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Sample records for efficacy safety tolerability

  1. Intragastric Balloon for Obesity Treatment: Safety, Tolerance, and Efficacy

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    Joana Ribeiro da Silva

    2017-12-01

    Full Text Available Background: Obesity is an increasing worldwide problem associated with a vast number of comorbidities. Decreasing body weight by only 5-10% has been shown to slow and even prevent the onset of obesity-related comorbidities. Between pharmacological therapy and bariatric surgery a great variety of endoscopic techniques are available, the most common being intragastric balloon (IGB. The purpose of this study was to assess the safety, tolerance, and kinetics of IGBs in weight loss. The kinetics of weight loss were evaluated in 2 different contexts and phases: after the IGB's removal and after follow-up that varied between 6 and 12 months. Successful weight loss was defined as ≥10% weight loss after 6-12 months. Methods: The study included 51 patients who had undergone Orbera® IGB placement between September 2014 and February 2016. Inclusion criteria were age between 18 and 65 years; body mass index (BMI 28-35 with severe obesity-related disorders; or BMI 35-40. The IGB was removed 6 months later. All patients were followed for a minimum period of 6-12 months. Results: Of 51 patients, 16 were excluded (7 due to intolerance and 35 patients entered the study, of which 83% were followed for more than 6-12 months. The average weight loss (WL and % excess WL (%EWL after 6 months of treatment were 11.94 kg and 42.16%, respectively. At 6-12 months, after removal of the IGB, the mean WL was 8.25 kg and %EWL was 30.27%. Nineteen patients attained a WL of ≥10% the baseline value at IGB removal and 12 maintained their weight below this threshold during the 6-12 following months. Conclusions: After temporary IGB implantation in overweight or obese individuals, a WL that was ≥10% of weight at baseline was achieved in 54.3% and sustained at 6-12 months in 41.4% of participants. IGBs are an attractive intermediate option between diet and exercise programs and bariatric surgery. In general, IGB placement is a safe and well-tolerated procedure.

  2. Efficacy, safety and tolerability of simvastatin in children with familial hypercholesterolaemia - Rationale, design and baseline characteristics

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    de Jongh, S.; Stalenhoef, A. F. H.; Tuohy, M. B.; Mercuri, M.; Bakker, H. D.; Kastelein, J. J. P.

    2002-01-01

    Objective: To describe the rationale, design and baseline data of a study conducted to determine the efficacy, safety and tolerability of simvastatin in children and adolescents with heterozygous familial hypercholesterolaemia (heFH). Methods: Patients were recruited from nine lipid clinics

  3. Efficacy, safety and tolerability of rasagiline as adjunctive therapy in elderly patients with Parkinson's disease.

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    Tolosa, E; Stern, M B

    2012-02-01

    Rasagiline, an MAO-B inhibitor, is indicated for the treatment of Parkinson's disease (PD). In this post hoc analysis, the efficacy, safety and tolerability of rasagiline as an adjunct to levodopa were compared with placebo in elderly (≥70 years) and younger (Rasagiline: Efficacy and Safety on the Treatment of 'OFF' and Lasting effect in Adjunct therapy with Rasagiline Given Once daily randomized, double-blind, placebo-controlled trials with the primary efficacy end-point being the reduction from baseline in daily OFF time. Secondary efficacy end-points included scores for Clinical Global Improvement (CGI)-Examiner during ON time, Unified Parkinson's Disease Rating Scale (UPDRS)-ADL during OFF time, UPDRS-Motor during ON time and total daily ON time with and without troublesome dyskinesia. Tolerability was evaluated from adverse events (AEs) in the two age groups. Rasagiline decreased daily OFF time versus placebo (Prasagiline but were not significant. Between-group comparisons (≥70 vs. efficacy was unaffected by age for all end-points (P>0.1), and rasagiline was well tolerated amongst both groups of patients with a comparable incidence of total and dopaminergic AEs (P>0.1). Adjunct rasagiline is efficacious and well tolerated in elderly non-demented patients (≥70 years) with moderate to advanced PD. Confirmation of the efficacy and safety of rasagiline in the elderly patient subgroup is especially relevant because of the increasing number of elderly patients with PD. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

  4. Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

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    Gajofatto A

    2015-12-01

    Full Text Available Alberto Gajofatto,1,2 Marco Turatti,2 Salvatore Monaco,1,2 Maria Donata Benedetti2 1Department of Neurological, Biomedical and Movement Sciences, University of Verona, Verona, Italy; 2Division of Neurology B, Verona University Hospital, Verona, Italy Abstract: Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS, a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. Keywords: multiple sclerosis, fingolimod, safety, tolerability, efficacy

  5. Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

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    Denilson C. Albuquerque

    2005-08-01

    Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

  6. Tolerability, safety, and efficacy of PEG 3350 as a 1-day bowel preparation in children.

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    Walia, Ritu; Steffen, Rita; Feinberg, Lisa; Worley, Sarah; Mahajan, Lori

    2013-02-01

    The aim of the study was to evaluate the tolerability, safety, and efficacy of polyethylene glycol (PEG) 3350 without electrolytes as a 1-day bowel preparation for colonoscopy in children. A prospective study of 45 children undergoing colonoscopy prescribed PEG 3350 without electrolytes mixed with a commercial electrolyte beverage was performed. Patients PEG 3350 without electrolytes mixed in 32 ounces of Gatorade. Patients ≥ 45 kg were given 255 g of PEG 3350 without electrolytes in 64 ounces of Gatorade A basic metabolic panel was performed at the time of the clinic visit and just before colonoscopy. Patients completed a survey related to bowel preparation. Endoscopists graded bowel preparation and noted the proximal extent of the examination. A total of 44 patients (14 ± 3 years) completed the study. One patient was excluded due to protocol breach. All subjects reported the preparation was easy (61%) or tolerable (39%). Adverse events included nausea (34%), abdominal pain (23%), vomiting (16%), abdominal distension (20%), bloating (23%), and dizziness (7%). Although significant changes in serum glucose and CO2 were noted, no therapeutic interventions were indicated. Significant changes in sodium, potassium chloride, blood urea nitrogen, or creatinine did not occur. Colonic preparation was rated as excellent in 23%, good in 52%, fair in 23%, and poor in 2% of patients. Intubation of the ileum was successful in 100%. One-day bowel preparation with high dose PEG 3350 mixed with commercial electrolyte solution is tolerable, safe, and effective in children before colonoscopy.

  7. Dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: safety, tolerability, and efficacy

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    Mary Elizabeth Cox

    2010-01-01

    Full Text Available Mary Elizabeth Cox1, Jennifer Rowell1, Leonor Corsino1, Jennifer B Green1,21Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition. Duke University Medical Center, Durham, NC, USA; 2Department of Medicine, Division of Endocrinology, Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: Although glycemic control is an important and effective way to prevent and minimize the worsening of diabetes-related complications, type 2 diabetes is a progressive disease which often proves difficult to manage. Most affected patients will eventually require therapy with multiple medications in order to reach appropriate glycemic targets. The dipeptidyl peptidase-4 (DPP-4 inhibitors constitute a relatively new class of oral medications for the treatment of type 2 diabetes, which has become widely incorporated into clinical practice. This review summarizes the available data on the efficacy, safety, and tolerability of these medications.Keywords: type 2 diabetes, pharmacotherapy, DPP-4 inhibitor, sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin

  8. Long-term efficacy, safety and tolerability of Remoxy for the management of chronic pain.

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    Pergolizzi, Joseph V; Zampogna, Gianpietro; Taylor, Robert; Raffa, Robert B

    2015-03-01

    Historically, chronic pain generally went under-treated for a variety of objective and subjective reasons, including difficulty to objectively diagnose and manage over a long period of time, potential serious adverse effects of commonly available medications, and patient, healthcare and societal concerns over opioid medications. More recently, in an effort to redress the under-treatment of pain, the number of prescriptions of opioid analgesics has risen dramatically. However, paralleling the increased legitimate use has been a concomitant increase in opioid abuse, misuse and diversion. Pharmaceutical companies have responded by developing a variety of opioid formulations designed to deter abuse by making the products more difficult to tamper with. One such product is Remoxy(®), an extended-release formulation of the strong opioid oxycodone. We review the efficacy, safety and tolerability of this formulation based on the available published literature.

  9. Tolerability, safety and efficacy of Iloprost infusion without peristaltic pump in systemic sclerosis

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    S. Tosi

    2011-09-01

    Full Text Available Objective. To evaluate safety, tolerability and efficacy on Raynaud’s phenomenon (Rp of iloprost infusion without peristaltic pump in patients with systemic sclerosis (SSc. Patients and methods. The inclusion criteria were diagnosis of SSc, age between 18 and 65 years, presence of Rp, and absence of any controindication to the use of iloprost. The treatment was carried out in a day hospital setting and consisted first of 5 consecutive days of iloprost infusion (from an initial dose of 1.0 ng/Kg/min up to 2 ng/kg/min, and then of 2 days of infusions at the maximum possible dose every 45 days for one year. All of the adverse events were carefully recorded and the changes in the Rp were measured by a 5 grade scale (worsened, unmodified, slightly improved, very improved, disappeared. Results. Thirty-eight SSc patients (all females, mean age 49 years (range 18.5-65, disease duration 1.5 years (range 0.5-10.8 were enrolled in the study. During the first cycle of therapy, 14 avderse events occurred in 11 (28.9% patients and during the next cycles, 3 adverse events were seen in 3 (7.9% patients. In all of the cases they were mild and transient. Rp was considered very improved in 15 (39.5% patients, slightly improved in 13 (34.2%, unmodified in 8 (21% and worse in 2 (5.2%. Discussion. In this study intravenous iloprost without peristaltic pump proved to be safe, well tolerated, and as effective as traditional infusion through peristaltic pump in improving Rp in patients with SSc.

  10. Clinical efficacy, safety and tolerance of the Kerawort (imiquimod cream used for treatment of anogenital warts

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    M. R. Rakhmatulina

    2015-01-01

    Full Text Available Goal of the study. To assess the efficacy and safety of Kerawort (Imiquimod, 5% cream for topical administration vs. placebo used for treatment of anogenital warts. Methods and materials. The single-blind comparative placebo-controlled study involved 90 patients (44 female and 46 male with anogenital warts. The patients were randomized into two groups: the main group (n = 45 receiving treatment with Kerawort (Imiquimod, 5% cream and the control group (n = 45 receiving placebo. The diagnosis was confirmed by the identification of human papillomavirus by the polymerase chain reaction method. The patients received treatment three times a week until clinical signs disappeared but for not more than 16 weeks. Results. In 95.6% of patients from the main group and 8.9% of patients from the control group, anogenital warts disappeared completely or the quantity/area of pathological eruptions reduced at least by 70% as compared to the baseline. No relapses occurred during the treatment and follow-up period (28 days after the completion of treatment in patients from the main group. An increase in the size and/or area of anogenital warts and/or development of new eruptions on the skin and mucous membrane of the genitals were recorded in 11.1% of patients from the control group. No serious adverse events were revealed during the study. Conclusion. Higher efficacy (р < 0.0000001 and comparable safety of Kerawort (Imiquimod, 5% cream for topical administration used for treatment of anogenital warts vs. placebo were reliably established.

  11. Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study.

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    Ballard, C; Sauter, M; Scheltens, P; He, Y; Barkhof, F; van Straaten, E C W; van der Flier, W M; Hsu, C; Wu, S; Lane, R

    2008-09-01

    The aim was to evaluate the efficacy, safety and tolerability of rivastigmine capsules in patients diagnosed with probable vascular dementia (VaD). VantagE (Vascular Dementia trial studying Exelon) was a 24-week, multicentre, double-blind study. VaD patients aged 50-85 years were randomized to rivastigmine capsules (3-12 mg/day) or placebo. Efficacy assessments included global and cognitive performances, activities of daily living and neuropsychiatric symptoms. Adverse events were recorded. Additional exploratory analyses determined whether heterogeneity in pathologies and symptoms extended to differential treatment effects. NCT00099216. 710 patients were randomized. Rivastigmine demonstrated superiority over placebo on three measures of cognitive performance (Vascular Dementia Assessment Scale, Alzheimer's Disease Assessment Scale cognitive subscale, Mini-Mental State Examination; all p or =75 years old), assumed more likely to also have Alzheimer's disease (AD) pathology, demonstrated significant cognitive responses to rivastigmine and a safety profile similar to that seen in AD patients. Younger patients, assumed less likely to have concomitant AD pathology, showed no efficacy response and were associated with slight elevations of blood pressure, cerebrovascular accidents and mortality. Rivastigmine-placebo differences in patients with, versus those without, medial temporal atrophy (also suggestive of concomitant AD) showed a numerical difference similar to that seen between the older versus younger patients, but did not attain statistical significance. Consistent with trials evaluating other cholinesterase inhibitors, rivastigmine did not provide consistent efficacy in probable VaD. The efficacy apparent on cognitive outcomes was derived from effects in older patients likely to have concomitant Alzheimer pathology. This is supportive of an existing argument that the putative cholinergic deficit in VaD reflects the presence of concomitant Alzheimer pathology.

  12. Efficacy, tolerability, and safety of non-pharmacological therapies for chronic pain: An umbrella review on various CAM approaches.

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    Houzé, Bérengère; El-Khatib, Héjar; Arbour, Caroline

    2017-10-03

    Complementary and alternative medicine (CAM) therapies may be used as a non-pharmacological approach to chronic pain management. While hundreds of trials about individual CAM modality have been conducted, a comprehensive overview of their results is currently lacking for pain clinicians and researchers. This umbrella review synthesized the quality of meta-analytic evidence supporting the efficacy, tolerability and safety of CAM therapies for the management of chronic pain. MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from October 1991 to November 2016. Reviews of clinical trials (randomized and non-randomized) with meta-analysis investigating the utility of any CAM modality for chronic pain were eligible. Pain relief post-intervention was the main outcome and secondary outcomes included patients' adherence and incidence of adverse effects during CAM protocol. Twenty-six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities, falling under natural products, mind and body practices or other complementary health approaches were included. Inhaled cannabis, graded motor imagery, and Compound Kushen injection (a form of Chinese medicine) were found the most efficient (with moderate-to-high effect sizes and low heterogeneity) and tolerable (≥80% of adherence to study protocols) for chronic pain relief. When reported, adverse effects related to these CAM were minor. Although several CAM were found effective for chronic pain relief, it remains unclear when these modalities are a reasonable choice against or in conjunction with mainstream treatments. In that sense, future research with a clear emphasis on concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Commonly used preparations for colonoscopy: Efficacy, tolerability and safety – A Canadian Association of Gastroenterology position paper

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    Barkun, Alan; Chiba, Naoki; Enns, Robert; Marcon, Margaret; Natsheh, Susan; Pham, Co; Sadowski, Dan; Vanner, Stephen

    2006-01-01

    INTRODUCTION: The increased demand for colonoscopy, coupled with the introduction of new bowel cleansing preparations and recent caution advisories in Canada, has prompted a review of bowel preparations by the Canadian Association of Gastroenterology. METHODS: The present review was conducted by the Clinical Affairs group of committees including the endoscopy, hepatobiliary/transplant, liaison, pediatrics, practice affairs and regional representation committees, along with the assistance of Canadian experts in the field. An effort was made to systematically assess randomized prospective trials evaluating commonly used bowel cleansing preparations in Canada. RESULTS: Polyethylene glycol (PEG)-; sodium phosphate (NaP)-; magnesium citrate (Mg-citrate)-; and sodium picosulphate, citric acid and magnesium oxide (PSMC)-containing preparations were reviewed. Regimens of PEG 2 L with bisacodyl (10 mg to 20 mg) or Mg-citrate (296 mL) are as effective as standard PEG 4 L regimens, but are better tolerated. NaP preparations appear more effective and better tolerated than standard PEG solutions. PSMC has good efficacy and tolerability but head-to-head trials with NaP solutions remain few, and conclusions equivocal. Adequate hydration during preparation and up to the time of colonoscopy is critical in minimizing side effects and improving bowel cleansing in patients receiving NaP and PSMC preparations. All preparations may cause adverse events, including rare, serious outcomes. NaP should not be used in patients with cardiac or renal dysfunction (PEG solution is preferable in these patients), bowel obstruction or ascites, and caution should be exercised when used in patients with pre-existing electrolyte disturbances, those taking medications that may affect electrolyte levels and elderly or debilitated patients. Health Canada’s recommended NaP dosing for most patients is two 45 mL doses 24 h apart. However, both safety and efficacy data on this dosing schedule are lacking

  14. Structured versus long-chain triglycerides: a safety, tolerance, and efficacy randomized study in colorectal surgical patients.

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    Bellantone, R; Bossola, M; Carriero, C; Malerba, M; Nucera, P; Ratto, C; Crucitti, P; Pacelli, F; Doglietto, G B; Crucitti, F

    1999-01-01

    After trauma or surgery, researchers have suggested that medium-chain triglycerides have metabolic advantages, although they are toxic in large doses. To try to reduce this potential toxicity, structured lipids, which provide a higher oxidation rate, faster clearance from blood, improved nitrogen balance, and less accumulation in the reticuloendothelial system, could be used. Therefore, we evaluated, through a blind randomized study, the safety, tolerance, and efficacy of structured triglycerides, compared with long-chain triglycerides (LCT), in patients undergoing colorectal surgery. Nineteen patients were randomized to receive long-chain or structured triglycerides as a lipid source. They received the same amount of calories (27.2/kg/d), glucose (4 g/kg/d), protein (0.2 g/kg/d), and lipids (11.2 kcal/kg/d). Patients were evaluated during and after the treatment for clinical and laboratory variables, daily and cumulative nitrogen balance, urinary excretion of 3-methyl-histidine, and urinary 3-methylhistidine/creatinine ratio. No adverse effect that required the interruption of the treatment was observed. Triglyceride levels and clinical and laboratory variables were similar in the two groups. A predominantly positive nitrogen balance was observed from day 2 until day 5 in the LCT group and from day 1 until day 4 in the structured triglycerides group. The cumulative nitrogen balance (in grams) for days 1 to 3 was 9.7+/-5.2 in the experimental group and 4.4+/-11.8 in the control group (p = .2). For days 1 to 5 it was 10.7+/-10.5 and 6.5+/-17.9 (p = .05), respectively. The excretion of 3-methylhistidine was higher in the control group but decreased in the following days and was similar to the experimental group on day 5. This study represents the first report in which structured triglycerides are administered in postoperative patients to evaluate safety, tolerance, and efficacy. It suggests that Fe73403 is safe, well tolerated, and efficacious in terms of nitrogen

  15. Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder.

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    Moreno, Francisco A; Wiegand, Christopher B; Taitano, E Keolani; Delgado, Pedro L

    2006-11-01

    Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD. Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004. Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p

  16. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB : systematic review and meta-analysis

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    Sotgiu, Giovanni; Centis, Rosella; D'Ambrosio, Lia; Alffenaar, Jan-William C.; Anger, Holly A.; Caminero, Jose A.; Castiglia, Paolo; De Lorenzo, Saverio; Ferrara, Giovanni; Koh, Won-Jung; Schecter, Giesela F.; Shim, Tae S.; Singla, Rupak; Skrahina, Alena; Spanevello, Antonio; Udwadia, Zarir F.; Villar, Miquel; Zampogna, Elisabetta; Zellweger, Jean-Pierre; Zumla, Alimuddin; Migliori, Giovanni Battista

    2012-01-01

    Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from

  17. Pitavastatin demonstrates long-term efficacy, safety and tolerability in elderly patients with primary hypercholesterolaemia or combined (mixed) dyslipidaemia

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    Stender, Steen; Budinski, Dragos; Hounslow, Neil

    2013-01-01

    Aims: To assess the long-term efficacy, safety and tolerability of pitavastatin (2 and 4 mg) in elderly patients (≥65 years of age) with primary hypercholesterolaemia or combined (mixed) dyslipidaemia.Design: Patients (n = 545) who had completed a 12-week double-blind comparative study (core study...... Cholesterol Education Program Adult Treatment Plan III (NCEP ATP III) targets for low-density lipoprotein cholesterol (LDL-C) was determined.Results: Of the patients enrolled, 539 received at least one dose of pitavastatin (safety population: men, 45.5%; Caucasian, 99.1%; mean age, 70.3 years; range, 65......-89 years). Only 17% of patients required up-titration to pitavastatin 4 mg. After 60 weeks, NCEP ATP III and EAS targets were attained by 93.8% and 89.0% of patients, respectively. Plasma LDL-C declined by 43.4% and high-density lipoprotein cholesterol increased by 9.6% versus core-study baseline values...

  18. Efficacy and safety assessment of microbiological feed additive for chicken broilers in tolerance studies

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    Kupryś-Caruk Marta

    2018-03-01

    Full Text Available Introduction: One aim of the study was to evaluate the impact when added to feed of the two potentially probiotic strains of lactic acid bacteria (LAB Lactobacillus plantarum K KKP 593/p and Lactobacillus rhamnosus KKP 825 on production performance, health, and the composition of gut microbiota. The complementary aim was to assess the safety of these strains in broiler rearing.

  19. Efficacy, safety, and improved tolerability of travoprost BAK-free ophthalmic solution compared with prior prostaglandin therapy

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    J Charles Henry

    2008-10-01

    Full Text Available J Charles Henry1, James H Peace2, Jeanette A Stewart3,4, William C Stewart3,41Little Rock Eye Clinic, Little Rock, AR, USA; 2Diabetic Eye Medical Clinic, Inglewood, CA, USA; 3PRN Pharmaceutical Research Network, LLC, Dallas,TX, USA; 4Carolina Eye Institute, University of South Carolina, School of Medicine, Columbia, SC, USAPurpose: To evaluate the efficacy, safety and tolerability of changing to travoprost BAK-free from prior prostaglandin therapy in patients with primary open-angle glaucoma or ocular hypertension.Design: Prospective, multi-center, historical control study.Methods: Patients treated with latanoprost or bimatoprost who needed alternative therapy due to tolerability issues were enrolled. Patients were surveyed using the Ocular Surface Disease Index (OSDI to evaluate OSD symptoms prior to changing to travoprost BAK-free dosed once every evening. Patients were re-evaluated 3 months later.Results: In 691 patients, travoprost BAK-free demonstrated improved mean OSDI scores compared to either latanoprost or bimatoprost (p < 0.0001. Patients having any baseline OSD symptoms (n = 235 demonstrated significant improvement after switching to travoprost BAK-free (p < 0.0001. In 70.2% of these patients, symptoms were reduced in severity by at least 1 level. After changing medications to travoprost BAK-free, mean intraocular pressure (IOP was significantly decreased (p < 0.0001. Overall, 72.4% preferred travoprost BAK-free (p < 0.0001, travoprost BAK-free vs prior therapy. Travoprost BAK-free demonstrated less conjunctival hyperemia than either prior therapy (p < 0.0001.Conclusions: Patients previously treated with a BAK-preserved prostaglandin analog who are changed to travoprost BAK-free have clinically and statistically significant improvement in their OSD symptoms, decreased hyperemia, and equal or better IOP control.Keywords: glaucoma, prostaglandin analog, travoprost, latanoprost, bimatoprost, preservative, benzalkonium chloride

  20. Efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome: systematic review and meta-analysis.

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    Schaefert, Rainer; Klose, Petra; Moser, Gabriele; Häuser, Winfried

    2014-06-01

    To assess the efficacy, tolerability, and safety of hypnosis in adult irritable bowel syndrome by a meta-analysis of randomized controlled trials. Studies were identified by a literature search of the databases Allied and Complementary Medicine Database, Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, PubMed, PsycINFO, and Scopus (from inception to June 30, 2013). Primary outcomes were adequate symptom relief, global gastrointestinal score, and safety. Summary relative risks (RRs) with number needed to treat (NNT) and standardized mean differences (SMDs) with 95% confidence intervals (95% CIs) were calculated using random-effects models. Eight randomized controlled trials with a total of 464 patients and a median of 8.5 (7-12) hypnosis sessions over a median of 12 (5-12) weeks were included into the analysis. At the end of therapy, hypnosis was superior to control conditions in producing adequate symptom relief (RR, 1.69 [95% CI = 1.14-2.51]; NNT, 5 [3-10]) and in reducing global gastrointestinal score (SMD, 0.32 [95% CI = -0.56 to -0.08]). At long-term follow-up, hypnosis was superior to controls in adequate symptom relief (RR, 2.17 [95% CI = 1.22-3.87]; NNT, 3 [2-10]), but not in reducing global gastrointestinal score (SMD, -0.57 [-1.40 to 0.26]). One (0.4%) of 238 patients in the hypnosis group dropped out due to an adverse event (panic attack). This meta-analysis demonstrated that hypnosis was safe and provided long-term adequate symptom relief in 54% of patients with irritable bowel syndrome refractory to conventional therapy.

  1. The Efficacy, Safety and Tolerability of Retapamulin as a Treatment Option for Impetigo and Other Uncomplicated Superficial Skin Infections: A Meta-analysis

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    Rudy Ciulianto

    2015-04-01

    Full Text Available BACKGROUND: The treatment of impetigo, secondarily infected dermatitis and infected traumatic lesions continue to develop as new generations of drugs are being formulated. Bacteria causing impetigo show growing resistance rates for commonly used antibiotics. Retapamulin being a new drug has been recently approved as topical antibiotic in children and adult. This study aimed to ascertain the efficacy, safety and tolerability of retapamulin as the treatment option for impetigo and other uncomplicated superficial skin infections. METHODS: A search for studies published from 2006-2014 was done in Pubmed, EBSCO, OVID, Science Direct, and Cochrane using the search strategy. The search was limited to studies conducted in human subjects and published in the English language. Randomized controlled trials evaluating the efficacy, safety and tolerability of retapamulin as treatment for impetigo and other uncomplicated superficial skin infections in children and adult were included and extracted independently and the qualities of the studies were appraised using critical appraisal tools. Data analysis was conducted by using RevMan 5. RESULTS: This study has high heterogeneity and found Retapamulin has no statistically significant difference in the clinical success after seven days and follow up among per-protocol-patients, bacteriogical confirmed patients and intention-to-treat patients with impetigo and other secondary infected traumatic lesions compared to other regimens. However, Retapamulin has beneficial effect in the clinical success, well tolerated and safe for children and adults. CONCLUSIONS: Retapamulin is comparably effective and safe as a treatment option for impetigo and other uncomplicated superficial skin infections. KEYWORDS: efficacy, safety, tolerability, retapamulin, impetigo, meta-analysis.

  2. [Tolerance, safety and efficacy of the one-day preparation of PEG3350 + bisacodyl compared to 2 days of PEG3350 + bisacodyl in pediatric patients].

    Science.gov (United States)

    Portillo Canizalez, Ligia Marcela; Blanco Rodriguez, Gerardo; Teyssier Morales, Gustavo; Penchyna Grub, Jaime; Trauernicht Mendieta, Sean; Zurita-Cruz, Jessie Nallely

    Multiple intestinal preparations have been used in children undergoing colonoscopy, with variable limitation due to acceptance, tolerance, and proper cleaning. The objective of this study was to compare the tolerability, safety and efficacy of the colonoscopy preparation with 1 day with PEG 3350 (poliethylenglycol) (4g/kg/day) + bisacodyl compared to 2 days of preparation with PEG 3350 (2g/kg/day) + bisacodyl in pediatric patients. A clinical, randomized, and blind trial was performed. Patients aged 2 to 18 years scheduled for colonoscopy were included. Patients were randomized into two groups: 1 day of preparation with PEG 3350 4g/kg/day + bisacodyl and 2 days of preparation with PEG 3350 2g/kg/day + bisacodyl. Through a questionnaire, physical examination and endoscopic evaluation (Boston scale), the tolerance, safety and efficacy of the 2 preparations to be evaluated were determined. Student's t test was performed for quantitative variables and χ 2 for qualitative variables. There were no significant differences in compliance rates, adverse effects, and extent of colonoscopic evaluation. Tolerance and safety between the intestinal preparation for 1-day colonoscopy with PEG 3350 (4g/kg/day) + bisacodyl and the 2-day preparation with PEG 3350 (2g/kg/day) + bisacodyl were similar. The quality of cleanliness was good in both groups, being partially more effective in the 1-day group with PEG 3350 (4g/kg/day). Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  3. 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

  4. Sulfasalazine efficacy and tolerability in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    V. V. Badokin

    2005-01-01

    Full Text Available Sulfasalazine is one of the main disease modifying drugs for the treatment of chronic inflammatory joint and spine diseases. The article describes mechanism of action of sulfasalazine and its main metabolites. Detailed information about anti-inflammatory and immunosuppressive action of the drug is presented. Results of many studies of sulfasalazine efficacy in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis are discussed from the evidence based medicine point of view. Data on sulfasalazine tolerability and safety are presented with separate discussion of hypersensitivity and dose-dependent adverse reactions so as their treatment and prophylaxis.

  5. Switching to aripiprazole in outpatients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues with risperidone: a randomized, multicentre, open-label study.

    Science.gov (United States)

    Ryckmans, V; Kahn, J P; Modell, S; Werner, C; McQuade, R D; Kerselaers, W; Lissens, J; Sanchez, R

    2009-05-01

    This study evaluated the safety/tolerability and effectiveness of aripiprazole titrated-dose versus fixed-dose switching strategies from risperidone in patients with schizophrenia experiencing insufficient efficacy and/or safety/tolerability issues. Patients were randomized to an aripiprazole titrated-dose (starting dose 5 mg/day) or fixed-dose (dose 15 mg/day) switching strategy with risperidone down-tapering. Primary endpoint was rate of discontinuation due to adverse events (AEs) during the 12-week study. Secondary endpoints included positive and negative syndrome scale (PANSS), clinical global impressions - improvement of illness scale (CGI-I), preference of medication (POM), subjective well-being under neuroleptics (SWN-K) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia) scales. Rates of discontinuations due to AEs were similar between titrated-dose and fixed-dose strategies (3.5% vs. 5.0%; p=0.448). Improvements in mean PANSS total scores were similar between aripiprazole titrated-dose and fixed-dose strategies (-14.8 vs. -17.2; LOCF), as were mean CGI-I scores (2.9 vs. 2.8; p=0.425; LOCF) and SWN-K scores (+8.6 vs.+10.3; OC,+7.8 vs.+9.8; LOCF). Switching can be effectively and safely achieved through a titrated-dose or fixed-dose switching strategy for aripiprazole, with down-titration of risperidone.

  6. Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder.

    Science.gov (United States)

    Ward, Kristen; Citrome, Leslie

    2018-02-01

    The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

  7. Safety, efficacy, and tolerability of differential treatment to prevent and treat vaginal dryness and vulvovaginitis in diabetic women.

    Science.gov (United States)

    Carati, D; Zizza, A; Guido, M; De Donno, A; Stefanizzi, R; Serra, R; Romano, I; Ouedraogo, C; Megha, M; Tinelli, A

    2016-01-01

    Problems affecting the vaginal tract in diabetic women are very often neglected. The efficacy and safety of three gynecological treatments in diabetic women have been assessed. A single-blind randomized progressive trial on 48 diabetic women affected by vaginal dryness, dyspareunia, and recurrent Candida infections was carried out. The ICIQ Vaginal Symptoms (ICIQ-VS) questionnaire was administered. The analysis of the parameters of ICIQ-VS questionnaire among the three groups showed significant difference only for "dragging pain" (p = 0.0 19) and "soreness" (p = 0.028). In all groups and for all parameters of the questionnaire, improvement of symptoms was observed. In particular, in Group 1 for all symptoms a highly significant difference was observed, to support the already known benefits of the products and of the proposed combination. Significant improvement was also observed in Group 2. The proposed treatment with DermoXEN® Ultracalming Special for diabetics and DermoXEN® Vitexyl vaginal gel exert effective moisturizing and soothing action. Indeed, the aforementioned products have been proven effective for the main gynecological problems of diabetic women.

  8. Injection-associated pain in femoral arteriography: A European multicenter study comparing safety, tolerability, and efficacy of iodixanol and iopromide

    International Nuclear Information System (INIS)

    Justesen, Per; Downes, Mark; Grynne, Birthe Hougens; Lang, Hanne; Rasch, Wenche; Seim, Eva

    1997-01-01

    Purpose. To evaluate injection-associated pain, safety, and efficacy with the isotonic contrast medium iodixanol (Visipaque 270 mg I/ml) compared with iopromide (Ultravist 300 mg I/ml) in femoral arteriography. Methods. A multicenter, double-blind, randomized, parallel-group clinical investigation was carried out in 54 hospitals in Europe. Of the patients evaluated, 1225 received iodixanol and 1227 iopromide in conventional and/or digital subtraction angiography. Results. The iodixanol group reported statistically significantly less injection-associated pain (0.9%) than the iopromide group (9.5%) (p<0.001). Further, 4.1% in the iodixanol group experienced pain and/or severe heat sensation vs 19.8% in the iopromide group (p<0.001). In the iodixanol group, 1.8% of the patients experienced contrast-related adverse events vs 2.4% in the iopromide group (p=NS). Overall diagnostic information was optimal for 94.1% in the iodixanol group and 95.3% in the iopromide group (p=NS). Conclusions. Iodixanol 270 mg I/ml causes significantly less injection-associated pain during femoral arteriography and is as safe and efficatious as iopromide 300 mg I/ml

  9. Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm.

    Science.gov (United States)

    Checa, Rocío; Montoya, Ana; Ortega, Nieves; González-Fraga, José Luis; Bartolomé, Adrián; Gálvez, Rosa; Marino, Valentina; Miró, Guadalupe

    2017-03-13

    Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml. Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity. Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result. IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended

  10. A randomized double-masked study to compare the ocular safety, tolerability, and efficacy of bromfenac 0.075% compared with vehicle in cataract surgery subjects

    Directory of Open Access Journals (Sweden)

    Hosseini K

    2016-11-01

    Full Text Available Kamran Hosseini,1 Thomas Walters,2 Robert DaVanzo,3 Richard L Lindstrom4 1InSite Vision Inc., Alameda, CA, 2Texan Eye, Austin, TX, 3Cornerstone Health Care, High Point, NC, 4Minnesota Eye Consultants, Bloomington, MN, USA Purpose: The aim of this study was to evaluate the safety, tolerability, and efficacy of a low-dose version of bromfenac 0.075% in DuraSite® (bromfenac 0.075% compared with DuraSite® vehicle (vehicle alone for the treatment of postoperative inflammation and ocular pain after cataract surgery.Methods: A multicenter, double-masked, vehicle-controlled, parallel-group clinical trial of 240 subjects randomized in a 2:1 ratio to bromfenac 0.075% or vehicle was conducted. Subjects were dosed BID beginning 1 day before the cataract surgery, the day of surgery, and 14 days after surgery. A slit lamp biomicroscopy examination was performed to evaluate the signs of inflammation, including anterior chamber cells (ACC and anterior chamber flare (ACF. The primary efficacy variable was the proportion of subjects with an ACC grade of 0 at Day 15. Secondary efficacy endpoints included the proportion of subjects who achieved a pain score of 0 at each postsurgical visual analog scale (VAS assessment and the proportion of subjects with an ACF grade of 0 at Day 15.Results: At Day 15, proportionally more subjects in the bromfenac 0.075% group than in the vehicle group had an ACC grade of 0 (57.1% vs 18.8%, respectively; P<0.001. At each of the postsurgical time points (Days 1, 8, 15, and 29, proportionally more bromfenac 0.075%-treated subjects (76.8%, 90.5%, 92.9%, and 85.1%, respectively had no pain (a VAS score of 0 compared with the vehicle-treated subjects (48.2%, 38.8%, 42.4%, and 47.1%, respectively, and at each time point, these differences in proportions were statistically significant (P<0.001. More subjects in the bromfenac 0.075% group had complete ACF resolution (151/167; 90.4% compared to those in the vehicle group (54/85; 63

  11. A randomized double-masked study to compare the ocular safety, tolerability, and efficacy of bromfenac 0.075% compared with vehicle in cataract surgery subjects

    Science.gov (United States)

    Hosseini, Kamran; Walters, Thomas; DaVanzo, Robert; Lindstrom, Richard L

    2016-01-01

    Purpose The aim of this study was to evaluate the safety, tolerability, and efficacy of a low-dose version of bromfenac 0.075% in DuraSite® (bromfenac 0.075%) compared with DuraSite® vehicle (vehicle) alone for the treatment of postoperative inflammation and ocular pain after cataract surgery. Methods A multicenter, double-masked, vehicle-controlled, parallel-group clinical trial of 240 subjects randomized in a 2:1 ratio to bromfenac 0.075% or vehicle was conducted. Subjects were dosed BID beginning 1 day before the cataract surgery, the day of surgery, and 14 days after surgery. A slit lamp biomicroscopy examination was performed to evaluate the signs of inflammation, including anterior chamber cells (ACC) and anterior chamber flare (ACF). The primary efficacy variable was the proportion of subjects with an ACC grade of 0 at Day 15. Secondary efficacy endpoints included the proportion of subjects who achieved a pain score of 0 at each postsurgical visual analog scale (VAS) assessment and the proportion of subjects with an ACF grade of 0 at Day 15. Results At Day 15, proportionally more subjects in the bromfenac 0.075% group than in the vehicle group had an ACC grade of 0 (57.1% vs 18.8%, respectively; P<0.001). At each of the postsurgical time points (Days 1, 8, 15, and 29), proportionally more bromfenac 0.075%-treated subjects (76.8%, 90.5%, 92.9%, and 85.1%, respectively) had no pain (a VAS score of 0) compared with the vehicle-treated subjects (48.2%, 38.8%, 42.4%, and 47.1%, respectively), and at each time point, these differences in proportions were statistically significant (P<0.001). More subjects in the bromfenac 0.075% group had complete ACF resolution (151/167; 90.4%) compared to those in the vehicle group (54/85; 63.5%). There were no new safety signals reported. Conclusion Bromfenac 0.075% in DuraSite is safe, well tolerated, and effective at reducing inflammation and preventing pain associated with cataract surgery. PMID:27920490

  12. Pilot, Multicenter, Open-Label Evaluation of Safety, Tolerability and Efficacy of a Novel, Topical Multipotent Growth Factor Formulation for the Periorbital Region.

    Science.gov (United States)

    Sundaram, Hema; Gold, Michael; Waldorf, Heidi; Lupo, Mary; Nguyen, Vivien L; Karnik, Jwala

    2015-12-01

    This multicenter, open-label pilot study evaluated safety, efficacy and tolerability of a topical formulation containing a multipotent growth factor resignaling complex (MRCx), when applied to infraorbital and lateral canthal skin. Thirty-nine female subjects with mean age of 56.8 years who had periorbital lines and wrinkles, uneven skin texture, puffiness, and lack of skin firmness were enrolled, and 38 completed the study. All subjects applied the multipotent growth factor formulation bilaterally to the periorbital area, twice daily for 60 days. Efficacy and treatment-related adverse events were evaluated at Baseline and days 14, 30, and 60. Investigators rated the periorbital areas based on 10-point scales. Subjects' self-reported compliance with treatment was greater than 99% throughout the study. At day 60, all subjects had improvement in infraorbital brightness (≥ 2 points), moistness (≥ 2 points), wrinkles (≥ 1 point), sallowness (≥ 1 point), crepiness (≥ 1 point), smooth texture (≥ 1 point), skin tightness (≥ 1 point), and skin tone (≥ 1 point). Investigator-rated assessments showed ≥ 1-point improvement for lateral canthal wrinkles, dyschromia/mottled pigmentation, skin tone, overall brightness, and moistness. Investigator-rated scoring on the Global Aesthetic Improvement Scale (GAIS) demonstrated that 67.6% of subjects were much improved/improved at day 14, and 63.1% remained improved at day 60. Overall, 76.2% and 79.0% of subjects were very pleased/pleased/mostly pleased with the appearance of their infraorbital and lateral canthal areas at day 60. Adverse events comprised one case of mild canthal erythema, and one case of mild eye irritation, both of which were respectively resolved. This pilot study demonstrated that the topical multipotent growth factor formulation was safe, effective and well tolerated for periorbital skin rejuvenation.

  13. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  14. Study of the Efficacy, Safety and Tolerability of Low-Molecular-Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients with Embolic Stroke due to Atrial Fibrillation.

