn A

2013-01-01

Δ9-tetrahydrocannabinol (THC) promotes sleep in animals; clinical use of THC is associated with somnolence. Human laboratory studies of oral THC have not shown consistent effects on sleep. We prospectively evaluated self-reported sleep parameters during controlled oral THC administration to research volunteers. Thirteen male chronic daily cannabis smokers (mean ± SD age 24.6± 3.7 years, self-reported smoking frequency of 5.5 ± 5.9 (range 1-24) joint-equivalents daily at study entry) were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg daily) starting the afternoon after admission. The St. Mary's Hospital Sleep Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active metabolite) concentrations were measured in venous blood samples collected every evening. Changes in sleep characteristics over time and associations between sleep characteristics and plasma cannabinoid concentrations were evaluated with repeated measures mixed linear regression. Higher evening THC and 11-OH-THC concentrations were significantly associated with shorter sleep latency, less difficulty falling asleep, and more daytime sleep the following day. In contrast, the duration of calculated and self-reported nighttime sleep decreased slightly (3.54 and 5.34 minutes per night, respectively) but significantly during the study. These findings suggest that tolerance to the somnolent effects of THC may have occurred, but results should be considered preliminary due to design limitations. Somnolence from oral THC may dissipate with chronic, high-dose use. This has implications for patients who may take chronic oral THC for medicinal purposes, including cannabis dependence treatment. (Am J Addict 2013;22:510-514). Copyright © American Academy of Addiction Psychiatry.

The evolution of anti-ulcer therapy with cimetidine. Is a single large nocturnal dose of cimetidine the right therapy for duodenal ulcer?

Science.gov (United States)

Barbara, L; Corinaldesi, B; Stanghellini, V; Paternicò, A; Fabbri, L; Sacco, T

1986-01-01

Peptic ulcer results from the prevalence of agents causing endoluminal lesions over the defence mechanisms of the mucosa of the upper GI tract. Particularly, in the case of duodenal ulcer, the pathogenetic relevance of non-buffered acid secretion of the early nighttime period has been emphasized. This is indeed confirmed by the fact that a single night dose of 800 mg cimetidine has apparently been proved able--in numerous controlled clinical trials--to provide results that are similar to those obtained with the classic dose of 1 g daily or 400 mg twice daily. Our centre carried out a crossover double-blind controlled trial aimed at evaluating titrable acidity and pH during the 24-h period in seven patients with active duodenal ulcer. The single nighttime dose of cimetidine resulted in a significant and long-lasting inhibition of acid secretion during the entire night. During the day, secretory values returned to levels similar to those obtained with placebo, hence allowing normal digestive functions.

Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide

International Nuclear Information System (INIS)

Chawla, Sant P; Staddon, Arthur; Hendifar, Andrew; Messam, Conrad A; Patwardhan, Rita; Kamel, Yasser Mostafa

2013-01-01

The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy. Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD). Eighteen patients were enrolled and 15 received at least 1 dose of chemotherapy; 3 patients withdrew prior to receiving eltrombopag. Seven, 4, and 1 patients received 75 mg, 100 mg, and 150 mg eltrombopag daily, respectively. No dose-limiting toxicities were reported. Due to slow recruitment, the study was closed prior to identifying an OBD. The most common hematologic adverse events (AEs) were thrombocytopenia (80%), neutropenia (73%), and anemia (67%). The most common nonhematologic AEs were fatigue (53%), alanine aminotransferase increased, constipation, and nausea (47% each). Eleven of 12 patients who received eltrombopag completed at least 2 chemotherapy cycles; all had increased platelet counts on Day 1 of Cycle 2 (cycle with eltrombopag) compared to Day 1 of Cycle 1 (cycle without eltrombopag). Although data are limited, safety data were consistent with the known toxicities of AI combination chemotherapy or the side effect profile of eltrombopag seen in other studies. Available data suggest a potential pre- and post-chemotherapy dosing scheme for eltrombopag when administered with AI chemotherapy, and support further investigation of eltrombopag treatment in patients with chemotherapy-induced thrombocytopenia

Dienogest 2 mg Daily in the Treatment of Adolescents with Clinically Suspected Endometriosis: The VISanne Study to Assess Safety in ADOlescents.