    Science.gov (United States)

    Feiz, Farnia; Sedghi, Reyhane; Salehi, Alireza; Hatam, Nahid; Bahmei, Jamshid; Borhani-Haghighi, Afshin

    2016-06-01

    Anticoagulation with adjusted dose warfarin is a well-accepted treatment for the prevention of recurrent stroke in patients with atrial fibrillation. Meanwhile, using bridging therapy with heparin or heparinoids before warfarin for initiation of anticoagulation is a matter of debate. We compared safety, efficacy, and tolerability of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as a bridging method in patients with recent ischemic stroke due to atrial fibrillation. This study was a randomized single-blind controlled trial in patients with acute ischemic stroke due to atrial fibrillation who were eligible for receiving warfarin and were randomly treated with 60 milligrams (mg) of LMWH (enoxaparin) subcutaneously every 12 h, or 1000 units/h of continuous intravenous heparin. The primary efficacy endpoints were recurrence of new ischemic stroke, myocardial infarction and/or death. The primary safety endpoint was central nervous system and/or systemic bleeding. Seventy-four subjects were recruited. Baseline demographic and clinical characteristics of two groups were matched. Composite endpoint outcome of new ischemic stroke, myocardial infarction, and/or death in follow-up period was seen in 10 subjects (27.03%) in UFH group and in four subjects (10.81%) in LMWH group (p value: 0.136). All hemorrhages and symptomatic central nervous system (CNS) hemorrhages in follow-up period were in 7 (18.9%) and 4 (10.8%) patients in UFH group, in 5 (13.5%), and 3 (8.1%) patients in LMWH group (p values: 0.754 and 0.751), respectively. Drop out and major adverse-effects such as heparin-induced thrombocytopenia and drug hypersensitivity were not seen in any patient. Enoxaparin can be a safe and efficient alternative for UFH as bridging therapy.

  15. Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis.

    Science.gov (United States)

    Sepah, Yasir Jamal; Sadiq, Mohammad Ali; Chu, David S; Dacey, Mark; Gallemore, Ron; Dayani, Pouya; Hanout, Mostafa; Hassan, Muhammad; Afridi, Rubbia; Agarwal, Aniruddha; Halim, Muhammad Sohail; Do, Diana V; Nguyen, Quan Dong

    2017-11-01

    To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Randomized, controlled, multicenter clinical trial. STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6. A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated. Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials.

    Science.gov (United States)

    Majer, Istvan M; Gaughran, Fiona; Sapin, Christophe; Beillat, Maud; Treur, Maarten

    2015-01-01

    Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia. This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety. A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013. Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo. Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms. Data were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant

  17. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Directory of Open Access Journals (Sweden)

    Bramlage P

    2013-08-01

    Full Text Available Peter Bramlage,1 Claudia Zemmrich,1 Reinhard Ketelhut,2 Wolf-Peter Wolf,3 Eva-Maria Fronk,4 Roland E Schmieder5 1Institut für Pharmakologie und Präventive Medizin, Mahlow, Germany; 2Institut für Sportmedizin, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Daiichi Sankyo Europe GmbH, Munich, Germany; 5Universitätsklinikum Erlangen, Klinik für Nephrologie und Hypertensiologie, Erlangen, Germany Background: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19, and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001, but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients

  18. Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

    Science.gov (United States)

    Cahn, Pedro; Montaner, Julio; Junod, Patrice; Patterson, Patricia; Krolewiecki, Alejandro; Andrade-Villanueva, Jaime; Cassetti, Isabel; Sierra-Madero, Juan; Casiró, Arnaldo David; Bortolozzi, Raul; Lupo, Sergio Horacio; Longo, Nadia; Rampakakis, Emmanouil; Ackad, Nabil; Sampalis, John S

    2011-01-01

    To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in

  19. Pilot, Randomized Study Assessing Safety, Tolerability and Efficacy of Simplified LPV/r Maintenance Therapy in HIV Patients on the 1st PI-Based Regimen

    Science.gov (United States)

    Cahn, Pedro; Montaner, Julio; Junod, Patrice; Patterson, Patricia; Krolewiecki, Alejandro; Andrade-Villanueva, Jaime; Cassetti, Isabel; Sierra-Madero, Juan; Casiró, Arnaldo David; Bortolozzi, Raul; Lupo, Sergio Horacio; Longo, Nadia; Rampakakis, Emmanouil; Ackad, Nabil; Sampalis, John S.

    2011-01-01

    Objectives To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. Methods This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). Results Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. Conclusion At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re

  20. Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

    Directory of Open Access Journals (Sweden)

    Pedro Cahn

    Full Text Available To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART with a ritonavir-boosted protease inhibitor (PI/r and 2 nucleoside reverse-transcriptase inhibitors (NRTIs to lopinavir/ritonavir (LPV/r monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART.This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL, time-to-virologic rebound, patient-reported outcomes (PROs and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE.Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART patients completed treatment, while 9(2:LPV/r;7:HAART discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98% patients on LPV/r and 37(95% on HAART had VL<200 copies/mL (P = 0.61. Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%, headache (18% and influenza (16%. Four (10% patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART patients.At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in

  1. 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

  2. Atomoxetine and Methylphenidate Treatment in Children with ADHD: The Efficacy, Tolerability and Effects on Executive Functions

    Science.gov (United States)

    Yildiz, Ozlem; Sismanlar, Sahika G.; Memik, Nursu Cakin; Karakaya, Isik; Agaoglu, Belma

    2011-01-01

    The aim of this study was to compare the safety, efficacy, tolerability, and the effects of atomoxetine and OROS-MPH on executive functions in children with ADHD. This study was an open-label study that only included two medication groups. Children were randomized to open-label atomoxetine or OROS-MPH for 12 weeks. Primary efficacy measures were…

  3. A 24-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Tolerability of the Rivastigmine Patch in Japanese Patients with Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yu Nakamura

    2011-06-01

    Full Text Available Background: As of 2010, the rivastigmine patch was licensed for the treatment of Alzheimer’s disease (AD in 64 countries. Methods: This 24-week, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy, safety and tolerability of the 5-cm2 (9-mg loading dose; 4.6 mg/24 h delivery rate and 10-cm2 (18-mg loading dose; 9.5 mg/24 h delivery rate rivastigmine patch in Japanese patients with AD. Results: In the primary analysis population (intent-to-treat last observation carried forward at week 24, delayed deterioration was seen with the 10-cm2 patch versus placebo on the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-J cog; p = 0.005 and the Japanese version of the Clinician’s Interview-Based Impression of Change plus Caregiver Input (CIBIC plus-J; p = 0.067. Participants receiving the rivastigmine patch showed numerically less decline versus placebo at week 24 on the CIBIC plus-J, although this did not reach statistical significance. Statistical significance for the CIBIC plus-J was met following adjustment for body weight and baseline Mini-Mental State Examination score as dynamic allocation factors (p = 0.042 and on the Disability Assessment for Dementia (DAD; p = 0.024 and Mental Function Impairment (MENFIS; p = 0.016 subscales. Serious adverse events were rare and were consistent with the known safety profile of the rivastigmine patch. Conclusion: The rivastigmine patch has a favorable efficacy and tolerability profile in Japanese patients with AD.

  4. Safety and efficacy of opicinumab in acute optic neuritis (RENEW)

    DEFF Research Database (Denmark)

    Cadavid, Diego; Balcer, Laura J; Galetta, Steven L

    2017-01-01

    BACKGROUND: The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode. METHODS: This randomised, doub...

  5. Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.

    Science.gov (United States)

    Ormerod, Anthony D; van Voorst Vader, Pieter C; Majewski, Slovomir; Vanscheidt, Wolfgang; Benjamin, Nigel; van der Meijden, Willem

    2015-08-01

    Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003. Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily). The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety. Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose

  6. Libertas: rationale and study design of a multicentre, Phase II, double-blind, randomised, placebo-controlled investigation to evaluate the efficacy, safety and tolerability of locally applied NRL001 in patients with faecal incontinence.

    Science.gov (United States)

    Siproudhis, L; Jones, D; Shing, R Ng Kwet; Walker, D; Scholefield, J H

    2014-03-01

    Faecal incontinence affects up to 8% of adults. Associated social isolation and subsequent depression can have devastating effects on quality of life (QoL). Faecal incontinence is an underreported health problem as the social isolation and stigma that patients experience makes it difficult for sufferers to discuss their condition with a physician. There have been few well-designed, placebo-controlled clinical trials of treatment for faecal incontinence and little clinical evidence is available to inform the most appropriate management strategies. Libertas, a robustly designed study will investigate the efficacy and safety of NRL001 (1R,2S-methoxamine), an α1 -adrenoceptor agonist, in the treatment of faecal incontinence. Libertas is a multicentre, Phase II, double-blind, randomised, placebo-controlled, parallel group study. Patient recruitment took place across 55 study centres in Europe. Patients suffering with faecal incontinence were randomised into four groups (approximately 110 each) to receive once daily self-administered doses of NRL001 (5, 7.5 or 10 mg or placebo in a suppository formulation) for 8 weeks. The primary objective of Libertas is to assess the impact of once daily administration of NRL001 on the severity and frequency of incontinence episodes as assessed by the Wexner score at 4 weeks, compared with placebo. Secondary outcomes include measures of efficacy of NRL001 compared with placebo following 8 weeks treatment; safety and tolerability; evaluation of plasma pharmacokinetics; establishment of any pharmacokinetic/pharmacodynamic relationship to adverse events; dose-response relationship; the efficacy of NRL001 therapy at 4 and 8 weeks assessed by the Vaizey score; and QoL using the Faecal Incontinence Quality of Life and the EQ-5D-5L Healthcare Questionnaires following 4 and 8 weeks NRL001 therapy. Overall patient satisfaction with the treatment will also be evaluated. This is the first randomised controlled study to investigate the efficacy

  7. Efficacy, tolerability, and safety of an oral enzyme combination vs diclofenac in osteoarthritis of the knee: results of an individual patient-level pooled reanalysis of data from six randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Ueberall MA

    2016-11-01

    Full Text Available Michael A Ueberall,1 Gerhard HH Mueller-Schwefe,2 Rainer Wigand,3 Ute Essner4 1Institute of Neurological Sciences, Nuremberg, 2Interdisciplinary Center for Pain and Palliative Care Medicine, Göppingen, 3Interdisciplinary Center for Rheumatology and Immunology, Frankfurt, 4O.Meany Consultancy, Hamburg, Germany Objective: To compare efficacy, safety, and tolerability of an oral enzyme combination (OEC containing proteolytic enzymes and bioflavonoid vs diclofenac (DIC, a nonselective nonsteroidal anti-inflammatory drug in the treatment of osteoarthritis of the knee.Materials and methods: This was an individual patient-level pooled reanalysis of patient-reported data from prospective, randomized, double-blind, parallel-group studies in adult patients with moderate-to-severe osteoarthritis of the knee treated for at least 3 weeks with OEC or DIC. Appropriate trials were identified with a systemic literature and database search. Data were extracted from the original case-report forms and reanalyzed by a blinded evaluation committee. The primary end point was the improvement of the Lequesne algofunctional index (LAFI score at study end vs baseline. Secondary end points addressed LAFI response rates, treatment-related pain-intensity changes, adverse events, and laboratory parameters.Results: Six trials were identified that enrolled in total 774 patients, of whom 759 had postbaseline data for safety analysis, 697 (n=348/349 with OEC/DIC for intent to treat, 524 for per protocol efficacy analysis, and 500 for laboratory evaluation. LAFI scores – the primary efficacy end point – decreased comparably with both treatments and improved with both ­treatments significantly vs baseline (OEC 12.6±2.4 to 9.1±3.9, DIC 12.7±2.4 to 9.1±4.2, effect size 0.9/0.88; P<0.001 for each. In parallel, movement-related 11-point numeric rating-scale pain intensity improved significantly (P<0.001 and comparably with both treatments from baseline (6.4±1.9/6.6±1.8 to

  8. Desonide: a review of formulations, efficacy and safety.

    Science.gov (United States)

    Kahanek, Nr; Gelbard, Cg; Hebert, Aa

    2008-07-01

    Desonide is a low-potency topical corticosteroid that has been used for decades in the treatment of steroid-responsive dermatoses. The favorable safety profile of this topical agent makes it ideal for patients of all ages. This article provides a review of desonide's history, pharmacodynamic properties, vehicle technology, efficacy and safety. Randomized controlled trials, as well as open-label and non-comparative studies, case series and reports, experimental models, and data from the Galderma pharmacovigiliance program were reviewed in order to address the clinical efficacy and safety of desonide. Clinical efficacy and safety have been proven in multiple clinical trials. In addition to cream, lotion and ointment formulations, the recently developed hydrogel and foam preparations have increased desonide's versatility and patient tolerability.

  9. Tolerability and safety aspects of mirtazapine.

    Science.gov (United States)

    Nutt, David J

    2002-06-01

    The tolerability and safety profile of the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine reflects its unique pharmacological profile. The 5-HT(2) blocking effect contributes towards its anxiolytic effects and benefits on sleep, as well as preventing the sexual dysfunction that may occur with non-specific stimulation of the serotonin system by drugs such as the selective serotonin reuptake inhibitors (SSRIs). In addition, 5-HT(3) blockade by mirtazapine helps to prevent nausea and vomiting. Weight gain is the most commonly reported side-effect of mirtazapine, although there is evidence to suggest that this is not a significant problem during long-term treatment. In conclusion, mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants. Copyright 2002 John Wiley & Sons, Ltd.

  10. Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

    Science.gov (United States)

    Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

    2015-12-01

    In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  11. Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts A Randomized Clinical Trial

    NARCIS (Netherlands)

    Ormerod, Anthony D.; van Voorst Vader, Pieter C.; Majewski, Slovomir; Vanscheidt, Wolfgang; Benjamin, Nigel; van der Meijden, Willem

    IMPORTANCE Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. OBJECTIVE To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. DESIGN, SETTING, AND PARTICIPANTS A

  12. Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis.

    NARCIS (Netherlands)

    Kerkhof, P.C.M. van de; Berth-Jones, J.; Griffiths, C.E.; Harrison, P.V.; Honigsmann, H.; Marks, R.; Roelandts, R.; Schopf, E.; Trompke, C.

    2002-01-01

    BACKGROUND: As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term. OBJECTIVES: The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 microg g(-1)) ointment

  13. Tolerability and safety of antifungal drugs

    Directory of Open Access Journals (Sweden)

    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  14. Fenticonazole nitrate for treatment of vulvovaginitis: efficacy, safety, and tolerability of 1-gram ovules, administered as ultra-short 2-day regimen.

    Science.gov (United States)

    Fernández-Alba, J; Valle-Gay, A; Dibildox, M; Vargas, J A; González, J; García, M; López, L H

    2004-04-01

    Because of its potential as a low cost first-line monotherapy for the most common vulvovaginal infections, we evaluated fenticonazole nitrate in a prospective, open-label, multicenter pilot study with 101 sexually active women (per-protocol; 16 to 61 years of age) with vulvovaginitis involving single or mixed infections with Candida albicans, Trichomonas vaginalis, and/or Gardnerella vaginalis. Fenticonazole nitrate (1 g) was administered as vaginal ovules, once daily on days 1 and 3. Eradication (direct phase-contrast microscopy of vaginal swabs and/or microbiological culture) on day 8 was 90% (C. albicans, 26/29, p vulvovaginitis with acceptable broad-spectrum efficacy against the most commonly involved pathogens and with a low rate of early relapse, reserving antibiotics for patients with treatment failure or relapse of infection. Our results should encourage further examination of this approach in larger and well controlled clinical trials.

  15. Efficacy and Tolerability of Intravenous Levetiracetam in Children

    Directory of Open Access Journals (Sweden)

    Jose eAceves

    2013-08-01

    Full Text Available Intractable epilepsy in children poses a serious medical challenge. Acute repetitive seizures and status epilepticus leads to frequent emergency room visits and hospital admissions. Permanent neurological damage can occur if there is delay in treatment. It has been shown that these children continue to remain intractable even after acute seizure management with approved FDA agents. Intravenous levetiracetam, a second-generation anticonvulsant was approved by the FDA in 2006 in patients 16 years and older as an alternative when oral treatment is not an option. It has been shown that oral levetiracetam can be used in the treatment of status epilepticus and acute repetitive seizures. Data have been published showing that intravenous levetiracetam is safe and efficacious, and can be used in an acute inpatient setting. This current review will discuss the recent data about the safety and tolerability of intravenous levetiracetam in children and neonates, and emphasize the need for a larger prospective multicenter trial to prove the efficacy of this agent in acute seizure management.

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

    Science.gov (United States)

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

    2011-01-01

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

  17. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Goday, A; Bellido, D; Sajoux, I; Crujeiras, A B; Burguera, B; García-Luna, P P; Oleaga, A; Moreno, B; Casanueva, F F

    2016-09-19

    Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. Evaluating the short-term safety and tolerability of a VLCK diet (diet), and 44 to the standard low-calorie diet. No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both Pdiet group (Pdiet group declined at last follow-up. The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.

  18. Safety, patient's tolerance, and efficacy of a 2-liter vitamin C-enriched macrogol bowel preparation: a randomized, endoscopist-blinded prospective comparison with a 4-liter macrogol solution

    NARCIS (Netherlands)

    Mathus-Vliegen, E. M. H.; van der Vliet, K.

    2013-01-01

    Optimal bowel preparation is associated with lower polyp miss rates, but patients have difficulties in complying with the usual 4-L bowel preparation. This study aimed to compare the safety, acceptance, and efficacy of 2-L polyethylene glycol electrolyte solution enriched in vitamin C with 4-L

  19. Eficácia, tolerabilidade e segurança do uso do sirolimo após o transplante renal Sirolimus efficacy, tolerability, and safety for treatment after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Nagilla Ione Oliveira

    2009-12-01

    Full Text Available INTRODUÇÃO: Sirolimo (SRL é um imunossupressor com conhecida eficácia e perfil de segurança na profilaxia da rejeição aguda após o transplante renal. OBJETIVOS: Avaliar eficácia, tolerabilidade e segurança do uso do SRL e de prednisona em associação a ciclosporina (CSA ou tacrolimo (TAC após o transplante renal. METODOLOGIA: Estudo retrospectivo de 332 receptores de transplantes renais realizados entre 1999 e 2006. O desfecho primário foi a falha de tratamento, definida como a incidência cumulativa de rejeição aguda confirmada por biópsia (RACB, perda do enxerto, óbito ou descontinuação do SRL. RESULTADOS: Dos 332 transplantes, 92% foram com doador vivo. A média de idade dos receptores foi de 37 anos, sendo 65% homens, 46% brancos e 6% diabéticos. SRL foi associado a CSA ou TAC em 70,8% e 29,2% dos pacientes. A incidência de falha de tratamento foi de 22,2% e de 47,8% no final do primeiro e do quinto ano de transplante, sem diferença entre pacientes recebendo CSA ou TAC. Ao final do quinto ano, as sobrevidas do paciente, do enxerto, do enxerto censorando o óbito e livre de RACB foram de 92,8%, 86,1%, 92,7% e 82,2%, respectivamente. O tratamento com SRL foi interrompido em 27,1% dos pacientes: 22,9% em razão de reações adversas e 3,3% devido à ineficácia. Os principais motivos de suspensão do SRL foram dislipidemia (6,0%, disfunção do enxerto (5,2%, proteinúria (4,5%, infecções (1,5%, dificuldade de cicatrização (1,2% e anemia (0,9%. CONCLUSÃO: Na população estudada, a eficácia e a segurança do SRL foram semelhantes quando combinado com CSA ou TAC. A tolerabilidade oral foi adequada considerando-se a relativa baixa taxa de interrupção do uso de SRL.INTRODUCTION: Sirolimus (SRL is an immunosuppressive drug with confirmed efficacy and safety profile in the prophylaxis of acute rejection after renal transplantation. OBJECTIVES: To assess the efficacy, safety, and tolerability of SRL and prednisone in

  20. A 6-month study comparing efficacy, safety, and tolerability of the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% versus each of its individual preservative-free components.

    Science.gov (United States)

    Pfeiffer, Norbert; Traverso, Carlo E; Lorenz, Katrin; Saarela, Ville; Liinamaa, Johanna; Uusitalo, Hannu; Astakhov, Yury; Boiko, Ernest; Ropo, Auli

    2014-12-01

    The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months. A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m. In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55 mmHg (32%) for FC and -7.35 mmHg (28%) for TIM. The model-based treatment difference (FC-TIM) was -0.885 mmHg [95% confidence interval (CI) -1.745 to -0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61 mmHg (33%) for FC and -7.23 mmHg (28%) for TAF. The model-based treatment difference (FC-TAF) was -1.516 mmHg (95% CI -2.044 to -0.988; p preservative-free fixed combination of tafluprost and

  1. Approaches to document the efficacy and safety of microdermabrasion procedure.

    Science.gov (United States)

    Spencer, James M; Kurtz, Ellen S

    2006-11-01

    Microdermabrasion is a popular cosmetic procedure for skin rejuvenation, which is achieved by mechanical abrasion of the skin at a superficial level. The objective was to study the efficacy of microdermabrasion in photoaging and to investigate the compatibility of a cleanser and a lotion with microdermabrasion. Sixteen women underwent microdermabrasion to the face once a week for a total of six treatments. Subjects were also given a personal skin care regimen (cleanser and lotion). Colorimetry values as well as investigator and patients ratings for safety and efficacy were analyzed at various time points and compared to baseline. There were no significant changes in safety and tolerance variables throughout the study. Clinical efficacy variables (fine wrinkles, dullness, pigmentation, and large pores) significantly improved by the third treatment, with further improvement by the end of the study (six treatments). Subjects perceived improvement in facial photoaging variables. Colorimetry showed increased brightness and decreased yellowness of target skin sites on the face throughout the study. Multiple microdermabrasions were effective in significantly improving various facial photoaging variables. The personal skin care regimen used was well tolerated by the subjects.

  2. Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery.

    Science.gov (United States)

    Jamdade, P T; Porwal, A; Shinde, J V; Erram, S S; Kamat, V V; Karmarkar, P S; Bhagtani, K; Dhorepatil, S; Irpatgire, R; Bhagat, H; Kolte, S S; Shirure, P A

    2011-01-01

    Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8 hours (P = .02), and SAPID( 0-8 hours ) (P dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety.

  3. Efficacy of Tissue Tolerable Plasma (TTP against Ixodes ricinus

    Directory of Open Access Journals (Sweden)

    Bender, Claudia

    2014-03-01

    Full Text Available [english] The efficacy of Tissue Tolerable Plasma (TTP against ticks was tested, as data from the literature has demonstrated its efficacy against other acari.The study was carried out by using the KINPen09 (Argon as carrier gas on (n=24. Treatment times of 1 and 3 minutes led to a reversible inactivation of the ticks. After 5 min of treatment, they died.Thanks to the acaricidal effect of TPP, a new treatment strategy using the KINPen09 for tick-infested pets is now available.

  4. Development and implementation of setpoint tolerances for special safety systems

    International Nuclear Information System (INIS)

    Oliva, A.F.; Balog, G.; Parkinson, D.G.; Archinoff, G.H.

    1991-01-01

    The establishment of tolerances and impairment limits for special safety system setpoints is part of the process whereby the plant operator demonstrates to the regulatory authority that the plant operates safely and within the defined plant licensing envelope. The licensing envelope represents the set of limits and plant operating state and for which acceptably safe plant operation has been demonstrated by the safety analysis. By definition, operation beyond this envelope contributes to overall safety system unavailability. Definition of the licensing envelope is provided in a wide range of documents including the plant operating licence, the safety report, and the plant operating policies and principles documents. As part of the safety analysis, limits are derived for each special safety system initiating parameter such that the relevant safety design objectives are achieved for all design basis events. If initiation on a given parameter occurs at a level beyond its limit, there is a potential reduction in safety system effectiveness relative to the performance credited in the plant safety analysis. These safety system parameter limits, when corrected for random and systematic instrument errors and other errors inherent in the process of periodic testing or calibration, are then used to derive parameter impairment levels and setpoint tolerances. This paper describes the methodology that has evolved at Ontario Hydro for developing and implementing tolerances for special safety system parameters (i.e., the shutdown systems, emergency coolant injection system and containment system). Tolerances for special safety system initiation setpoints are addressed specifically, although many of the considerations discussed here will apply to performance limits for other safety system components. The first part of the paper deals with the approach that has been adopted for defining and establishing setpoint limits and tolerances. The remainder of the paper addresses operational

  5. Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

    Science.gov (United States)

    Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

    2018-05-01

    This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Efficacy and Safety of Fingolimod in an Unselected Patient Population.

    Directory of Open Access Journals (Sweden)

    Maria Rasenack

    Full Text Available Fingolimod is a first in class oral compound approved for the treatment of relapsing-remitting multiple sclerosis (RR-MS. The aim of this study was to evaluate clinical and neuroradiological responses to fingolimod as well as the safety and tolerability in RR-MS patients in clinical practice. In addition, a panel of pro-inflammatory serum cytokines was explored as potential biomarker for treatment response.We conducted a retrospective, non-randomized, open-label, observational study in 105 patients with RR-MS and measured cytokines in longitudinal serum samples.Compared to the year before fingolimod start the annualized relapse rate was reduced by 44%. Also, the percentage of patients with a worsening of the EDSS decreased. Accordingly, the fraction of patients with no evidence of disease activity (no relapse, stable EDSS, no new active lesions in MRI increased from 11% to 38%. The efficacy and safety were comparable between highly active patients or patients with relevant comorbidities and our general patient population.The efficacy in reducing relapses was comparable to that observed in the phase III trials. In our cohort fingolimod was safe and efficacious irrespective of comorbidities and previous treatment.

  7. A 24-Week, Randomized, Controlled Study to Evaluate the Tolerability, Safety and Efficacy of 2 Different Titration Schemes of the Rivastigmine Patch in Japanese Patients with Mild to Moderate Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Yu Nakamura

    2015-09-01

    Full Text Available Aim: To investigate whether 1-step titration of the rivastigmine patch (initiated at 5 cm2 and titrated to 10 cm2 after 4 weeks is well tolerated in Japanese patients with Alzheimer's disease (AD as compared to 3-step titration (initiated at 2.5 cm2 and titrated by 2.5 cm2 every 4 weeks to 10 cm2. Methods: A 24-week, multicenter, randomized, double-blind study was conducted in Japan between July 2012 and May 2014. Patients with mild to moderate AD aged 50-85 years were randomized 1:1 to 1-step or 3-step titration of the rivastigmine once-daily patch. The primary endpoint was the proportion of patients with adverse events leading to discontinuation. Results: Of 216 patients randomized, 215 (1-step, n = 107; 3-step, n = 108 were included in the safety analysis. The primary endpoint outcome was 15.0% in the 1-step group and 18.5% in the 3-step group. The observed treatment difference was −3.6% (95% confidence interval: −17.0, 9.6, falling within the prespecified acceptance range. Conclusion: The tolerability of two different titration schemes was similar in Japanese patients with AD.

  8. Women's perceptions of contraceptive efficacy and safety.

    Science.gov (United States)

    Kakaiya, Roshni; Lopez, Lia L; Nelson, Anita L

    2017-01-01

    Adoption of contraceptive implants and intrauterine devices has been less than might be expected given their superior efficacy and convenience. The purpose of this study was to assess knowledge and beliefs held by women, which may influence their contraceptive choices and theirongoing utilization of contraceptive methods. English speaking, nonpregnant, reproductive-age women, who were not surgically sterilized, were individually interviewed to obtain limited demographic characteristics and to assess their knowledge about the efficacy of various contraceptive methods in typical use and about the relative safety of oral contraceptives. A convenience sample of 500 women aged 18-45 years, with education levels that ranged from middle school to postdoctoral level was interviewed. The efficacy in typical use of both combined oral contraceptives and male condoms was correctly estimated by 2.2%; over two-thirds of women significantly over estimated the efficacy of each of those methods in typical use. Oral contraceptives were thought to be at least as hazardous to a woman's health as pregnancy by 56% of women. The majority of reproductive aged women surveyed substantially overestimated the efficacy of the two most popular contraceptive methods, often saying that they were 99% effective. Women with higher education levels were most likely to overestimate efficacy of oral contraceptives. Women of all ages and education levels significantly overestimated the health hazards of oral contraceptives compared to pregnancy. Overestimation of effectiveness of these methods of contraception, may contribute to lower adoption of implants and intrauterine devices. When individualizing patient counselling, misperceptions must be identified and addressed with women of all educational backgrounds. Not applicable.

  9. AN OPEN-LABEL MULTICENTER OBSERVATIONAL STUDY OF THE EFFICACY, TOLERABILITY, AND SAFETY OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG AMTOLMETIN GUACIL IN PATIENTS WITH KNEE OSTEOARTHRITIS AND DYSPEPSIA

    Directory of Open Access Journals (Sweden)

    E. S. Tsvetkova

    2016-01-01

    Full Text Available Objective: to investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs in patients with knee osteoarthritis (OA and signs of dyspepsia.Subjects and methods. The open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%, lower extremity varicose veins (6.4%, and diabetes mellitus (6%. Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA scale was used to rate dyspepsia.Results and discussion. AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p <0.001 reduction in the WOMAC index (pain and stiffness and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p < 0.001 and “satisfaction with treatment”. Overall assessment of AMG tolerability was only positive: excellent (33%, good (56%, and satisfactory (11%. There were no serious adverse events (AE. AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients. Conclusion. The findings suggest that AMG offers good prospects for knee OA treatment.

  10. Single-center, noninterventional clinical trial to assess the safety, efficacy, and tolerability of a dimeticone-based medical device in facilitating the removal of scales after topical application in patients with psoriasis corporis or psoriasis capitis

    Directory of Open Access Journals (Sweden)

    Hengge UR

    2017-06-01

    Full Text Available Ulrich R Hengge,1 Kristina Röschmann,2 Henning Candler3 1Skin Center, Düsseldorf, 2Department of Clinical Research, 3Department of Medical Affairs, G. Pohl‑Boskamp GmbH & Co. KG, Hohenlockstedt, Germany Introduction: Psoriasis is a frequent inflammatory skin disease affecting ~2%–3% of the population in western countries. Scaling of the psoriatic lesions is the most impairing symptom in patients with psoriasis. In contrast to conventional keratolytic treatment concepts containing salicylic acid or urea, a dimeticone-based medical device (Loyon® removes scales in a physical way without any pharmacological effect.Objective: To assess the efficacy and tolerability of a dimeticone-based medical device in removal of scales in patients with psoriasis corporis/capitis under real-life conditions.Methods: Forty patients with psoriasis capitis or corporis were included and received once-daily treatments for 7 days. Clinical assessment of the psoriasis area severity index score (psoriasis corporis and the psoriasis scalp severity index score (psoriasis capitis was performed and evaluated at baseline, after 3 and 7 days of treatment. Baseline scaling scores and redness scores were calculated for two target lesions of the scalp or the body on a 5-point scale each.Results: For the primary efficacy variable scaling score, a statistically significant decrease was observed after treatment, with a relative reduction in scaling of 36.8% after 7 days of treatment within patients affected by psoriasis capitis. Treatment success was achieved in 76.8% of patients with psoriasis capitis, and time to treatment success was evaluated to be 4.14 days for these patients and 4.33 days for patients suffering from psoriasis corporis.Conclusion: In conclusion, this trial demonstrated that the dimeticone-based medical device is a safe, well-tolerated, practicable, and efficient keratolytic compound, which can be well implemented in and recommended for standard therapy

  11. REVIEW OF SAFETY AND TOLERANCE OF OMALIZUMAB

    Directory of Open Access Journals (Sweden)

    A.V. Emel'yanov

    2008-01-01

    Full Text Available The review of safety of monoclonal anti-ige-antibodies (xolair — a new medication for the treatment of severe allergic bronchial asthma is presented. Local and system adverse events, originating after injection of medicament in clinical studies and following administration in patients are discussed.Key words: children, bronchial asthma, monoclonal anti Ige antibodies.

  12. The SIESTA Trial: A Randomized Study Investigating the Efficacy, Safety, and Tolerability of Acupressure versus Sham Therapy for Improving Sleep Quality in Patients with End-Stage Kidney Disease on Hemodialysis

    Directory of Open Access Journals (Sweden)

    Kunyu Shen

    2017-01-01

    Full Text Available Objectives. To compare the effectiveness of real acupressure versus sham acupressure therapy in improving sleep quality in patients receiving hemodialysis (HD or hemodiafiltration (HDF. Methods. A multicenter, single-blind, randomized controlled trial was conducted in two Australian dialysis units located in Princess Alexandra Hospital and Logan Hospital, respectively. Forty-two subjects with self-reported poor sleep quality were randomly assigned to real (n=21 or sham (n=21 acupressure therapy delivered thrice weekly for four consecutive weeks during routine dialysis sessions. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI score measured at week four adjusted for baseline PSQI measurements. Secondary outcomes were quality of life (QOL (SF-8, adverse events, and patient acceptability (treatment acceptability questionnaire, TAQ. Results. The two groups were comparable on global PSQI scores (difference 0.19, 95% confidence interval [CI] −1.32 to 1.70 and on the subscale scores. Similar results were observed for QOL both in the mental (difference −3.88, 95% CI −8.63 to 0.87 and the physical scores (difference 2.45, 95% CI −1.69 to 6.58. There were no treatment-related adverse events and acupressure was perceived favorably by participants. Conclusion. Acupressure is a safe, well-tolerated, and highly acceptable therapy in adult hemodialysis patients in a Western healthcare setting with uncertain implications for therapeutic efficacy.

  13. Safety and efficacy of Bolus administration of magnesium sulphate ...

    African Journals Online (AJOL)

    Safety and efficacy of Bolus administration of magnesium sulphate for preeclampsia. ... On-going research is addressing its administration in terms of dosage, duration and safety. Objective: We evaluated a ... Keywords: safety, efficacy, bolus magnesium sulphate, preeclampsia, University of Benin Teaching Hospital

  14. Safety and Tolerability Profile of Artemisinin-Based Antimalarial ...

    African Journals Online (AJOL)

    The WHO in 2001 advocated artemisinin- based antimalarial combination therapy (ACT), which was adopted by Nigeria in 2005. The objective of this study was to characterize the safety and tolerability profile of the ACTs in adult patients with uncomplicated malaria. A descriptive longitudinal study was conducted in the ...

  15. Safety, Tolerability, and Immunogenicity of Interferons

    Directory of Open Access Journals (Sweden)

    Michael G. Tovey

    2010-04-01

    Full Text Available Interferons (IFNs are class II cytokines that are key components of the innate immune response to virus infection. Three IFN sub-families, type I, II, and III IFNs have been identified in man, Recombinant analogues of type I IFNs, in particular IFNα2 and IFNβ1, have found wide application for the treatment of chronic viral hepatitis and remitting relapsing multiple sclerosis respectively. Type II IFN, or IFN gamma, is used principally for the treatment of chronic granulomatous disease, while the recently discovered type III IFNs, also known as IFN lambda or IL-28/29, are currently being evaluated for the treatment of chronic viral hepatitis. IFNs are in general well tolerated and the most common adverse events observed with IFNα or IFNβ therapy are “flu-like” symptoms such as fever, headache, chills, and myalgia. Prolonged treatment is associated with more serious adverse events including leucopenia, thrombocytopenia, increased hepatic transaminases, and neuropsychiatric effects. Type I IFNs bind to high-affinity cell surface receptors, composed of two transmembrane polypeptides IFNAR1 and IFNAR2, resulting in activation of the Janus kinases Jak1 and Tyk2, phosphorylation and activation of the latent cytoplasmic signal transducers and activators of transcription (STAT1 and STAT2, formation of a transcription complex together with IRF9, and activation of a specific set of genes that encode the effector molecules responsible for mediating the biological activities of type I IFNs. Systemic administration of type I IFN results in activation of IFN receptors present on essentially all types of nucleated cells, including neurons and hematopoietic stem cells, in addition to target cells. This may well explain the wide spectrum of IFN associated toxicities. Recent reports suggest that certain polymorphisms in type I IFN signaling molecules are associated with IFN-induced neutropenia and thrombocytopenia in patients with chronic hepatitis C. IFN

  16. Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

    Directory of Open Access Journals (Sweden)

    Mpimbaza Arthur

    2008-06-01

    Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

  17. Efficacy and Tolerability of Indiplon in Transient Insomnia

    Science.gov (United States)

    Rosenberg, Russell; Roth, Thomas; Scharf, Martin B.; Lankford, D. Alan; Farber, Robert

    2007-01-01

    Objectives: The efficacy of indiplon was evaluated by polysomnography (PSG) in an experimental model of transient insomnia consisting of the first night effect combined with a 2-hour phase advance. Methods: Healthy volunteers age 21–64 years (N=593; 62% female; mean (± SEM) years, 32±0.39) were randomized to double-blind treatment with a single nighttime dose of indiplon (10 mg or 20 mg) or placebo. PSG assessments included latency to persistent sleep (LPS, primary endpoint) and total sleep time (TST); self-report assessments included sleep quality (SQ); next day residual effects were evaluated by the Digit Symbol Substitution Test (DSST), Symbol Copying Test (SCT), and a Visual Analog Scale of sleepiness (VAS). Results: LPS mean (± SEM) values were significantly reduced on indiplon 10 mg (21.2±1.5 minutes) and indiplon 20 mg (16.8±1.1 minutes) compared to placebo (33.1±2.5minutes; p inducing sleep, increasing sleep duration, and improving overall sleep quality without next day residual effects in healthy volunteers in a model of transient insomnia. Citation: Rosenberg R; Roth T; Scharf MB et al. Efficacy and tolerability of indiplon in transient insomnia. J Clin Sleep Med 2007;3(4):374-379. PMID:17694726

  18. [Human papillomavirus vaccine. Efficacy and safety].

    Science.gov (United States)

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

    Science.gov (United States)

    Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

    2016-02-01

    Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

  20. Desensitization to Oxcarbazepine: Long-Term Efficacy and Tolerability

    Science.gov (United States)

    Lee, Jiwon; Park, Eu Gene; Lee, Munhyang

    2017-01-01

    Background and Purpose Antiepileptic drug (AED)-associated cutaneous adverse drug reactions can lead to the discontinuation of medications. The aim of this study was to determine the long-term efficacy and safety of performing desensitization to oxcarbazepine. Methods This study involved 20 patients who exhibited cutaneous adverse drug reactions associated with oxcarbazepine use between July 2009 and March 2016 at Samsung Medical Center. All of the participants had to discontinue oxcarbazepine despite presenting initially positive responses. Human leukocyte antigen genotyping was performed to detect the genetic predisposition to Stevens-Johnson syndrome. The desensitization to oxcarbazepine was performed with a starting dosage of 0.1 mg/day. Efficacy was evaluated by comparing the frequency of seizures before and at 1 and 3 years after desensitization. Adverse events occurring during desensitization and the retention rate after desensitization were also investigated. Results Nineteen patients (95%) safely completed the desensitization protocol. One withdrew owing to emotional problems that appeared to be associated with oxcarbazepine. The follow-up period was 4.6±1.2 years (mean±SD), and oxcarbazepine was maintained for more than 3 years after desensitization in 15 patients (83.3%). The response rates were 84.2% and 77.8% at 1 and 3 years after desensitization, respectively. Eight patients remained seizure-free for 3 years, and two discontinued all AEDs. Transient adverse reactions such as mild rash and itching were reported by five patients during desensitization. Conclusions This study has demonstrated the long-term efficacy and safety of desensitization to oxcarbazepine in patients exhibiting cutaneous adverse drug reactions. This favorable outcome should encourage the implementation of desensitization in patients presenting with hypersensitivity to oxcarbazepine as an alternative strategy in clinical practice. PMID:27730770

  1. Safety and efficacy of drugs in pregnancy.

    Science.gov (United States)

    Knoppert, David

    2011-01-01

    Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

  2. Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery

    Directory of Open Access Journals (Sweden)

    P. T. Jamdade

    2011-01-01

    Full Text Available Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID at 8 hours, sum of analogue of pain intensity differences (SAPID, and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P=.007, PID at 8 hours (P=.02, and SAPID 0–8 hours (P<.0001. It also showed faster onset of action (42 minutes and longer duration of action (6.5 hours. The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety.

  3. Safety, Efficacy and Recurrence rate following tenosynovectomy and ...

    African Journals Online (AJOL)

    Objective: This study was conducted to compare the safety, efficacy and recurrence rate of primary tenosynovectomy versus intralesional steroid injection in the treatment of sclerosing tenosynovitis of deQuervain. Method: A prospective, comparative study of the safety, efficacy and recurrence rate following intralesional ...

  4. Efficacy and safety of histamine-2 receptor antagonists

    NARCIS (Netherlands)

    van der Pol, Rachel; Langendam, Miranda; Benninga, Marc; van Wijk, Michiel; Tabbers, Merit

    2014-01-01

    Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable. To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD. PubMed,

  5. MR arthrography: pharmacology, efficacy and safety in clinical trials

    International Nuclear Information System (INIS)

    Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K.; Wegener, R.; Balzer, T.

    2003-01-01

    A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost the same

  6. Efficacy and tolerability of preservative-free eye drops containing a fixed combination of dorzolamide and timolol in glaucoma patients.

    Science.gov (United States)

    Renieri, Giulia; Führer, Katrin; Scheithe, Karl; Lorenz, Katrin; Pfeiffer, Norbert; Thieme, Hagen

    2010-12-01

    To evaluate the efficacy and tolerability of preservative-free eye drops (dorzolamide/timolol) in routine management of preservative-sensitive glaucoma patients. Data from 2,298 glaucoma patients requiring intraocular pressure (IOP) reduction and suffering from intolerance to benzalkonium chloride or active agents of previously used eye drops were valid for baseline and safety analysis in this prospective, open, noncomparative, multicenter, noninterventional study. Patients were treated with preservative-free dorzolamide/timolol eye drops for 12 weeks. Main efficacy endpoint was IOP reduction after 12 weeks of treatment. Two thousand forty-nine patients were considered for efficacy analysis. Tolerability was assessed by evaluating adverse drug reactions. Mean baseline IOP was 20.8 mmHg. Baseline IOP was reduced to 16.7 mmHg after 12 weeks of treatment corresponding to a mean absolute (percent) change of -4.1 mmHg (-17.3%). The proportion of patients with IOP ≤21 mmHg increased from 59.9% at baseline to 94.6% after 12 weeks. The most frequently reported ocular adverse drug reactions were burning eyes (2.4%) and hyperemia (0.9%). Local tolerability improved in 79.3% of patients compared to their previous glaucoma therapy. This observational study confirms the IOP lowering effect of preservative-free eye drops containing the fixed combination of dorzolamide/timolol in a large patient's population. The drug was well tolerated and improved the local tolerability in the vast majority of patients.

  7. Fall Protection Characteristics of Safety Belts and Human Impact Tolerance.

    Science.gov (United States)

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-08-23

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt 1) , which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness 2, 3) , which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference 4-9) to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model 10) was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls.

  8. A comparison of the efficacy and tolerability of oxcarbazepine oral suspension between infants and children with epilepsy: a retrospective chart review at a single medical center in Taiwan.

    Science.gov (United States)

    Wei, Shu-Hao; Liu, Cheng-Chao; Fan, Pi-Chuan

    2014-02-01

    Few clinical studies have assessed the efficacy and safety of oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly in infants. The aim of this study was to investigate and compare the efficacy, tolerability, and side effects of OXC oral suspension in Taiwanese infants and children with various types of epilepsy. A retrospective review of the efficacy, tolerability, and side effects of OXC oral suspension in a tertiary medical center in Taiwan was conducted and included children (1-9 years old) and infants (effects (30 vs. 21 %, p = 0.525) after OXC oral suspension treatment. The efficacy was significantly correlated with the epilepsy subtype (p effective and well tolerated in both infants and children with partial epilepsy in Taiwan. Treatment efficacy was related to epilepsy subtype and number of combined AEDs before OXC treatment. Monotherapy had an excellent therapeutic response in partial epilepsy but not in multifocal epilepsy.

  9. Review of key Belotero Balance safety and efficacy trials.

    Science.gov (United States)

    Lorenc, Z Paul; Fagien, Steven; Flynn, Timothy C; Waldorf, Heidi A

    2013-10-01

    Belotero Balance is a novel highly cross-linked hyaluronic acid that uses cohesive polydensified matrix technology to achieve cohesive gel; improved adaptation by the dermis; and a soft, smooth fill. Several studies have now compared Belotero Balance to bovine collagen and other hyaluronic acids. Two pivotal studies demonstrated the noninferiority and superiority of Belotero Balance to bovine collagen. In the first study, more than half of the patients maintained optimal correction at 6 months on the Belotero-treated side of the face. The second of those two studies followed patients to week 96 and demonstrated that the effects of Belotero Balance in this long-term, open-label study persisted in the majority of subjects without repeated treatment for at least one interval of 48 weeks. The filler was well tolerated, with only one of 34 total adverse events (injection-site bruising) considered to be related to the study device. A third study compared the safety and efficacy of other hyaluronic acids (i.e., Juvéderm and Restylane) with Belotero Balance. In this study, the safety profiles of all three hyaluronic acids were generally favorable, with site-specific adverse events mild to moderate and comparable across each hyaluronic acid. Aesthetic results were also similar, although Belotero Balance resulted in greater evenness than Restylane at 4 weeks by one indicator used in the study. Finally, a 5-year retrospective safety review of 317 patients treated with Belotero Balance over a 5-year period revealed no severe adverse events in any patients, including the absence of persistent nodules or granulomas.

  10. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2012-11-01

    Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

  11. 11 Efficacy and Tolerability of HDM Injective Immunotherapy With Monomeric Allergoid

    Science.gov (United States)

    Compalati, Enrico; Atzeni, Isabella; Cabras, Sergio; Fancello, Paolo; Gaspardini, Giulio; Longo, Rocco; Patella, Vincenzo; Tore, Giorgio

    2012-01-01

    Background Subcutaneous immunotherapy (SCIT) is an effective treatment of respiratory allergy and carbamylated monomeric allergoids (monoids), by virtue of their reduced IgE-binding activity, resulted clinically safe by sublingual administration. Purpose of this study was to investigate the efficacy and tolerability of immunotherapy with house dust mites (HDM) monoid administered by injective route in patients with allergic rhinoconjunctivitis (AR). Methods A preparation of 0.70 mL of 10 BU/mL containing modified extract with 50% Dermatophagoides pteronyssinus and 50% Dermatophagoides farinae (amount of major allergen: 4 μg of group 1 per milliliter) was delivered monthly for 12 months, following a 5-week build-up induction phase (0.10–0.20–0.30–0.50–0.70 mL), to 58 patients (60% males, mean age 25.1 ± 12.7) suffering from AR due to mites for at least 2 years, whereas 60 patients with similar baseline characteristics were observed as controls. All patients were allowed to assume traditional drug therapy for their condition. At the end of the study changes from baseline in symptoms scores, in number of days with drug assumption, in severity of AR (according to ARIA classification) were compared between the 2 groups; moreover an overall assessment of clinical efficacy and tolerability was based on patients' and physicians' judgements (unsatisfactory, mild, good, optimal). Results In respect to baseline both groups showed, after 1 year, an improvement in symptoms score (P allergoid was associated with a significant clinical benefit observed through objective and subjective outcomes; the traditional safety of monomeric allergoids was confirmed by the subjective judgements of tolerability.

  12. Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach

    Directory of Open Access Journals (Sweden)

    Christophi GP

    2016-05-01

    Full Text Available George P Christophi, Arvind Rengarajan, Matthew A Ciorba Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA Abstract: Ulcerative colitis (UC is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect ­profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side-effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2 after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5. However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations. Keywords: inflammatory bowel disease, treatment cost effectiveness, Crohn’s disease, ulcerative colitis, colon mucosa, proctitis suppositories, topical immunosuppressive therapy

  13. A comprehensive comparison of the efficacy and tolerability of racecadotril with other treatments of acute diarrhea in adults

    Directory of Open Access Journals (Sweden)

    Wolfgang Fischbach

    2016-10-01

    Full Text Available Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain and meteorism; it was also consistent across countries in Africa, Asia and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. A seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea racecadotril is more efficacious than placebo or Saccharomyces boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or Saccharomyces boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults.

  14. Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma

    DEFF Research Database (Denmark)

    Dahl, Ronald; Engel, Michael; Dusser, Daniel

    2016-01-01

    BACKGROUND: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. OBJECTIVE: To evaluate safety and tolerability of tiotro...

  15. Comparison of the efficacy and safety of budesonide turbuhaler ...

    African Journals Online (AJOL)

    Comparison of the efficacy and safety of budesonide turbuhaler administered once daily with twice the dose of beclomethasone dipropionate using pressurised metered dose inhaler in patients with mild to moderate asthma.

  16. Preclinical efficacy and safety of herbal formulation for management ...

    African Journals Online (AJOL)

    Preclinical efficacy and safety of herbal formulation for management of wounds. ... The effects of the treatments on rate of wound closure, epithelialisation time ... inflammation and better tissue remodeling for rats treated with herbal product.

  17. Efficacy and safety of a transdermal contraceptive system.

    Science.gov (United States)

    Smallwood, G H; Meador, M L; Lenihan, J P; Shangold, G A; Fisher, A C; Creasy, G W

    2001-11-01

    To evaluate the efficacy, cycle control, compliance, and safety of a transdermal contraceptive system that delivers norelgestromin 150 microg and ethinyl estradiol 20 microg daily. In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week. The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.

  18. Pharmacotherapy of Insomnia with Ramelteon: Safety, Efficacy and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Seithikurippu R. Pandi-Perumal

    2011-01-01

    Full Text Available Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT 1 and MT 2 melatonin receptors. Ramelteon is the first melatonin receptor agonist approved by the Food and Drug Administration (FDA for the treatment of insomnia characterized by sleep onset difficulties. Ramelteon is both a chronobiotic and a hypnotic that has been shown to promote sleep initiation and maintenance in various preclinical and in clinical trials. The efficacy and safety of ramelteon in patients with chronic insomnia was initially confirmed in short-term placebo-controlled trials. These showed little evidence of next-day residual effects, withdrawal symptoms or rebound insomnia. Other studies indicated that ramelteon lacked abuse potential and had a minimal risk of producing dependence or adverse effects on cognitive or psychomotor performance. A 6-month placebo-controlled international study and a 1-year open-label study in the USA demonstrated that ramelteon was effective and well tolerated. Other potential off-label uses of ramelteon include circadian rhythm sleep disorders such as shift-work and jet lag. At the present time the drug should be cautiously prescribed for short-term treatment only.

  19. Safety and Efficacy of Glucomannan for Weight Loss in Overweight and Moderately Obese Adults

    Directory of Open Access Journals (Sweden)

    Joyce K. Keithley

    2013-01-01

    Full Text Available Background. Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. Methods. Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. Results. A total of 53 participants (18–65 years of age; BMI 25–35 kg/m2 were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (−.40±.06 and −.43±.07, resp. or other efficacy outcomes or in any of the safety outcomes. Conclusions. Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600.

  20. Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic Acid in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Parry, Gareth J; Rodrigues, Cecilia M P; Aranha, Marcia M; Hilbert, Sarah J; Davey, Cynthia; Kelkar, Praful; Low, Walter C; Steer, Clifford J

    2010-01-01

    Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 to 5 years. Neuronal cell death offers a potential target for therapeutic intervention. Ursodeoxycholic acid is a cytoprotective, endogenous bile acid that has been shown to be neuroprotective in experimental Huntington and Alzheimer diseases, retinal degeneration, and ischemic and hemorrhagic stroke. The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration. Eighteen patients were randomly assigned to receive ursodeoxycholic acid at doses of 15, 30, and 50 mg/kg of body weight per day. Serum and cerebrospinal fluid were obtained for analysis after 4 weeks of treatment. Treatment-emergent clinical and laboratory events were monitored weekly. Our data indicated that ursodeoxycholic acid is well tolerated by all subjects at all doses. We also showed that ursodeoxycholic acid is well absorbed after oral administration and crosses the blood-brain barrier in a dose-dependent manner. These results show excellent safety and tolerability of ursodeoxycholic acid. The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis.

  1. Selection of tolerable risk criteria for dam safety decision making

    International Nuclear Information System (INIS)

    Nielsen, N.M.; Hartford, D.N.D.; MacDonald, T.F.

    1994-01-01

    Risk assessment has received increasing attention in recent years as a means of aiding decision making on dams by providing systematic and rational methods for dealing with risk and uncertainty. Risk assessment is controversial and decisions affecting risk to life are the most controversial. Tolerable criteria, based on the risks that society is prepared to accept in order to avoid excessive costs, set bounds within which risk-based decisions may be made. The components of risk associated with dam safety are addressed on an individual basis and criteria established for each component, thereby permitting flexibility in the balance between component risk and avoiding the problems of placing a monetary value on life. The guiding principle of individual risk is that dams do not impose intolerable risks on any individual. A risk to life of 1 in 10 4 per annum is generally considered the maximum tolerable risk. When considering societal risk, the safety of a dam should be proportional to the consequences of its failure. Risks of financial losses beyond the corporation's ability to finance should be so low as to be considered negligible. 17 refs., 3 figs

  2. Efficacy and Safety of Atomoxetine in the Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Michael R. Kohn

    2012-01-01

    Full Text Available Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD. Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication.

  3. Efficacy and Safety of Atomoxetine in the Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder

    Science.gov (United States)

    Kohn, Michael R.; Tsang, Tracey W.; Clarke, Simon D.

    2012-01-01

    Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication. PMID:23641171

  4. Efficacy and tolerability of antihypertensive drugs in diabetic and nondiabetic patients

    Directory of Open Access Journals (Sweden)

    Maria Aslam

    2017-01-01

    Full Text Available Objectives of the Study: The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs with essential hypertension. Material and Methods: The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP above 130 mmHg and diastolic blood pressure (DBP above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI, beta-blocker (βB, calcium-channel blocker (CCB, diuretics (D, angiotensin receptor blocker (ARB as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July–October. After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. Results: Significant control in mean BP by all drug groups was observed in “both groups that is patients with diabetes and without diabetes.” The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus βBs, ARB's plus CCBs plus diuretic plus βBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus βBs, three-drug combination therapy with βBs plus ACEI plus D was found more effective in controlling SBP as well

  5. Tolerability of risk, safety assessment principles and their implications for probabilistic safety analysis

    International Nuclear Information System (INIS)

    Ewing, D.J.F.; Campbell, J.F.

    1994-01-01

    This paper gives a regulatory view of probabilistic safety assessment as seen by the Nuclear Installations Inspectorate (NII) and in the light of the general regulatory risk aims set out in the Health and Safety Executive's (HSE) The tolerability of risk from nuclear power stations (TOR) and in Safety assessment principles for nuclear plants (SAPs), prepared by NII on behalf of the HSE. Both of these publications were revised and republished in 1992. This paper describes the SAPs, together with the historical background, the motivation for review, the effects of the Sizewell and Hinkley Point C public inquiries, changes since the original versions, comparison with international standards and use in assessment. For new plant, probabilistic safety analysis (PSA) is seen as an essential tool in balancing the safety of the design and in demonstrating compliance with TOR and the SAPs. (Author)

  6. Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

    Science.gov (United States)

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

    2017-01-01

    Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

  7. Paliperidone ER in the Treatment of Borderline Personality Disorder: A Pilot Study of Efficacy and Tolerability

    Directory of Open Access Journals (Sweden)

    Silvio Bellino

    2011-01-01

    Full Text Available Antipsychotics are recommended for the treatment of impulsive dyscontrol and cognitive perceptual symptoms of borderline personality disorder (BPD. Three reports supported the efficacy of oral risperidone on BPD psychopathology. Paliperidone ER is the metabolite of risperidone with a similar mechanism of action, and its osmotic release reduces plasmatic fluctuations and antidopaminergic effects. The aim of this study is to evaluate efficacy and safety of paliperidone ER in BPD patients. 18 outpatients with a DSM-IV-TR diagnosis of BPD were treated for 12 weeks with paliperidone ER (3–6 mg/day. They were assessed at baseline, week 4, and week 12, using the CGI-Severity item, the BPRS, the HDRS, the HARS, the SOFAS, the BPD Severity Index (BPDSI, and the Barratt Impulsiveness Scale (BIS-11. Adverse events were evaluated with the DOTES. Paliperidone ER was shown to be effective and well tolerated in reducing severity of global symptomatology and specific BPD symptoms, such as impulsive dyscontrol, anger, and cognitive-perceptual disturbances. Results need to be replicated in controlled trials.

  8. Tolerance and efficacy of emamectin benzoate and ivermectin for the treatment of Pseudocapillaria tomentosa in laboratory zebrafish (Danio rerio).

    Science.gov (United States)

    Collymore, Chereen; Watral, Virginia; White, Julie R; Colvin, Michael E; Rasmussen, Skye; Tolwani, Ravi J; Kent, Michael L

    2014-10-01

    Tolerance of adult zebrafish and efficacy of emamectin benzoate and ivermectin in eliminating Pseudocapillaria tomentosa infection were evaluated. In the tolerance study, behavioral changes, fecundity, histopathology, and mortality were evaluated for in-feed administration of emamectin (0.05, 0.10, and 0.25 mg/kg) and ivermectin (0.05 and 0.10 mg/kg). All doses of emamectin were well tolerated. Ivermectin 0.05 mg/kg administration resulted in mild behavioral changes and a transient decrease in fecundity. Ivermectin 0.10 mg/kg administration resulted in severe behavioral changes and some mortality. In the efficacy study, emamectin (0.05 and 0.25 mg/kg) and ivermectin (0.05 mg/kg) were evaluated for their efficacy in eliminating P. tomentosa infection. Emamectin reduced parasite burden in infected zebrafish, and ivermectin eliminated intestinal nematode infections. Despite a small margin of safety, ivermectin 0.05 mg/kg was effective at eliminating P. tomentosa infection in adult zebrafish. Higher doses or a longer course of treatment may be needed for complete elimination of P. tomentosa infection using emamectin. In this study, we propose two possible treatments for intestinal nematode infections in zebrafish.

  9. Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

    Science.gov (United States)

    Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

    2013-11-01

    Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

  10. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    Science.gov (United States)

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

  11. Efficacy and safety of cinitapride in functional dyspepsia

    International Nuclear Information System (INIS)

    Baqi, M.; Malik, M.N.

    2013-01-01

    Objective: To study the efficacy and safety of cinitapride in the treatment of functional dyspepsia, and to evaluate the improvement of patients quality of life. Methods: The prospective cross-sectional multi-centre phase IV study was conducted at Jinnah Hospital, Lahore, Ziauddin Medical University, Karachi and Pakistan Railways General Hospital, Rawalpindi, from July 2009 to June 2010 and comprised 121 patients of functional dyspepsia who were given cinitapride 1mg thrice daily 15 minutes before meals and were followed up for four weeks. Primary clinical response was assessed by using the Global Index Score. Secondary response was seen by percentage change of the total score as well as of each dyspepsia symptom compared with baseline and the overall subjective assessment of patients by using the 7-point Likert's scale. Reduction in Nepean Dyspepsia Index-Short Farm was used to evaluate the improvement in quality of life of patients at week 2 and 4. SPSS 15 used for statistical analysis. Results: After 4 weeks of treatment, the Global Index Score showed statistically significant reduction in 58 (48.92%) patients (p<0.01). Similar reduction (p<0.01) was seen in individual dyspepsia symptoms; early satiety, post-prandial fullness, and abdominal distension. The 7 point Likert's scale also showed similar improvement in subjective response (p<0.01). The quality of life also improved significantly at week 2 and 4 (p<0.01). No abnormal results were seen in vital signs, physical and laboratory examination except an unexplained rise in globulin level. Only one adverse event (sore throat) was reported during the study. Conclusion: The drug was effective in minimising dyspepsia symptoms, and improving the quality of life of patients. It was well tolerated and was almost free of side effects. (author)

  12. Efficacy and Safety of Topical Niacinamide for Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    Zeynep Nurhan Saraçoğlu

    2011-06-01

    Full Text Available Background and Design: To investigate the efficacy and safety of topical 4% naicinamide gel cream in the treatment of mild to moderate acne vulgaris and to assess the quality of life of acne patients.Material and Method: Twenty-nine female patients aged 16-38 (mean: 23.57±5.42 years with mild to moderate acne vulgaris who presented in dermatology outpatient clinic were enrolled in the study. All patients applied 4% niacinamide gel cream (Vivatinell-acnecinamide gel cream® on their faces twice daily for eight weeks. The number of lesions (inflammatory and non-inflammatory was counted at 0, 2, 4 and 8 weeks. The side effects (erythema, desquamation, burning and dryness were recorded. The Skindex-29, a quality-of-life measure for patients with skin disease, was administered to the subjects at the beginning and the end of treatment.Results: The decrease in the mean number of inflammatory lesions was statistically significant at the end of the treatment (pre-treatment vs. post-treatment: 12.24 vs. 6.14; p =0.000. However, there was no statistically significant decrease in the number of non-inflammatory lesions at the end of the eight weeks. The niacinamide gel cream was generally well tolerated. There was statistically significant improvement in the Skindex-29 scale scores (p =0.000 at the end of the treatment.Conclusion: Topical 4% niacinamide gel cream may be an alternative treatment for inflammatory lesions of mild to moderate acne vulgaris.

  13. Polyhexanide - safety and efficacy as an antiseptic.

    Science.gov (United States)

    Fjeld, Hilde; Lingaas, Egil

    2016-05-01

    BACKGROUND Polyhexamethylene biguanide hydrochloride/polyhexanide/polyaminopropyl biguanide (PHMB) is used as a disinfectant and antiseptic. This article discusses the use of the substance as an antiseptic. We summarise published data on its antimicrobial effect in vitro and its clinical effect and safety when used on skin, wounds and mucosa.MATERIAL AND METHOD A literature search was conducted in PubMed for articles published in the last five years. Articles available as of June 2014 were considered.RESULTS Of 332 articles identified, 27 were included. In vitro studies have demonstrated an antimicrobial effect on Gram-negative bacteria, Gram-positive bacteria and Candida albicans. The clinical studies are small, not well controlled and frequently sponsored by industry. Few adverse effects from the substance were reported.INTERPRETATION Better designed, larger-scale clinical studies of effect and safety are needed in order to give recommendations on the use of polyhexanide on skin, wounds and mucosa.

  14. Management of atopic dermatitis: safety and efficacy of phototherapy

    Directory of Open Access Journals (Sweden)

    Patrizi A

    2015-10-01

    Full Text Available Annalisa Patrizi, Beatrice Raone, Giulia Maria RavaioliDepartment of Specialized, Diagnostic and Experimental Medicine, Division of Dermatology, University of Bologna, Bologna, ItalyAbstract: Atopic dermatitis (AD is a common chronic inflammatory skin disease that can affect all age groups. It is characterized by a relapsing course and a dramatic impact on quality of life for patients. Environmental interventions together with topical devices represent the mainstay of treatment for AD, in particular emollients, corticosteroids, and calcineurin inhibitors. Systemic treatments are reserved for severe cases. Phototherapy represents a valid second-line intervention in those cases where non-pharmacological and topical measures have failed. Different forms of light therapy are available, and have showed varying degrees of beneficial effect against AD: natural sunlight, narrowband (NB-UVB, broadband (BB-UVB, UVA, UVA1, cold-light UVA1, UVA and UVB (UVAB, full-spectrum light (including UVA, infrared and visible light, saltwater bath plus UVB (balneophototherapy, Goeckerman therapy (coal tar plus UVB radiation, psoralen plus UVA (PUVA, and other forms of phototherapy. In particular, UVA1 and NB-UVB have gained importance in recent years. This review illustrates the main trials comparing the efficacy and safety of the different forms of phototherapy. No sufficiently large randomized controlled studies have been performed as yet, and no light modality has been defined as superior to all. Parameters and dosing protocols may vary, although clinicians mainly refer to the indications included in the American Academy of Dermatology psoriasis guidelines devised by Menter et al in 2010. The efficacy of phototherapy (considering all forms in AD has been established in adults and children, as well as for acute (UVA1 and chronic (NB-UVB cases. Its use is suggested with strength of recommendation B and level of evidence II. Home phototherapy can also be performed

  15. Feasibility, safety and tolerability of accelerated dobutamine stress echocardiography

    Directory of Open Access Journals (Sweden)

    Pavaci Herribert

    2007-11-01

    Full Text Available Abstract A continuous infusion of a single high dose of dobutamine has been, recently, suggested as a simple and effective protocol of stress echocardiography. The present study assesses the feasibility, safety, and tolerability of an accelerated dobutamine stress protocol performed in patients with suspected or known coronary artery disease. Two hundred sixty five consecutive patients underwent accelerated dobutamine stress echocardiography: the dobutamine was administered at a constant dose of 50 μg/kg/min for up to 10 minutes. The mean weight-adjusted cumulative dose of dobutamine used was 330 ± 105.24 μg/kg. Total duration of dobutamine infusion was 6.6 ± 2.1 min. Heart rate rose from 69.9 ± 12.1 to 123.1 ± 22.1 beats/min at peak with a concomitant change in systolic blood pressure (127.6 ± 18.1 vs. 167.6 ± 45.0 mmHg. Dobutamine administration produced a rapid increase in heart rate (9.4 ± 5.9 beats/min2. The side effects were similar to those described with the standard protocol; the most common were frequent premature ventricular complexes (21.5%, frequent premature atrial complexes (1.5% and non sustained ventricular tachycardia (1.5%; among non cardiac symptoms the most frequent were nausea (3.4%, headache (1.1% and symptomatic hypotension (1.1%. No major side effects were observed during the test. Our data demonstrate that a continous infusion of a single high dose of dobutamine is a safe and well tolerated method of performing stress echocardiography in patients with suspected or known coronary artery disease. This new protocol requires the administration of lower cumulative dobutamine dose than standard protocol and results in a significant reduction in test time.

  16. Efficacy and Tolerability of an Herbal Formulation for Weight Management

    OpenAIRE

    Stern, Judith S.; Peerson, Jan; Mishra, Artatrana T.; Mathukumalli, Venkata Sadasiva Rao; Konda, Poorna Rajeswari

    2013-01-01

    The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m2. Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/da...

  17. Possible biomarkers modulating haloperidol efficacy and/or tolerability.

    Science.gov (United States)

    Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

    2016-04-01

    Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

  18. Biologics in pediatric psoriasis - efficacy and safety.

    Science.gov (United States)

    Dogra, Sunil; Mahajan, Rahul

    2018-01-01

    Childhood psoriasis is a special situation that is a management challenge for the treating dermatologist. As is the situation with traditional systemic agents, which are commonly used in managing severe psoriasis in children, the biologics are being increasingly used in the recalcitrant disease despite limited data on long term safety. Areas covered: We performed an extensive literature search to collect evidence-based data on the use of biologics in pediatric psoriasis. The relevant literature published from 2000 to September 2017 was obtained from PubMed, using the MeSH words 'biologics', 'biologic response modifiers' and 'treatment of pediatric/childhood psoriasis'. All clinical trials, randomized double-blind or single-blind controlled trials, open-label studies, retrospective studies, reviews, case reports and letters concerning the use of biologics in pediatric psoriasis were screened. Articles covering the use of biologics in pediatric psoriasis were screened and reference lists in the selected articles were scrutinized to identify other relevant articles that had not been found in the initial search. Articles without relevant information about biologics in general (e.g. its mechanism of action, pharmacokinetics and adverse effects) and its use in psoriasis in particular were excluded. We screened 427 articles and finally selected 41 relevant articles. Expert opinion: The available literature on the use of biologics such as anti-tumor necrosis factor (TNF)-α agents, and anti-IL-12/23 agents like ustekinumab suggests that these are effective and safe in managing severe pediatric psoriasis although there is an urgent need to generate more safety data. Dermatologists must be careful about the potential adverse effects of the biologics before administering them to children with psoriasis. It is likely that with rapidly evolving scenario of biologics in psoriasis, these will prove to be very useful molecules particularly in managing severe and recalcitrant

  19. Efficacy and tolerability of hydrogen carbonate-rich water for heartburn

    Science.gov (United States)

    Beer, André-Michael; Uebelhack, Ralf; Pohl, Ute

    2016-01-01

    AIM: To investigate the efficacy and safety of mineral water with a high content of hydrogen carbonate in patients with heartburn. METHODS: This open, single-center, single-arm clinical pilot study enrolled 50 patients, 18-64 years old, who had been suffering from heartburn at least twice a week for at least 3 mo before entering the study. Pharmacological treatment of heartburn was not permitted, and patients with severe organic diseases were excluded. After a run-in period of one week, the participants received 1.5 L of the test water for the following 6 wk; 300 mL with meals t.i.d., the remainder to be drunk throughout the day. During the trial, there were five visits at the study center (screening, baseline, two interim visits and the final visit). The efficacy endpoints included incidence and duration of heartburn episodes per week by patient’s self-assessment (heartburn diary) as well as changes in symptom severity as per symptom specific questionnaires [Reflux Disease Questionnaire (RDQ); Quality of Life in Reflux and Dyspepsia (QOLRAD); Gastrointestinal Quality of Life Index] and overall health-related quality of life per SF-12 (12-question short form) at each visit. At the end of the study, patients and investigators independently rated the overall efficacy of the test water on a 4-point Likert scale. Safety was assessed by evaluation of adverse events (AEs), vital signs (heart rate, blood pressure) and laboratory parameters. Changes from initial to final examinations were assessed by the non-parametric Wilcoxon test; categorical variables were compared using the χ2 test, and for more than 5 categories, by the U-test. RESULTS: Twenty-eight participants were men, 22 women. The mean age of the patients in the full analysis set/intention-to treat population (FAS/ITT) was 40.6 years. Forty-two participants completed the study according to the study protocol and formed the per-protocol set (PP population); 48 participants drank the water at least once as

  20. Clinical efficacy and safety of edaravone therapy in acute cerebral ...

    African Journals Online (AJOL)

    Purpose: To evaluate the clinical efficacy and safety of edaravone in the treatment of acute cerebral haemorrhage (ACH). Methods: This study recruited 120 patients who developed ACH. The patients were divided into control and treatment groups with 60 patients per group. The control group underwent conventional ...

  1. Efficacy and safety of telmisartan monotherapy in the black ...

    African Journals Online (AJOL)

    The use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in addition to control of blood pressure delays the development of end organ damage associated with hypertension. This study was undertaken to investigate the efficacy and safety of telmisartan as monotherapy in Nigerian black ...

  2. Double blind clinical trail comparing the safety and efficacy of ...

    African Journals Online (AJOL)

    Double blind clinical trail comparing the safety and efficacy of nimesulide (100g) and diclofenac in osteoarthrosis of the hip and knee joints. ... A significant proportion of the patients in the diclofenac group (50% vs 17.6%) had break through pain that warranted the use of at least two tablets of 500mg of paracetamol per week ...

  3. Safety and efficacy of procedural sedation and analgesia (PSA ...

    African Journals Online (AJOL)

    Safety and efficacy of procedural sedation and analgesia (PSA) conducted by medical officers in a level 1 hospital in Cape Town. ... Respiratory complications were treated with simple airway manoeuvres; no patient required intubation or experienced respiratory problems after waking up. There was no significant difference ...

  4. Efficacy and safety of ginger in osteoarthritis patients

    DEFF Research Database (Denmark)

    Bartels, E M; Folmer, V N; Bliddal, Henning

    2015-01-01

    The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing ...

  5. A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety ...

    African Journals Online (AJOL)

    A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of Lornoxicam with Diclofenac Sodium in Patients of Osteoarthritis Knee. ... All patients were assessed with visual analogue scale and 100 meter walking test before starting of therapy, at 15 days and at 1, 2 and 3 months of therapy.

  6. Tolerability and efficacy of gamma knife radiosurgery on hepatocellular carcinoma with portal vein tumor thrombosis

    Science.gov (United States)

    Lu, Xiao-Jie; Dong, Jing; Ji, Li-Juan; Xiao, Li-Xin; Ling, Chang-Quan; Zhou, Jun

    2016-01-01

    This is a retrospective study on the safety and efficacy of gamma knife radiosurgery (GKR) in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Patients with confirmed HCC and PVTT were allocated into two groups based on the treatments they received (palliative or GKR). A total of 138 patients were included (74 in the palliative group, 64 in GKR group). No significant differences in baseline characteristics existed between the two groups. Treatment-related adverse events (AEs) were recorded and compared between groups. The majority of AEs were mild to moderate and subsided naturally or after medication. There was no AE-induced death. The influences of baseline characteristics and treatment options on patients' OS were analyzed. The median OS of patients in the palliative and GKR group were 3.0 months (95% CI: 2.719-3.281) and 6.1 months (95% CI: 4.706-7.494) respectively (p = 0.003). Multivariate analysis revealed that GKR treatment, performance status 0-1, Child A, smaller tumor diameter and monolobar distribution were significant favorable prognosticators. Subgroup analyses showed OS benefit of GKR regardless of PVTT location (main or branch of PVTT). In conclusion, GKR is well tolerated in selected HCC-PVTT patients and can confer OS benefit, which needs validation in future prospective studies. PMID:26473291

  7. Efficacy, safety, and patient acceptability of the Essure™ procedure

    Directory of Open Access Journals (Sweden)

    Hopkins MR

    2011-04-01

    Full Text Available Collette R Lessard, Matthew R HopkinsDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota, USAAbstract: The Essure™ system for permanent contraception was developed as a less invasive method of female sterilization. Placement of the Essure™ coil involves a hysteroscopic transcervical technique. This procedure can be done in a variety of settings and with a range of anesthetic options. More than eight years have passed since the US Food and Drug Administration approval of Essure™. Much research has been done to evaluate placement success, adverse outcomes, satisfaction, pain, and the contraceptive efficacy of the Essure™. The purpose of this review is to summarize the available literature regarding the efficacy, safety, and patient satisfaction with this new sterilization technique.Keywords: hysteroscopic sterilization, Essure™, safety, efficacy, acceptability

  8. Effect of Coadministered Fat on the Tolerability, Safety, and Pharmacokinetic Properties of Dihydroartemisinin-Piperaquine in Papua New Guinean Children with Uncomplicated Malaria

    OpenAIRE

    Moore, B. R.; Benjamin, J. M.; Salman, S.; Griffin, S.; Ginny, E.; Page-Sharp, M.; Robinson, L. J.; Siba, P.; Batty, K. T.; Mueller, I.; Davis, T. M. E.

    2014-01-01

    Coadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age group. The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5-mg-base/...

  9. Efficacy and tolerability of an herbal formulation for weight management.

    Science.gov (United States)

    Stern, Judith S; Peerson, Jan; Mishra, Artatrana T; Mathukumalli, Venkata Sadasiva Rao; Konda, Poorna Rajeswari

    2013-06-01

    The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m². Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P<.0001), BMI (2.2 kg/m²; P<.0001), as well as waist (11.9 cm; P<.0001) and hip circumferences (6.3 cm; P=.0001) were observed in the herbal group compared with placebo. An increase in serum adiponectin concentration was also found in the herbal group versus placebo (P=.0008) at study conclusion along with reductions in fasting blood glucose (12.2%, P=.01), cholesterol (13.8%, P=.002), and triglyceride (41.6%, P<.0001) concentrations. No changes were seen across organ function panels, multiple vital signs, and no major adverse events were reported. The minor adverse events were equally distributed between the two groups. Our findings suggest that the herbal blend appears to be a well-tolerated and effective ingredient for weight management.

  10. Lithium safety and tolerability in mood disorders: a critical review

    Directory of Open Access Journals (Sweden)

    Ivan Aprahamian

    2014-04-01

    Full Text Available Background : Lithium is a first-line treatment for bipolar disorder in all phases, also indicated as add-on drug for unipolar depression and suicide prevention. This study encompasses a broad critical review on the safety and tolerability of lithium for mood disorders. Methods : A computerized search for English written human studies was made in MEDLINE, using the keywords “lithium” and “mood disorders”, starting from July 1993 through July 2013 (n = 416. This initial search aimed to select clinical trials, prospective data, and controlled design studies of lithium treatment for mood disorders reporting adverse effects (n = 36. The final selection yielded 91 studies. Results : The most common general side effects in patients on lithium treatment were thirst, frequent urination, dry mouth, weight gain, fatigue and cognitive complaints. Lithium users showed a high prevalence of hypothyroidism, hyperparathyroidism, and decrease in urinary concentration ability. Reduction of glomerular filtration rate in patients using lithium was also observed, but in a lesser extent. The evidence of teratogenicity associated with lithium use is not well established. Anti-inflammatory non-steroidal drugs, thiazide diuretics, angiotensin-converting enzyme inhibitors, and alprazolam may increase serum lithium and the consequent risk for intoxication. Discussion : Short-term lithium treatment is associated with mild side effects. Medium and long-term lithium treatment, however, might have effects on target organs which may be prevented by periodical monitoring. Overall, lithium is still a safe option for the treatment of mood disorders.

  11. Hospital disinfection: efficacy and safety issues.

    Science.gov (United States)

    Dettenkofer, Markus; Block, Colin

    2005-08-01

    To review recent publications relevant to hospital disinfection (and cleaning) including the reprocessing of medical instruments. The key question as to whether the use of disinfectants on environmental surfaces rather than cleaning with detergents only reduces nosocomial infection rates still awaits conclusive studies. New disinfectants, mainly peroxygen compounds, show good sporicidal properties and will probably replace more problematical substances such as chlorine-releasing agents. The safe reprocessing of medical devices requires a well-coordinated approach, starting with proper cleaning. New methods and substances show promising activity for preventing the transmission of prions. Different aspects of virus inactivation have been studied, and the transmissibility, e.g. of norovirus, shows the need for sound data on how different disinfectant classes perform. Biofilms or other forms of surface-adherent organisms pose an extraordinary challenge to decontamination. Although resistance to biocides is generally not judged to be as critical as antibiotic resistance, scientific data support the need for proper use, i.e. the avoidance of widespread application, especially in low concentrations and in consumer products. Chemical disinfection of heat-sensitive instruments and targeted disinfection of environmental surfaces are established components of hospital infection control. To avoid danger to staff, patients and the environment, prudent use as well as established safety precautions are required. New technologies and products should be evaluated with sound methods. As emerging resistant pathogens will challenge healthcare facilities in the future even more than at present, there is a need for well-designed studies addressing the role of disinfection in hospital infection control.

  12. Efficacy and tolerability of agomelatine in the treatment of depression

    Directory of Open Access Journals (Sweden)

    Plesničar BK

    2014-05-01

    Full Text Available Blanka Kores Plesničar Ljubljana University Psychiatric Hospital, Ljubljana, Slovenia Abstract: Depression is a severe and usually recurrent mental disorder which often leads to a significant impairment of everyday functioning, a reduced quality of life, and also great suffering of the patients. The treatment of a depressive disorder is not only limited to acute treatment; it also requires prolonged management. Patient compliance is of utmost importance. Unpleasant adverse effects and their impact on everyday living often lead to a premature discontinuation of antidepressant treatment and result in an unfavorable treatment outcome. The new antidepressant agomelatine, a melatonergic MT1/MT2 agonist and 5-HT2C receptor antagonist, has exhibited good antidepressant efficacy in acute, short-term, and long-term treatment. The adverse effect profile of agomelatine has been proven to be favorable and comparable to placebo, which is very important for good treatment compliance and adherence. Keywords: agomelatine, circadian rhythms, depression

  13. Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

    Science.gov (United States)

    Morgan, Michael M; Christie, MacDonald J

    2011-10-01

    Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  14. Efficacy and safety of pirfenidone for idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Takeda Y

    2014-03-01

    many of these are mild and manageable. Clinical experience has shown that reduction in pirfenidone dose and the supportive use of gastrointestinal drugs are effective ways to manage these symptoms. Thus, pirfenidone treatment provides a means of intervention in the clinical course of IPF, and is a promising candidate for improving patient prognosis. For future development, it is important to establish the appropriate modality of treatment with pirfenidone and/or novel potential drugs. Keywords: pirfenidone, safety, efficacy, anti-fibrotic drugs

  15. A novel and well tolerated mite allergoid subcutaneous immunotherapy: evidence of clinical and immunologic efficacy

    Science.gov (United States)

    Roger, Albert; Depreux, Nathalie; Jurgens, Yani; Heath, Matthew D; Garcia, Gloria; Skinner, Murray A

    2014-01-01

    Allergy to house dust mite is one of the most common causes of allergic rhinitis. A novel tyrosine-adsorbed, modified allergen product, Acarovac Plus, developed for the treatment of perennial mite allergy seeks to address the underlying cause of allergic rhinitis in this instance. One of two dosing regimens may be used, either the Conventional Regimen or the Cluster Regimen. We sought to compare the efficacy and safety of a specific immunotherapy, developed for the treatment of perennial mite allergy, administered under a Conventional and Clustered dosing schedule in patients with persistent allergic rhinitis. Thirty adult patients, between 18 and 65 years old, with allergic rhinitis and/or asthma secondary to hypersensitivity to Dermatophagoides pteronyssinus were administered with either conventional or cluster initial regime, with a final visit one week after the last dose administration. The efficacy to the Conventional and Cluster regimens was measured using a Nasal Challenge Test monitoring clinical symptoms and peak nasal inspiratory flow. Total IgE, serum-specific inmunoglobulins (IgE and IgG4) to Dermatophagoides pteronyssinus and relevant cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13) were assessed. A Satisfaction Questionnaire (TSQM) was completed after each patient's final visit. The tolerability of the vaccine was assessed monitoring adverse reactions. No adverse events were recorded in either conventional or cluster regime. The specific Nasal Challenge Test led to a decrease in symptom scores and a significant decrease in mean nasal peak inspiratory flow drop was recorded in both dosing regimen groups. A significant increase in IgG4-specific antibody titres was assessed. No significant changes were observed in concentrations of total IgE, specific IgE or cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13). Patients declared themselves most satisfied in relation to “Secondary effects”, with high overall satisfaction in both groups. Cluster and

  16. Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine : efficacy, safety and dosing

    NARCIS (Netherlands)

    van den Broek, Marcel P. H.; Rademaker, Carin M. A.; van Straaten, Henrica L. M.; Huitema, Alwin D. R.; Toet, Mona C.; de Vries, Linda S.; Egberts, Antoine C. G.; Groenendaal, Floris

    BACKGROUND: Lidocaine is an antiarrythmicum used as an anticonvulsant for neonatal seizures, also during therapeutic hypothermia following (perinatal) asphyxia. Hypothermia may affect the efficacy, safety and dosing of lidocaine in these patients. OBJECTIVE: To study the efficacy and safety of

  17. Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Gu, Aiqin; Shi, Chunlei; Xiong, Liwen; Chu, Tianqing; Pei, Jun; Han, Baohui

    2013-02-01

    To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (Picotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

  18. Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics

    DEFF Research Database (Denmark)

    Wise, Robert; Calverley, Peter Ma; Dahl, Ronald

    2015-01-01

    BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety...... in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. AIMS: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy...... the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. CONCLUSIONS: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy....