Science.gov (United States)

Ebert, Andreas D; Dong, Liying; Merz, Martin; Kirsch, Bodo; Francuski, Maja; Böttcher, Bettina; Roman, Horace; Suvitie, Pia; Hlavackova, Olga; Gude, Kerstin; Seitz, Christian

2017-10-01

To study the safety and efficacy of dienogest 2 mg in adolescents with suspected endometriosis. A 52-week, open-label, single-arm study. In 21 study centers, in 6 European countries. Adolescents aged 12 to younger than 18 years with clinically suspected or laparoscopically confirmed endometriosis. Dienogest 2 mg once daily. The primary end point was relative change in lumbar spine (L2-L4) bone mineral density (BMD) measured using dual-energy x-ray absorptiometry. A key secondary end point was change in endometriosis-associated pain assessed using a visual analogue scale. Of 120 patients screened, 111 comprised the full-analysis set (ie, patients who took ≥1 dose of study drug and had ≥1 post-treatment observation) and 97 (87.4%) completed the study. Mean lumbar BMD at baseline was 1.1046 (SD, 0.1550) g/cm 2 . At the end of dienogest treatment (EOT; defined as at 52 weeks or premature study discontinuation), mean relative change in BMD from baseline was -1.2% (SD, 2.3%; n = 103). Follow-up measurement 6 months after EOT in the subgroup with decreased BMD at EOT (n = 60) showed partial recovery in lumbar BMD (mean change from baseline: -2.3% at EOT, -0.6% 6 months after EOT). Mean endometriosis-associated pain score was 64.3 (SD, 19.1) mm at baseline and decreased to 9.0 (SD, 13.9) mm by week 48. In adolescents with suspected endometriosis, dienogest 2 mg for 52 weeks was associated with a decrease in lumbar BMD, followed by partial recovery after treatment discontinuation. Endometriosis-associated pain was substantially reduced during treatment. Because bone accretion is critical during adolescence, results of the VISanne study to assess safety in ADOlescents (VISADO) study highlights the need for tailored treatment in this population, taking into account the expected efficacy on endometriosis-associated pain and an individual's risk factors for osteoporosis. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published

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

Science.gov (United States)

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

2015-09-01

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

Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release.

Science.gov (United States)

Fass, Ronnie; Inadomi, John; Han, Cong; Mody, Reema; O'Neil, Janet; Perez, M Claudia

2012-03-01

Many patients with gastroesophageal reflux disease (GERD) take a proton pump inhibitor (PPI) twice daily to control symptoms. Once-daily dexlansoprazole modified release (MR) has a dual-delayed release formulation, making it attractive for step-down management of patients whose symptoms are well controlled on twice-daily PPIs. We investigated whether step-down to once-daily dexlansoprazole controls heartburn in patients with GERD who were receiving twice-daily PPI therapy. Patients 18 years and older taking a twice-daily PPI for symptom control were enrolled (n = 178) in a single-blind, multicenter study; 163 patients completed the study and 142 patients met criteria for the efficacy analysis. During the 6-week screening and treatment periods, patients recorded the presence of heartburn symptoms twice daily in electronic diaries. Patients' heartburn was considered well controlled if they had an average of 1 symptom or fewer per week during the last 4 weeks of screening and treatment. After screening, qualified patients were switched to masked dexlansoprazole MR 30 mg and placebo for 6 weeks. The primary efficacy end point was the proportion of patients whose heartburn remained well controlled after step-down. GERD-related symptoms and quality of life (QOL) also were evaluated using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM) and the PAGI-QOL questionnaires, respectively. After step-down to once-daily dexlansoprazole MR 30 mg, heartburn remained well controlled in 88% of patients (125 of 142). These patients were able to maintain their GERD-related symptom severity and QOL, indicated by marginal changes in the PAGI-SYM and PAGI-QOL total and subscale scores, respectively. Most patients with GERD who take twice-daily PPI to control heartburn are able to successfully step down to once-daily dexlansoprazole 30 mg. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Dose comparison and side effect profile of metformin extended release versus metformin immediate release

International Nuclear Information System (INIS)

Hameed, M.; Khan, K.; Salman, S.; Mehmood, N.