  19. Determining animal drug combinations based on efficacy and safety.

    Science.gov (United States)

    Kratzer, D D; Geng, S

    1986-08-01

    A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

  20. Safety and efficacy of aneurysm treatment with WEB

    DEFF Research Database (Denmark)

    Pierot, Laurent; Costalat, Vincent; Moret, Jacques

    2016-01-01

    OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide......-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical....... RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting...

  1. Safety aspects of genetically modified crops with abiotic stress tolerance

    NARCIS (Netherlands)

    Liang, C.; Prins, T.W.; Wiel, van de C.C.M.; Kok, E.J.

    2014-01-01

    Abiotic stress, such as drought, salinity, and temperature extremes, significantly reduce crop yields. Hence, development of abiotic stress-tolerant crops by modern biotechnology may contribute to global food security. Prior to introducing genetically modified crops with abiotic stress tolerance to

  2. Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Abrouk M

    2016-12-01

    Full Text Available Michael Abrouk,1 Ethan Levin,2 Merrick Brodsky,1 Jessica R Gandy,1 Mio Nakamura,2 Tian Hao Zhu,3 Benjamin Farahnik,4 John Koo,2 Tina Bhutani2 1Irvine School of Medicine, Irvine, 2Department of Dermatology, Psoriasis and Skin Treatment Center, University of California, San Francisco, 3Department of Dermatology, University of Southern California Keck School of Medicine, Los Angeles, CA, 4Department of Dermatology, University of Vermont College of Medicine, Burlington, VT, USA Introduction: The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods: A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results: The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion: Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. Keywords: excimer, laser, 308 nm, psoriasis, safety, efficacy

  3. Sibutramine: efficacy and safety of prescribing in routine clinical practice

    Directory of Open Access Journals (Sweden)

    Tat'yana Ivanovna Romantsova

    2015-11-01

    Full Text Available The 17th European Congress of endocrinology was held in Dublin in May 2015. Within the section «Obesity» the preliminary results of the observational program "PRIMAVERA" in the form of an oral report were presented. This article presents a brief review of the literature, reflecting the issues of mechanism of action, efficacy and safety of sibutramine and also includes an extended version of the main provisions of the report.

  4. Safety and efficacy of venom immunotherapy: a real life study.

    Science.gov (United States)

    Kołaczek, Agnieszka; Skorupa, Dawid; Antczak-Marczak, Monika; Kuna, Piotr; Kupczyk, Maciej

    2017-04-01

    Venom immunotherapy (VIT) is recommended as the first-line treatment for patients allergic to Hymenoptera venom. To analyze the safety and efficacy of VIT in a real life setting. One hundred and eighty patients undergoing VIT were studied to evaluate the safety, efficacy, incidence and nature of symptoms after field stings and adverse reactions to VIT. Significantly more patients were allergic to wasp than bee venom (146 vs. 34, p bees, and were not associated with angiotensin convertase inhibitors (ACEi) or β-adrenergic antagonists use. Systemic reactions were observed in 4 individuals on wasp VIT (2.7%) and in 6 patients allergic to bees (17.65%). The VIT was efficacious as most patients reported no reactions (50%) or reported only mild local reactions (43.75%) to field stings. The decrease in sIgE at completion of VIT correlated with the dose of vaccine received ( r = 0.53, p = 0.004). Beekeeping (RR = 29.54, p venom allergy. Venom immunotherapy is highly efficacious and safe as most of the adverse events during the induction and maintenance phase are mild and local. Side effects of VIT are more common in subjects on bee VIT. Beekeeping and female sex are associated with a higher risk of allergy to Hymenoptera venom.

  5. Testosterone Replacement Therapy: Long-Term Safety and Efficacy

    Directory of Open Access Journals (Sweden)

    Giovanni Corona

    2017-08-01

    Full Text Available Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG or late-onset hypogonadism (LOH. The former is the consequence of congenital or acquired “organic” damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T therapy (TTh. In addition, concerns related to cardiovascular (CV safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an “ex-juvantibus” criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.

  6. EFFICACY AND SAFETY OF THE INFLUENZA VACCINE AMONG CHILDREN WITH DIFFERENT HEALTH CONDITIONS

    OpenAIRE

    M.G. Galitskaya

    2007-01-01

    Efficacy and safety of vaccine «Grippol» among children with different health status was analyzed. The most efficacy of the influenza vaccine revealed in the group of children with compromised health status, as well as in the group of allergic children. The safety of influenza vaccination was confirmed in children with different health conditions.Key words: children, vaccination, influenza, efficacy, safety.

  7. Maximum tolerable radiation doses recommended by the Israel Advisory Committee on nuclear safety

    International Nuclear Information System (INIS)

    Tadmor, J.; Litai, D.; Lubin, E.

    1978-01-01

    Maximum tolerable doses have been recommended by the Israel Advisory Committee on Nuclear Safety. The recommendations which are based on a comparison with risks tolerated in other human activities, are for doses to radiation workers, for individual members of the population at the fence of a nuclear installation, and for the population at large, for both normal operating and accident conditions. Tolerable whole-body doses and doses to different critical organs are listed

  8. Longterm Safety and Efficacy of Subcutaneous Abatacept in Patients with Rheumatoid Arthritis: 5-year Results from a Phase IIIb Trial.

    Science.gov (United States)

    Genovese, Mark C; Pacheco-Tena, César; Covarrubias, Arturo; Leon, Gustavo; Mysler, Eduardo; Keiserman, Mauro; Valente, Robert M; Nash, Peter; Simon-Campos, J Abraham; Box, Jane; Legerton, Clarence W; Nasonov, Evgeny; Durez, Patrick; Elegbe, Ayanbola; Wong, Robert; Li, Xiaohui; Banerjee, Subhashis; Alten, Rieke

    2018-04-15

    To assess 5-year safety, tolerability, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA). The Abatacept Comparison of sub[QU]cutaneous versus intravenous in Inadequate Responders to methotrexatE (ACQUIRE) phase IIIb, randomized, double-dummy, multinational trial compared efficacy and safety of SC and intravenous (IV) ABA in patients with RA. In the initial 6-month double-blind (DB) period, patients received IV or SC ABA, plus MTX, and in the subsequent open-label longterm extension (LTE) period, all patients received SC ABA (125 mg/wk). The final 5-year safety, tolerability, and efficacy analyses are reported. Of 1385 patients who completed the DB period, 1372 entered LTE and 945 (68.8%) completed ≥ 5 years of treatment. During LTE, 97 (7.1%) patients discontinued treatment because of an adverse event (AE). Incidence rate (IR; event/100 patient-yrs of exposure; based on LTE data, 95% CI) for AE of interest were the following: serious AE 7.73 (6.96-8.58), infection 38.60 (36.24-41.12), serious infection 1.68 (1.35-2.07), malignancies 1.09 (0.84-1.42), and autoimmune disorders 1.33 (1.05-1.69), and were stable over time. No association between immunogenicity and either worsening of ABA safety or loss of efficacy was noted. Efficacy in the LTE was consistent with the DB period and was maintained to the end of the study. These 5-year data establish that SC ABA (125 mg/wk) has a consistent safety profile and durable efficacy for longterm treatment of patients with RA who had an inadequate response to MTX.

  9. Evaluation of efficacy, pharmacokinetics and tolerability of peptidomimetic aspartic proteinase inhibitors as cream formulation in experimental vaginal candidiasis.

    Science.gov (United States)

    De Bernardis, Flavia; Arancia, Silvia; Tringali, Giuseppe; Greco, Maria Cristina; Ragazzoni, Enzo; Calugi, Chiara; Trabocchi, Andrea; Sandini, Silvia; Graziani, Sofia; Cauda, Roberto; Cassone, Antonio; Guarna, Antonio; Navarra, Pierluigi

    2014-08-01

    It has been previously shown that the treatment with the two protease inhibitors APG12 and APG19 confers protection in a rat model of mucosal candidiasis; in this study, we examined whether these peptidomimetic inhibitors are also effective as a cream formulation in reducing Candida albicans vaginal infection. These efficacy studies were performed in a rat model of estrogen-dependent rat vaginitis by C. albicans on both azole-susceptible and azole-resistant C. albicans, and on both caspofungin-susceptible and caspofungin-resistant C. albicans strains. In vivo studies were also conducted in female albino rats and rabbits to obtain information about the safety, local tolerability and principal pharmacokinetics parameters of the two compounds. Both hit compounds showed remarkable results within the 48-h range as effective inhibitors of the infection, particularly causing rapid decay of vaginal C. albicans burden. Importantly, the two compounds showed marked acceleration of fungus clearance in the rats challenged with the fluconazole-resistant as well as with the capsofungin-resistant strain of C. albicans. Both compounds showed fast elimination rates when given by the intravenous route, and poor systemic absorption after intravaginal cream administration. Test drugs were also well tolerated in 7-day local tolerability experiments in the rabbit. © 2014 Royal Pharmaceutical Society.

  10. Safety and tolerability of transcranial direct current stimulation to stroke patients - A phase I current escalation study.

    Science.gov (United States)

    Chhatbar, Pratik Y; Chen, Rong; Deardorff, Rachael; Dellenbach, Blair; Kautz, Steven A; George, Mark S; Feng, Wuwei

    A prior meta-analysis revealed that higher doses of transcranial direct current stimulation (tDCS) have a better post-stroke upper-extremity motor recovery. While this finding suggests that currents greater than the typically used 2 mA may be more efficacious, the safety and tolerability of higher currents have not been assessed in stroke patients. We aim to assess the safety and tolerability of single session of up to 4 mA in stroke patients. We adapted a traditional 3 + 3 study design with a current escalation schedule of 1»2»2.5»3»3.5»4 mA for this tDCS safety study. We administered one 30-min session of bihemispheric montage tDCS and simultaneous customary occupational therapy to patients with first-ever ischemic stroke. We assessed safety with pre-defined stopping rules and investigated tolerability through a questionnaire. Additionally, we monitored body resistance and skin temperature in real-time at the electrode contact site. Eighteen patients completed the study. The current was escalated to 4 mA without meeting the pre-defined stopping rules or causing any major safety concern. 50% of patients experienced transient skin redness without injury. No rise in temperature (range 26°C-35 °C) was noted and skin barrier function remained intact (i.e. body resistance >1 kΩ). Our phase I safety study supports that single session of bihemispheric tDCS with current up to 4 mA is safe and tolerable in stroke patients. A phase II study to further test the safety and preliminary efficacy with multi-session tDCS at 4 mA (as compared with lower current and sham stimulation) is a logical next step. ClinicalTrials.gov Identifier: NCT02763826. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Efficacy and tolerance of systemic steroids in sciatica: a systematic review and meta-analysis.

    Science.gov (United States)

    Roncoroni, Cécile; Baillet, Athan; Durand, Marjorie; Gaudin, Philippe; Juvin, Robert

    2011-09-01

    The efficacy of pharmacological interventions in sciatica is limited and the use of systemic steroids is still controversial. We aimed at evaluating the efficacy and tolerance of systemic steroids in sciatica. A systematic literature search was performed in the Medline, Embase and Cochrane databases until February 2010. Randomized placebo-controlled trials evaluating the efficacy and the tolerance of systemic steroids in sciatica were included. Efficacy and tolerance were assessed using the relative risk (RR) and 95% CI with the inverse variance method (RR > 1 means that the event is more likely to occur in the steroid group). We explored the heterogeneity between the studies using subgroup analysis. Seven studies (383 patients) were included. The difference in the rate of responders between both groups was not statistically significant (RR = 1.22, 95% CI 0.96, 1.56). The rate of adverse events was 13.3% for the patients in the steroid group and 6.6% for the placebo group (RR = 2.01, 95% CI 1.06, 3.80). The number needed to harm was 20 (95% CI 10, ∞). Twenty (15.3%) patients in the steroid group and seven (5.7%) patients in the placebo group underwent surgery. A trend towards a higher requirement for spinal surgery was observed in the steroid group (RR = 1.14, 95% CI 0.74, 1.75). The methodological quality slightly influenced the results. We did not find any publication bias. Steroid efficacy is not superior to the placebo in sciatica, but it has more side effects. The tolerance : efficacy ratio indicates against the use of systemic steroids in sciatica.

  12. Quantitative evaluation of the fault tolerance of systems important to the safety of atomic power plants

    International Nuclear Information System (INIS)

    Malkin, S.D.; Sivokon, V.P.; Shmatkova, L.V.

    1989-01-01

    Fault tolerance is the property of a system to preserve its performance upon failures of its components. Thus, in nuclear-reactor technology one has only a qualitative evaluation of fault tolerance - the single-failure criterion, which does not enable one to compare and perform goal-directed design of fault-tolerant systems, and in the field of computer technology there are no generally accepted evaluations of fault tolerance that could be applied effectively to reactor systems. This paper considers alternative evaluations of fault tolerance and a method of comprehensive automated calculation of the reliability and fault tolerance of complex systems. The authors presented quantitative estimates of fault tolerance that develop the single-failure criterion. They have limiting processes that allow simple and graphical standardization. They worked out a method and a program for comprehensive calculation of the reliability and fault tolerance of systems of complex structure that are important to the safety of atomic power plants. The quantitative evaluation of the fault tolerance of these systems exhibits a degree of insensitivity to failures and shows to what extent their reliability is determined by a rigorously defined structure, and to what extent by the probabilistic reliability characteristics of the components. To increase safety, one must increase the fault tolerance of the most important systems of atomic power plants

  13. Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery

    OpenAIRE

    Jamdade, P. T.; Porwal, A.; Shinde, J. V.; Erram, S. S.; Kamat, V. V.; Karmarkar, P. S.; Bhagtani, K.; Dhorepatil, S.; Irpatgire, R.; Bhagat, H.; Kolte, S. S.; Shirure, P. A.

    2011-01-01

    Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain intensity differ...

  14. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  15. [Efficacy and safety of levofloxacin to non-gonorrheal urethritis].

    Science.gov (United States)

    Onodera, Shoichi; Onoe, Yasuhiko; Hosobe, Takahide; Kato, Tetsuro; Yoshida, Masaki

    2012-12-01

    We investigated the efficacy and safety of levofloxacin (LVFX) 500mg once a day in patients with non-gonorrheal urethritis. Men, aged 20 years or older, with urethritis symptoms, and detection of Chlamydia trachomatis (C. trachomatis) or Mycoplasma genitalium (M. genitalium) by a microbiological examination were eligible for this study. Patients were administered LVFX 500mg, orally, once a day and the dosage period was seven days. We assumed 22 patients for a safety and efficacy analysis. In 22 patients, 17 patients had urethritis with C. trachomatis, 4 patients urethritis with M. genitalium, and one patient mixed infection of C. trachomatis and M. genitalium. In the clinial study, the primary endpoint was set as the bacteriological eradication rate at two to four weeks after completion of treatment. The bacterial eradication rate in the urethritis was 86.4% (19/22). The bacterial eradication rate in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 94.1% (16/17), 50.0% (2/4), 100% (1/1), respectively. A significant difference was not recognized among the three groups. The clinical efficacy at two to four weeks after completion of treatment was 90.9% (20/22). The clinical efficacy rates in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 100% (17/17), 50.0% (2/4), 100% (1/1), respectively. The efficacy rate of urethritis with M. genitalium was significantly low. No adverse drug reactions were observed. These results suggest that once-a-day levofloxacin (500mg) is effective and safe treatment for non-gonorrheal urethritis.

  16. Efficacy and tolerance of lactitol supplementation for adult constipation: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Miller LE

    2014-07-01

    Full Text Available Larry E Miller,1 Julia Tennilä,2 Arthur C Ouwehand21Miller Scientific Consulting, Inc., Asheville, North Carolina, USA; 2Danisco Sweeteners Oy, Active Nutrition, Kantvik, FinlandBackground: Constipation is a common complaint in adults. Lactitol is an osmotic disaccharide laxative that increases fecal volume and stimulates peristalsis. In this paper, we present the first meta-analysis on the efficacy and tolerance of lactitol for adult constipation.Methods: We searched MEDLINE® and Embase, with no date or language restrictions, for studies of lactitol supplementation on adult constipation. A random-effects meta-analysis was performed on pre- to posttreatment changes in stool frequency and consistency with lactitol among all studies, as well as a comparison of efficacy and tolerance outcomes in randomized controlled trials (RCTs of lactitol versus lactulose.Results: A total of eleven studies representing 663 distinct patients were included in the final analysis, including five single-arm studies, four RCTs comparing lactitol with lactulose, one RCT comparing lactitol with placebo, and one nonrandomized controlled trial comparing lactitol with stimulant laxatives. Weekly stool frequency was significantly increased with lactitol compared with baseline (standardized mean difference [SMD]: 1.56, P<0.001. Stool consistency also improved over the supplementation period with lactitol (SMD: 1.04, P<0.001. Approximately one-third of patients experienced an adverse event; however, symptoms were generally mild and rarely (5% resulted in study withdrawal. In RCTs of lactitol versus lactulose, lactitol was slightly more effective than lactulose in increasing weekly stool frequency (SMD: 0.19, P=0.06. No statistically significant differences between lactitol and lactulose were identified in any other efficacy or tolerance outcome. Lactitol demonstrated favorable efficacy and tolerance in individual studies when compared to stimulant laxatives and placebo

  17. [Efficacy and tolerance of fenspiride in adult patients with acute respiratory tract infections].

    Science.gov (United States)

    Płusa, T; Nawacka, D

    1998-12-01

    Fenspiride is an antiinflammatory drug targeted for the respiratory tract. In our study clinical efficacy and tolerance of drug were evaluated in 392 adult patients with acute respiratory tract infections. According to clinical criteria all observed symptoms were classified as mild, moderate and severe. The most of observed patients were included into moderate symptom score. Cough and nose obturation were dominant symptoms. All noticed changes in the upper respiratory tract were decreased after fenspiride therapy in 7 days trial. In 168 observed patients systemic and in 60 local acting antibiotics were successfully applied. Excellent tolerance of fenspiride was documented in 59% and good tolerance --in 34% of patients. Observed adverse reactions were classified as mild and in 20 patients fenspiride was rejected. Authors suggest that fenspiride therapy is save and successful in patient with acute respiratory tract infection. Good results in patients with bronchitis in decreasing of bronchospasm indicate fenspiride as a good tool in bronchial infection.

  18. Efficacy and Tolerability of Tamsulosin 0.4 mg in Patients with Symptomatic Benign Prostatic Hyperplasia

    OpenAIRE

    Chung, Jae-Wook; Choi, Seock Hwan; Kim, Bum Soo; Kim, Tae-Hwan; Yoo, Eun Sang; Kim, Chun Il; Lee, Kyung Seop; Kwon, Tae Gyun

    2011-01-01

    Purpose To evaluate the efficacy and tolerability of tamsulosin 0.4 mg once daily in Korean patients with symptomatic benign prostatic hyperplasia (BPH) and investigate whether tamsulosin 0.4 mg can improve symptoms in patients with refractory lower urinary tract symptoms (LUTS) who were previously receiving tamsulosin 0.2 mg once daily. Materials and Methods A total of 116 patients from 3 urology centers participated. All study subjects entered a nonblind phase consisting of 8 weeks of tamsu...

  19. Efficacy and Safety of Antiintegrin Antibody for Inflammatory Bowel Disease

    Science.gov (United States)

    Lin, Lianjie; Liu, Xiang; Wang, Dongxu; Zheng, Changqing

    2015-01-01

    Abstract We sought to evaluate the safety and efficacy of available biologics that inhibit T-cell migration by blocking α4β7 integrins in inflammatory bowel diseases. The aim of this study is to evaluate whether Crohn disease (CD) patients receiving either vedolizumab or natalizumab have any different effect in CD Activity Index (CDAI). Using Medline, Excerpta Medica dataBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar until October 31, 2013, we identified 10 studies examining the safety and efficacy of specific integrin inhibitors—vedolizumab, which targets an epitope comprising the α4β7 heterodimer; natalizumab, which recognizes the α4 integrin subunit; etrolizumab, which is specific for the β7 subunit—in the treatment of CD and ulcerative colitis (UC). CD patients receiving either vedolizumab or natalizumab demonstrated a modest increase in remission rate, when compared with that of the placebo group. Further, although both treatments reduced the CDAI slightly, the observed clinical response was less robust than that of the remission rate. UC patients treated with vedolizumab and natalizumab were found to show more prominent increases in both remission and clinical response, compared with placebo, than patients with CD. Etrolizumab, however, was not found to significantly affect either response or remission rates in UC patients. Biologics targeting integrins show promise as therapeutics in the treatment of inflammatory bowel disease in patients who are either nonresponsive or intolerant to traditional approaches, though further research is necessary to optimize treatment efficacies. PMID:25761174

  20. Safety and Tolerability of Transitioning from Cangrelor to Ticagrelor in Patients Who Underwent Percutaneous Coronary Intervention.

    Science.gov (United States)

    Badreldin, Hisham A; Carter, Danielle; Cook, Bryan M; Qamar, Arman; Vaduganathan, Muthiah; Bhatt, Deepak L

    2017-08-01

    The 3 phase 3 CHAMPION (Cangrelor vs Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials collectively demonstrated the safety of transitioning from cangrelor, a potent, parenteral rapidly-acting P2Y 12 inhibitor, to clopidogrel in patients who underwent percutaneous coronary intervention (PCI). However, variation in timing of therapy, site-specific binding, and drug half-lives may theoretically complicate switching to other oral P2Y 12 inhibitors. Since regulatory approval, limited data are available regarding the "real-world" safety and tolerability of transitioning to these more potent oral P2Y 12 antagonists. From November 2015 to January 2017, we evaluated the clinical profiles and efficacy and safety outcomes in cangrelor-treated patients who underwent PCI transitioned to clopidogrel (n = 42) or ticagrelor (n = 82) at a large, tertiary care center. Most patients receiving cangrelor underwent PCI with a drug-eluting stent for acute coronary syndrome via a radial approach in the background of unfractionated heparin. Stent thrombosis within 48 hours was rare and occurred in 1 patient treated with ticagrelor. Global Use of Strategies to Open Occluded Coronary Arteries-defined bleeding occurred in 20% of patients switched to ticagrelor and 29% of patients switched to clopidogrel, but none were severe or life-threatening. In conclusion, rates of stent thrombosis and severe/life-threatening bleeding were low and comparable with those identified in the CHAMPION program, despite use of more potent oral P2Y 12 inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Safety and efficacy of Labisia pumila containing products

    Directory of Open Access Journals (Sweden)

    Muhammad Syafiq Saleh

    2016-01-01

    Full Text Available Labisia pumila is a traditional medicinal plant which has wide therapeutic application including induction of labor and treatment of dysentery, dysmenorrhea and gonorrhea. We aimed for systematic review of the efficacy andsafety of L. pumila extract or its other commercial products availabe in Malaysian market. The marketed 500 mg capsule is composed of 40 mg L. pumila, 10 mg C. caudatum extract and 450 mg excipient. The commercial products did not follow the registration guidelines of Malaysian National Pharmaceutical Control Bureau (NPCB and advertisement guidelines of Malaysian Advertisement Board. Randomized, placebo controlled clinical trials reported the safe consumpotion of L. pumila water extract on postmanoposal women. Information on the efficacy and safety of commercial products are not sufficiently available. Many unregistered products (mostly capsule form are flooded in Malaysian market without having scientific information. Consumption of those products may seriously impair the health of the people.

  2. Premarket safety and efficacy studies for ADHD medications in children.

    Directory of Open Access Journals (Sweden)

    Florence T Bourgeois

    Full Text Available Attention-deficit hyperactivity disorder (ADHD is a chronic condition and pharmacotherapy is the mainstay of treatment, with a variety of ADHD medications available to patients. However, it is unclear to what extent the long-term safety and efficacy of ADHD drugs have been evaluated prior to their market authorization. We aimed to quantify the number of participants studied and their length of exposure in ADHD drug trials prior to marketing.We identified all ADHD medications approved by the Food and Drug Administration (FDA and extracted data on clinical trials performed by the sponsor and used by the FDA to evaluate the drug's clinical efficacy and safety. For each ADHD medication, we measured the total number of participants studied and the length of participant exposure and identified any FDA requests for post-marketing trials.A total of 32 clinical trials were conducted for the approval of 20 ADHD drugs. The median number of participants studied per drug was 75 (IQR 0, 419. Eleven drugs (55% were approved after <100 participants were studied and 14 (70% after <300 participants. The median trial length prior to approval was 4 weeks (IQR 2, 9, with 5 (38% drugs approved after participants were studied <4 weeks and 10 (77% after <6 months. Six drugs were approved with requests for specific additional post-marketing trials, of which 2 were performed.Clinical trials conducted for the approval of many ADHD drugs have not been designed to assess rare adverse events or long-term safety and efficacy. While post-marketing studies can fill in some of the gaps, better assurance is needed that the proper trials are conducted either before or after a new medication is approved.

  3. Efficacy and safety of statin therapy in children with familial hypercholesterolemia - A randomized, double-blind, placebo-controlled trial with simvastatin

    NARCIS (Netherlands)

    de Jongh, Saskia; Ose, Leiv; Szamosi, Tamás; Gagné, Claude; Lambert, M.; Scott, Russell; Perron, P.; Dobbelaere, Dries; Saborio, M.; Tuohy, Mary B.; Stepanavage, Michael; Sapre, Aditi; Gumbiner, Barry; Mercuri, Michele; van Trotsenburg, A. S. Paul; Bakker, Henk D.; Kastelein, John J. P.

    2002-01-01

    Background-A multicenter, randomized, double-blind, placebo-controlled study was conducted to evaluate LDL cholesterol-lowering efficacy, overall safety, and tolerability and the influence on growth and pubertal development of simvastatin in a large cohort of boys and girls with heterozygous

  4. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study

    NARCIS (Netherlands)

    Kastelein, John J. P.; Nissen, Steven E.; Rader, Daniel J.; Hovingh, G. Kees; Wang, Ming-Dauh; Shen, Tong; Krueger, Kathryn A.

    2016-01-01

    Aims The objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of

  5. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine

    DEFF Research Database (Denmark)

    Dodick, David W; Goadsby, Peter J; Silberstein, Stephen D

    2014-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo-contro...

  6. Safety and Efficacy of Paliperidone Extended-Release in Acute and Maintenance Treatment of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Edoardo Spina

    2011-01-01

    Full Text Available Paliperidone, the major active metabolite of risperidone, is a second-generation antipsychotic that has been developed as an extended-release (ER tablet formulation that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and constant drug delivery. Paliperidone ER has demonstrated efficacy in the reduction of acute schizophrenia symptoms in 6-week, placebo-controlled, double-blind trials and clinical benefits were maintained in the longer-term according to extension studies of up to 52 weeks in duration. Compared with quetiapine, paliperidone ER was associated with a more rapid symptom improvement. In addition, it was more effective than placebo in the prevention of symptom recurrence. Paliperidone ER is generally well tolerated with a predictable adverse event profile. Like risperidone, it is associated with a dose-dependent risk of extrapyramidal symptoms and prolactin elevation. Short-and longer-term studies have indicated a low liability for paliperidone ER to cause metabolic (ie, weight gain, hyperglycaemia and lipid dysregulation or cardiovascular adverse effects. Available safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of paliperidone ER in the treatment of schizophrenia in relation to other currently available second-generation antipsychotics, particularly risperidone.

  7. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Délia Szok

    2015-07-01

    Full Text Available Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.

  8. [Safety and efficacy of ketamine for pain relief].

    Science.gov (United States)

    Niesters, Marieke; Dahan, Albert; van Kleef, Maarten

    2016-01-01

    Intravenous ketamine treatment is frequently used for the management of chronic pain, especially in those patients who do not benefit from other therapies. In this commentary we discuss the efficacy of ketamine for relief of chronic pain and ketamine's safety profile. A review of the literature indicates that only a few studies show that intravenous ketamine has analgesic effects that persist beyond the infusion period, an effect that occurs in about two-thirds of patients. Ketamine has multiple safety issues, ranging from psychotomimetic and schizotypal symptoms, sympathetic stimulation, tachycardia and hypertension, and damage to the liver and the urogenital tract. Damage to the urogenital tract seems to be restricted to individuals who chronically abuse ketamine. We indicate the need for large randomized trials in which ketamine is compared with an 'active' placebo.

  9. Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

    Directory of Open Access Journals (Sweden)

    Sandeep Devabhakthuni

    2013-01-01

    Full Text Available The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects.

  10. Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

    Science.gov (United States)

    Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

    2017-07-01

    Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

  11. Efficacy and safety of superficial chemical peeling in treatment of active acne vulgaris.

    Science.gov (United States)

    Al-Talib, Hassanain; Al-Khateeb, Alyaa; Hameed, Ayad; Murugaiah, Chandrika

    2017-01-01

    Acne vulgaris is an extremely common condition affecting the pilosebaceous unit of the skin and characterized by presence of comedones, papules, pustules, nodules, cysts, which might result in permanent scars. Acne vulgaris commonly involve adolescents and young age groups. Active acne vulgaris is usually associated with several complications like hyper or hypopigmentation, scar formation and skin disfigurement. Previous studies have targeted the efficiency and safety of local and systemic agents in the treatment of active acne vulgaris. Superficial chemical peeling is a skin-wounding procedure which might cause some potentially undesirable adverse events. This study was conducted to review the efficacy and safety of superficial chemical peeling in the treatment of active acne vulgaris. It is a structured review of an earlier seven articles meeting the inclusion and exclusion criteria. The clinical assessments were based on pretreatment and post-treatment comparisons and the role of superficial chemical peeling in reduction of papules, pustules and comedones in active acne vulgaris. This study showed that almost all patients tolerated well the chemical peeling procedures despite a mild discomfort, burning, irritation and erythema have been reported; also the incidence of major adverse events was very low and easily manageable. In conclusion, chemical peeling with glycolic acid is a well-tolerated and safe treatment modality in active acne vulgaris while salicylic acid peels is a more convenient for treatment of darker skin patients and it showed significant and earlier improvement than glycolic acid.

  12. Five-grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

    DEFF Research Database (Denmark)

    Halken, Susanne; Agertoft, Lone; Seidenberg, Jürgen

    2010-01-01

    The efficacy and safety of five-grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and o...

  13. Safety and tolerability of zoledronic acid and other bisphosphonates in osteoporosis management

    Directory of Open Access Journals (Sweden)

    Luca Dalle Carbonare

    2010-08-01

    Full Text Available Luca Dalle Carbonare, Mirko Zanatta, Adriano Gasparetto, Maria Teresa ValentiClinic of Internal Medicine D, Department of Medicine, University of Verona, ItalyAbstract: Bisphosphonates (BPs are widely used in the treatment of postmenopausal ­osteoporosis and other metabolic bone diseases. They bind strongly to bone matrix and reduce bone loss through inhibition of osteoclast activity. They are classified as nitrogen- and non-nitrogen-containing bisphosphonates (NBPs and NNBPs, respectively. The former inhibit farnesyl diphosphate synthase while the latter induce the production of toxic analogs of adenosine triphosphate. These mechanisms of action are associated with different antifracture efficacy, and NBPs show the most powerful action. Moreover, recent evidence indicates that NBPs can also stimulate osteoblast activity and differentiation. Several randomized control trials have demonstrated that NBPs significantly improve bone mineral density, suppress bone turnover, and reduce the incidence of both vertebral and nonvertebral fragility fractures. Although they are generally considered safe, some side effects are reported (esophagitis, acute phase reaction, hypocalcemia, uveitis, and compliance with therapy is often inadequate. In particular, gastrointestinal discomfort is frequent with the older daily oral administrations and is responsible for a high proportion of discontinuation. The most recent weekly and monthly formulations, and in particular the yearly infusion of zoledronate, significantly improve persistence with treatment, and optimize clinical, densitometric, and antifracture outcomes.Keywords: bisphosphonates, osteoporosis, safety, tolerability, zoledronic acid

  14. Efficacy and safety of adalimumab in ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Mounach A

    2014-08-01

    Full Text Available Aziza Mounach, Abdellah El MaghraouiRheumatology Department, Military Hospital Mohammed V, Rabat, MoroccoAbstract: Ankylosing spondylitis (AS is the most common and most severe subtype of spondyloarthritis. It also may be an outcome of any of the other spondyloarthritis subtypes. AS preferentially affects the sacroiliac joints and the tip of the column, with a tendency to later ankylosis. Peripheral joints, enthesis, and other extra-articular involvement may be observed. Tumor necrosis factor (TNF inhibitors are now well-established, effective drugs in the treatment of AS symptoms. Adalimumab, which is a fully human monoclonal antibody that binds to and neutralizes TNF, has demonstrated efficacy in treating AS symptoms, including axial involvement, peripheral arthritis, enthesitis, uveitis, gut involvement, and psoriasis. Furthermore, adalimumab has showed an overall acceptable safety profile. In this paper, we review the efficacy and safety profile of adalimumab in the treatment of AS, and discuss its differences from the other anti-TNF drugs reported in the literature.Keywords: ankylosing spondylitis, spondyloarthritis, adalimumab, tumor necrosis factor-α

  15. Animal models for microbicide safety and efficacy testing.

    Science.gov (United States)

    Veazey, Ronald S

    2013-07-01

    Early studies have cast doubt on the utility of animal models for predicting success or failure of HIV-prevention strategies, but results of multiple human phase 3 microbicide trials, and interrogations into the discrepancies between human and animal model trials, indicate that animal models were, and are, predictive of safety and efficacy of microbicide candidates. Recent studies have shown that topically applied vaginal gels, and oral prophylaxis using single or combination antiretrovirals are indeed effective in preventing sexual HIV transmission in humans, and all of these successes were predicted in animal models. Further, prior discrepancies between animal and human results are finally being deciphered as inadequacies in study design in the model, or quite often, noncompliance in human trials, the latter being increasingly recognized as a major problem in human microbicide trials. Successful microbicide studies in humans have validated results in animal models, and several ongoing studies are further investigating questions of tissue distribution, duration of efficacy, and continued safety with repeated application of these, and other promising microbicide candidates in both murine and nonhuman primate models. Now that we finally have positive correlations with prevention strategies and protection from HIV transmission, we can retrospectively validate animal models for their ability to predict these results, and more importantly, prospectively use these models to select and advance even safer, more effective, and importantly, more durable microbicide candidates into human trials.

  16. Efficacy and dermal tolerance of a novel alcohol-based skin antiseptic in horses.

    Science.gov (United States)

    Tannahill, Victoria J; Cogan, Tristan; Allen, Kate; Acutt, Elizabeth; Busschers, Evita

    2018-04-14

    To determine the efficacy and dermal tolerance of a novel alcohol-based skin antiseptic (ABSA) in horses. Experimental study. Systemically healthy horses (n = 25) with no history or clinical signs of skin disease. Four clipped sites on the abdomen were randomly assigned to a skin preparation protocol: saline (negative control; NC), chlorhexidine gluconate followed by isopropyl alcohol (positive control; PC), saline followed by the ABSA (ABSA A), or a commercially available horse shampoo followed by the ABSA (ABSA B). Microbiological swabs were obtained from each site and cultured on MacConkey and mannitol salt agar plates. Colony-forming units were counted 18-24 hours later. All sites were scored for signs of skin reaction before, immediately after, 1 hour after, and 24 hours after skin preparation. The PC, ABSA A, and ABSA B methods reduced skin microbial burden compared with the NC method (P horses required veterinary treatment. The ABSA preparations tested in this study were as effective and well tolerated as a chlorhexidine gluconate-based method, but required less time in healthy horses. The ABSA tested here provides an efficacious, fast-acting, and well-tolerated alternative to achieve skin antisepsis in healthy horses. These results justify further investigation in clinical cases. © 2018 The American College of Veterinary Surgeons.

  17. Efficacy and safety of febuxostat in elderly female patients

    Directory of Open Access Journals (Sweden)

    Mizuno T

    2014-09-01

    Full Text Available Tomohiro Mizuno,1,2 Takahiro Hayashi,3 Sayo Hikosaka,1 Yuka Shimabukuro,1 Maho Murase,1 Kazuo Takahashi,2 Hiroki Hayashi,2 Yukio Yuzawa,2 Tadashi Nagamatsu,1 Shigeki Yamada3 1Department of Analytical Pharmacology, Graduate School of Pharmacy, Meijo University, Nagoya, Japan; 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, Japan; 3Department of Clinical Pharmacy, School of Medicine, Fujita Health University, Toyoake, Japan Background: Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyper­uricemia remain unclear.Objective: The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients.Methods: We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results: We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53 and female (n=29 groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days than in the male group (71 days. There were no significant differences in adverse events between the 2 groups.Conclusion: Our

  18. Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

    Directory of Open Access Journals (Sweden)

    Marvin Omar Delgado-Guay

    2010-11-01

    Full Text Available Marvin Omar Delgado-GuayDivision of Geriatrics and Palliative Medicine, The University of Texas, Medical School at Houston, Houston, TX, USAAbstract: More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF in patients with cancer pain. Literature was identified through searches of Medline (PubMed. Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients.Keywords: fentanyl buccal soluble film, cancer pain

  19. Efficacy and safety of fentanyl buccal for cancer pain management by administration through a soluble film: an update

    International Nuclear Information System (INIS)

    Delgado-Guay, Marvin Omar

    2010-01-01

    More than half of patients receiving prescription medicine for cancer pain have been reported to experience inadequate pain relief or breakthrough pain. Buccal administration can deliver lipophilic opioids rapidly to the systemic circulation through the buccal mucosa, limiting gastrointestinal motility and first-pass metabolism. This review updates the safety and efficacy of fentanyl buccal soluble film (FBSF) in patients with cancer pain. Literature was identified through searches of Medline (PubMed). Search terms included combinations of the following: cancer pain, fentanyl, fentanyl buccal soluble film, pharmacology, kinetics, safety, efficacy and toxicity. FBSF is an oral transmucosal form of fentanyl citrate developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. Studies have shown that it is well tolerated in the oral cavity, with adequate bioavailability and safety in cancer patients. Further studies are warranted to evaluate, in comparison with other short-acting opioids, its efficacy in the management of breakthrough cancer pain, its addictive potential and its economic impact in cancer patients

  20. Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study.

    Science.gov (United States)

    Kunz, M; Urosevic-Maiwald, M; Goldinger, S M; Frauchiger, A L; Dreier, J; Belloni, B; Mangana, J; Jenni, D; Dippel, M; Cozzio, A; Guenova, E; Kamarachev, J; French, L E; Dummer, R

    2016-02-01

    Patients with severe oral lichen planus refractory to standard topical treatment currently have limited options of therapy suitable for long-term use. Oral alitretinoin (9-cis retinoic acid) was never systematically investigated in clinical trials, although case reports suggest its possible efficacy. To assess the efficacy and safety of oral alitretinoin taken at 30 mg once daily for up to 24 weeks in the treatment of severe oral lichen planus refractory to standard topical therapy. We conducted a prospective open-label single arm pilot study to test the efficacy and safety of 30 mg oral alitretinoin once daily for up to 24 weeks in severe oral lichen planus. Ten patients were included in the study. Primary end point was reduction in signs and symptoms measured by the Escudier severity score. Secondary parameters included pain and quality of life scores. Safety parameters were assessed during a follow-up period of 5 weeks. A substantial response at the end of treatment, i.e. >50% reduction in disease severity measured by the Escudier severity score, was apparent in 40% of patients. Therapy was well tolerated. Adverse events were mild and included headache, mucocutaneous dryness, musculoskeletal pain, increased thyroid-stimulating hormone and dyslipidaemia. Alitretinoin given at 30 mg daily reduced disease severity of severe oral lichen planus in a substantial proportion of patients refractory to standard treatment, was well tolerated and may thus represent one therapeutic option for this special group of patients. © 2015 European Academy of Dermatology and Venereology.

  1. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Science.gov (United States)

    Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

    2017-01-01

    Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

  2. Efficacy and Safety of Human Retinal Progenitor Cells

    Science.gov (United States)

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  3. Long-term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease.

    Science.gov (United States)

    Bakris, George L; Zhao, Lin; Kupfer, Stuart; Juhasz, Attila; Hisada, Michie; Lloyd, Eric; Oparil, Suzanne

    2018-04-01

    An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability. ©2018 Wiley Periodicals, Inc.

  4. Deferasirox: appraisal of safety and efficacy in long-term therapy

    Directory of Open Access Journals (Sweden)

    Chaudhary P

    2013-08-01

    Full Text Available Preeti Chaudhary, Vinod PullarkatJane Ann Nohl Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USAAbstract: Deferasirox is a once-daily, oral iron chelator that is widely used in the management of patients with transfusional hemosiderosis. Several Phase II trials along with their respective extension studies as well as a Phase III trial have established the efficacy and safety of this novel agent in transfusion-dependent patients with β-thalassemia, sickle-cell disease and bone marrow-failure syndromes, including myelodysplastic syndrome and aplastic anemia. Data from various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes serum ferritin levels and liver iron concentration, while a dose of 30–40 mg/kg/day reduces these parameters and achieves negative iron balance in red cell transfusion-dependent patients with iron overload. Across various pivotal clinical trials, deferasirox was well tolerated, with the most common adverse events being gastrointestinal disturbances, skin rash, nonprogressive increases in serum creatinine, and elevations in liver enzyme levels. Longer-term extension studies have also confirmed the efficacy and safety of deferasirox. However, it is essential that patients on deferasirox therapy are monitored regularly to ensure timely management for any adverse events that may occur with long-term therapy.Keywords: deferasirox, iron overload, thalassemia, sickle-cell disease, myelodysplastic syndrome

  5. Profile of vildagliptin in type 2 diabetes: efficacy, safety, and patient acceptability

    Directory of Open Access Journals (Sweden)

    Pan CY

    2013-05-01

    Full Text Available CY Pan,1 XL Wang21Chinese PLA General Hospital, Beijing, People's Republic of China; 2Medical Affairs Department, Beijing Novartis Pharma Co, Ltd, Beijing, People's Republic of ChinaAbstract: Vildagliptin is a selective and potent dipeptidyl peptidase-4 inhibitor that improves glycemic control by inhibiting the degradation of both endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with type 2 diabetes. Clinical evidence has proven that it effectively decreases hemoglobin A1c with a low risk of hypoglycemia and is weight neutral. The addition of vildagliptin to metformin improves glucose control and significantly reduces gastrointestinal adverse events, particularly in patients inadequately controlled with metformin monotherapy. Its long-term advantages include preservation of β-cell function, reduction in total cholesterol, decrease in fasting lipolysis in adipose tissue, and triglyceride storage in non-fat tissues. Vildagliptin is well tolerated with a low incidence of AEs, and it does not increase the risk of cardiovascular/cerebrovascular (CCV events. It can be taken before or after meals, and has little drug interaction, thus it will be well accepted.Keywords: dipeptidyl peptidase-4, incretin hormones, vildagliptin, efficacy, safety, patient acceptability

  6. Safety and clinical efficacy of some radiation-sterilized medical products and pharmaceuticals

    International Nuclear Information System (INIS)

    Kulkarni, R.D.; Gopal, N.G.S.

    1975-01-01

    Medical products and pharmaceuticals must conform to certain minimum physico-chemical microbiological and biological requirements. The biological requirements comprise principally testing for toxicity, safety, and pyrogens. Besides the above-mentioned criteria, there are two other important characteristics, viz. clinical efficacy and tolerance in animal and/or human beings. These latter requirements, expected from the final product released for general human use, are not carried out routinely. In the present-day pharmaceutical and medical technology, numerous mew products are appearing, many of them requiring radiation sterilization as they are not stable towards the other conventional methods of sterilization. While the post-irradiation physicochemical changes in a product may not be significant, the bio-availability or biological activity of the product may be affected to a more significant extent. Some evidence of this has recently been reported. Hence, it is desirable to carry out studies on safety as well as clinical efficacy on irradiated products. This paper describes some studies on plastic-based medical products, a pharmaceutical raw material, a typical infusion fluid such as normal saline, antibiotics and their ointments. (author)

  7. 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...

  8. Enteral feeding pumps: efficacy, safety, and patient acceptability

    Directory of Open Access Journals (Sweden)

    White H

    2014-08-01

    Full Text Available Helen White, Linsey King Nutrition and Dietetic Group, School of Health and Wellbeing, Faculty Health and Social Science, Leeds Metropolitan University, Leeds, United Kingdom Abstract: Enteral feeding is a long established practice across pediatric and adult populations, to enhance nutritional intake and prevent malnutrition. Despite recognition of the importance of nutrition within the modern health agenda, evaluation of the efficacy of how such feeds are delivered is more limited. The accuracy, safety, and consistency with which enteral feed pump systems dispense nutritional formulae are important determinants of their use and acceptability. Enteral feed pump safety has received increased interest in recent years as enteral pumps are used across hospital and home settings. Four areas of enteral feed pump safety have emerged: the consistent and accurate delivery of formula; the minimization of errors associated with tube misconnection; the impact of continuous feed delivery itself (via an enteral feed pump; and the chemical composition of the casing used in enteral feed pump manufacture. The daily use of pumps in delivery of enteral feeds in a home setting predominantly falls to the hands of parents and caregivers. Their understanding of the use and function of their pump is necessary to ensure appropriate, safe, and accurate delivery of enteral nutrition; their experience with this is important in informing clinicians and manufacturers of the emerging needs and requirements of this diverse patient population. The review highlights current practice and areas of concern and establishes our current knowledge in this field. Keywords: nutrition, perceptions, experience

  9. Assessment of Tolerability and Safety of Monocomponent Complementary Food Products in the Diet of Infants With Risk for Allergic Diseases

    Directory of Open Access Journals (Sweden)

    L. S. Namazova-Baranova

    2016-01-01

    Full Text Available Background: Children with burdened allergological history and/or having preliminary allergy manifestations need the effective prevention of allergy from the first months of life.Objective: Our aim was to assess the tolerability, safety, and efficacy of monocomponent complementary food products in the diet of infants with high risk for allergic diseases.Methods: Tolerability, safety, and efficacy of monocomponent complementary food products (vegetable puree, fruit juices, and after 6 months — meat sauce were studied in a singlecentre, prospective, comparative study. The symptoms of indigestion, skin allergy symptoms were registered, the results of coprological research and immunogenicity of complementary food products were assessed.Results: The study included 200 children in the age from 5 months from the risk group of allergy developing. Children were divided into 4 groups of 50 people. It was found that complementary food products were well tolerated and assimilated by children, did not cause skin and gastrointestinal allergic reactions in healthy children with risk of allergy developing. Food antigens of complementary food components (pumpkin, rabbit meat, turkey meat, apples, pears, plums were characterized by low immunogenicity: the level of specific IgE to the specified products did not change in blood serum and remained at a low level at the beginning and at the end of the study (ranging from 0.01 to 0.03 kE/l.Conclusion: Studied complementary food products (vegetable-, fruit- and meat-based can be used in the diet of children with high risk for allergy.

  10. Understanding Risk Tolerance and Building an Effective Safety Culture

    Science.gov (United States)

    Loyd, David

    2018-01-01

    Estimates range from 65-90 percent of catastrophic mishaps are due to human error. NASA's human factors-related mishaps causes are estimated at approximately 75 percent. As much as we'd like to error-proof our work environment, even the most automated and complex technical endeavors require human interaction... and are vulnerable to human frailty. Industry and government are focusing not only on human factors integration into hazardous work environments, but also looking for practical approaches to cultivating a strong Safety Culture that diminishes risk. Industry and government organizations have recognized the value of monitoring leading indicators to identify potential risk vulnerabilities. NASA has adapted this approach to assess risk controls associated with hazardous, critical, and complex facilities. NASA's facility risk assessments integrate commercial loss control, OSHA (Occupational Safety and Health Administration) Process Safety, API (American Petroleum Institute) Performance Indicator Standard, and NASA Operational Readiness Inspection concepts to identify risk control vulnerabilities.

  11. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Senabre-Gallego JM

    2013-09-01

    Full Text Available José Miguel Senabre-Gallego,1 Carlos Santos-Ramirez,2 Gregorio Santos-Soler,1 Esteban Salas-Heredia,1 Mabel Sánchez-Barrioluengo,3 Xavier Barber,4 José Rosas1 On behalf of the AIRE-MB group 1Rheumatology, Hospital Marina Baixa, Villajoyosa, 2Rheumatology, Hospital Marina Salud, Denia, 3INGENIO (Instituto de Gestión de la Inovación y del Conocimiento (CSIC [Consejo Superior de Investigaciones Científicas]-UPV [Universidad Politécnica de Valencia], Universitat Politècnica de València, Valencia, 4CIO (Centro de Investigación Operativa-UMH (Universidad Miguel Hernández, Universidad Miguel Henández, Elche, Spain Abstract: To date, anti-tumor necrosis factor alfa (anti-TNF-α therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of

  12. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    is linked to a different set of circumstances than the ones suggested by existing models in contemporary democratic theory. Reorienting the discussion of tolerance, the book raises the question of how to disclose new possibilities within our given context of affect and perception. Once we move away from......Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated...... by the desire to experiment and to become otherwise. The objective is to discuss what gets lost, conceptually as well as politically, when we neglect the subsistence of active tolerance within other practices of tolerance, and to develop a theory of active tolerance in which tolerance's mobilizing character...

  13. The Tolerability and Efficacy of Rapid Infliximab Infusions in Patients with Inflammatory Bowel Disease.

    Science.gov (United States)

    Qazi, Taha; Shah, Bhavesh; El-Dib, Mohammed; Farraye, Francis A

    2016-02-01

    Few studies have assessed the loss of efficacy or patient and caregiver satisfaction with rapid infliximab infusions. The aim of this study is to assess the tolerability, loss of efficacy and to describe the impact on resource utilization and patient satisfaction in rapid infliximab infusions. Subjects with inflammatory bowel disease receiving rapid infliximab infusions were included in the study. Subjects received maintenance infusions from June 2011 to June 2013. Incidence of adverse reactions and the total number of rapid infliximab infusions were recorded. Efficacy was compared to published studies evaluating the long-term efficacy of infliximab infusions. Patient satisfaction was addressed through a survey following the implementation of the rapid infusion protocol. Seventy-five subjects with IBD were included in the study. Five hundred and twenty-two rapid infliximab infusions were provided to patients. There were no acute or delayed infusion reactions. Ten subjects (13 %) required either a dose escalation or interval adjustment between infliximab infusions. A majority of patients reported increased satisfaction with 1-h infliximab infusions, and 97 % of surveyed patients opted to continue rapid infusions. The rapid infliximab infusion protocol increased infusion unit efficiency by increasing capacity by 15 %. Cost savings in the elimination of nursing time translated to approximately $108,150 savings at our institution. Rapid infliximab infusions do not appear to increase the risk of loss of response compared to historical studies of long-term infliximab efficiency. A rapid infliximab infusion protocol improved efficiency in our infusion unit and increased patient and nursing satisfaction.

  14. Efficacy and safety of intravenous fentanyl administered by ambulance personnel

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

    2016-01-01

    BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

  15. A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy

    Directory of Open Access Journals (Sweden)

    Manyando Christine

    2012-05-01

    Full Text Available Abstract Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO recommends artemisinin-based combination therapy (ACT to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the

  16. Enhanced Maritime Safety through Diagnosis and Fault Tolerant Control

    DEFF Research Database (Denmark)

    Blanke, Mogens

    2001-01-01

    Faults in steering, navigation instruments or propulsion machinery are serious on a marine vessel since the consequence could be loss of maneuvering ability, and imply risk of damage to vessel personnel or environment. Early diagnosis and accomodation of faults could enhance safety. Fault...... of properties of a falty system; means to determine remedial actions. The paper illustrates the techniques by two marine examples, sensor fusion for automatic steering and control of the main engine....

  17. Bitter melon (Momordica charantia): a review of efficacy and safety.

    Science.gov (United States)

    Basch, Ethan; Gabardi, Steven; Ulbricht, Catherine

    2003-02-15

    The pharmacology, clinical efficacy, adverse effects, drug interactions, and place in therapy of bitter melon are described. Bitter melon (Momordica charantia) is an alternative therapy that has primarily been used for lowering blood glucose levels in patients with diabetes mellitus. Components of bitter melon extract appear to have structural similarities to animal insulin. Antiviral and antineoplastic activities have also been reported in vitro. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however. Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches. Bitter melon may have additive effects when taken with other glucose-lowering agents. Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.

  18. Efficacy and safety of methimazole ointment for patients with hyperthyroidism.

    Science.gov (United States)

    Wu, Xi; Liu, Hong; Zhu, Xixing; Shen, Jun; Shi, Yongquan; Liu, Zhimin; Gu, Mingjun; Song, Zhimin

    2013-11-01

    Oral methimazole has been widely used to treat hyperthyroidism, but its usage is restricted by its adverse systemic effects. The aim of this study was to investigate the efficacy and safety of methimazole ointment for the treatment of hyperthyroidism. One hundred forty-four subjects with hyperthyroidism were initially enrolled. These patients were initially divided into two groups and given the following treatments for 12 weeks: patients in group A received 5% methimazole ointment applied to the skin around the thyroid and an oral placebo; and patients in group B received methimazole tablets and placebo ointment. One hundred thirty-one subjects were included in the final analysis. Therapeutic efficacy was assessed via the levels of free triiodothyronine and thyroxine in the serum and by biweekly monitoring of the symptoms of thyrotoxicosis. Adverse effects were recorded. Fifty-nine (89.40%) patients in group A and 57 (87.69%) patients in group B were euthyroid and experienced alleviation of thyrotoxicosis symptoms (complete control; p>0.05). The median times required to achieve complete control for the patients in the two groups were 6.5 weeks and 6.4 weeks for groups A and B, respectively (p>0.05). Systemic adverse effects (e.g., rash, liver dysfunction, leucopenia, etc.) were significantly less common in group A (1.5%) than in group B (12.3%; peffects in patients with hyperthyroidism. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Safety and efficacy of quetiapine in bipolar depression.

    Science.gov (United States)

    Bogart, Gregory T; Chavez, Benjamin

    2009-11-01

    To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression. Searches of MEDLINE and PubMed (1977-July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials. Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion. There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%. Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.

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

    LENUS (Irish Health Repository)

    Ní Ainle, Fionnuala

    2008-10-01

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

  1. Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis.

    Science.gov (United States)

    Mei, Changlin; Chen, Nan; Ding, Xiaoqiang; Yu, Xueqing; Wang, Li; Qian, Jiaqi; Wang, Mei; Jiang, Gengru; Li, Xuemei; Hou, Fanfan; Zuo, Li; Wang, Niansong; Liu, Hong

    2016-10-01

    Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double-blind, multicenter, placebo-controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium-phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels. © 2016 International Society for Hemodialysis.

  2. Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

    Directory of Open Access Journals (Sweden)

    Eiji Kirino

    2014-01-01

    Full Text Available Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.

  3. A Comparison of the Efficacy and Tolerability of the Treatments for Sciatica: A Network Meta-Analysis.

    Science.gov (United States)

    Guo, Jian-Rong; Jin, Xiao-Ju; Shen, Hua-Chun; Wang, Huan; Zhou, Xun; Liu, Xiao-Qian; Zhu, Na-Na

    2017-12-01

    There remains a lack of a systematic summary of the efficacy and safety of various medicines for sciatica, and discrepancies among these exist. The aim of this study is to comprehensively assess the efficacy of and tolerance to several medical options for the treatment of sciatica. We performed a network meta-analysis and illustrated the results by the mean difference or odds ratio. The surface under the cumulative ranking curve (SUCRA) was used for indicating the preferable treatments. All data analyses and graphs were achieved via R 3.3.2 and Stata 13.0. The subcutaneous anti-tumor necrosis factor-α (anti-TNF-α) was superior to the epidural steroid + anesthetic in reducing lumbar pain in both acute + chronic sciatica patients and acute sciatica patients. The epidural steroid demonstrated a better ability regarding the Oswestry disability score (ODI) compared to the subcutaneous anti-TNF-α. In addition, for total pain relief, the use of nonsteroidal antiinflammatory drugs was inferior to the epidural steroid + anesthetic. The epidural anesthetic and epidural steroid + anesthetic both demonstrated superiority over the epidural steroid and intramuscular steroid. The intravenous anti-TNF-α ranked first in leg pain relief, while the subcutaneous anti-TNF-α ranked first in lumbar pain relief, and the epidural steroid ranked first in the ODI on the basis of SUCRA. In addition, their safety outcome (withdrawal) rankings were all medium to high. Intravenous and subcutaneous anti-TNF-α were identified as the optimal treatments for both acute + chronic sciatica patients and acute sciatica patients. In addition, the epidural steroid was also recommended as a good intervention due to its superiority in reducing ODI.

  4. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  5. A review on safety and efficacy of products containing Longifolia

    Directory of Open Access Journals (Sweden)

    Abdul Hafeez Ahmad Hamdi

    2016-01-01

    Full Text Available Eurycoma longifolia (commonly called tongkat ali is a flowering plant in the family Simaroubaceae, native to Indonesia, Malaysia, and, to a lesser extent, Thailand, Vietnam and also Laos. The roots extract of E. longifolia, is a well-known traditional herbal medicine in Asia used for many purposes such as sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. It is very important to conserve this valuable medicinal plant for the health benefit of future generations. The purpose of this review article is to evaluate and summarize the existing literatures regarding the efficacy and safety of products which contain E. longifolia as its main ingredient. In summary, based on the literature evaluated in this review article, products which contain tongkat ali showed a clinical benefit on improving erectile dysfunction as well as a good safety profile. We recommend consumers to check the level of the bioactive compound “eurycomanone” as their guide before choosing any E. longifolia product.

  6. Hyperfractionated abdominal radiotherapy in children. Efficacy and tolerance in 13 cases

    International Nuclear Information System (INIS)

    Lagrange, J.L.; Roullet, B.; Cosset, J.M.; Sarrazin, D.; Lemerle, J.

    1984-01-01

    The experience at IGR has shown that hyperfractionation, especially abdominal has been well tolerated in adult patients. This finding led to employ this technic in the pediatric population who had failed standard treatment. An experience with hyperfractionated radiotherapy of the abdomen and liver in children, is reported. The children were treated 4 days per week, receiving 5 fractions daily of 0.7 Gy, with a 2 hours interval between each treatment. A total dose of 28 Gy was delivered in 40 fractions over 12 days. A second course of irradiation was delivered in 5 patients, 3 with abdominal treatment and 2 with liver irradiation. The vital organs were shielded with blocks at normal dose tolerance levels. The results are encouraging since an immediate efficacy was observed in 8 of 13 patients. Long term survivals were observed in 4 patients with nephroblastomas and 1 patient with a hepatoblastoma. On the other hand acute gastrointestinal tolerance seemed less good in the children than previously observed in the adults. Five radiation hepatitis appeared, immediately after the irradiation, whom four children irradiated to the entire abdomen [fr

  7. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  8. Understanding the safety and tolerability of facial filling therapeutics.

    Science.gov (United States)

    Kulichova, Daniela; Borovaya, Alyona; Ruzicka, Thomas; Thomas, Peter; Gauglitz, Gerd G

    2014-09-01

    Aesthetic medicine represents an emerging field for many specialties. Nowadays, a plethora of approaches are available to rejuvenate the human body and face, the latter being a frequent target for the placement of filling substances to correct wrinkles and volume loss. Nevertheless, based on the many products on the market, treating clinicians must pay specific attention to the properties of the respective materials, their associated side effects and any specific handling requirements to prevent potential short- and long-term adverse events. Types of filling materials, including biodegradable and non-biodegradable products, related complications, their conservative and invasive treatment options, as well as prevention strategies are described in this review. A profound knowledge of the facial anatomy as well as extensive experience with the various filling techniques and suitable materials for the respective areas remains crucial to prevent adverse events associated with filling procedures to the human face. Since side effects such as malar edema and foreign body granuloma do affect patients physically and psychologically to a significant extent and their successful treatment still remains challenging, further in depth studies on the tolerability of many filling materials utilized are required.

  9. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  10. Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

    NARCIS (Netherlands)

    Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

    2007-01-01

    Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

  11. Safety and Tolerability of Atomoxetine over 3 to 4 Years in Children with ADHD

    Science.gov (United States)

    Donnelly, Craig; Bangs, Mark; Trzepacz, Paula; Jin, Ling; Zhang, Shuyu; Witte, Michael M.; Ball, Susan G.; Spencer, Thomas J.

    2009-01-01

    Data from 13 double-blind, placebo-controlled trials and three open-label extension studies were pooled to examine the safety of atomoxetine for treating attention deficit hyperactivity disorder in children and adolescents for less than or equal to three or four years. Results show that atomoxetine is safe and well tolerated in the subjects.

  12. Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

    Science.gov (United States)

    Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

    2017-10-02

    Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

  13. Balsam “Mercana-Artrovit warming” — efficacy and tolerability in knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    E S Tsvetkova

    2007-01-01

    Full Text Available Objective. To assess efficacy, local and systemic tolerability of balsam “Mercana-Artrovit warming” (BMAW containing methylnicotinat, mint and eucalyptus ethereal oils, propylene glycol extracts of eucalyptus, linden, nettle, elecampane, common wormwood, tansy, terpentine oil in knee osteoarthritis (KOA Material and methods. 60 pts were included in a two-week double blind placebo controlled randomized study. BMAW 5 ml was administered in 30 pts (the main group twice a day (in the morning and in the evening on the target knee joint. 30 pts of control group received placebo containing only components of stuff. Demographic and clinical parameters in the main and the control groups were comparable. Inclusion criteria: age from 40 to 70 years, pain intensity in the target joint at least 40 mm on VAS, I-III radiological stage according to Kellgren, Leqesne score 4-10, treatment with NSAIDs during the previous 3 months. Exclusion criteria: indications for intra-articular glucocorticoid injection, clinically significant disturbances of internal organs function and skin damages in the region of knee joint. Clinical efficacy was assessed by WOMAC index, pain at movement and at rest, time of 15 meters walking, general assessment of efficacy (separately by the pt and by the doctor. Frequency and character of adverse events was registered. Results. Local BMAW administration provided statistically significant decrease of WO MAC summated score (p=0,008, pain at movement (p<0,001 and at rest (p<0,005. So analgesic effect of the drug is sufficient for improvement of functional activity of pts with KOA. General efficacy assessment was significantly higher in the main group (Fisher exact test, p<0,005. Placebo did not significantly change efficacy measures. Adverse events were absent in both groups. Conclusion. The results of the study allows to recommend BMAW for local therapy of KOA

  14. A COMPARATIVE STUDY OF EFFICACY AND TOLERABILITY OF TRAMADOL AND ACECLOFENAC IN TREATMENT OF OSTEOARTHRITIS

    Directory of Open Access Journals (Sweden)

    Ganga

    2016-02-01

    Full Text Available Osteoarthritis (OA is a leading cause of musculoskeletal disability in elderly patients. It is a slow evolving disorder causing degeneration of articular cartilage associated with symptoms of joint tenderness, stiffness and limitation of movement. These symptoms get more worsened with weight bearing and movement. Non-steroidal anti- inflammatory (NSAIDS drugs and often Opioid analgesics offers a symptomatic relief in the management of osteoarthritis. So, the present study is conducted to compare the efficacy and tolerability of Tramadol and Aceclofenac in patients of osteoarthritis. MATERIALS AND METHODS The present study is a randomized, single centered, prospective clinical study and was conducted on 140 patients. INCLUSION CRITERIA Patients of sex, aged 40-60 years, suffering with symptoms of OA of knee who are radiologically diagnosed. EXCLUSION CRITERIA  Patients 60 years of age.  Patients with a history of peptic ulcers and hypersensitivity to NSAIDs/Opioids.  Patients with history of bleeding tendencies, cirrhosis and oesophageal varices.  Patients who have previously received Tramadol or Aceclofenac for treatment of osteoarthritis. After initial clinical assessment and baseline investigations, Aceclofenac tablet was given to 70 patients and Tramadol tablet was given orally to another 70 patients for 8 weeks. At the follow up, the results were analysed and compared statistically by paired t- test, unpaired t-test, Fischer’s exact test. RESULTS Aceclofenac has shown significant change than Tramadol in efficacy parameters like Western Ontario Mac Master (WOMAC scores (p<0.0001, joint tenderness (p<0.0001, investigator assessment for disease status (p=0.01 and response to therapy (p=0.038. Incidence of adverse effects is significant with Tramadol (p=0.02. DISCUSSION Aceclofenac was found superior than Tramadol in improving the patient’s clinical condition. Aceclofenac was found to be well tolerated than Tramadol in terms of

  15. Infusion of iloprost without a peristaltic pump: Safety and tolerability

    Directory of Open Access Journals (Sweden)

    Paola Faggioli

    2013-04-01

    Full Text Available Introduction: Iloprost is a potent prostacyclin (PGI2 analogue that is effective in the treatment of peripheral arterial disease, vasculitis, pulmonary hypertension, and secondary Raynaud’s phenomenon. Intravenous infusions are generally administered with the aid of a peristaltic pump to reduce the risk of adverse reactions caused by unintentional increases in the infusion rate. This increases the cost of care in terms of equipment and personnel and may limit the use of this drug. Materials and methods: We retrospectively analyzed 18,432 iloprost infusions administered between 1999 and 2009 to 272 patients with systemic sclerosis (n = 253 and 19 with peripheral arterial disease (n = 19. All infusions were administered in the day hospital over 6 h with a normal IV set-up with a roller flow regulator. Flow rates were set to deliver iloprost at 1-2 ng/kg/min. Rates were verified by direct drop counts during the first 15-20 minutes of the infusion and at each subsequent check. Results: There were no adverse events that were fatal, life-threatening, or associated with prolongation of hospitalization and very few events requiring intensive care or continuous monitoring. The latter included 4 cases of tachycardia/arrhythmia (extrasystoles in most cases, 3 cases of hypotension (systolic pressure < 80 mmHg, and 2 cases of hypertension (BP > 170/100 mmHg. All other adverse reactions were mild, reversible, and similar to those seen with iloprost infusion with peristaltic pump. Only one patient had to be switched to another prostanoid (due to intolerance. Discussion: Iloprost infusion administered with a normal IV flow regulator appears to be as safe, well tolerated, and effective as traditional infusion with a peristaltic pump.

  16. Transparent reliability model for fault-tolerant safety systems

    International Nuclear Information System (INIS)

    Bodsberg, Lars; Hokstad, Per

    1997-01-01

    A reliability model is presented which may serve as a tool for identification of cost-effective configurations and operating philosophies of computer-based process safety systems. The main merit of the model is the explicit relationship in the mathematical formulas between failure cause and the means used to improve system reliability such as self-test, redundancy, preventive maintenance and corrective maintenance. A component failure taxonomy has been developed which allows the analyst to treat hardware failures, human failures, and software failures of automatic systems in an integrated manner. Furthermore, the taxonomy distinguishes between failures due to excessive environmental stresses and failures initiated by humans during engineering and operation. Attention has been given to develop a transparent model which provides predictions which are in good agreement with observed system performance, and which is applicable for non-experts in the field of reliability

  17. [Safety and tolerability of GLP-1 receptor agonists].

    Science.gov (United States)

    Soldevila, Berta; Puig-Domingo, Manel

    2014-09-01

    Glucagon-like peptide-1 receptor agonists (GLP-1ra) are a new group of drugs with a glucose-lowering action due to their incretin effect. The GLP-1 receptor is expressed in various human tissues, which could be related to the pleiotropic effects of human GLP-1, as well as to the adverse effects described in patients treated with GLP-1ra. The risk of hypoglycaemia is low, which is one of the main considerations in the safety of this family of compounds and is also important to patients with diabetes. The most frequent adverse effect is nausea, which usually occurs at the start of treatment and is transient in 20-60% of affected patients. This article also reviews the information available on antibody formation, the potential effect on the thyroid gland, and the controversial association between this group of drugs with pancreatitis and cancer. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Evaluation of safety and efficacy of telmisartan-amlodipine combination in treating hypertension.

    Science.gov (United States)

    Faruqui, Arif A

    2008-09-01

    The objective of this open, non-comparative, prospective postmarketing surveillance (PMS) study was to identify, validate and quantify the safety and efficacy associated with the use of fixed dose combination (FDC) of telmisartan 40 mg + amlodipine 5 mg (T40+A5) in hypertensive patients with or without concomitant diabetes. The data was collected from 72 centres from all over India during the period of June 2007 to February 2008. A total of 251 patients of either sex and those who were newly diagnosed stage II hypertension, or those who were uncontrolled on monotherapy with or without diabetes mellitus were included in this study. Patients were prescribed with T40+A5 combination orally. Systolic BP (SBP), diastolic BP (DBP) and heart rate (HR) were measured at the start and at the end of 2, 4 and 8 weeks of treatment. Primary efficacy end points were reduction in clinical SBP/ DBP from baseline to study end and number of patients achieving JNC VII goals. Tolerability was assessed by treatment-emergent adverse events. Out of 251 patients, 208 patients had completed the study (120 males and 88 females), 42 were lost to follow-up the study and one patient was withdrawn due to adverse effects. The mean age of the patients was 54.5 +/- 0.98 years for males and 52.94 +/- 1.078 years for females. Diabetes mellitus was seen in 64.9% of cases, dyslipidaemia in 2.88%, previous IHD in 7.2% cases and chronic obstructive pulmonary disease (COPD) in 0.50% of cases. Reduction in the mean SBP was found to be 12.08%, 18.92% and 22.90% at the end of 2, 4 and 8 weeks respectively (p hypertensive patients and 70% diabetic hypertensive patients achieved the JNC VII recommended goals. The overall incidence of ADRs was 7.69% with headache (1.92%) and vertigo (1.44%), as the commonest side-effect. According to physician's assessment of efficacy and tolerability 99.5% of total cases showed good to excellent response. In the treatment of stage II hypertensive patient the FDC of T40+A5

  19. National and foreign research of Anaferon Kid: efficacy, safety and experience of application (review

    Directory of Open Access Journals (Sweden)

    Yu. V. Lobzin

    2015-01-01

    Full Text Available Interest in acute respiratory viral infections (ARVI in children does not tend to decrease and is determined by their high prevalence, relatedness to «uncontrollable infections» in most cases and presence of age limits in the use of antiviral drugs. Presently, focus on the use of national drugs is made in the RF clinical practice. An innovative drug Anaferon for children was developed by the Russian pharmaceutical company OOO «NPF «Materia Medica Holding» and registered in Russia in 2002.The summary purpose is to classify and analyze national and international publications on the results of non-clinical and clinical investigation of Anaferon for children efficacy and safety in ARVI and other viral infections.Study method: exploratory and analytical.Results: the summary presents the data of non-clinical studies justifying the drug mechanism of action at molecular level ensuring its combined antiviral and immunomodulating efficacy. The results obtained in the experiment were verified by clinical studies and are reflected in numerous scientific publications including international ones. The summary contains analysis of the results of clinical studies of the drug in children with ARVI including influenza. Anaferon for children was found to reduce duration of the main clinical symptoms of ARVI and influenza, incidence of bacterial complications, it is well-tolerated and has high safety profile. The open-label randomized comparative study of Anaferon for children efficacy and safety vs. Oseltamivir in influenza demonstrated clinical efficacy of these drugs. Numerous publications evidence that Anaferon for children exerts antiviral effect against most viruses causing acute respiratory viral infections as well as herpes viruses, viruses causing intestinal infections and tick-borne encephalitis. The list of scientific publications on the drug consists of approximately 800 references including more than 50 articles in

  20. Safety and efficacy of Mangafodipir trisodium in patients with liver lesions and cirrhosis

    International Nuclear Information System (INIS)

    Marti-Bonmati, Luis; Fog, Amura F.; de Beeck, Bart Op; Kane, Pauline; Fagertun, Hans

    2003-01-01

    Mangafodipir trisodium (Mn-DPDP, Teslascan) is a well-tolerated liver contrast agent. Although the enhancement characteristics of the cirrhotic liver after Mangafodipir trisodium administration have been studied, at present there is no published data on the impact that cirrhosis might have on the safety and efficacy profiles of this agent. Our objective is to evaluate by means of a retrospective comparison the safety and efficacy of Mangafodipir trisodium in patients with underlying cirrhosis who were examined for suspicion of focal liver lesions. A total of 923 patients received Mangafodipir trisodium (5 μmol/kg) in 11 prospective randomized European clinical trials. Adverse events and discomfort were recorded and graded in all patients. The efficacy analyses were performed on the subsets consisting of 617 patients with independent lesion counts (detection), and on the subset with 399 patients with independent and onsite final lesion diagnosis (characterization). Of the 399 patients, 149 had histologic confirmation. One hundred eighty of 923 patients (19.5%) had cirrhosis. There were no main differences between cirrhotic and non-cirrhotic patients. Adverse events were observed in 64 patients (6.9%), 6.7% in the cirrhotic group and 7.0% in the non-cirrhotic group, a non-significant difference. Adverse events in most patients were mild or moderate. The presence and intensity of the events did not differ between groups. Discomfort was recorded in 79 patients (8.6%), equally distributed in cirrhotic (6.1%) and non-cirrhotic (9.2%) patients. Regarding lesion count, significantly more lesions were found in the post- than in the precontrast images in both the cirrhotic and non-cirrhotic groups (p<0.0001). This increase was not influenced by the presence of liver cirrhosis (p=0.94). Lesion characterization was significantly improved in cirrhotic patients after administration of Mangafodipir trisodium (p=0.002) but not in non-cirrhotic patients (p=0.13). Mangafodipir

  1. Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience.

    Science.gov (United States)

    Lovett, Grace C; Nguyen, Tin; Iser, David M; Holmes, Jacinta A; Chen, Robert; Demediuk, Barbara; Shaw, Gideon; Bell, Sally J; Desmond, Paul V; Thompson, Alexander J

    2017-01-08

    To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI

  2. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Wahn, Ulrich; Tabar, Ana; Kuna, Piotr

    2009-01-01

    BACKGROUND: The efficacy and safety of the 300-index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults. OBJECTIVE: We sought to assess the efficacy and safety of this tab...

  3. Efficacy and safety of pregabalin in generalised anxiety disorder : A critical review of the literature

    NARCIS (Netherlands)

    Baldwin, David S.; den Boer, Johan A.; Lyndon, Gavin; Emir, Birol; Schweizer, Edward; Haswell, Hannah

    2015-01-01

    The aim of this review is to summarise the literature on the efficacy and safety of pregabalin for the treatment of generalised anxiety disorder (GAD). Of 241 literature citations, 13 clinical trials were identified that were specifically designed to evaluate the efficacy and safety of pregabalin in

  4. The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Facial Acne Vulgaris.

    Science.gov (United States)

    Hashim, Peter W; Chen, Tinley; Harper, Julie C; Kircik, Leon H

    2018-06-01

    Azelaic acid demonstrates anti-inflammatory, anti-oxidative, anti-comedogenic, and anti-microbial effects. Azelaic acid 20% cream is currently approved for the treatment of acne vulgaris, and azelaic acid 15% foam has recently been approved for rosacea. Given the favorable tolerability profile of foam preparations, it is reasonable to assume that azelaic acid 15% foam could serve as a viable treatment option for facial acne. To examine the efficacy and safety of azelaic acid 15% foam in the treatment of moderate-to-severe facial acne Methods: Twenty subjects with moderate-to-severe facial acne vulgaris were enrolled in this two-center, open-label pilot study. All study subjects were treated with azelaic acid 15% foam for 16 weeks. Efficacy analyses were based on the change in facial investigator global assessment (FIGA) and changes in total, inflammatory, non-inflammatory lesion counts between baseline and week 16. There was a significant reduction in FIGA scores from baseline to week 16 (p = .0004), with 84% of subjects experiencing at least a 1 grade improvement, and 63% of subjects achieving a final grade of Clear or Almost Clear. All subjects experienced reductions in inflammatory and total lesion counts by week 16, and 89% of subjects experienced reductions in non-inflammatory lesions. Azelaic acid 15% foam was well tolerated, with almost all instances of erythema, dryness, peeling, oiliness, pruritus, and burning being of mild or trace degree, and most adverse effects resolving by the end of the study. Azelaic acid 15% foam is effective and safe in the treatment of facial acne vulgaris. Given the convenience of foam vehicles, azelaic acid 15% foam should be considered as a viable treatment option for this condition. J Drugs Dermatol. 2018;17(6):641-645.

  5. EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    M. S. Naumtseva

    2015-01-01

    Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

  6. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

    Directory of Open Access Journals (Sweden)

    Schoedel KA

    2014-06-01

    Full Text Available Kerri A Schoedel,1 Sarah A Morrow,2 Edward M Sellers3,4 1Altreos Research Partners, Inc., Toronto, 2Western University, London, 3DL Global Partners, Inc., Toronto, 4University of Toronto, Toronto, Ontario, Canada Abstract: Pseudobulbar affect (PBA is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a

  7. Efficacy and safety of topical application of 15% and 10% potassium hydroxide for the treatment of Molluscum contagiosum.

    Science.gov (United States)

    Teixidó, Concepció; Díez, Olga; Marsal, Josep R; Giner-Soriano, Maria; Pera, Helena; Martinez, Mireia; Galindo-Ortego, Gisela; Schoenenberger, Joan A; Real, Jordi; Cruz, Ines; Morros, Rosa

    2018-02-26

    Molluscum contagiosum is the most common skin infection in children. One topical treatment used for Molluscum contagiosum is potassium hydroxide. The objective of this study was to compare the efficacy of potassium hydroxide topical treatment at different concentrations with that of placebo in terms of complete clearing of Molluscum contagiosum lesions and to assess the safety and tolerance of potassium hydroxide topical treatment. This was a double-blind randomized clinical trial of three treatments (potassium hydroxide 10%, potassium hydroxide 15%, placebo) applied once daily up to complete clearing of lesions (maximum duration 60 days) in 53 children aged 2-6 years in primary health care pediatric offices in Catalonia, Spain. In the intention-to-treat analysis, potassium hydroxide 10% (58.8%, P = .03) and potassium hydroxide 15% (64.3%, P = .02) had efficacy superior to that of placebo (18.8%). The number of Molluscum contagiosum lesions was significantly reduced with potassium hydroxide 10% and 15%. The main efficacy outcome was achieved in 58.8% of children in the potassium hydroxide 10% group (P = .03 vs placebo) and in 64.3% of children in the potassium hydroxide 15% group (P = .02 vs placebo). Potassium hydroxide 10% and 15% were not significantly different in efficacy from each other. Potassium hydroxide 10% and placebo were better tolerated than potassium hydroxide 15%. No adverse events were reported during the study period. Potassium hydroxide 10% and 15% demonstrated high rates of efficacy in clearing Molluscum contagiosum lesions, with potassium hydroxide 10% being better tolerated. © 2018 Wiley Periodicals, Inc.