2017-01-01

Diabetes Mellitus type 2 is very common worldwide, with majority of cases in Asia Pacific region. Metformin is the first line therapy, along with lifestyle modification for all type 2 diabetics as recommended by ADA. Metformin is available as conventional Metformin Immediate Release (MIR) and Metformin Extended Release (MXR). Metformin XR has better gastrointestinal tolerability and fewer side effects as compared to Metformin IR, with similar efficacy regarding anti-hyperglycaemic effects. The objective of this study was to determine whether metformin XR is as effective as Metformin IR in maintaining glycaemic control at equivalent doses or even at reduced doses; and to compare the side effect profile of the two preparations. Methods: This randomized control trial was conducted at Medical and Endocrinology OPD of Jinnah Hospital Lahore A total of 90 type 2 diabetics of both genders were recruited using nonprobability purposive sampling. Patients were randomized into 3 groups; 30 in each group. Group 1 received Metformin IR 1000 mg twice daily; group 2 received metformin XR 1000mg twice daily; and group 3 received metformin XR 500 mg twice daily, for a period of three months. HbA1c was done at baseline and after three months of therapy along with fasting blood sugars and random blood sugars weekly. Results: The mean age of patients was 46+-9 years, with 54% being males and 46% being females. There was a 1% reduction in HbA1c in group 1, 0.7% reduction in group 2 and only 0.4% reduction in group 3. Similarly, all three therapies were equally effective in reducing blood sugar fasting and blood sugar random at three months. Side effects namely diarrhoea, dyspepsia and flatulence were greatest with Metformin IR (40%) but less than half with Metformin XR at equivalent dose and negligible at half the dose. Conclusions: All three Metformin groups were effective in reduction of HbA1C and glycaemic control clinically and there is no statistical difference in HbA1c reduction

Effectiveness and gastrointestinal tolerability during conversion and titration with once-daily OROS® hydromorphone extended release in opioid-tolerant patients with chronic low back pain

Science.gov (United States)

Hale, Martin E; Nalamachu, Srinivas R; Khan, Arif; Kutch, Michael

2013-01-01

Purpose To describe the efficacy and safety of hydromorphone extended-release tablets (OROS hydromorphone ER) during dose conversion and titration. Patients and methods A total of 459 opioid-tolerant adults with chronic moderate to severe low back pain participated in an open-label, 2- to 4-week conversion/titration phase of a double-blind, placebo-controlled, randomized withdrawal trial, conducted at 70 centers in the United States. Patients were converted to once-daily OROS hydromorphone ER at 75% of the equianalgesic dose of their prior total daily opioid dose (5:1 conversion ratio), and titrated as frequently as every 3 days to a maximum dose of 64 mg/day. The primary outcome measure was change in pain intensity numeric rating scale; additional assessments included the Patient Global Assessment and the Roland–Morris Disability Questionnaire scores. Safety assessments were performed at each visit and consisted of recording and monitoring all adverse events (AEs) and serious AEs. Results Mean (standard deviation) final daily dose of OROS hydromorphone ER was 37.5 (17.8) mg. Mean (standard error of the mean [SEM]) numeric rating scale scores decreased from 6.6 (0.1) at screening to 4.3 (0.1) at the final titration visit (mean [SEM] change, −2.3 [0.1], representing a 34.8% reduction). Mean (SEM) change in Patient Global Assessment was −0.6 (0.1), and mean change (SEM) in the Roland–Morris Disability Questionnaire was −2.8 (0.3). Patients achieving a stable dose showed greater improvement than patients who discontinued during titration for each of these measures (P < 0.001). Almost 80% of patients achieving a stable dose (213/268) had a ≥30% reduction in pain. Commonly reported AEs were constipation (15.4%), nausea (11.9%), somnolence (8.7%), headache (7.8%), and vomiting (6.5%); 13.0% discontinued from the study due to AEs. Conclusion The majority of opioid-tolerant patients with chronic low back pain were successfully converted to effective doses of

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)

Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

Science.gov (United States)

Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

2017-12-01

Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

Science.gov (United States)

Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

2016-01-01

In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

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.

A phase I and pharmacokinetic study of a powder-filled capsule formulation of oral irinotecan (CPT-11) given daily for 5 days every 3 weeks in patients with advanced solid tumors.

Science.gov (United States)

Pitot, Henry C; Adjei, Alex A; Reid, Joel M; Sloan, Jeff A; Atherton, Pamela J; Rubin, Joseph; Alberts, Steven R; Duncan, Barbara A; Denis, Louis; Schaaf, Larry J; Yin, Donghua; Sharma, Amarnath; McGovren, Patrick; Miller, Langdon L; Erlichman, Charles

2006-08-01

Intravenous (i.v.) irinotecan is a cytotoxic topoisomerase I inhibitor with broad clinical activity in metastatic colorectal cancer and other tumors. The development of an oral formulation of irinotecan could enhance convenience and lessen the expense of palliative irinotecan delivery. This phase I study evaluated the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of irinotecan given as a powder-filled capsule (PFC) daily for 5 days every 3 weeks. Patients with advanced solid tumors received escalating doses of oral irinotecan daily for 5 days every 3 weeks. Plasma samples were collected following the first and fifth doses of irinotecan during Cycle 1 to determine the PK of irinotecan and its major circulating metabolites: SN-38, SN-38G, and APC. 20 patients (median age 61.5 years, range 40-75; M/F 12/8; ECOG PS 0=5, 1=11, 2=4) received oral irinotecan at dose levels of 30 (n=3), 40 (n=3), 50 (n=6), and 60 (n=8) mg/m(2)/day. Of the eight patients enrolled at 60 mg/m(2), three patients experienced DLT (> or = grade 3) consisting of nausea (three patients), vomiting (three patients), diarrhea (two patients), and febrile neutropenia (two patients) for which all the three patients required hospitalization. Treatment of six patients at the 50-mg/m(2) dose level resulted in no DLT. Other toxicities observed include abdominal pain, alopecia, anorexia, and asthenia. After oral administration, irinotecan was rapidly absorbed into systemic circulation and converted to the active metabolite SN-38. Increasing dose levels resulted in a dose-dependent increase in mean exposure parameters (Cmax and AUC) of irinotecan and metabolites. Systemic exposure parameters (Cmax and AUC(0-24)) of irinotecan and SN-38 were comparable between days 1 and 5. The extent of conversion from irinotecan to SN-38 was approximately threefold higher after the oral administration compared to that previously observed after i.v. administration. The exposure

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

Science.gov (United States)

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard; Johnstone, David W.; Watson, Thomas; Smudzin, Therese; Keng, Peter C.

2008-01-01

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m 2 , 20 mg/m 2 , and 25 mg/m 2 were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3 pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m 2 ), II (20 mg/m 2 ), and III (25 mg/m 2 ), the mean peak plasma level was 0.23 ± 0.06 μmol/l, 0.32 ± 0.05 μmol/l, and 0.52 ± 0.14 μmol/l, respectively; AUC was 0.44 ± 0.09 μmol/l, 0.61 ± 0.1 μmol/l, and 0.96 ± 0.23 μmol/l, respectively; and duration of drug concentration >0.05 μmol/l (t > 0.05 μmol/l) was 1.6 ± 0.3 h, 1.9 ± 0.2 h, and 3.0 ± 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 μmol/l for a minimum of 1.6 h was sufficient for effective radiosensitization

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).

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.

Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through Telomerase Activity Increase in Middle-Aged Men.

Science.gov (United States)

Janić, Miodrag; Lunder, Mojca; Cerkovnik, Petra; Prosenc Zmrzljak, Uršula; Novaković, Srdjan; Šabovič, Mišo

2016-04-01

Previously, we have shown that slightly to moderately aged arteries in middle-aged males can be rejuvenated functionally by sub-therapeutic, low-dose fluvastatin and valsartan treatment. Here, we explore whether this treatment could also increase telomerase activity. We hypothesized that telomerase activity might be associated with (1) an improvement of arterial wall properties and (2) a reduction of inflammatory/oxidative stress parameters (both observed in our previous studies). The stored blood samples from 130 apparently healthy middle-aged males treated with fluvastatin (10 mg daily), valsartan (20 mg daily), fluvastatin and valsartan combination (10 and 20 mg), respectively, and placebo (control), were analyzed. The samples were taken before and after treatment lasting 30 days, and 5 months after treatment discontinuation. Telomerase activity was measured in blood leukocytes by a TaqMan Gene Expression Assay. Low-dose fluvastatin or valsartan increased telomerase activity (106.9% and 59.5% respectively; both p valsartan substantially increased telomerase activity, which significantly correlated with an improvement of endothelial function and a decrease of inflammation/oxidative stress. These findings could lead to a new innovative approach to arterial rejuvenation.