  8. Tranexamic Acid in Total Joint Arthroplasty: Efficacy and Safety

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    Mohammad Reza Rasouli

    2015-01-01

    relatively rare, the majority of studies that evaluated the efficacy of TA are underpowered for evaluation of its safety. In a recent study by Poeran et al. using a large national database including 872,416 patients who had total hip or knee arthroplasty, the authors suggested that TA is effective in reducing the need for blood transfusions while not increasing the risk of VTE and renal complications (8. However, it is still advised that patients with cardiac stents and previous thromboembolic events including ischemic stroke not be administered TA. TA can also cause gastrointestinal disturbance and its dose needs to be adjusted in patients with renal impairment (5.   In conclusion, administration of TA in TJA patient is a cost-effective blood conservation strategy and there is strong evidence to support the efficacy and safety of the drug in reducing blood loss and transfusion in TJA patients. Given the adverse effects of allogeneic blood transfusion on the outcome of TJA, administration of TA should be considered in patients with no contraindication for its use.

  9. Efficacy and Safety of Dual Antiplatelet Therapy After Complex PCI.

    Science.gov (United States)

    Giustino, Gennaro; Chieffo, Alaide; Palmerini, Tullio; Valgimigli, Marco; Feres, Fausto; Abizaid, Alexandre; Costa, Ricardo A; Hong, Myeong-Ki; Kim, Byeong-Keuk; Jang, Yangsoo; Kim, Hyo-Soo; Park, Kyung Woo; Gilard, Martine; Morice, Marie-Claude; Sawaya, Fadi; Sardella, Gennaro; Genereux, Philippe; Redfors, Bjorn; Leon, Martin B; Bhatt, Deepak L; Stone, Gregg W; Colombo, Antonio

    2016-10-25

    Optimal upfront dual antiplatelet therapy (DAPT) duration after complex percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains unclear. This study investigated the efficacy and safety of long-term (≥12 months) versus short-term (3 or 6 months) DAPT with aspirin and clopidogrel according to PCI complexity. The authors pooled patient-level data from 6 randomized controlled trials investigating DAPT durations after PCI. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or chronic total occlusion. The primary efficacy endpoint was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. The primary safety endpoint was major bleeding. Intention-to-treat was the primary analytic approach. Of 9,577 patients included in the pooled dataset for whom procedural variables were available, 1,680 (17.5%) underwent complex PCI. Overall, 85% of patients received new-generation DES. At a median follow-up time of 392 days (interquartile range: 366 to 710 days), patients who underwent complex PCI had a higher risk of MACE (adjusted hazard ratio [HR]: 1.98; 95% confidence interval [CI]: 1.50 to 2.60; p PCI group (adjusted HR: 0.56; 95% CI: 0.35 to 0.89) versus the noncomplex PCI group (adjusted HR: 1.01; 95% CI: 0.75 to 1.35; p interaction  = 0.01). The magnitude of the benefit with long-term DAPT was progressively greater per increase in procedural complexity. Long-term DAPT was associated with increased risk for major bleeding, which was similar between groups (p interaction  = 0.96). Results were consistent by per-treatment landmark analysis. Alongside other established clinical risk factors, procedural complexity is an important parameter to take into account in tailoring upfront duration of DAPT. Copyright © 2016 American College

  10. The Efficacy, Safety and Applications of Medical Hypnosis.

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    Häuser, Winfried; Hagl, Maria; Schmierer, Albrecht; Hansen, Ernil

    2016-04-29

    The efficacy and safety of hypnotic techniques in somatic medicine, known as medical hypnosis, have not been supported to date by adequate scientific evidence. We systematically reviewed meta-analyses of randomized controlled trials (RCTs) of medical hypnosis. Relevant publications (January 2005 to June 2015) were sought in the Cochrane databases CDSR and DARE, and in PubMed. Meta-analyses involving at least 400 patients were included in the present analysis. Their methodological quality was assessed with AMSTAR (A Measurement Tool to Assess Systematic Reviews). An additional search was carried out in the CENTRAL and PubMed databases for RCTs of waking suggestion (therapeutic suggestion without formal trance induction) in somatic medicine. Out of the 391 publications retrieved, five were reports of metaanalyses that met our inclusion criteria. One of these meta-analyses was of high methodological quality; three were of moderate quality, and one was of poor quality. Hypnosis was superior to controls with respect to the reduction of pain and emotional stress during medical interventions (34 RCTs, 2597 patients) as well as the reduction of irritable bowel symptoms (8 RCTs, 464 patients). Two meta-analyses revealed no differences between hypnosis and control treatment with respect to the side effects and safety of treatment. The effect size of hypnosis on emotional stress during medical interventions was low in one meta-analysis, moderate in one, and high in one. The effect size on pain during medical interventions was low. Five RCTs indicated that waking suggestion is effective in medical procedures. Medical hypnosis is a safe and effective complementary technique for use in medical procedures and in the treatment of irritable bowel syndrome. Waking suggestions can be a component of effective doctor-patient communication in routine clinical situations.

  11. Efficacy and safety of a polyherbal formulation in hemorrhoids

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    Raakhi K Tripathi

    2015-01-01

    Full Text Available Background: The medical management of hemorrhoids should include an integrated approach. This integrated approach can be achieved by polyherbal formulations containing anti-inflammatory, styptics, analgesics, and laxative effect which reduce inflammation, pain, and bleeding, and increase gastro-intestinal motility and soften stools. One such polyherbal kit is "Arshkeyt™, a 7 day kit," which consists of oral tablets and powder along with topical cream. Objective: Efficacy and safety of Arshkeyt™, a 7 day kit, a marketed polyherbal formulation was evaluated in comparison with conventional therapy practiced in surgery outpatient departments. Materials and Methods: Patients (n = 90 with hemorrhoids were randomly allocated to receive either Arshkeyt™ or standard therapy (combination of oral Isabgul powder and 2% lidocaine gel for 14 days. Assessment on the basis of rectal symptoms and proctoscopic examination was done on day 0, 7, and 14 to derive a "composite score" which ranged from 0 to 25 by a blinded evaluator. The primary endpoint was number of patients achieving composite score 0 at the end of therapy (day 14. Inter-group analysis was done using Chi-square test. Results: On day 14, the composite score of 0 was achieved in 15 patients of Arshkeyt™ group versus 6 patients receiving standard therapy. The symptoms and signs which showed significant improvement in Arshkeyt™ group compared to standard treatment group were the tenesmus (visual analog score score (P = 0.047, anal sphincter spasm (P = 0.0495 and a decrease in the grade of hemorrhoids (P = 0.0205 on day 14. Arshkeyt™ was also more beneficial in case of bleeding hemorrhoids as compared to nonbleeding hemorrhoids (P < 0.05. The incidence of adverse drug reactions in both groups was comparable and no patient required any treatment for the same. Conclusion: "Arshkeyt™, a 7 day kit," was effective in the treatment of hemorrhoids and had a good safety profile.

  12. Efficacy and safety of alendronic acid in the treatment of osteoporosis in children

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    Alberto Martín Siguero

    2015-11-01

    Full Text Available Objectives: to describe the efficacy and safety of the off-label use of alendronate in the treatment of osteoporosis in children and adolescents. Method: a retrospective study (2008-2014 of all patients under 18 years who were dispensed alendronate for this indication. The criteria for initiating treatment were: bone mineral density with a Z-score ≤ -2.5 SD, a past history of bone fractures without a previous traumatism, and persistent pain. The variables collected were: demographic, treatment-related, clinical. and safety data. The treatment was considered to be effective when there was an increase in bone mineral density up to a Z-score > -2.5 SD. Results: a total of 12 patients, 8 of them male, with a mean age of 11 years (} 3 SD, were treated with alendronate. After a mean time of treatment of 2.15 years (} 1.2 SD, there was an increase in bone mineral density in all patients, 9 of which achieved a Z-score > -2.5 SD, so the drug was considered effective in 75% of cases. No patient had bone fractures or expressed adverse effects during treatment. Conclusions: alendronate increased bone mineral density and was well tolerated in all patients, therefore it could be considered as a therapeutic option in the treatment of osteoporosis in children.

  13. A review of the efficacy and safety of canagliflozin in elderly patients with type 2 diabetes.

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    Elmore, Lindsey K; Baggett, Sara; Kyle, Jeffrey A; Skelley, Jessica W

    2014-01-01

    To review the efficacy and safety of canagliflozin (CAN) in elderly patients with type 2 diabetes mellitus (T2DM). Studies were identified using PubMed, International Pharmaceutical Abstracts, MEDLINE, Academic Search Premier, SCOPUS, and Google Scholar from 2011 to August 2013. The following key words were reviewed: canagliflozin, canagliflozin elderly, canagliflozin geriatrics, dapagliflozin, sodium glucose cotransporter 2 (SGLT2) inhibitors, and SGLT2 receptor inhibitors. Articles evaluating CAN for diabetes that were published in English and used human subjects were selected. Fifteen clinical trials were identified and evaluated. Of 15 identified articles, 2 articles, 2 published posters, and unpublished information from the manufacturer were chosen based on the mean age of the study subjects. Evidence that elderly patients with T2DM have less A1C reduction with CAN is presented; the benefit on A1C is significant. Systolic blood pressure (SBP) and body weight reduction in the elderly were consistent with younger patients. Adverse effects such as increased urinary frequency, genital mycotic infections, and urinary tract infections may discourage the use of CAN in the elderly patient. Treatment with CAN improves A1C levels, reduces SBP and body weight, and is overall well tolerated in older subjects with T2DM. Risks and benefits of treatment with CAN should be assessed in geriatric patients on a case-by-case basis. Safety in elderly patients was consistent with that of other phase 3 trials in the general population. Additional longterm cardiovascular studies are needed.

  14. Real-life safety and efficacy of vildagliptin as add-on to metformin in patients with type 2 diabetes in Turkey--GALATA study.

    Science.gov (United States)

    Ayvaz, Goksun; Keskin, Lezzan; Akin, Fulya; Dokmetas, Hatice Sebile; Tasan, Ertugrul; Ar, Idilhan Baloglu; Uren, Emel

    2015-04-01

    To evaluate tolerability/safety and the efficacy of the combination of vildagliptin plus metformin in a real-life population of patients with type 2 diabetes mellitus (T2DM). This multicenter, single-arm, 6 month, observational, prospective cohort study was conducted at 39 centers across Turkey. T2DM patients on vildagliptin and metformin for ≤4 weeks were enrolled regardless of their previous antidiabetic therapy. Efficacy was evaluated by measuring hemoglobin A1c (HbA1c) levels. Tolerability/safety parameters evaluated included hypoglycemic events, gastrointestinal events, peripheral edema and weight gain. This study enrolled 665 patients with a mean ± standard deviation (SD) age of 55.1 ± 10.2 years and female predominance (n = 394, 59.2%). Safety was assessed in all enrolled patients. Hypoglycemia was reported in 10 (1.5%) patients (95% confidence interval = 0.8-2.7%). Efficacy was assessed in 289 (43.5%) patients treated for 6 ± 1 months; these patients showed a mean decrease in HbA1c of 0.8% from baseline value of 7.8% (p 65 years) and body mass index (vildagliptin and metformin combination was associated with significant improvements in reaching target HbA1c levels, even in elderly and obese patients with T2DM. Moreover, vildagliptin and metformin demonstrated a good overall tolerability/safety profile.

  15. ANTI-B-CELL THERAPY AT IMMUNE INFLAMMATORY RHEUMATIC DISEASES: EFFICACY AND TOLERABILITY IN 229 PATIENTS

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    L. P. Ananieva

    2014-01-01

    Full Text Available Objective: to assess the efficacy and tolerability of Rituximab treatment in patients with serious immune inflammatory rheumatic diseases (IRD like systemic lupus erythematosus (SLE, systemic sclerosis (SS, systemic vasculitis (SV, Sjogren syndrome (SjS, dermatomyositis/polymyositis (DM/PM.Subjects and methods. The clinical efficacy has been analyzed in 229 patients with IRD: SLE (n=97, SV (n=50, SS (n=40, SjS (n=23 and DM/PM (n=19. Rituximab treatment was accompanied by administration of glucocorticoids and/or immunosuppressive drugs. Most patients demonstrated resistance to or low tolerability of standard therapy. Efficacy of treatment was analyzed in each group with the criteria relevant for each disease. To compare clinical response to the treatment between the groups we used gradations accepted by international registries: complete (good response, partial response, no response. Average duration of monitoring comprised 72 (1–288 weeks after the first introduction of Rituximab. Average Rituximab dose administered to patients over the period of monitoring was low and varied from 1.6±0.84 in DM/PM to 3.1±1.75 in SV. About 80% of patients received one or two courses of Rituximab except for patients with SS (half of them received three and more courses.Results. «Complete response» was observed in 50.6%, «partial response» – in 35% of patients. Rituximab courses provided positive dynamics in clinical scores and allowed to reduce supportive dose of glucocorticoids and to lower the dose or withdraw of immune-stimulating drugs. Multiple Rituximab courses provided stable and longlasting effect. Recurrences were observed less frequently, whereas efficacy of the therapy increased during a year and longer. Occurrence of adverse events and mortality rate were comparable to data of other national Rituximab registries.Conclusion. The results of the study may prove administration of Rituximab in patients with resistance to standard

  16. The efficacy and tolerability of leflunomide (Arava® in therapy for psoriatic arthritis

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    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available The paper gives data on differentiated disease-modifying anti-rheumatic therapy for psoriatic arthritis (PsA. When performing the therapy, account must be taken of the presence and magnitude of the major manifestations of this disease: the pattern of arthritis and spondylosis, the number of inflamed entheses, the number of swollen fingers or toes, the pattern of psoriasis in terms of its extent and stage, the presence and magnitude of systemic manifestations and the functional state of involved organs. There are data on the biological activity of leflunomide, its effect on the main manifestations of PsA with an analysis of its efficacy and tolerability, as well as the results of a comparative investigation of disease-modifying anti-rheumatic drugs used for the therapy of this disease.

  17. Tolerance and Efficacy of Emamectin Benzoate and Ivermectin for the Treatment of Pseudocapillaria tomentosa in Laboratory Zebrafish (Danio rerio)

    OpenAIRE

    Collymore, Chereen; Watral, Virginia; White, Julie R.; Colvin, Michael E.; Rasmussen, Skye; Tolwani, Ravi J.; Kent, Michael L.

    2014-01-01

    Tolerance of adult zebrafish and efficacy of emamectin benzoate and ivermectin in eliminating Pseudocapillaria tomentosa infection were evaluated. In the tolerance study, behavioral changes, fecundity, histopathology, and mortality were evaluated for in-feed administration of emamectin (0.05, 0.10, and 0.25 mg/kg) and ivermectin (0.05 and 0.10 mg/kg). All doses of emamectin were well tolerated. Ivermectin 0.05 mg/kg administration resulted in mild behavioral changes and a transient decrease i...

  18. Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts.

    Science.gov (United States)

    Ha, E J; Baek, S M; Baek, J H; Shin, S Y; Han, M; Kim, C-H

    2017-12-01

    Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst. Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%-80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated. The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8-49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0-3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%-100.0%; P branchial cleft cysts who refuse, or are ineligible for, an operation. © 2017 by American Journal of Neuroradiology.

  19. Potential benefit of dolutegravir once daily: efficacy and safety

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    Fantauzzi A

    2013-02-01

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

  20. Ibuprofen versus steroids: risk and benefit, efficacy and safety

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    M. Giovannini

    2013-10-01

    Full Text Available In the last few years we have observed an upward trend in the employment of ibuprofen as anti-inflammatory and antipyretic therapy. Therefore the pediatrician has often a precious option in the anti-inflammatory and antipyretic treatment in children instead of using steroids and paracetamol. In clinical practice ibuprofen can be used in the treatment of headache, toothache, otalgy, dysmenorrhea, neuralgia, arthralgia, myalgia, abdominal pain and fever: it is the first choice for these common diseases. However, the use of steroids is a routine, even if non-corticosteroid anti-inflammatory molecules could be useful. Certainly steroids are powerful anti-inflammatory, indicated for the treatment of chronic inflammatory disorders and in acute respiratory and allergic diseases. Beside, thanks to their chemical and pharmacological profile, they also provide patients with an antipyretic effect. However, the use of steroids must be reserved to cases in which other classical antipyretics such as non-steroidal anti-inflammatory drugs are not effective. The possible side effects and risks associated with stepping down steroids must be considered. Although “steroids-phobia” should be discouraged, steroids are to be reserved only as the first indication. In all other cases the pediatrician can use ibuprofen, whose efficacy and safety are widely demonstrated by now.

  1. Pharmacovigilance: Boon for the safety and efficacy of Ayuvedic formulations

    Science.gov (United States)

    Chaudhary, Anand; Singh, Neetu; Kumar, Neeraj

    2010-01-01

    Pharmacovigilance is a corrective process originating in pharmaco-epidemiology. The 1997 Erice Declaration, presented at the World Health Organisation, became the basis on which the concept was implemented internationally for conventional systems of medicine. The increasing international acceptance of Ayurveda, led regulators to implement a similar program for Ayurveda, particularly as some medical professionals, scientists and members of the public reported adverse reactions after taking Ayurvedic formulations. The World Health Organisation therefore persuaded the Department of AYUSH, Ministry of Health and Family Welfare, Government of India, to implement a pharmacovigilance program for Ayurveda, as a means to ensuring the safety and efficacy of Ayurvedic medicines. After a year of due diligence, the pharmacovigilance program was launched nationally on 29 September 2008. Since that time, Ayurveda, Siddha and Unani medicines have been monitored according to the provisions of a protocol prepared by the National Pharmacovigilance Resource Centre, IPGTRA, Jamnagar, and approved by Department of AYUSH. The program was reviewed, first, on 21st January 2009 by the National Pharmaco-vigilance Consultative Committee for ASU drugs (NPCC-ASU), and again, on 15 Feburary, 2010, when an evaluation meeting effectively rubber stamped the program. Among the outcomes of these meetings were several suggestions of measures to improve the program’s efficiency. Recent developments include the constitution of pharmacovigilance centers at all Ayurveda Teaching institutes and research centers. PMID:21731371

  2. Safety and Efficacy of Warfarin Therapy in Kawasaki Disease.

    Science.gov (United States)

    Baker, Annette L; Vanderpluym, Christina; Gauvreau, Kimberly A; Fulton, David R; de Ferranti, Sarah D; Friedman, Kevin G; Murray, Jenna M; Brown, Loren D; Almond, Christopher S; Evans-Langhorst, Margaret; Newburger, Jane W

    2017-10-01

    To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Current treatment for anorexia nervosa: efficacy, safety, and adherence

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    Lindsay P Bodell

    2010-10-01

    Full Text Available Lindsay P Bodell, Pamela K KeelDepartment of Psychology, Florida State University, Tallahassee, FL, USAAbstract: Anorexia nervosa (AN is a serious psychiatric illness associated with significant medical and psychiatric morbidity, psychosocial impairment, increased risk of death, and chronicity. Given the severity of the disorder, the establishment of safe and effective treatments is necessary. Several treatments have been tried in AN, but few favorable results have emerged. This paper reviews randomized controlled trials in AN, and provides a synthesis of existing data regarding the efficacy, safety, and adherence associated with pharmacologic and psychological interventions. Randomized controlled trials for the treatment of AN published in peer-reviewed journals were identified by electronic and manual searches. Overall, pharmacotherapy has limited benefits in the treatment of AN, with some promising preliminary findings associated with olanzapine, an antipsychotic agent. No single psychological intervention has demonstrated clear superiority in treating adults with AN. In adolescents with AN, the evidence base is strongest for the use of family therapy over alternative individual psychotherapies. Results highlight challenges in both treating individuals with AN and in studying the effects of those treatments, and further emphasize the importance of continued efforts to develop novel interventions. Treatment trials currently underway and areas for future research are discussed.Keywords: anorexia nervosa, treatment, pharmacotherapy, psychotherapy, randomized controlled trials

  4. Rotavirus vaccines: safety, efficacy and public health impact.

    Science.gov (United States)

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  5. Analysis of the clinical experience with perampanel in the Moscow Region: Efficacy, tolerability, individual choice priorities

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    I. G. Rudakova

    2017-01-01

    Full Text Available Objective: to analyze our clinical experience with perampanel (PER, by evaluating the efficacy, tolerability, and individual choice priorities.Patients and methods. The investigation enrolled 28 patients with drug-resistant focal epilepsy; the patients' mean age was 38.3±10.7 years. The proportion of men was 46.4%; the disease duration was 8 to 33 years (mean 20.2 years. Antiepileptic drugs (AEDs were changed 7–10 times in 66% of the patients and 5–6 times in 23%. The efficacy and tolerability of AEDs and the electroclinical features of epilepsy were compared in two groups: responders and non-responders.Results and discussion. The responder and non-responder groups had a substantial preponderance of patients with frontal lobe epilepsy and diffuse epileptiform electroencephalographic (EEG patterns (80%:46% and 80%:38%, respectively; p = 0.0001, but those with temporal lobe epilepsy and isolated regional EEG patterns were 2–3 times fewer (20%: 53.8% and 20%:61.5%; p = 0.0001. Only one of 10 combinations of carbamazepine (CBM and PER was successful. Aggression, fear, and psychosis, which occurred in 5 (17.8% patients taking PER 2–6 mg/day, were the most common adverse reactions associated with its discontinuation. PER is an effective agent to overcome of drug resistance in epilepsy. The benefit of the drug is that it may be used in undifferentiated antiepileptic therapy regimens. When predicting the effects of PER, preliminary switch from CBZ to oxcarbazepine or eslicarbazepine is reasonable. 

  6. Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation

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    Mary E. Westerman

    Full Text Available ABSTRACT Introduction: Hemorrhagic cystitis (HC represents a challenging clinical entity. While various intravesical agents have been utilized in this setting, limited data exist regarding safety or efficacy. Herein, then, we evaluated the effectiveness and complications associated with intravesical alum instillation for HC in a contemporary cohort. Materials and Methods: We identified 40 patients treated with intravesical alum for HC between 1997-2014. All patients had failed previous continuous bladder irrigation with normal saline and clot evacuation. Treatment success was defined as requiring no additional therapy beyond normal saline irrigation after alum instillation. Results: Median patient age was 76.5 years (IQR 69, 83. Pelvic radiation was the most common etiology for HC (n=38, 95%. Alum use decreased patient's transfusion requirement, with 82% (32/39 receiving a transfusion within 30 days before alum instillation (median 4 units versus 59% (23/39 within 30 days after completing alum (median 3 units (p=0.05. In total, 24 patients (60% required no additional therapy prior to hospital discharge. Moreover, at a median follow-up of 17 months (IQR 5, 38.5, 13 patients (32.5% remained without additional treatment for HC. Adverse effects were reported in 15 patients (38%, with bladder spasms representing the most common event (14/40; 35%. No clinical evidence of clinically significant systemic absorption was detected. Conclusion: Intravesical alum therapy is well-tolerated, with resolution of HC in approximately 60% of patients, and a durable response in approximately one-third. Given its favorable safety/efficacy profile, intravesical alum may be considered as a first-line treatment option for patients with HC.

  7. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension.

    Science.gov (United States)

    Beghetti, Maurice; Rudzinski, Andrzej; Zhang, Min

    2017-07-04

    Despite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1-17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension. This was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil. Of 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non-Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population. Sildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias. Study received, September 8, 2005 (retrospectively registered); Study start

  8. Chronic electrical stimulation with a suprachoroidal retinal prosthesis: a preclinical safety and efficacy study.

    Directory of Open Access Journals (Sweden)

    David A X Nayagam

    Full Text Available To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.Seven normally-sighted feline subjects were implanted for 96-143 days with a suprachoroidal electrode array and six were chronically stimulated for 70-105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG, optical coherence tomography (OCT and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11-15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained

  9. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  10. Efficacy and safety of omalizumab in Japanese and Korean patients with refractory chronic spontaneous urticaria.

    Science.gov (United States)

    Hide, Michihiro; Park, Hae-Sim; Igarashi, Atsuyuki; Ye, Young-Min; Kim, Tae-Bum; Yagami, Akiko; Roh, Jooyoung; Lee, Jae-Hyun; Chinuki, Yuko; Youn, Sang Woong; Lee, Soo-Keol; Inomata, Naoko; Choi, Jeong-Hee; Fukunaga, Atsushi; Wang, Junyi; Matsushima, Soichiro; Greenberg, Steve; Khalil, Sam

    2017-07-01

    Many patients with chronic spontaneous/idiopathic urticaria (CSU/CIU) do not respond adequately to treatment with non-sedating H1 antihistamines (H1AH). There are limited studies on use of omalizumab as add-on therapy for treatment of CSU in an Asian population. The POLARIS study (NCT02329223), representing the first randomized, double-blind, placebo-controlled phase III trial of omalizumab for CSU in an Eastern Asian population, evaluated efficacy and safety of omalizumab as add-on therapy for treatment of CSU. This 26-week multicenter (41 Japanese/Korean sites) study enrolled patients (12-75 years) who were symptomatic despite H1AH treatment. Eligible participants (N=218) were randomized 1:1:1 to receive three subcutaneous injections of omalizumab 300mg, 150mg, or placebo every 4 weeks, followed by 12 weeks of follow-up. Primary outcome was change from baseline to Week 12 (Wk12) in weekly itch severity score (ISS7). Safety was assessed through the summary of adverse events (AEs). Baseline demographics and disease characteristics were generally well balanced across treatment groups. At Wk12, statistically significant decreases from baseline were observed in ISS7 with omalizumab vs placebo (mean changes -10.22, -8.80, and -6.51 for omalizumab 300mg, 150mg and placebo; pomalizumab 300mg, 150mg, and placebo groups, respectively); nasopharyngitis was the most frequently reported AE in all treatment arms. The POLARIS study demonstrates that omalizumab is an efficacious and well-tolerated add-on therapy in Japanese and Korean H1AH-refractory patients with CSU. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. [Efficacy and safety profile of cranberry in infants and children with recurrent urinary tract infection].

    Science.gov (United States)

    Fernández-Puentes, V; Uberos, J; Rodríguez-Belmonte, R; Nogueras-Ocaña, M; Blanca-Jover, E; Narbona-López, E

    2015-06-01

    Cranberry prophylaxis of recurrent urinary tract infection in infants has proven effective in the experimental model of the adult. There are few data on its efficacy, safety and recommended dose in the pediatric population. A controlled, double-blind Phase III clinical trial was conducted on children older than 1 month of age to evaluate the efficacy and safety of cranberry in recurrent urinary tract infection. The assumption was of the non-inferiority of cranberry versus trimethoprim. Statistical analysis was performed using Kaplan Meier analysis. A total of 85 patients under 1 year of age and 107 over 1 year were recruited. Trimethoprim was prescribed to 75 patients and 117 received cranberry. The cumulative rate of urinary infection associated with cranberry prophylaxis in children under 1 year was 46% (95% CI; 23-70) in children and 17% (95% CI; 0-38) in girls, effectively at doses inferior to trimethoprim. In children over 1 year-old cranberry was not inferior to trimethoprim, with a cumulative rate of urine infection of 26% (95% CI; 12-41). The cranberry was well tolerated and with no new adverse effects. Our study confirms that cranberry is safe and effective in the prophylaxis of recurrent urinary tract infection in infants and children. With the doses used, their efficiency is not less than that observed for trimethoprim among those over 1 year-old. (Clinical Trials Registry ISRCTN16968287). Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  12. Efficacy and tolerability assessment of a topical formulation containing copper sulfate and hypericum perforatum on patients with herpes skin lesions: a comparative, randomized controlled trial.

    Science.gov (United States)

    Clewell, Amy; Barnes, Matt; Endres, John R; Ahmed, Mansoor; Ghambeer, Daljit K S

    2012-02-01

    Topical Acyclovir has moderate efficacy on recurrent HSV symptoms, requiring repeat applications for several days. Topical Dynamiclear, which requires only a single dose application, may provide a more effective and convenient treatment option for symptomatic management of HSV. The study assessed the comparative efficacy and tolerability of a single use, topical formulation containing copper sulfate pentahydrate and Hypericum perforatum that is marketed as Dynamiclear™ to a topical 5% Acyclovir cream standard preparation and use. A prospective, randomized, multi-centered, comparative, open-label clinical study was conducted. A total of 149 participants between 18 and 55 years of age with active HSV-1 and HSV-2 lesions were recruited for the 14-day clinical trial. Participants were randomized into two groups: A (n=61), those receiving the Dynamiclear formulation, and B (n=59), those receiving 5% Acyclovir. Efficacy parameters were assessed via physical examination at baseline (day 1), day 2, 3, 8, and 14. Laboratory safety tests were conducted at baseline and on day 14. Use of the Dynamiclear formulation was found to have no significant adverse effects and was well tolerated by participants. All hematological and biochemical markers were within normal range for the Dynamiclear group. Statistically, odds for being affected by burning and stinging sensation were 1.9 times greater in the Acyclovir group in comparison to the Dynamiclear group. Similarly, the odds of being affected by symptoms of acute pain, erythema and vesiculation were 1.8, 2.4, and 4.4 times higher in the Acyclovir group in comparison to the Dynamiclear group. The Dynamiclear formulation was well tolerated, and efficacy was demonstrated in a number of measured parameters, which are helpful in the symptomatic management of HSV-1 and HSV-2 lesions in adult patients. Remarkably, the effects seen from this product came from a single application.

  13. Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy.

    Science.gov (United States)

    Kim, Dong Wook; Gu, Nami; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Kim, Hwa Suk; Oh, Jeeyoung; Lee, Sang Kun

    2012-01-01

    The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  14. Efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia.

    Science.gov (United States)

    Shenoy, K T; Veenasree; Leena, K B

    2003-06-01

    To document the clinical efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia an open-label, non-comparative study, was undertaken at the Medical College, Thiruvananthapuram, among patients with endoscopically confirmed diagnosis of non-ulcer dyspepsia or chronic gastritis. Itopride hydrochloride 50 mg (1 tablet) thrice a day for 2 weeks was administered among them. Relief of symptoms at the end of two weeks treatment, assessed as marked/complete, moderate, slight, none or worse; QT interval on ECG; adverse events; haemogram; serum chemistry for hepatic and renal functions. None had QT prolongation on ECG. At the end of 2 weeks' treatment, moderate to complete relief of symptoms was reported by 22 patients (73%), whereas 5 (17%) reproted slight improvement, and 3 (10%) reported no improvement. Clinical tolerability was excellent in 28 patients (93%) and good in 2 (7%). None of the patients had any prolongation of QT on ECG, nor did any patient show any abnormality in haemogram or serum chemistry during the treatment.

  15. Efficacy and tolerability of tegaserod in constipation dominant irritable bowel syndrome

    International Nuclear Information System (INIS)

    Shah, S.H.A.; Jafri, S.W.; Gul, M.; Butt, J.A.; Naqvi, A.; Rasheed, I.

    2004-01-01

    Objective: To determine the efficacy and tolerability of tegaserod in the treatment of symptoms of irritable bowel syndrome (IBS) IBS-C patients. Patients and Methods: Tegaserod was administered in a dose of 6 mg (twice-a-day) orally for a period of 6 weeks. Symptoms were assessed before and during treatment using a questionnaire. Results: The mean age of patients was 37.5 years and 81 (69.2%) were males. The study enrolled 117 patients and 101 patients completed the study. Number of bowel movements, symptoms of straining at defecation, stool consistency, bloating, urgency and abdominal pain improved significantly following treatment (p<0.05). Analysis of data in both genders separately showed statistically significant improvement in symptoms of urgency, straining at defecation, abdominal pain and number of bowel movements following treatment. Side effects of diarrhea and vertigo (6 and 1 patients respectively) necessitating discontinuation of treatment were infrequent. Conclusion: Tegaserod given in a dose of 6 mg b.d. is effective and well tolerated in IBS-C patients. It is equally effective in males and females in relieving the symptoms of abdominal pain, bloating, straining at defecation as well as increased in the mean number of bowel movements per week. (author)

  16. Tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in moderate to severe COPD patients

    DEFF Research Database (Denmark)

    Kerstjens, Huib A; Bjermer, Leif; Eriksson, Leif

    2010-01-01

    OBJECTIVE: This study evaluated the tolerability and efficacy of inhaled AZD4818, a CCR1 antagonist, in patients with COPD. METHODS: This double-blind, placebo-controlled study (NCT00629239) randomised patients with moderate to severe COPD to AZD4818 300mug or placebo twice daily via Turbuhaler....... These findings in COPD are in line with other studies reporting a lack of clinical efficacy with CCR1 antagonists in other therapy areas....

  17. Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

    Science.gov (United States)

    Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

    2011-10-01

    The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

  18. Efficacy and safety of intravenous daptomycin in Japanese patients with skin and soft tissue infections.

    Science.gov (United States)

    Aikawa, Naoki; Kusachi, Shinya; Mikamo, Hiroshige; Takesue, Yoshio; Watanabe, Shinichi; Tanaka, Yoshiyuki; Morita, Akiko; Tsumori, Keiko; Kato, Yoshiaki; Yoshinari, Tomoko

    2013-06-01

    Daptomycin is a lipopeptide antibiotic active against gram-positive organisms and recently approved for marketing in Japan. This study investigates the efficacy and safety of daptomycin in Japanese patients with skin and soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) for regulatory filing in Japan. Overall, 111 Japanese patients with SSTI were randomized in this open-label, randomized, active-comparator controlled, parallel-group, multicenter, phase III study. Patients received intravenous daptomycin 4 mg/kg once daily or vancomycin 1 g twice daily for 7-14 days. Efficacy was determined by a blinded Efficacy Adjudication Committee. Among patients with SSTIs caused by MRSA, 81.8 % (95 % CI, 69.1-90.9) of daptomycin recipients and 84.2 % (95 % CI, 60.4-96.6) of vancomycin recipients achieved a successful clinical response at the test-of-cure (TOC) visit. The microbiological success rate against MRSA at the TOC visit was 56.4 % (95 % CI, 42.3-69.7) with daptomycin and 47.4 % (95 % CI, 24.4-71.1) with vancomycin. Daptomycin was generally well tolerated; most adverse events were of mild to moderate severity. The measurement of daptomycin concentration in plasma revealed that patients with mild or moderate impaired renal function showed similar pharmacokinetics profiles to patients with normal renal function. Clinical and microbiological responses, stratified by baseline MRSA susceptibility, suggested that patients infected with MRSA of higher daptomycin MIC showed a trend of lower clinical success with a P value of 0.052 by Cochran-Armitage test. Daptomycin was clinically and microbiologically effective for the treatment of MRSA-associated SSTIs in Japanese patients.

  19. Efficacy and tolerability of a facial serum for fine lines, wrinkles, and photodamaged skin.

    Science.gov (United States)

    McCall-Perez, Fred; Stephens, Thomas J; Herndon, James H

    2011-07-01

    Dermatology visits for the prevention and treatment of aging skin are rapidly increasing. The clinical sequelae including wrinkling, pigmentary changes, roughness, laxity, and telangiectasia can all result in the appearance of aging skin, impacting quality of life. A facial serum was developed with ingredients associated with an improvement in the appearance of fine lines and wrinkles and increase in stratum corneum barrier function. Patients were instructed to use a gentle wash before applying the formulation and a moisturizer afterwards. To assess the efficacy and tolerability of a facial serum in improving the appearance of fine lines, wrinkles, and signs of photodamage. Thirty-four female subjects (Fitzpatrick classification I-IV) with early to advanced photodamaged skin in a 12-week, single-arm, open-label clinical trial. Visits were scheduled at Baseline and Weeks 4, 8, and 12. Efficacy was assessed using visual grading of facial and periocular skin (modified 10-point scales); changes in viscoelasticity properties were assessed by cutometry. Cutaneous tolerability was evaluated both clinically and subjectively using a 4-point scale and monitoring adverse events. Digital photography documented treatment-related changes in skin appearance. Subjects completed self-assessments at Baseline and Weeks 4, 8, and 12. Significant improvements in all parameters and skin condition were seen as early as Week 4 (p≤0.05). There was an 18-percent improvement in overall appearance by Week 12 (p≤0.05). Fine lines and coarse winkles improved by 27 and 15 percent, respectively (both p≤0.05). Significant improvements were also seen in uneven pigmentation, firmness/elasticity, toned/resiliency, skin radiance, tone, and tactile roughness/smoothness (10%, 11%, 18%, 21%, 16%, and 47%, respectively; allp≤0.05). By Week 12 subjects reported a 43-percent improvement in overall facial skin appearance and 24-percent reduction in mean scores for facial lines and wrinkles (bothp≤0

  20. Investigating Change in Adolescent Self-Efficacy of Food Safety through Educational Interventions

    Science.gov (United States)

    Beavers, Amy S.; Murphy, Lindsay; Richards, Jennifer K.

    2015-01-01

    A successfully targeted intervention can influence food safety knowledge, attitudes, and behaviors, as well as encourage participants to recognize their own responsibility for safe food handling. This acknowledgement of an individual's responsibility and capacity to address food safety can be understood as self-efficacy of food safety (SEFS). This…

  1. Sorafenib in Advanced Hepatocellular Carcinoma: A Nationwide Retrospective Study of Efficacy and Tolerability

    Directory of Open Access Journals (Sweden)

    Anne Helene Køstner

    2013-01-01

    Full Text Available Background. Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we explore the role of alpha-fetoprotein (αFP as a potential biomarker for treatment efficacy and correlation to survival. Methods. Seventy-six patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib between 2007 and 2009 were included. Followup was until 2011. Results. Patients in PS 0-1 had a median overall survival (mOS of 6.2 months, compared to 1.8 months in patients with poorer PS (P=0.005. Child-Pugh A patients had a mOS of 6.6 months versus 3.6 months among patients in Child-Pugh B or C (P=0.0001. Serum αFP ≥ 200 at baseline was prognostic for a shorter survival. All patients with radiologically verified tumor response and baseline αFP ≥ 200 experienced a significant decline in αFP within the first four weeks of treatment. Conclusion. The survival of patients with advanced HCC treated with sorafenib is dependent on performance status and liver function. Treatment of patients with compromised liver function and poor performance status cannot be recommended. The correlation between αFP and objective tumor response warrants further investigation.

  2. Efficacy and tolerance of sodium phosphates oral solution after diet liberalization.

    Science.gov (United States)

    Scott, Sherrie R; Raymond, Patricia L; Thompson, William O; Galt, Deborah J B

    2005-01-01

    Bowel cleansing regimens commonly require adherence to liquid diets for 24 to 48 hours before examination, which often leads to poor compliance, reduced cleansing, and ultimately inadequate examinations. The authors investigated the efficacy and tolerability of diet liberalization before bowel cleansing with sodium phosphates oral solution. Two hundred patients were randomized into two treatment groups. One group received the standard light breakfast followed by clear liquids the day before colonoscopy; the second had a normal breakfast followed by a low-residue lunch the day before colonoscopy. Both groups had the same bowel preparation with sodium phosphates oral solution (2 x 45-mL, 7 p.m./6 a.m.). There was no difference in clinical efficacy between the two diet regimens (excellent/good in 93% standard, 95% low-residue). Fewer patients receiving the low-residue diet reported hunger, and more patients receiving the low-residue regimen reported energy to perform usual activities. This study supports offering patients a regular breakfast and a low-residue lunch before bowel cleansing with sodium phosphates oral solution.

  3. The efficacy and safety of on-demand Elonza; a generic product of sildenafil in Thai men with erectile dysfunction.

    Science.gov (United States)

    Wijitsettakul, Udomsak; Pempongkosol, Sompol

    2013-06-01

    To evaluate the efficacy and safety of Elonza (generic product of sildenafil) 100 mg, a phosphodiesterase type 5 (PDE5) inhibitor, in Thai men with erectile dysfunction (ED). This prospective, Cohort study was conducted for eight weeks. Two hundred ten male patients, older than 20 years of age with ED were enrolled to receive generic product of sildenafil 100 mg taken as needed. Efficacy is evaluated through the International Index of Erectile Function (IIEF) scores for the five separate response domains, erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction domain. After sildenafil administration, erectile function domain scores were significantly increased from baseline, 5.02 (p product of sildenafil, was an effective and well-tolerated treatment for ED in Thai men.