Prospective direct comparison of antihypertensive effect and safety between high-dose amlodipine or indapamide in hypertensive patients uncontrolled by standard doses of angiotensin receptor blockers and amlodipine.

Science.gov (United States)

Okamura, Keisuke; Shirai, Kazuyuki; Totake, Nao; Okuda, Tetsu; Urata, Hidenori

2018-01-01

When hypertension is uncontrolled by routine treatment with an angiotensin II receptor blocker (ARB) and the calcium channel blocker amlodipine (5 mg), the dose of amlodipine can be increased or a diuretic can be added. We investigated the more effective option in a prospective multicenter open-label study. Hypertensive patients were recruited if the target blood pressure (BP) in The Japanese Society of Hypertension 2009 guideline could not be achieved with standard-dose ARB therapy and amlodipine (5 mg). Patients were divided into three groups. Group-1 was switched to a combination of irbesartan (100 mg) and amlodipine (10 mg). Group-2A was changed to a combination of irbesartan (100 mg), amlodipine (5 mg), and indapamide, while Group-2B received a standard-dose ARB and amlodipine (5 mg) plus indapamide. Patients were assigned by their attending physicians and were followed for 6 months. The primary endpoint was the antihypertensive effect of each regimen. Group-1 contained 85 patients, Group-2A had 49 patients, and Group-2B had 4 patients. We only analyzed Group-1 and Group-2A due to the small size of Group-2B. In both groups, systolic BP and diastolic BP were significantly decreased up to 6 months (all p < 0.001). Reduction of systolic BP was greater in Group-1 than Group-2A after 1 month and 6 months (both p < 0.05). Uric acid was increased in Group-2A after 3 months, but not at 6 months. Although both regimens were effective for reducing BP, increasing amlodipine to 10 mg daily controlled hypertension without elevation of serum uric acid.

High dose tetrabromobisphenol A impairs hippocampal neurogenesis and memory retention.

Science.gov (United States)

Kim, Ah Hyun; Chun, Hye Jeong; Lee, Seulah; Kim, Hyung Sik; Lee, Jaewon

2017-08-01

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant that is commonly used in commercial and household products, such as, computers, televisions, mobile phones, and electronic boards. TBBPA can accumulate in human body fluids, and it has been reported that TBBPA possesses endocrine disruptive activity. However, the neurotoxic effect of TBBPA on hippocampal neurogenesis has not yet been investigated. Accordingly, the present study was undertaken to evaluate the effect of TBBPA on adult hippocampal neurogenesis and cognitive function. Male C57BL/6 mice were orally administrated vehicle or TBBPA (20 mg/kg, 100 mg/kg, or 500 mg/kg daily) for two weeks. TBBPA was observed to significantly and dose-dependently reduce the survival of newly generated cells in the hippocampus but not to affect the proliferation of newly generated cells. Numbers of hippocampal BrdU and NeuN positive cells were dose-dependently reduced by TBBPA, indicating impaired neurogenesis in the hippocampus. Interestingly, glial activation without neuronal death was observed in hippocampi exposed to TBBPA. Furthermore, memory retention was found to be adversely affected by TBBPA exposure by a mechanism involving suppression of the BDNF-CREB signaling pathway. The study suggests high dose TBBPA disrupts hippocampal neurogenesis and induces associated memory deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

Science.gov (United States)

Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

1992-12-01

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

Science.gov (United States)

Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2018-01-01

Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

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

Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL.

Science.gov (United States)

Barr, Paul M; Brown, Jennifer R; Hillmen, Peter; O'Brien, Susan; Barrientos, Jacqueline C; Reddy, Nishitha M; Coutre, Steven; Mulligan, Stephen P; Jaeger, Ulrich; Furman, Richard R; Cymbalista, Florence; Montillo, Marco; Dearden, Claire; Robak, Tadeusz; Moreno, Carol; Pagel, John M; Burger, Jan A; Suzuki, Samuel; Sukbuntherng, Juthamas; Cole, George; James, Danelle F; Byrd, John C

2017-05-11

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or TP53 status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials.gov as #NCT01578707. © 2017 by The American Society of Hematology.

Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

Science.gov (United States)

Andrews, J; Honeybourne, D; Jevons, G; Boyce, M; Wise, R; Bello, A; Gajjar, D

2003-03-01

A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

Directory of Open Access Journals (Sweden)

Hong-xia Xue

2015-01-01

Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

Science.gov (United States)

Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

2013-02-01

This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

DEFF Research Database (Denmark)

Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth

2005-01-01

To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

Pregnancies following the use of sequential treatment of metformin and incremental doses of letrozole in clomiphen-resistant women with polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Jafar Alavy Toussy

2012-01-01

Full Text Available Background: Clomiphen citrate (CC is the first line therapy for women with infertility and poly cystic ovary syndrome( PCOS. However, 20-25% of women are resistant to CC and do not ovulate. Objective: The objective of this study was to evaluate the efficacy of sequential treatment of metformin and incremental doses of letrozole in induction of ovulation in cases of CC-resistant PCOS patients. Materials and Methods: In this prospective before-after study, we enrolled 106 anovulatory PCOS women who failed to ovulate with CC alone from Amir-Almomenin University Hospital in Semnan, Iran. After an initial 6-8 weeks of metformin treatment, they received 2.5 mg letrozole daily on days 3-7 after menes. If they did not ovulate with 2.5 mg letrozole, the doses were increased to 5 to 7.5 mg daily in subsequent cycles. The main outcomes were ovulatory rate, pregnancy rate and cumulative pregnancy rate. Results: 13.33% of patients conceived with metformin alone. Ovulation occurred in 83 out of remaining 91 patients (91.2%. 78.02% of patients responded to lower doses of letrozole. Cumulative pregnancy rate was 60/ 105 (57.14%.Conclusion: We suggest that treatment in CC-resistant PCOS patients should begin at first with lower doses of letrozole and could increase to the higher dose depending on the patient response before considering more aggressive therapeutic alternatives such as gonadotropins.

Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye

Directory of Open Access Journals (Sweden)

Sarezky D

2016-09-01

Full Text Available Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Purpose: Alpha lipoic acid (ALA is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. Patients and methods: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time. Results: The 600 mg dose was well tolerated. At the 800 mg dose, one subject had an intolerable flushing sensation. At the 1,200 mg dose, two subjects had intolerable upper gastrointestinal side effects and one subject had an intolerable flushing sensation. Subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects. Conclusion: High-dose ALA is not completely tolerated by the elderly. These preliminary data suggest that gastrointestinal prophylaxis may improve tolerability. (ClinicalTrials.gov, NCT02613572. Keywords: age-related macular degeneration, geographic atrophy, antioxidant, gastrointestinal, dietary supplements, lipoic acid

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

Science.gov (United States)

Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

2015-11-01

Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Uncertainty assessment and comparison of different dose algorithms used to evaluate a two element LiF:Mg,Ti TL personal dosemeter

International Nuclear Information System (INIS)

Stadtmann, H.; Hranitzky, F.C.

2008-01-01

This paper presents the results of an uncertainty assessment and comparison study of different dose algorithms used for evaluating our routine two element TL whole body dosemeter. Due to the photon energy response of the two different filtered LiF:Mg,Ti detector elements the application of dose algorithms is necessary to assess the relevant photon doses over the rated energy range with an acceptable energy response. Three dose algorithms are designed to calculate the dose for the different dose equivalent quantities, i.e. personal dose equivalent H p (10) and H p (0.07) and photon dose equivalent H x used for personal monitoring before introducing personal dose equivalent. Based on experimental results both for free in air calibration as well as calibration on the ISO water slab phantom (type test data) a detailed uncertainty analysis war performed by means of Monte Carlo simulation techniques. The uncertainty contribution of the individual detector element signals was taken into special consideration. (author)

Chitin Oligosaccharide (COS) Reduces Antibiotics Dose and Prevents Antibiotics-Caused Side Effects in Adolescent Idiopathic Scoliosis (AIS) Patients with Spinal Fusion Surgery.

Science.gov (United States)

Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu

2017-03-14

Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p antibiotics ( p antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.

Randomized, double-blind, crossover study comparing DFN-11 injection (3 mg subcutaneous sumatriptan) with 6 mg subcutaneous sumatriptan for the treatment of rapidly-escalating attacks of episodic migraine.

Science.gov (United States)

Cady, Roger K; Munjal, Sagar; Cady, Ryan J; Manley, Heather R; Brand-Schieber, Elimor

2017-12-01

A 6-mg dose of SC sumatriptan is the most efficacious and fast-acting acute treatment for migraine, but a 3-mg dose of SC sumatriptan may improve tolerability while maintaining efficacy. This randomized, double-blind, crossover study compared the efficacy and tolerability of 3 mg subcutaneous (SC) sumatriptan (DFN-11) with 6 mg SC sumatriptan in 20 adults with rapidly-escalating migraine attacks. Eligible subjects were randomized (1:1) to treat 1 attack with DFN-11 and matching placebo autoinjector consecutively or 2 DFN-11 autoinjectors consecutively and a second attack similarly but with the alternative dose (3 mg or 6 mg). The proportions of subjects who were pain-free at 60 min postdose, the primary endpoint, were similar following treatment with 3 mg SC sumatriptan and 6 mg SC sumatriptan (50% vs 52.6%, P  =  .87). The proportions of subjects experiencing pain relief (P  ≥  .48); reductions in migraine pain intensity (P  ≥  .78); and relief from nausea, photophobia, or phonophobia (P  ≥  .88) with 3 mg SC sumatriptan and 6 mg SC sumatriptan were similar, as were the mean scores for satisfaction with treatment (M  =  2.6 vs M  =  2.4, P  =  .81) and the mean number of rescue medications used (M  =  .11 vs M  =  .26, P  =  .32). The most common adverse events with the 3- and 6-mg doses were triptan sensations - paresthesia, neck pain, flushing, and involuntary muscle contractions of the neck - and the incidence of adverse events with both doses was similar (32 events total: 3 mg, n  =  14 [44%]; 6 mg, n  =  18 [56%], P  =  .60). Triptan sensations affected 4 subjects with the 6-mg dose only, 1 subject with the 3-mg dose only, and 7 subjects with both sumatriptan doses. Chest pain affected 2 subjects (10%) treated with the 6-mg dose and no subjects (0%) treated with the 3-mg dose of DFN-11. There were no serious adverse events. The 3-mg SC dose

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

Science.gov (United States)

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

2017-09-28

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

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.

Evaluation of the repeated-dose liver micronucleus assay using 2,4-dinitrotoluene: a report of a collaborative study by CSGMT/JEMS.MMS.

Science.gov (United States)

Maeda, Akihisa; Tsuchiyama, Hiromi; Asaoka, Yoshiji; Hirakata, Mikito; Miyoshi, Tomoya; Oshida, Keiyu; Miyamoto, Yohei

2015-03-01

The liver micronucleus assay using young adult rats has the potential to detect liver carcinogens by repeated dosing, and could be expected to be integrated into repeated-dose toxicity studies using a hepatocyte isolation method without the traditional in situ collagenase perfusion. In this study, to assess the performance of the repeated-dose liver micronucleus assay, 2,4-dinitrotoluene (DNT), which is a rodent liver carcinogen, was administered orally to male rats at doses of 50, 100 and 200 mg/kg/day once daily for 14 or 28 consecutive days, and the frequencies of micronucleated hepatocytes (MNHEPs) and micronucleated immature erythrocytes (MNIMEs) were examined. Significant increases in the MNHEPs were observed at 50 mg/kg/day or more in the 14-day treatment, and 50 and 100 mg/kg/day in the 28-day treatment. These increases were dependent on both the dose and the number of administrations, which indicates the possibility that the MNHEPs accumulate as a result of repeated dosing. In contrast, no increase in the MNIMEs was observed. In conclusion, the repeated-dose liver micronucleus assay using young adult rats is sufficiently sensitive to detect the genotoxicity of 2,4-DNT at a low dose.

Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

Science.gov (United States)

Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

2010-06-01

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

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.

Respiratory outcomes following 100 mg/kg v. 200 mg/kg of poractant ...

African Journals Online (AJOL)

In keeping with current evidence, the initial dose of poractant alpha was increased from 100 mg/kg to 200 mg/kg. e outcomes of newborns requiring treatment with surfactant before and aer this change were reviewed. Methods. Electronic clinical records were reviewed of infants admitted to ACH who received surfactant ...

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.