  4. Allopregnanolone preclinical acute pharmacokinetic and pharmacodynamic studies to predict tolerability and efficacy for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ronald W Irwin

    Full Text Available To develop allopregnanolone as a therapeutic for Alzheimer's disease, we investigated multiple formulations and routes of administration in translationally relevant animal models of both sexes. Subcutaneous, topical (transdermal and intranasal, intramuscular, and intravenous allopregnanolone were bolus-administered. Pharmacokinetic analyses of intravenous allopregnanolone in rabbit and mouse indicated that peak plasma and brain levels (3-fold brain/plasma ratios at 5min were sufficient to activate neuroregenerative responses at sub-sedative doses. Slow-release subcutaneous suspension of allopregnanolone displayed 5-fold brain/plasma ratio at Cmax at 30min. At therapeutic doses by either subcutaneous or intravenous routes, allopregnanolone mouse plasma levels ranged between 34-51ng/ml by 30min, comparable to published endogenous human level in the third trimester of pregnancy. Exposure to subcutaneous, topical, intramuscular, and intravenous allopregnanolone, at safe and tolerable doses, increased hippocampal markers of neurogenesis including BrdU and PCNA in young 3xTgAD and aged wildtype mice. Intravenous allopregnanolone transiently and robustly phosphorylated CREB within 5min and increased levels of neuronal differentiation transcription factor NeuroD within 4h. Neurogenic efficacy was achieved with allopregnanolone brain exposure of 300-500hr*ng/g. Formulations were tested to determine the no observable adverse effect level (NOAEL and maximally tolerated doses (MTD in male and female rats by sedation behavior time course. Sex differences were apparent, males exhibited ≥40% more sedation time compared to females. Allopregnanolone formulated in sulfobutyl-ether-beta-cyclodextrin at optimized complexation ratio maximized allopregnanolone delivery and neurogenic efficacy. To establish the NOAEL and MTD for Allo-induced sedation using a once-per-week intravenous regenerative treatment regimen: In female rats the NOAEL was 0.5mg/kg and MTD 2mg

  5. Reliability analysis of repairable safety systems of a reprocessing plant allowing for tolerable system downtimes

    International Nuclear Information System (INIS)

    Schaefer, H.

    1987-01-01

    GRS has been engaged in safety analysises of the German Reprocessing Plant for several years. The development and verification of appropriate reliability analysis methods, the generation of data as well as the search for an adequate structural presentation of the results to form a basis of recommendations for technical or administrative measures or contributions to risk oriented evaluations have been or are in the process of being established. In contrast to NPP-studies, the reliability assessment of safety systems of a reprocessing plant is applied to repairable and often relatively small systems allowing for tolerable system downtimes. A sketch of the diverse cooling systems of a vessel containing a selfheating solution is given. The interruption of the cooling function for about one day might be tolerable before boiling will be reached. This interval is suitable for transfer of the solution to a spare vessel or for repairing the failed components, thus restoring the cooling function

  6. Phase I safety, tolerability and pharmacokinetic study of recombinant human mannan-binding lectin

    DEFF Research Database (Denmark)

    Petersen, K.A.; Matthiesen, F.; Agger, T.

    2006-01-01

    (rhMBL) is in development as a novel therapeutic approach. To assess the safety, tolerability, and pharmacokinetics of rhMBL, a placebo-controlled double-blinded study was performed in MBL-deficient healthy male subjects. rhMBL was administered as both single intravenous (i.v.) infusions (0.01, 0...... mild and no serious adverse events were recorded. There were no clinically significant changes in laboratory evaluations, ECG or vital signs, and no anti-MBL antibodies were detected following rhMBL administration. After single i.v. doses of rhMBL the maximal plasma levels increased in a dose...... of the complement system without non-specific activation of the complement cascade.In conclusion, no safety or tolerability concern was raised following rhMBL administration no signs of immunogenicity detected, and an rhMBL plasma level judged sufficient to achieve therapeutic benefit (>1000 ng/mL) can be achieved....

  7. The safety and tolerance of phytotherapies in menopausal medicine – a review of the literature

    Directory of Open Access Journals (Sweden)

    Piotr Czuczwar

    2017-04-01

    Full Text Available Phytoestrogens are polyphenol, non-steroidal substances of plant origin, resembling 17-estradiol in structure. These substances can act as either agonists or antagonists of oestrogen receptors  and . Phytoestrogens are widely used to alleviate menopausal symptoms, such as hot flushes and night sweats. Most of the currently available products of plant origin registered to soften climacteric symptoms consist of extracts obtained from soy, red clover, or black cohosh. Non-hormonal phytotherapy is a new alternative for patients suffering from menopausal symptoms. Active ingredients such as PI 82-GC FEM extract do not show any direct hormonal mechanisms of action typical for oestrogens and phytoestrogens. There are concerns about the safety and tolerability of phytoestrogens. In this review we summarise the current literature regarding the clinical aspect of safety and tolerance of different phytotherapies used to relieve menopausal symptoms.

  8. Electronic Cigarettes Efficacy and Safety at 12 Months: Cohort Study.

    Directory of Open Access Journals (Sweden)

    Lamberto Manzoli

    Full Text Available To evaluate the safety and efficacy as a tool of smoking cessation of electronic cigarettes (e-cigarettes, directly comparing users of e-cigarettes only, smokers of tobacco cigarettes only, and smokers of both.Prospective cohort study. Final results are expected in 2019, but given the urgency of data to support policies on electronic smoking, we report the results of the 12-month follow-up.Direct contact and structured questionnaires by phone or via internet.Adults (30-75 years were included if they were smokers of ≥1 tobacco cigarette/day (tobacco smokers, users of any type of e-cigarettes, inhaling ≥50 puffs weekly (e-smokers, or smokers of both tobacco and e-cigarettes (dual smokers. Carbon monoxide levels were tested in a sample of those declaring tobacco smoking abstinence.Sustained smoking abstinence from tobacco smoking at 12 months, reduction in the number of tobacco cigarettes smoked daily.We used linear and logistic regression, with region as cluster unit.Follow-up data were available for 236 e-smokers, 491 tobacco smokers, and 232 dual smokers (overall response rate 70.8%. All e-smokers were tobacco ex-smokers. At 12 months, 61.9% of the e-smokers were still abstinent from tobacco smoking; 20.6% of the tobacco smokers and 22.0% of the dual smokers achieved tobacco abstinence. Adjusting for potential confounders, tobacco smoking abstinence or cessation remained significantly more likely among e-smokers (adjusted OR 5.19; 95% CI: 3.35-8.02, whereas adding e-cigarettes to tobacco smoking did not enhance the likelihood of quitting tobacco and did not reduce tobacco cigarette consumption. E-smokers showed a minimal but significantly higher increase in self-rated health than other smokers. Non significant differences were found in self-reported serious adverse events (eleven overall.Adding e-cigarettes to tobacco smoking did not facilitate smoking cessation or reduction. If e-cigarette safety will be confirmed, however, the use of e

  9. Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

    Directory of Open Access Journals (Sweden)

    A. Porwal

    2012-01-01

    Full Text Available Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n=109 or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n=108, intramuscularly. Pain intensity (PI was self-evaluated by patients on visual analogue scale (VAS at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID at 8 hours, and sum of analogue of pain intensity differences (SAPID. Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P<0.0001, PID at 8 hours (P=0.002, and SAPID0–8 hours (P=0.004. The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic.

  10. Efficacy and Tolerability of Fixed-Dose Combination of Dexketoprofen and Dicyclomine Injection in Acute Renal Colic

    Science.gov (United States)

    Porwal, A.; Mahajan, A. D.; Oswal, D. S.; Erram, S. S.; Sheth, D. N.; Balamurugan, S.; Kamat, V.; Enadle, R. P.; Badadare, A.; Bhatnagar, S. K.; Walvekar, R. S.; Dhorepatil, S.; Naik, R. C.; Basu, I.; Kshirsagar, S. N.; Keny, J. V.; Sengupta, S.

    2012-01-01

    Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID0–8 hours (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic. PMID:22577544

  11. Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    S Yu Vorotnikova

    2012-09-01

    Full Text Available Реферат по статье: Assessment of efficacy and tolerability of once-daily extended release metformin in patients with type 2 diabetes mellitus Juliana Levy, Roberta A Cobas, Marilia B Gomes. Diabetol Metab Syndr. 2010 Mar 18; 2:16.

  12. Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

    Directory of Open Access Journals (Sweden)

    Hee Chul Nam

    2016-06-01

    Full Text Available Background/Aims: The treatment strategy for hepatitis C virus (HCV has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV and asunaprevir (ASV. We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. Methods: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12 and safety. Results: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN and ribavirin (RBV treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation occurring in two patients. Conclusion: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

  13. Multicenter analysis of tolerance and clinical safety of the extracellular MR contrast agent gadobenate dimeglumine (MultiHance registered)

    International Nuclear Information System (INIS)

    Herborn, Christoph U.; Jaeger-Booth, I.; Goyen, M.; Lodemann, K.P.; Spinazzi, A.

    2009-01-01

    Purpose: Retrospective analysis of the occurrence of adverse events and the diagnostic efficacy of a paramagnetic contrast agent with weak intermittent protein binding and high relaxivity. Materials end methods: Postmarketing surveillance studies for gadobenate dimeglumine (MultiHance, BRACCO Altana Pharma, Constance) were conducted in Germany between 1998 and 2006 and then retrospectively analyzed. Demographic data, relevant comorbidities, and allergies were recorded. The safety and tolerability of MultiHance were logged on a standardized data sheet. Results: A total of 38568 patients were included in the study. 829 patients (2.1%) had a known intolerance against contrast media. The examined regions included the central nervous system, the liver, and the vascular bed. The injection rate with automated injectors (n = 10456) varied between 1.0 und 3.0 ml/sec in 86.5% of patients. Adverse events totaled 1.2%. 11 patients (0.03%) experienced serious adverse events. The most frequent findings were nausea, vomiting and a feeling of warmth. Conclusion: MultiHance is a safe and very well tolerated contrast agent for magnetic resonance imaging (MRI) with a profile and frequency of adverse events similar to other extracellular MR contrast materials. (orig.)

  14. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations.

    Science.gov (United States)

    Smith, Mark C; Zimmerman, M Bridget; Burke, Diane K; Bauman, Nancy M; Sato, Yutaka; Smith, Richard J H

    2009-01-01

    To determine the efficacy and safety of the immunostimulant OK-432 (Picibanil) as a treatment option in the management of children with cervicofacial lymphatic malformations. A prospective, randomized, multi-institutional phase II clinical trial at 27 U.S. academic medical centers. 182 patients with lymphatic malformations (LM) were enrolled between January 1998 and November 2004. Of the 151 patients with complete case report forms, 117 patients were randomized into immediate or delayed treatment groups; 34 patients were nonrandomized and assigned to the open-label group. Treatment consisted of a four-dose intralesional injection series of OK-432 at eight-week intervals. Patients randomized into the delayed treatment group served as observational controls for spontaneous regression. Response to therapy was measured radiographically by quantitating change in lesion size and graded as complete (90%-100%), substantial (60%-89%), intermediate (20%-59%), or none (<20%). Of 117 patients randomized with intent-to-treat, 68% demonstrated a complete or substantial response to OK-432 immunotherapy. Response data for macrocystic LM were higher, with a complete or substantial response in 94% of patients; 63% of patients with mixed macrocystic-microcystic LM responded to treatment; no patients with microcystic LM responded to treatment. Spontaneous resolution occurred in less than 2% of patients. Median follow-up of 2.9 years demonstrated a 9% recurrence rate. Major adverse effects related to therapy occurred in 11 patients. As compared to historical surgical data on LM, OK-432 immunotherapy is more effective (P < .001) and has a lower morbidity (P < .001). OK-432 immunotherapy is an effective, safe, and simple treatment option for the management of macrocystic cervicofacial LM. ClinicalTrials.gov Identifier: NCT00010452.

  15. Efficacy and safety of topical tranexamic acid in knee arthroplasty.

    Science.gov (United States)

    López-Hualda, Álvaro; Dauder-Gallego, Cristina; Ferreño-Márquez, David; Martínez-Martín, Javier

    2018-02-26

    Tranexamic acid (TXA) is commonly used to control postoperative blood loss in total knee arthroplasty. In order to avoid adverse effects associated with intravenous administration, topical use has been proposed as an alternative. Our aim was to evaluate the efficacy and safety of topical TXA in total knee arthroplasty. A total of 90 patients scheduled for unilateral total knee arthroplasty were included in a prospective randomised study. All surgeries were performed under spinal anaesthesia, tourniquet and the same postoperative protocol. Patients were allocated to one of the 3 groups according to the application of TXA: group A (n=30) 1g of topical TXA; group B (n=30) 1g of TXA intravenous and in group C or the control group (n=30) no drug was administrated. Parameters related to blood loss and drain outputs were compared between the 3 groups. The results revealed that post-operative decrease in haemoglobin level was significantly lower in group A (1.95g/dL) than group B (2.25g/dL) and group C (2.96g/dL), P<.01. Total postoperative blood loss was lower in group A (195mL) than group B (466mL) and group C (718mL), P<.01. There was no significant difference in complications and allogenic blood transfusion rate between the 3 groups. According to the results, topical application of 1g TXA significantly reduced blood loss in patients undergoing total knee arthroplasty more than intravenous or no administration of TXA. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  16. Preliminary safety analysis of the PWR with accident-tolerant fuels during severe accident conditions

    International Nuclear Information System (INIS)

    Wu, Xiaoli; Li, Wei; Wang, Yang; Zhang, Yapei; Tian, Wenxi; Su, Guanghui; Qiu, Suizheng; Liu, Tong; Deng, Yongjun; Huang, Heng

    2015-01-01

    Highlights: • Analysis of severe accident scenarios for a PWR fueled with ATF system is performed. • A large-break LOCA without ECCS is analyzed for the PWR fueled with ATF system. • Extended SBO cases are discussed for the PWR fueled with ATF system. • The accident-tolerance of ATF system for application in PWR is illustrated. - Abstract: Experience gained in decades of nuclear safety research and previous nuclear accidents direct to the investigation of passive safety system design and accident-tolerant fuel (ATF) system which is now becoming a hot research point in the nuclear energy field. The ATF system is aimed at upgrading safety characteristics of the nuclear fuel and cladding in a reactor core where active cooling has been lost, and is preferable or comparable to the current UO 2 –Zr system when the reactor is in normal operation. By virtue of advanced materials with improved properties, the ATF system will obviously slow down the progression of accidents, allowing wider margin of time for the mitigation measures to work. Specifically, the simulation and analysis of a large break loss of coolant accident (LBLOCA) without ECCS and extended station blackout (SBO) severe accident are performed for a pressurized water reactor (PWR) loaded with ATF candidates, to reflect the accident-tolerance of ATF

  17. Efficacy and tolerability of urate-lowering drugs in gout : a randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol

    NARCIS (Netherlands)

    Reinders, Mattheus; van Roon, E.N.; Jansen, T.L.; Delsing, J.; Griep, E.N.; Hoekstra, M.; van de Laar, M.F.; Brouwers, J.R.

    Objectives: To investigate the efficacy and tolerability of allopurinol as the first-choice antihyperuricaemic treatment for gout, and compare the efficacy and tolerability of benzbromarone and probenecid as second-choice treatment. Methods: Prospective, multicentre, open-label, two-stage randomised

  18. Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.

    Directory of Open Access Journals (Sweden)

    Astrid Yeo

    Full Text Available Darapladib, a lipoprotein-associated phospholipase A2 (Lp-PLA2 inhibitor, failed to demonstrate efficacy for the primary endpoints in two large phase III cardiovascular outcomes trials, one in stable coronary heart disease patients (STABILITY and one in acute coronary syndrome (SOLID-TIMI 52. No major safety signals were observed but tolerability issues of diarrhea and odor were common (up to 13%. We hypothesized that genetic variants associated with Lp-PLA2 activity may influence efficacy and tolerability and therefore performed a comprehensive pharmacogenetic analysis of both trials. We genotyped patients within the STABILITY and SOLID-TIMI 52 trials who provided a DNA sample and consent (n = 13,577 and 10,404 respectively, representing 86% and 82% of the trial participants using genome-wide arrays with exome content and performed imputation using a 1000 Genomes reference panel. We investigated baseline and change from baseline in Lp-PLA2 activity, two efficacy endpoints (major coronary events and myocardial infarction as well as tolerability parameters at genome-wide and candidate gene level using a meta-analytic approach. We replicated associations of published loci on baseline Lp-PLA2 activity (APOE, CELSR2, LPA, PLA2G7, LDLR and SCARB1 and identified three novel loci (TOMM5, FRMD5 and LPL using the GWAS-significance threshold P≤5E-08. Review of the PLA2G7 gene (encoding Lp-PLA2 within these datasets identified V279F null allele carriers as well as three other rare exonic null alleles within various ethnic groups, however none of these variants nor any other loci associated with Lp-PLA2 activity at baseline were associated with any of the drug response endpoints. The analysis of darapladib efficacy endpoints, despite low power, identified six low frequency loci with main genotype effect (though with borderline imputation scores and one common locus (minor allele frequency 0.24 with genotype by treatment interaction effect passing the GWAS

  19. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma.

    Science.gov (United States)

    Weber, Jeffrey S; Kudchadkar, Ragini Reiney; Yu, Bin; Gallenstein, Donna; Horak, Christine E; Inzunza, H David; Zhao, Xiuhua; Martinez, Alberto J; Wang, Wenshi; Gibney, Geoffrey; Kroeger, Jodi; Eysmans, Cabell; Sarnaik, Amod A; Chen, Y Ann

    2013-12-01

    Nivolumab, a human immunoglobulin G4-blocking antibody against the T-cell programmed death-1 checkpoint protein, has activity against metastatic melanoma. Its safety, clinical efficacy, and correlative biomarkers were assessed with or without a peptide vaccine in ipilimumab-refractory and -naive melanoma. In this phase I study, 90 patients with unresectable stage III or IV melanoma who were ipilimumab naive and had experienced progression after at least one prior therapy (cohorts 1 to 3, 34 patients) or experienced progression after prior ipilimumab (cohorts 4 to 6, 56 patients) received nivolumab at 1, 3, or 10 mg/kg every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. Nivolumab with vaccine was well tolerated and safe at all doses. The RECIST 1.1 response rate for both ipilimumab-refractory and -naive patients was 25%. Median duration of response was not reached at a median of 8.1 months of follow-up. High pretreatment NY-ESO-1 and MART-1-specific CD8(+) T cells were associated with progression of disease. At week 12, increased peripheral-blood T regulatory cells and decreased antigen-specific T cells were associated with progression. PD-L1 tumor staining was associated with responses to nivolumab, but negative staining did not rule out a response. Patients who experienced progression after nivolumab could respond to ipilimumab. In patients with ipilimumab-refractory or -naive melanoma, nivolumab at 3 mg/kg with or without peptide vaccine was well tolerated and induced responses lasting up to 140 weeks. Responses to nivolumab in ipilimumab-refractory patients or to ipilimumab in nivolumab-refractory patients support combination or sequencing of nivolumab and ipilimumab.

  20. Efficacy and Safety of Oral Spray Containing Lysozyme and Cetylpyridinium: Subjective Determination of Patients with Tonsillopharyngitis.

    Science.gov (United States)

    Catic, Tarik; Mehic, Meliha; Binakaj, Zahida; Sahman, Bilsena; Cordalija, Vedina; Kerla, Amra; Martinovic, Igor; Eskic, Hajra

    2016-12-01

    Tonsillopharyngitis (sore throat) is a common disease mainly related to the seasonal common cold. To relieve unpleasant symptoms and discomfort of acute tonsillopharyngitis associated with common cold, patients usually take some non-prescription drugs. The primary aim of this study was to assess subjective determinations of the efficacy and the safety/tolerability of an oral spray comprising a combination of lysozyme chloride and cetylpyridinium chloride in those patients. The study involved 1727 patients with tonsillopharyngitis associated with common cold and treated with the studied drug, in the period from December 2014 through March 2015. In total, 95% of patients rated the studied drug to be well, very well and excellently effective. In 32% of patients, the symptoms were relieved 10 minutes after the application of the spray. Significant correlations were found between the two subjective assessments of the drug efficiency with the total of 74.11% (95% CI: 73.41, 77.47%) of patients who said that the feeling of pain in the throat completely disappeared after the drug administration, evaluated the impact/effect of the drug was very good or good (Pearson Chi Square=391.401, p<0.001). The effectiveness was significantly better in patients with up to two episodes of common cold a year (Pearson Chi Square=6.101; p=0.014). The studied drug was rated to be well, very well and excellently tolerated by 97% of patients. According to patients' subjective assessment, the combination of lysozyme chloride and cetylpyridinium chloride in a formulation of spray can quickly, efficiently and safely resolve the symptoms of acute tonsillopharyngitis associated with common cold.

  1. A pilot study evaluating the safety and efficacy of modafinal for cancer-related fatigue.

    Science.gov (United States)

    Blackhall, Leslie; Petroni, Gina; Shu, Jianfen; Baum, Lora; Farace, Elena

    2009-05-01

    Fatigue is a common symptom that lowers the quality of life of patients with cancer, affecting between 60% and 90% of patients. Relatively few options are available for the treatment of this debilitating condition. Modafinal, a psychostimulant developed for the treatment of narcolepsy, has been used to treat fatigue in other diseases such as multiple sclerosis, but little data support its use in cancer patients. The primary objective of this open-label pilot study was to evaluate the safety, and efficacy of modafinil in improving cancer-related fatigue (CRF) as measured by the Brief Fatigue Inventory (BFI). The effect of this agent on depression, quality of life, functional status, and cognitive function was also assessed. Modafinal was self-administered at a dose of 100 mg/d during weeks 1-2, and 200 mg during weeks 3-4. Assessments were performed at baseline, 2, and 4 weeks. BFI score was improved in 46% of patients at 2 weeks and 75% at 4 weeks (p = 0.025). Hospital Anxiety and Depression Scale scores declined at 2 and 4 weeks (p < 0.001). Most scales for neurocognitive function were unchanged. Score for all Functional Assessment of Cancer Therapy-Brain (FACT-BR) subscales (measuring quality of life), except social/family well-being, were improved (p < 0.05) at 2 and 4 weeks. Significant changes in Eastern Cooperative Oncology Group (ECOG) performance status were noted, with 40% of patients improving at least one level. Modafinil was well-tolerated with only one patient discontinuing treatment due to drug-related toxicity. In this pilot study modafinil was well-tolerated and effective for fatigue in patients with cancer. Improvements were also seen in mood, quality of life, and functional status.

  2. Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Qi, Wei; Gevonden, Martin; Shalev, Arieh

    2017-02-01

    Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

  3. Vaginal Use of Ibuprofen Isobutanolammonium (Ginenorm): Efficacy, Tolerability, and Pharmacokinetic Data: A Review of Available Data

    Science.gov (United States)

    Milani, Massimo; Iacobelli, Piero

    2012-01-01

    Vaginal infection and inflammation with or without vulvar involvement are very common gynecologicaly clinical conditions associated with morbidity and reduced quality of life. Vaginal infections are commonly treated with causal antimicrobial treatments. In addition to specific antimicrobial treatment, anti-inflammatory therapy, both systemic or topical (vaginal douche), could be useful in the integrated treatment approach of these conditions reducing symptoms and speeding up the recovery in vulvovaginitis. Ibuprofen is a well-known effective and well-tolerated anti-COX (anti-COX1 and COX2) compound. In addition, several in vitro studies suggest that Ibuprofen shares antimicrobial and antifungal activities. Ibuprofen isobutanolammonium (Ib-isb) (Ginenorm) is a soluble salt from formulation suitable for external and intravaginal use. This salt completely dissociates in aqueous solution. Ib-isob is available in sachet and vaginal douche pharmaceutical formulations. Clinical efficacy of Ib-isob has been documented in 10 clinical studies (6 controlled and 4 open trials) which have enrolled in total 399 women with vulvovaginitis. The six controlled clinical trials were performed both versus placebo (2 studies) or versus active comparators such as benzydamine. In these studied, Ib-Isb has been used in general for 7 consecutive days with a twice application daily regimen at the dose of 1 g per application. Topical application of Ib-isob induced a marked and rapid reduction in signs (erythema, oedema) and symptoms (itching and burning sensation) of vulvovaginitis. In head-to-head studies carried out in comparison with other topical products, Ib-isob induced a more rapid reduction in both subjective and objective symptoms. In particular a remarkable significant improvement of all the symptoms has been observed in the group of patients treated with Ib-isob in comparison with women receiving benzydamine. The clinical data available for Ib-isob confirm that this salt

  4. Tolerance and efficacy of nasogastric enteral nutrition for severe acute pancreatitis: a metaanalysis

    Directory of Open Access Journals (Sweden)

    Shu-fen FENG

    2013-02-01

    Full Text Available Objective  To evaluate the tolerance and efficacy of nasogastric enteral nutrition (NGEN in the treatment of severe acute pancreatitis (SAP. Methods  PUBMED, Web of Science and The Cochrane Central Register of Controlled Trials from 1966 to 2011 (up to October and Chinese Journals Full-text Database (CNKI, Database for Chinese Technical Periodicals (VIP and Wanfang Digital Journal Full-text Database from 1978 to 2011 (up to October were retrieved to collect clinical randomized controlled trials of NGEN to compare with nasojejunal enteral nutrition (NJEN in the treatment of SAP. Two reviewers independently screened the literature for eligibility and evaluated the quality with confirmation of cross-check. Different opinions would be decided by the third party. Statistical analysis was performed by meta-analysis using Review Manager 4.2. Results  Three randomized controlled trails including 159 patients with SAP met the inclusion criteria, involving 82 patients in NGEN group and 77 in NJEN group. There was no significant difference between NGEN and NJEN group in the risk of mortality of SAP (RR=0.69, 95%CI: 0.37-1.29, P=0.25, conversion to surgery (RR=2.09, 95% CI: 0.55-7.92, P=0.28, diarrhea subsequent to enteral nutrition (RR=1.43, 95% CI: 0.59-3.45, P=0.43, rate of tube displacement (RR=0.42, 95%CI: 0.08-2.17, P=0.30 and pain related with enteral nutrition (RR=0.94, 95%CI: 0.32-2.70, P=0.90. While compared with NJEN, the risk of infectious complications was lower than NGEN (RR=0.64, 95%CI: 0.42-0.99, P=0.04. Conclusion  In enteral nutrition support of SAP, NGEN is comparable to NJEN in efficacy and tolerance, but the former has the lower rate of infectious complications and easier to operate, and there is a tendency of NEGN to replace the latter.

  5. Efficacy and Safety of Rituximab in Children with Refractory Nephrotic Syndrome; A Multicenter Clinical Trial

    Directory of Open Access Journals (Sweden)

    Yo Han Ahn

    2014-06-01

    Conclusions: In this interim analysis of clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS, RTX treatment for refractory NS was safe and effective, especially in patients with DNS.

  6. Safety, feasibility and efficacy of a rapid ART initiation in pregnancy ...

    African Journals Online (AJOL)

    Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot programme in Cape Town, South Africa. S Black, R Zulliger, L Myer, R Marcus, S Jeneker, R Taliep, D Pienaar, R Wood, L-G Bekker ...

  7. The efficacy and safety of diphenylcyclopropenone solutions in propylene glycol and isopropanol. A comparative study of two formulas used for the treatment of 100 patients with alopecia areata

    Directory of Open Access Journals (Sweden)

    Katarzyna Borowska

    2017-10-01

    Full Text Available Alopecia areata (AA is a T cell-mediated autoimmune disease involving hair follicles characterized by hair loss. 2,3-diphenylcyclopropenone (DCP is a topically administered drug intended for treating AA. The study investigates an efficacy and safety of DCP for the purpose of the treatment of AA. It presents a comparative study of two formulas: DCP in propylene glycol and DCP in isopropanol. While the treatment efficacy in both groups was very simmilar, the tolerance of the DCP in isopropanol was better than DCP in propylene glycol. Authors indicate the potential clinical applications of latter formula.

  8. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jan K Buitelaar

    2009-08-01

    Full Text Available Jan K Buitelaar1, J Antoni Ramos-Quiroga2, Miguel Casas2, J J Sandra Kooij3, Asko Niemelä4, Eric Konofal5, Joachim Dejonckheere6, Bradford H Challis7, Rossella Medori81Department of Psychiatry, University Medical Center, St. Radboud and Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands; 2Department of Psychiatry, Hospital Universitari Vall d’Hebron and Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 3PsyQ, Psycho-Medical Programs, Program Adult ADHD, Den Haag, The Netherlands; 4Oulu University Hospital, Department of Psychiatry, Oulu, Finland; 5Groupe Hospitalier Pitie-Salpetriere, Paris, France; 6SGS Life Sciences, Mechelen, Belgium; 7Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ, USA; 8Janssen-Cilag EMEA, Neuss, GermanyAbstract: The osmotic release oral system (OROS methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety and tolerability of OROS methylphenidate in a flexible dose regimen (18–90 mg daily for the treatment of adults diagnosed with ADHD (N = 370. Medication was adjusted to optimize efficacy and tolerability for each patient. Adverse events, vital signs, and laboratory parameters were assessed. Most patients (337; 91% completed the seven-week treatment and the final dispensed dose was 18 mg (8%, 36 mg (29%, 54 mg (34%, 72 mg (20%, or 90 mg (9%. Adverse events were reported in 253 (68% patients and most were mild or moderate in severity; most frequently reported included headache (17%, decreased appetite (13%, and insomnia (11%. Adverse events were rarely serious (<1%; 2/370. Small mean increases in systolic and diastolic blood pressure (both 2.4 mmHg and pulse (3.2 bpm were observed. Body weight decreased

  9. Efficacy and safety of once-daily aclidinium in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Bateman Eric D

    2011-04-01

    Full Text Available Abstract Background The long-term efficacy and safety of aclidinium bromide, a novel, long-acting muscarinic antagonist, were investigated in patients with moderate to severe chronic obstructive pulmonary disease (COPD. Methods In two double-blind, 52-week studies, ACCLAIM/COPD I (n = 843 and II (n = 804, patients were randomised to inhaled aclidinium 200 μg or placebo once-daily. Patients were required to have a post-bronchodilator forced expiratory volume in 1 second (FEV1/forced vital capacity ratio of ≤70% and FEV1 1 at 12 and 28 weeks. Secondary endpoints were health status measured by St George's Respiratory Questionnaire (SGRQ and time to first moderate or severe COPD exacerbation. Results At 12 and 28 weeks, aclidinium improved trough FEV1 versus placebo in ACCLAIM/COPD I (by 61 and 67 mL; both p Conclusion Aclidinium is effective and well tolerated in patients with moderate to severe COPD. Trial registration ClinicalTrials.gov: NCT00363896 (ACCLAIM/COPD I and NCT00358436 (ACCLAIM/COPD II.

  10. Safety, efficacy and patient acceptability of the combined estrogen and progestin transdermal contraceptive patch: a review

    Directory of Open Access Journals (Sweden)

    Alessandra Graziottin

    2008-11-01

    Full Text Available Alessandra GraziottinCenter of Gynecology and Medical Sexology, H San Raffaele Resnati, Via Santa Croce 10/a, 20123 Milano, ItalyAbstract: The worldwide introduction of the first, unique patch for hormonal contraception (ethinyl estradiol/norelgestromin, EE/NGMN patch was widely recognized as a significant event in the development of drug delivery systems. This innovation offers a number of advantages over the oral route, and extensive clinical trials have proved its safety, efficacy, effectiveness, and tolerability. The weekly administration and ease of use/simplicity of the EE/NGMN patch contribute to its acceptability, and help to resolve the two main problems of non-adherence, namely early discontinuation and inconsistent use. The patch offers additional benefits to adolescents (improvement of dysmenorrhea and acne, adults (improvement in emotional and physical well-being, premenstrual syndrome, and menstrual irregularities, and perimenopausal women (correction of hormonal imbalance, modulation of premenopausal symptoms, thus providing high satisfaction rates (in nearly 90% of users. Since its introduction, the transdermal contraceptive patch has proved to be a useful choice for women who seek a convenient formulation which is easy to use, with additional, non-contraceptive tailored benefits for all the ages.Keywords: transdermal, hormonal contraceptive, patient satisfaction, patient adherence

  11. Efficacy and safety of lung recruitment in pediatric patients with acute lung injury.

    Science.gov (United States)

    Boriosi, Juan P; Sapru, Anil; Hanson, James H; Asselin, Jeanette; Gildengorin, Ginny; Newman, Vivienne; Sabato, Katie; Flori, Heidi R

    2011-07-01

    To assess the safety and efficacy of a recruitment maneuver, the Open Lung Tool, in pediatric patients with acute lung injury and acute respiratory distress syndrome. Prospective cohort study using a repeated-measures design. Pediatric intensive care unit at an urban tertiary children's hospital. Twenty-one ventilated pediatric patients with acute lung injury. Recruitment maneuver using incremental positive end-expiratory pressure. The ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (Pao2/Fio2 ratio) increased 53% immediately after the recruitment maneuver. The median Pao2/Fio2 ratio increased from 111 (interquartile range, 73-266) prerecruitment maneuver to 170 (interquartile range, 102-341) immediately postrecruitment maneuver (p interquartile range, 116-257) 4 hrs postrecruitment maneuver (p interquartile range, 127-236) 12 hrs postrecruitment maneuver (p interquartile range, 44-60) prerecruitment maneuver compared with 48 torr (interquartile range, 43-50) immediately postrecruitment maneuver (p = .69), 45 torr (interquartile range, 41-50) at 4 hrs postrecruitment maneuver (p interquartile range, 38-51) at 12 hrs postrecruitment maneuver. Recruitment maneuvers were well tolerated except for significant increase in Paco2 in three patients. There were no serious adverse events related to the recruitment maneuver. Using the modified open lung tool recruitment maneuver, pediatric patients with acute lung injury may safely achieve improved oxygenation and ventilation with these benefits potentially lasting up to 12 hrs postrecruitment maneuver.

  12. Diode laser cyclophotocoagulation in Indian eyes: efficacy and safety.

    Science.gov (United States)

    Singh, Kirti; Jain, Divya; Veerwal, Vikas

    2017-02-01

    Diode laser cyclophotocoagulation (DLCP) has emerged as a time-tested procedure for end-stage glaucoma with fewer complications. By means of this study, we have evaluated its wide indications, its efficacy, and safety in darkly pigmented Asian Indian eyes. Ninety-one eyes with uncontrolled glaucoma presenting to glaucoma clinic of a tertiary care center over a period of 6 years were scheduled for DLCP. The semiconductor diode laser with a G probe was used with laser energy delivered about 1.5 mm behind the surgical limbus. The extent of clock hours of laser application was determined by pretreatment intraocular pressure (IOP) and superior area was spared in cases where future filtration surgery was contemplated. The DLCP was repeated earliest at 1 month in case of non-response and a maximum of three laser procedures were performed for any patient. Ninety-one eyes of 89 patients (40 males, 49 females) were included. Common indications included secondary glaucoma (37.3 %), failed trabeculectomies (27.4 %), angle closure glaucoma (17.5 %), etc. Laser power delivered ranged from 990 to 1800 mW, (mean 1396 + 182.14 mW) with an average of 17 spots. Patients improved from pretreatment IOP of 38.18 + 8.96 mmHg (range 20.6-64) to post treatment IOP of 17.86 + 7.75 mmHg (range 10-42). Qualified success was defined as final IOP of 20 mm Hg or less on topical medications that could be achieved in 70 % eyes with one or repeat treatment. Pre op visual acuity ranged from PL+ to 6/18 showing a slight improvement to PL+ to 6/12 post op. A 58.5 % reduction of IOP was noted. No incidence of serious complications was noted during follow-up ranging from 9 months to 3 years. DLCP is an effective and safe tool to be used in Indian population for control of IOP. It can be safely used as a primary modality to bring IOP to permissible levels before trabeculectomy.

  13. Efficacy and safety of benazepril for advanced chronic renal insufficiency.

    Science.gov (United States)

    Hou, Fan Fan; Zhang, Xun; Zhang, Guo Hua; Xie, Di; Chen, Ping Yan; Zhang, Wei Ru; Jiang, Jian Ping; Liang, Min; Wang, Guo Bao; Liu, Zheng Rong; Geng, Ren Wen

    2006-01-12

    Angiotensin-converting-enzyme inhibitors provide renal protection in patients with mild-to-moderate renal insufficiency (serum creatinine level, 3.0 mg per deciliter or less). We assessed the efficacy and safety of benazepril in patients without diabetes who had advanced renal insufficiency. We enrolled 422 patients in a randomized, double-blind study. After an eight-week run-in period, 104 patients with serum creatinine levels of 1.5 to 3.0 mg per deciliter (group 1) received 20 mg of benazepril per day, whereas 224 patients with serum creatinine levels of 3.1 to 5.0 mg per deciliter (group 2) were randomly assigned to receive 20 mg of benazepril per day (112 patients) or placebo (112 patients) and then followed for a mean of 3.4 years. All patients received conventional antihypertensive therapy. The primary outcome was the composite of a doubling of the serum creatinine level, end-stage renal disease, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Of 102 patients in group 1, 22 (22 percent) reached the primary end point, as compared with 44 of 108 patients given benazepril in group 2 (41 percent) and 65 of 107 patients given placebo in group 2 (60 percent). As compared with placebo, benazepril was associated with a 43 percent reduction in the risk of the primary end point in group 2 (P=0.005). This benefit did not appear to be attributable to blood-pressure control. Benazepril therapy was associated with a 52 percent reduction in the level of proteinuria and a reduction of 23 percent in the rate of decline in renal function. The overall incidence of major adverse events in the benazepril and placebo subgroups of group 2 was similar. Benazepril conferred substantial renal benefits in patients without diabetes who had advanced renal insufficiency. (ClinicalTrials.gov number, NCT00270426.) Copyright 2006 Massachusetts Medical Society.

  14. Safety and efficacy of antibiotics among acutely decompensated cirrhosis patients.

    Science.gov (United States)

    Habib, Shahid; Patel, Nehali; Yarlagadda, Sandeep; Hsu, Chiu-Hsieh; Patel, Sarah; Schader, Lindsey; Walker, Courtney; Twesigye, Innocent

    2018-04-26

    Infection is a leading precipitant of acute-on-chronic liver failure. This study aims to determine the safety and efficacy of antibiotics within acute-on-chronic liver failure. Retrospective study of 457 acute-on-chronic liver failure patients admitted to the University of Arizona Health Network between January 1 and December 31, 2014. Eligibility criteria were as follows: at least 18 years of age and 6 months follow-up, data available to calculate systemic inflammatory response syndrome (SIRS), and acute-on-chronic liver failure. This study collected patient's clinical features and historical data. Key data points were infection, antibiotic use, and SIRS. This study used Cox proportional hazards to model the effects of clinical factors on risk of death. A total of 521 of 1243 met the inclusion criteria, and 64 had missing data, leaving 457 patients. Infection resulted in higher hazard (hazard ratio [HR] = 1.6, confidence interval [CI]: 1.1-1.3, P = 0.01). Patients with infections and antibiotics, compared with non-infected patients without antibiotics, had higher hazard (HR = 1.633, CI: 1.022-2.609, P = .04). Of those infected patients with antibiotics, SIRS patients experienced higher hazard (HR = 1.9, CI: 1.1-3.0, P = .007). Multivariable Cox proportional hazards associated the following with higher hazard: SIRS (HR = 1.866, CI: 1.242-2.804, P = 0.003), vancomycin (HR = 1.640, CI: 1.119-2.405, P = 0.011), Model for End-Stage Liver Disease (HR = 1.051, CI: 1.030-1.073, P < 0.001), gastrointestinal bleeding (HR = 1.727, CI: 1.180-2.527, P = 0.005), and hepatic encephalopathy (HR = 1.807, CI: 1.247-2.618, P = 0.002). Overall, treatment of infection with antibiotics did not improve survival; however, patients not meeting SIRS criteria had better outcomes, and vancomycin was associated with poorer survival among acute-on-chronic liver failure patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley

  15. Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis

    DEFF Research Database (Denmark)

    Bartels, E. M.; Bliddal, Henning; Schøndorff, P. K.

    2010-01-01

    To estimate the efficacy and safety of diacerein as a pain-reducing agent in the treatment of osteoarthritis (OA), using meta-analysis of published randomized placebo-controlled trials (RCTs).......To estimate the efficacy and safety of diacerein as a pain-reducing agent in the treatment of osteoarthritis (OA), using meta-analysis of published randomized placebo-controlled trials (RCTs)....

  16. Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

    OpenAIRE

    Xie, Chen; Tang, Yurong; Wang, Yunfeng; Yu, Ting; Wang, Yun; Jiang, Liuqin; Lin, Lin

    2015-01-01

    Aim The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. Methods We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. Results Twelve randomized controlled trials were...

  17. The Evidence Base on the Efficacy and Safety of Ibuprofen in Pediatrics

    Directory of Open Access Journals (Sweden)

    Yu.V. Marushko

    2013-10-01

    Full Text Available The article deals with an analysis of the world literature of recent years, the aim of which was to study the efficacy and safety of ibuprofen use as first-line antipyretic in pediatric practice. Special attention was paid to researches on the study the pharmacokinetics, efficacy and safety of ibuprofen in fever in children of all ages, as well as the use of different forms of ibuprofen (suspension, suppositories.

  18. Safety and efficacy of fenproporex for obesity treatment: a systematic review

    OpenAIRE

    Paumgartten,Francisco José Roma; Pereira,Sabrina Schaaf Teixeira Costa; Oliveira,Ana Cecilia Amado Xavier de

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to trea...

  19. Nab-paclitaxel for the treatment of breast cancer: efficacy, safety, and approval

    Directory of Open Access Journals (Sweden)

    Iwase H

    2011-07-01

    Full Text Available Yutaka Yamamoto1, Ichiro Kawano2, Hirotaka Iwase11Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 2Department of Surgery, Asahino General Hospital, Kumamoto, JapanAbstract: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel is a novel formulation of paclitaxel that does not require solvents such as polyoxyethylated castor oil and ethanol. Use of these solvents has been associated with toxic response, including hypersensitivity reactions and prolonged sensory neuropathy, as well as a negative impact in relation to the therapeutic index of paclitaxel. nab-paclitaxel displays greater antitumor activity and less toxicity than solvent-base paclitaxel. In a phase I trial of single nab-paclitaxel, the maximum tolerated dose was 300 mg/m2 with the dose limiting toxicities being sensory neuropathy, stomatitis, and superficial keratopathy. In the metastatic setting, a pivotal comparative randomized phase III study demonstrated that nab-paclitaxel (at 260 mg/m2 over 30 minutes infusion without premedication every 3 weeks mediated a superior objective response rate and prolonged time to progression compared with solvent-based paclitaxel (at 175 mg/m2 over a 3-hour injection with standard premedication. The nab-paclitaxel-treated group showed a higher incidence of sensory neuropathy than the solvent-based paclitaxel group. However, these adverse side effects rapidly resolved after interruption of treatment and dose reduction. Weekly administration of nab-paclitaxel was also more active and displayed less toxicity compared with 100 mg/m2 docetaxel given triweekly. Nab-paclitaxel has already been approved in 42 countries for the treatment of metastatic breast cancer previously treated with anthracycline, based on confirmation of the efficacy and manageable toxicity in the metastatic setting. This review summarizes the most relevant knowledge on nab-paclitaxel for treating breast cancer

  20. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Bhusal S

    2016-02-01

    Full Text Available Santosh Bhusal,1 Sherilyn Diomampo,1 Marina N Magrey2 1Division of Rheumatology, Metrohealth Medical Center, 2Case Western Reserve University School of Medicine at Metrohealth Medical Center, Cleveland OH, USA Abstract: Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. Keywords: fibrositis, myofascial pain, diffuse pain syndrome, lyrica

  1. Efficacy and Safety of Inhaled Aztreonam Lysine for Airway Pseudomonas in Cystic Fibrosis

    Science.gov (United States)

    Retsch-Bogart, George Z.; Quittner, Alexandra L.; Gibson, Ronald L.; Oermann, Christopher M.; McCoy, Karen S.; Montgomery, A. Bruce; Cooper, Peter J.

    2009-01-01

    Background: We assessed the short-term efficacy and safety of aztreonam lysine for inhalation (AZLI [an aerosolized monobactam antibiotic]) in patients with cystic fibrosis (CF) and Pseudomonas aeruginosa (PA) airway infection. Methods: In this randomized, double-blind, placebo-controlled, international study (AIR-CF1 trial; June 2005 to April 2007), patients (n = 164; ≥ 6 years of age) with FEV1 ≥ 25% and ≤ 75% predicted values, and no recent use of antipseudomonal antibiotics or azithromycin were treated with 75 mg of AZLI (three times daily for 28 days) or placebo (1:1 randomization), then were monitored for 14 days after study drug completion. The primary efficacy end point was change in patient-reported respiratory symptoms (CF-Questionnaire-Revised [CFQ-R] Respiratory Scale). Secondary end points included changes in pulmonary function (FEV1), sputum PA density, and nonrespiratory CFQ-R scales. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored. Results: After 28 days of treatment, AZLI improved the mean CFQ-R respiratory score (9.7 points; p < 0.001), FEV1 (10.3% predicted; p < 0.001), and sputum PA density (− 1.453 log10 cfu/g; p < 0.001), compared with placebo. Significant improvements in Eating, Emotional Functioning, Health Perceptions, Physical Functioning, Role Limitation/School Performance, and Vitality CFQ-R scales were observed. Adverse events were consistent with symptoms of CF lung disease and were comparable for AZLI and placebo except the incidence of “productive cough” was reduced by half in AZLI-treated patients. PA aztreonam susceptibility at baseline and end of therapy were similar. Conclusions: In patients with CF, PA airway infection, moderate-to-severe lung disease, and no recent use of antipseudomonal antibiotics or azithromycin, 28-day treatment with AZLI significantly improved respiratory symptoms and pulmonary function, and was well tolerated. Trial registration: Clinicaltrials

  2. The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Truncal Acne Vulgaris.

    Science.gov (United States)

    Hoffman, Lauren K; Del Rosso, James Q; Kircik, Leon H

    2017-06-01

    INTRODUCTION: Truncal acne is often associated with facial acne, but there are fewer options for an effective topical treatment on the trunk. Given the advent of foam formulations with enhanced percutaneous absorption and convenient application due to easy spreadability on skin, the previously held idea that effective treatment of truncal acne requires oral treatment is challenged. Azelaic acid cream has been previously approved for acne vulgaris, thus azelaic acid foam may be a viable treatment option for truncal acne. STUDY DESIGN: A single-center, open label pilot study was conducted to investigate the efficacy and safety of azelaic acid 15% foam as a treatment modality for moderate truncal acne. Use for facial acne was also allowed and monitored during the study. RESULTS: Twice-daily application of azelaic acid 15% foam to affected areas resulted in a 1-grade reduction in truncal investigator global assessment (IGA) scores in nearly all patients (16/18). Eight out of 18 patients (44%) were rated as Clear or Almost Clear in the trunk by the end of the study. There were also improvements in facial IGA scores; 9 of 18 patients (50%) exhibited a 1-grade improvement in IGA scores and 11 of 18 were Clear or Almost Clear by the end of the study. A significant reduction in lesion counts was found throughout the study and the medication was well tolerated. CONCUSION: Azelaic acid 15% foam was effective in treating moderate truncal acne and facial acne in this pilot study. Given the efficacy and convenience of the foam vehicle, azelaic acid may be considered as a viable option for treatment of acne vulgaris, including on the trunk. Further studies are suggested in a larger population of patients, including adult females with acne. J Drugs Dermatol. 2017;16(6):534-538..

  3. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

    Directory of Open Access Journals (Sweden)

    Ángela María Ruiz-Sternberg

    2018-06-01

    Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

  4. Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

    Science.gov (United States)

    Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain

    2018-06-01

    A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.

  5. Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

    Science.gov (United States)

    Maiteki-Sebuguzi, Catherine; Jagannathan, Prasanna; Yau, Vincent M; Clark, Tamara D; Njama-Meya, Denise; Nzarubara, Bridget; Talisuna, Ambrose O; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Staedke, Sarah G

    2008-01-01

    Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP), artesunate + amodiaquine (AS+AQ), or artemether-lumefantrine (AL). Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years). At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7), or AS+AQ (anorexia: RR 2.10, 95% CI 1

  6. Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

    Directory of Open Access Journals (Sweden)

    Kamya Moses R

    2008-06-01

    Full Text Available Abstract Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP, artesunate + amodiaquine (AS+AQ, or artemether-lumefantrine (AL. Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years. At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7, or AS

  7. Efficacy and tolerability of intravenous morphine patient-controlled analgesia (PCA) in women undergoing cesarean delivery.

    Science.gov (United States)

    Andziak, Marta; Beta, Jarosław; Barwijuk, Michal; Issat, Tadeusz; Jakimiuk, Artur J

    2015-06-01

    The aim of the study was to evaluate analgesic efficacy and tolerability of patient-controlled analgesia (PCA) with intravenous morphine. Our observational study included 50 women who underwent a Misgav-Ladach or modified Misgav-Ladach cesarean section. Automated PCA infusion device (Medima S-PCA Syringe Pump, Medima, Krakow, Poland) was used for postoperative pain control. Time of morphine administration or initiation of intravenous patient-controlled analgesia (IV PCA) with morphine was recorded, as well as post-operative pain at rest assessed by a visual analogue scale (VAS). All patients were followed up for 24 hours after discharge from the operating room, taking into account patient records, worst pain score at rest, number of IV PCA attempts, and drug consumption. Median of total morphine doses used during the postoperative period was 42.9mg (IQR 35.6-48.5), with median infusion time of 687.0 min. (IQR 531.0-757.5). Pain severity and total drug consumption improved after the first 3 hours following cesarean delivery (p PCA attempts per patient was 33 (IQR: 24-37), with median of 11 placebo attempts (IQR: 3-27). Patient-controlled analgesia with morphine is an efficient and acceptable analgesic method in women undergoing cesarean section.

  8. Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

    Science.gov (United States)

    Aman, Michael G; Findling, Robert L; Hardan, Antonio Y; Hendren, Robert L; Melmed, Raun D; Kehinde-Nelson, Ola; Hsu, Hai-An; Trugman, Joel M; Palmer, Robert H; Graham, Stephen M; Gage, Allyson T; Perhach, James L; Katz, Ephraim

    2017-06-01

    Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension. A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15 mg/day. There was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p = 0.02) after 12 weeks. This trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.

  9. [Efficacy and tolerance of PDE-5 in the treatment of erectile dysfunction in schizophrenic patients: A literature review].

    Science.gov (United States)

    Bacconi, L; Gressier, F

    2017-02-01

    function, desire, satisfaction during intercourse, overall satisfaction, and even the quality of life when it was studied. However, very few patients were included. Little data are available on the use of PDE5 inhibitors in schizophrenic patients. The 6 studies included few patients which reduces the power and the scope of their conclusions. There is also an important bias due to the use of self-questionnaires. The methodologies of the studies differ in many aspects which limits the comparability. Inclusion and exclusion criteria, drugs used and scales varied among the studies. However, the management of erectile disorder seems to be a consistent target in an integrative approach for the overall well-being of schizophrenic patients. PDE-5 inhibitors appear to be safe and could improve erectile function in schizophrenic patients. In total, the current data suggest efficiency and good tolerance of the use of PDE-5 inhibitors in schizophrenic patients with erectile dysfunction. However, further studies focusing on PDE-5 inhibitors are needed to more deeply assess their efficacy and safety in patients with schizophrenia. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

  10. Randomised Study to Compare the Efficacy and Tolerability of Duloxetine and Escitalopram in subjects with Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kiran Haridas

    2015-02-01

    Full Text Available Management of depression presents a significant medical challenge. Drugs with improved efficacy and better tolerability are valuable additions to the present therapy of this disorder. Evidence suggests that therapy with a combined serotonin and noradrenaline reuptake inhibitor may be a more effective therapy of major depressive disorder (MDD than a single neurotransmitter inhibitor. The present study assessed the efficacy and tolerability between duloxetine (dual neurotransmitter reuptake inhibitor 40-60 mg/day and escitalopram (single neurotransmitter reuptake inhibitor 10-20mg/day in 24 patients as an open labeled randomized study over a duration of 12 weeks. The primary efficacy measure was the mean total change in 17 items Hamilton rating scale for depression (HAMD17 from baseline to end point using the last observation carrying forward. Tolerability was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. In the present study, the primary analysis detected a statistically significant difference at p=.025 using Fischer’s test between duloxetine and escitalopram in both response and remission rates. There was no significant difference detected in efficacy of onset between the two study groups. Response rate, remission rate and efficacy of onset were highly significant at p<0.05 using Wilcoxon signed rank test within each group. There were a few adverse effects that were mild and self limiting with both molecules. Duloxetine is superior to escitalopram in response and remission of treatment of MDD in similar clinical setting. Both duloxetine and escitalopram are well tolerated molecules at comparable doses.

  11. Safety and Efficacy of Bevacizumab With Hypofractionated Stereotactic Irradiation for Recurrent Malignant Gliomas

    International Nuclear Information System (INIS)

    Gutin, Philip H.; Iwamoto, Fabio M.; Beal, Kathryn; Mohile, Nimish A.; Karimi, Sasan; Hou, Bob L.; Lymberis, Stella; Yamada, Yoshiya; Chang, Jenghwa

    2009-01-01

    Purpose: Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas. Methods and Materials: After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab. Results: Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%. Discussion: Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.

  12. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India

    Directory of Open Access Journals (Sweden)

    K M Prasanna Kumar

    2016-01-01

    Full Text Available Background: This post hoc analysis evaluated the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM from India. Methods: Changes from baseline in HbA1c, fasting plasma glucose (FPG, body weight, and blood pressure (BP with canagliflozin 100 and 300 mg were evaluated in a subgroup of patients from India (n = 124 from 4 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 2313; Population 1. Safety was assessed based on adverse event (AE reports in these patients and in a broader subgroup of patients from India (n = 1038 from 8 randomized, double-blind, placebo- and active-controlled, Phase 3 studies (N = 9439; Population 2. Results: Reductions in HbA1cwith canagliflozin 100 and 300 mg were −0.74% and −0.88%, respectively, in patients from India, and −0.81% and −1.00%, respectively, in the 4 pooled Phase 3 studies. In the Indian subgroup, both canagliflozin doses provided reductions in FPG, body weight, and BP that were consistent with findings in the overall population. The incidence of overall AEs in patients from India was generally similar with canagliflozin 100 and 300 mg and noncanagliflozin. The AE profile in patients from India was generally similar to the overall population, with higher rates of genital mycotic infections and osmotic diuresis–related and volume depletion–related AEs with canagliflozin versus noncanagliflozin. Conclusion: Canagliflozin provided glycemic control, body weight reduction, and was generally well tolerated in patients with T2DM from India.

  13. Safety and efficacy of lansoprazole injection in upper gastrointestinal bleeding: a postmarketing surveillance conducted in Indonesia.

    Science.gov (United States)

    Syam, Ari F; Setiawati, Arini

    2013-04-01

    to assess the safety and effectiveness of lansoprazole injection (Prosogan®) in patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis. this study was a multicenter observational postmarketing study of lansoprazole (Prosogan®) injection. Patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis were given intravenous lansoprazole for a maximum of 7 days or until the bleeding stopped and the patients were able to take oral doses of lansoprazole. Primary outcome of the study was cessation of bleeding. Some laboratory parameters were also measured. among a total of 204 patients evaluable for safety, there was no adverse event reported during the study. A total of 200 patients were eligible for efficacy evaluation, 125 patients (62.5%) were males. Among these patients, upper GI bleeding stopped in 20 patients (10.0%) on day 1, in 71 patients (35.5%) on day 2, 75 patients (37.5%) on day 3, 24 patients (12.0%) on day 4, and 7 patients (3.5%) on day 5, making a cumulative of 197 patients (98.5%) on day 5. The hemostatic effect was rated as 'excellent' if the bleeding stopped within 3 days, and 'good' if the bleeding stopped within 5 days. Thus, the results were 'excellent' in 166 patients (83.0%) and 'good' in 31 patients (15.5%). These results were not different between males and females, between age below 60 years and 60 years and above, and between baseline Hb below 10 g/dL and 10 g/dL and above. the results of this observational postmarketing study in 200 patients with upper gastrointestinal bleeding due to peptic ulcers or erosive gastritis demonstrated that intravenous lansoprazole twice a day was well tolerated and highly effective.

  14. The efficacy and safety of etanercept in patients with rheumatoid arthritis and spondyloarthropathy on hemodialysis.

    Science.gov (United States)

    Senel, Soner; Kisacik, Bunyamin; Ugan, Yunus; Kasifoglu, Timucin; Tunc, Ercan; Cobankara, Veli

    2011-10-01

    We aimed to evaluate the efficacy and safety of long-term use of etanercept therapy in patients with spondyloarthropathy (SpA) and rheumatoid arthritis (RA) on hemodialysis (HD). Selected RA or SpA patients treated with etanercept under HD were retrospectively evaluated. Etanercept-related adverse events were closely recorded for all patients. At the follow-up, erythrocyte sedimentation rate and C-reactive protein levels were monitored. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for SpA patients and Disease Activity Score (DAS28) for RA patients were measured at every 3 or 6 months. In total five end-stage renal disease (ESRD) patients were enrolled to the study. The causes of ESRD in the study subjects were amyloidosis (n = 2), analgesic nephropathy (n = 2), and nephrolithiasis (n = 1). Three were diagnosed as SpA and two were RA. All patients used etanercept. The median age was 39 years (range 22-72 years). The median disease duration was 12 years (range 2-20 years). The median follow-up after etanercept therapy was 18 months (range 5-33 months). DAS28 score decreased after the treatment and did not increase during follow-up in RA patients. BASDAI score decreased after the treatment during follow-up in three patients with SpA. At the follow-up, only one patient was diagnosed with septic arthritis. As a result of our study, etanercept treatment in RA and SpA patients on HD seems to be safe, well tolerated, and effective in most of the patients. Above all, due to impaired host defense in patients with ESRD, enhanced risk of infections should be kept in mind during follow-up period and larger trials are needed to prove the safety of etanercept in HD patients.

  15. Long-term safety and efficacy of twice-daily aclidinium bromide in patients with COPD.

    Science.gov (United States)

    Gelb, Arthur F; Tashkin, Donald P; Make, Barry J; Zhong, Xiaoyun; Garcia Gil, Esther; Caracta, Cynthia

    2013-12-01

    Aclidinium is a novel, long-acting muscarinic antagonist indicated for maintenance treatment of COPD. In this 52-week, parallel-group, double-blind study, patients with moderate-to-severe COPD were randomized (1:1) to receive aclidinium twice-daily (BID) 200 μg or 400 μg via a novel, dry powder inhaler (Genuair(®)/Pressair(®)) [Registered trademarks of Almirall, SA, Barcelona, Spain for use within the European Union, Iceland, Norway, and Switzerland as Genuair(®) and within the United States as Pressair(®)]. Safety, the primary objective, was assessed via adverse events (AEs), clinical laboratory tests, vital signs, and 12-lead electrocardiograms. Efficacy was evaluated using spirometry, SGRQ, and rescue medication use. A total of 605 patients were randomized in the study. The percentage of patients reporting any treatment-emergent AE (TEAE) was comparable between groups; most TEAEs were mild or moderate. Anticholinergic TEAEs were reported by low percentages of patients in either treatment group (dry mouth: 200 μg, 1.3%; 400 μg, 2.7%; constipation: 200 μg, 2.9%; 400 μg, 1.7%). Cardiac TEAEs were also reported by a low percentage of patients (<2% for any event in any group) and did not appear to be dose dependent. There were no clinically relevant abnormalities in other safety outcomes. Both aclidinium 200 μg and 400 μg resulted in improvements from baseline to Week 52 in FEV1, with numerically greater increases observed with the higher dose. Clinically important improvements in SGRQ scores and a reduction in rescue medication use were observed throughout the study for both doses. Long-term treatment with aclidinium 200 μg or 400 μg BID was well tolerated, with sustained benefits in lung function and health status in patients with COPD throughout the 1-year study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. The safety and efficacy of lorcaserin in the management of obesity.

    Science.gov (United States)

    Hess, Rick; Cross, L Brian

    2013-11-01

    Lorcaserin represents a new serotonergic medication used as an adjunct to a reduced-calorie diet and increased physical activity treatment plan for chronic weight management in adult patients with an initial body mass index ≥ 30 kg/m 2 or in adult patients with an initial body mass index ≥ 27 kg/m 2 who have ≥ 1 comorbid condition associated with weight (eg, hypertension, dyslipidemia, or type 2 diabetes mellitus). In 2012, lorcaserin became the first obesity treatment medication to gain US Food and Drug Administration (FDA) approval since 1999. Lorcaserin is a centrally acting, selective serotonin C (5-HT2C) receptor full agonist that is associated with increased satiety and decreased food consumption in patients. The selectivity of lorcaserin for 5-HT2C receptors should reduce patient risk for the serious adverse complications that are associated with nonselective 5-HT agonist therapies, such as cardiac valvulopathy and pulmonary hypertension. The safety and efficacy of lorcaserin (10 mg twice daily) for ≥ 52 weeks has been evaluated in 3 separate Phase 3 trials. The primary outcome of patient weight loss in the 3 trials satisfied the FDA categorical benchmark but patient outcomes in the trials failed to achieve the FDA mean benchmark of patient weight loss. Secondary patient outcomes after lorcaserin therapy were favorable. Lorcaserin appears to be well tolerated in patients and the most common adverse events reported did not include serious complications. The incidence of FDA-defined valvulopathy in patients after 1 year of treatment was low and nonsignificant, but the statistical analysis of this safety endpoint was limited due to the small size of the study populations and high patient dropout rates. Continued post-marketing surveillance of patients taking lorcaserin is warranted.

  17. Efficacy and safety of parecoxib in the treatment of acute renal colic: a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Sidney Glina

    2011-12-01

    Full Text Available PURPOSE: Although nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs and opioids are effective treatments for acute renal colic, they are associated with adverse events (AEs. As cyclooxygenase-2 selective NSAIDs may provide a safer alternative, we compared the efficacy and safety of parecoxib versus an nsNSAID in subjects with acute renal colic. MATERIALS AND METHODS: Phase IV., multicenter, double-blind, noninferiority, active-controlled study: 338 subjects with acute renal colic were randomized to parecoxib 40 mg i.v. plus placebo (n = 174 or ketoprofen 100 mg IV plus placebo (n = 164. 338 subjects with acute renal colic were randomized to parecoxib 40 mg IV (n = 174 or ketoprofen 100 mg IV(n = 164 plus placebo. Subjects were evaluated 15, 30, 45, 60, 90 and 120 minutes after treatment start and 24 hours after discharge. Primary endpoint was the mean pain intensity difference (PID at 30 minutes by visual analog scale (VAS (per-protocol population. An ANCOVA model was used with treatment group, country, and baseline score as covariates. Non-inferiority of parecoxib to ketoprofen was declared if the lower bound of the 95% confidence interval (CI for the difference between the two groups excluded the pre-established margin of 10 mm for the primary endpoint. RESULTS: Baseline demographics were similar. The mean (SD mPID30 min was 33.84 (24.61 and 35.16 (26.01 for parecoxib and ketoprofen, respectively. For treatment difference (parecoxib-ketoprofen the lower bound of the 95% CI was 6.53. The mean change from baseline in VAS 30 minutes after study medication was ~43 mm; AEs were comparable between treatments. CONCLUSIONS: Parecoxib is as effective as ketoprofen in the treatment of pain due to acute renal colic, is well tolerated, and has a comparable safety profile.

  18. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

    Science.gov (United States)

    Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

    2015-05-01

    Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared

  19. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

    Directory of Open Access Journals (Sweden)

    Solmi M

    2017-06-01

    -generation antipsychotics (SGAs ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis. Keywords: antipsychotics, side effects, tolerability, safety, psychosis, psychiatry

  20. comparative efficacy and safety of cefixime and ciprofloxacin

    African Journals Online (AJOL)

    2011-09-31

    common cause of hospital admission in Nigeria, and, ... respiratory pathogens to antibacterials have raised concerns about the decreasing efficacy of currently ... community-acquired pneumonia, between July 1 and September 31, 2011 at two.

  1. Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

    OpenAIRE

    Qian, Men-Bao; Yap, Peiling; Yang, Yi-Chao; Liang, Hai; Jiang, Zhi-Hua; Li, Wei; Tan, Yu-Guang; Zhou, Hui; Utzinger, Jürg; Zhou, Xiao-Nong; Keiser, Jennifer

    2017-01-01

    In this randomized open-label trial, tribendimidine was shown to have an efficacy comparable to praziquantel for the treatment of Clonorchis sinensis infection. Patients treated with praziquantel experienced significantly more adverse events than tribendimidine recipients.

  2. Specific safety and tolerability considerations in the use of anticonvulsant medications in children

    Directory of Open Access Journals (Sweden)

    Crepeau A

    2012-06-01

    Full Text Available Amy Z Crepeau,1 Brian D Moseley,2 Elaine C Wirrell31Division of Epilepsy, Department of Neurology, Mayo Clinic, 2Department of Neurology, Mayo Clinic, 3Divisions of Epilepsy and Child and Adolescent Neurology, Mayo Clinic, Rochester, MN, USAAbstract: Epilepsy is one of the most common neurological disorders in the pediatric age range, and the majority of affected children can be safely and effectively treated with antiepileptic medication. While there are many antiepileptic agents on the market, specific drugs may be more efficacious for certain seizure types or electroclinical syndromes. Furthermore, certain adverse effects are more common with specific classes of medication. Additionally patient-specific factors, such as age, race, other medical conditions, or concurrent medication use may result in higher rates of side effects or altered efficacy. Significant developmental changes in gastric absorption, protein binding, hepatic metabolism, and renal clearance are seen over the pediatric age range, which impact pharmacokinetics. Such changes must be considered to determine optimal dosing and dosing intervals for children at specific ages. Furthermore, approximately one third of children require polytherapy for seizure control, and many more take concurrent medications for other conditions. In such children, drug–drug interactions must be considered to minimize adverse effects and improve efficacy. This review will address issues of antiepileptic drug efficacy, tolerability and ease of use, pharmacokinetics, and drug–drug interactions in the pediatric age range.Keywords: antiepileptic drugs, drug–drug interactions, pharmacokinetics

  3. Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

    Science.gov (United States)

    Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

    2012-01-01

    Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

  4. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Ottosen, M B; Gniadecki, R

    2018-01-01

    BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

  5. Efficacy and safety of omalizumab in children and adolescents with moderate-to-severe asthma: A systematic literature review.

    Science.gov (United States)

    Corren, Jonathan; Kavati, Abhishek; Ortiz, Benjamin; Colby, Jennifer A; Ruiz, Kimberly; Maiese, Brett A; Cadarette, Sarah M; Panettieri, Reynold A

    2017-07-01

    There are limited pediatric data about the use of omalizumab, especially the effectiveness and safety of omalizumab in the real-world management of allergic asthma. The objective of this study was to summarize the safety and efficacy of omalizumab in both randomized clinical trials (RCT) used for U.S. Food and Drug Administration registration and real-world studies (RWS) based on clinical care of children with moderate-to-severe asthma. Studies that evaluated omalizumab use in patients omalizumab RCTs. Overall, the mean rate of annual exacerbations was significantly lower after 6 months to 2 years of treatment with omalizumab in both RCTs and RWS. In two RCTs and three RWS, inhaled corticosteroid use was significantly reduced in patients who used omalizumab. Similar reductions in the use of rescue medication were also observed in the RCTs and RWS on omalizumab. Real-world evidence demonstrated improvement in forced expiratory volume in the first second of expiration (% predicted) in patients treated with omalizumab as well as significant improvement in the level of asthma control observed over 1 year. There also was evidence that omalizumab treatment reduced health care resource utilization, including fewer hospitalizations, emergency department visits, and unscheduled medical visits. Safety outcomes in all five RWS showed no new safety signals and demonstrated that omalizumab was well tolerated. Overall, RCT evidence strongly supported omalizumab efficacy and safety as add-on treatment in children 6 to 11 years old with moderate-to-severe persistent allergic asthma. RWS data confirmed these findings in an extended patient population of children and adolescents that is more generalizable to the actual day-to-day management of these patients.

  6. Efficacy and tolerability of treatment with single doses of diethylcarbamazine (DEC) and DEC plus albendazole (ABZ) for three consecutive years in lymphatic filariasis: a field study in India.

    Science.gov (United States)

    Kshirsagar, Nilima A; Gogtay, N J; Garg, B S; Deshmukh, P R; Rajgor, D D; Kadam, V S; Thakur, P A; Gupta, A; Ingole, N S; Lazdins-Helds, J K

    2017-10-01

    Lymphatic filariasis (LF) affects 73 countries, causes morbidity and impedes socioeconomic development. We had found no difference in safety and micro (Mf) and macro filarial action of single-dose diethylcarbamazine (DEC) and DEC + albendazole (ABZ) in an F01 study done in India (year 2000). There was a programmatic need to evaluate safety and efficacy of multiple annual treatments (F02). Subjects (155) from the F01 study, meeting inclusion-exclusion criteria, were enrolled in F02 and treated with further two annual doses of DEC or DEC + ABZ. Efficacy was evaluated for Mf positivity by peripheral smear (PS) and nucleopore (NP) filter, circulating filarial antigen (CFA) and filarial dance sign (FDS) positivity and Mf count at yearly follow-up. Safety was assessed for 5 days after drug administration. Total of 139 subjects evaluated for efficacy (69 DEC and 70 DEC + ABZ group). Mf positivity prevalence declined progressively by 95% (PS), 66% (NP), and 95% (PS) and 86% (NP); CFA positivity prevalence declined by 15% and 9%; FDS by 100% each; Mf count declined by 75.5 and 76.9% with three annual treatment of DEC and DEC + ABZ, respectively. Addition of ABZ did not show any advantage over DEC given as three annual rounds for LF. DEC and DEC + ABZ were well tolerated. There was no correlation between result of CFA and FDS, (both claimed to be indicative of adult worm). Analysis of published studies and our data indicate that macrofilaricidal effect of DEC/DEC + ABZ may be seen in children and not adults, with three or more annual dosing.

  7. Safety and tolerability of repetitive transcranial magnetic stimulation in patients with pathologic positive sensory phenomena: a review of literature

    Science.gov (United States)

    Muller, Paul A; Pascual-Leone, Alvaro; Rotenberg, Alexander

    2013-01-01

    BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable therapeutic and diagnostic tool. rTMS appears particularly promising for disorders characterized by positive sensory phenomena attributable to alterations in sensory cortex excitability. Among these are tinnitus, auditory and visual hallucinations, and pain syndromes. OBJECTIVE Despite studies addressing rTMS efficacy in suppression of positive sensory symptoms, the safety of stimulation of potentially hyperexcitable cortex has not been fully addressed. We performed a systematic literature review and metanalysis to describe the rTMS safety profile in these disorders. METHODS Using the PubMed database, we performed an English-language literature search from January 1985 to April 2011 to review all pertinent publications. Per study, we noted and listed pertinent details. From these data we also calculated a crude per-subject risk for each adverse event. RESULTS 106 publications (n = 1815 subjects) were identified with patients undergoing rTMS for pathologic positive sensory phenomena. Adverse events associated with rTMS were generally mild and occurred in 16.7% of subjects. Seizure was the most serious adverse event, and occurred in three patients with a 0.16% crude per-subject risk. The second most severe adverse event involved aggravation of sensory phenomena, occurring in 1.54%. CONCLUSIONS The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated procedure. However, published data are lacking in systematic reporting of adverse events, and safety risks of rTMS in these patient populations will have to be addressed in future prospective trials. PMID:22322098

  8. Antiremodelling Efficacy and Clinical Safety of Zofenopril in Patients with Grade 1and 2 Hypertension

    Directory of Open Access Journals (Sweden)

    Guzal J. Abdullaeva

    2015-12-01

    Full Text Available Objective: to estimate the antihypertensive, antiremodelling efficacy and clinical tolerability of the monotherapy with Zofenopril in patients with Grade 1 and 2 hypertension (HT 1 and 2 Materials and Methods: The study included 30 patients aged from 30 to 60 years with HT 1 and 2 (ESH/ESC, 2013 without severe comorbidities and cardiovascular complications. Zofenopril was prescribed as monotherapy to HT patients who had never been treated before or patients after one week of lavage from previous antihypertensive therapy, who did not reach target levels of BP. Before and during treatment all patients were checked on office BP using Korotkov’s method and ambulatory blood pressure monitoring (ABPM. Echocardiography and Doppler sonography were carried out by standard methods using the recommendations of the American Society of Echocardiography. Intima-media thickness (IMT of the carotid artery and brachial artery was measured by a 7.5MHz high-resolution ultrasound. Assessment of flow-mediated dilation (FMD of the brachial artery was used as a method of determining endothelial function. Results: A 12-week monotherapy with Zofenopril in average daily dose of 36.0±19.54 mg showed a high antihypertensive efficacy and a good safety profile without side effects. We noted a reliable decrease in systolic BP (SBP, diastolic BP (DBP, mean BP, and pulse pressure (PP by -19.53±5.93%, -18.64±7.18%, BP -19.05±6.14%, and -20.65±12.07%, respectively. Target SBP, DBP, and SBP+DBP were reached in 90%, 86.6%, and 83.3% of patients, respectively. We found a significant regression of LVH, significant improvement in volume indicators of LV echogeometry and parameters of FMD of the brachial artery, as well as a decrease in IMT of carotid and brachial arteries. Monotherapy with Zofenopril showed metabolic neutrality regarding the lipid and carbohydrate metabolism, a good safety profile without the side effects and undesired events.

  9. Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

    Science.gov (United States)

    Blonk, Maren I; Colbers, Angela P H; Hidalgo-Tenorio, Carmen; Kabeya, Kabamba; Weizsäcker, Katharina; Haberl, Annette E; Moltó, José; Hawkins, David A; van der Ende, Marchina E; Gingelmaier, Andrea; Taylor, Graham P; Ivanovic, Jelena; Giaquinto, Carlo; Burger, David M

    2015-09-01

    The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women. An open-label, multicenter, phase 4 study in HIV-infected pregnant women receiving raltegravir 400 mg twice daily was performed (Pharmacokinetics of Newly Developed Antiretroviral Agents in HIV-Infected Pregnant Women Network). Steady-state pharmacokinetic profiles were obtained in the third trimester and postpartum along with cord and maternal delivery concentrations. Safety and virologic efficacy were evaluated. Twenty-two patients were included, of which 68% started raltegravir during pregnancy. Approaching delivery, 86% of the patients had an undetectable viral load (HIV-infected. Exposure to raltegravir was highly variable. Overall area under the plasma concentration-time curve (AUC) and plasma concentration at 12 hours after intake (C12h) plasma concentrations in the third trimester were on average 29% and 36% lower, respectively, compared with postpartum: Geometric mean ratios (90% confidence interval) were 0.71 (.53-.96) for AUC0-12h and 0.64 (.34-1.22) for C12h. The median ratio of raltegravir cord to maternal blood was 1.21 (interquartile range, 1.02-2.17; n = 9). Raltegravir was well tolerated during pregnancy. The pharmacokinetics of raltegravir showed extensive variability. The observed mean decrease in exposure to raltegravir during third trimester compared to postpartum is not considered to be of clinical importance. Raltegravir can be used in standard dosages in HIV-infected pregnant women. NCT00825929. © The Author 2015. Published by Oxford University

  10. Observational study on safety and tolerability of duloxetine in the treatment of female stress urinary incontinence in German routine practice

    NARCIS (Netherlands)

    Michel, Martin C.; Minarzyk, Anette; Schwerdtner, Inka; Quail, Deborah; Methfessel, Hans D.; Weber, Hans-Joachim

    2013-01-01

    To evaluate the safety and tolerability of duloxetine during routine clinical care in women with stress urinary incontinence (SUI) in Germany, and in particular, to identify previously unrecognized safety issues as uncommon adverse reactions, and the influence of confounding factors present in

  11. Avaliação da eficácia, segurança e tolerabilidade de rabeprazol no tratamento de doenças ácido-pépticas Efficacy, safety and tolerability of rabeprazole in treatment of acid-peptic diseases

    Directory of Open Access Journals (Sweden)

    José Alves de FREITAS

    2002-03-01

    ção das lesões foi de 88,3% dos casos. Vinte e sete pacientes (15,2% relataram eventos adversos leves que não necessariamente estavam relacionados à medicação, sendo os mais freqüentes: diarréia, cefaléia e tonturas. Conclusões - O rabeprazol mostrou-se altamente eficaz para o alívio dos sintomas de pacientes com doenças ácido-pépticas. Da mesma forma, a droga proporcionou altos índices de cicatrização das lesões. O medicamento mostrou ser seguro, com efeitos colaterais transitórios e sem maiores conseqüências para os pacientes.Background - Rabeprazole, a substituted benzimidazole, represents a new generation of proton pump inhibitors that has recently been approved by the FDA and European Union for treatment of acid-related diseases. Objectives - To assess the efficacy and tolerability of rabeprazole 20 mg in actual conditions of use in everyday clinical practice on subjects with diagnosis of erosive gastroesophageal reflux disease and/or gastric and/or duodenal ulcer. Patients/Methods - A total of 171 outpatients (55% men, 45% women with a mean age of 42.5 years were enrolled in this trial. The majority of subjects (81.0% were Caucasians. Patients with endoscopically confirmed erosive/ulcerative gastroesophageal reflux disease (Savary-Miller classification, duodenal ulcer and/or benign gastric ulcer were eligible to receive rabeprazole 20 mg once daily for 4 to 8 weeks, depending on the diagnosis and at investigators' discretion. Patients were requested to record their symptoms in a diary card in a daily basis. Results - One hundred and sixty two patients completed the study in accordance with the protocol. Reflux esophagitis was diagnosed in 78 (48.1% patients, duodenal ulcer in 39 (24.1% and gastric ulcer in 24 (14.8%. Eleven (6.8% patients presented reflux esophagitis associated with duodenal ulcer and 7 (4.3% associated with gastric ulcer. Finally, 3 (1.9% presented both gastric and duodenal ulcer. Fifty-three percentage of patients were free of

  12. Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

    Science.gov (United States)

    Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

    2015-11-24

    Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

  13. Perceived Indications, Safety and Efficacy of Perinatal Use of ...

    African Journals Online (AJOL)

    Cheboi SK

    Subjects and Methods: A descriptive cross- sectional ... easy labour and safe delivery (39.6%); and treatment of common ailments (28.5%). Majority ... structures for censoring, training, regulation of TM practice and safety of remedies used.

  14. Efficacy and Safety of Pomegranate Medicinal Products for Cancer

    OpenAIRE

    Vlachojannis, Christian; Zimmermann, Benno F.; Chrubasik-Hausmann, Sigrun

    2015-01-01

    Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate ...

  15. Reactor Safety Gap Evaluation of Accident Tolerant Components and Severe Accident Analysis

    International Nuclear Information System (INIS)

    Farmer, Mitchell T.; Bunt, R.; Corradini, M.; Ellison, Paul B.; Francis, M.; Gabor, John D.; Gauntt, R.; Henry, C.; Linthicum, R.; Luangdilok, W.; Lutz, R.; Paik, C.; Plys, M.; Rabiti, Cristian; Rempe, J.; Robb, K.; Wachowiak, R.

    2015-01-01

    The overall objective of this study was to conduct a technology gap evaluation on accident tolerant components and severe accident analysis methodologies with the goal of identifying any data and/or knowledge gaps that may exist, given the current state of light water reactor (LWR) severe accident research, and additionally augmented by insights obtained from the Fukushima accident. The ultimate benefit of this activity is that the results can be used to refine the Department of Energy's (DOE) Reactor Safety Technology (RST) research and development (R&D) program plan to address key knowledge gaps in severe accident phenomena and analyses that affect reactor safety and that are not currently being addressed by the industry or the Nuclear Regulatory Commission (NRC).

  16. Reactor Safety Gap Evaluation of Accident Tolerant Components and Severe Accident Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, Mitchell T. [Argonne National Lab. (ANL), Argonne, IL (United States); Bunt, R. [Southern Nuclear, Atlanta, GA (United States); Corradini, M. [Univ. of Wisconsin, Madison, WI (United States); Ellison, Paul B. [GE Power and Water, Duluth, GA (United States); Francis, M. [Argonne National Lab. (ANL), Argonne, IL (United States); Gabor, John D. [Erin Engineering, Walnut Creek, CA (United States); Gauntt, R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Henry, C. [Fauske and Associates, Burr Ridge, IL (United States); Linthicum, R. [Exelon Corp., Chicago, IL (United States); Luangdilok, W. [Fauske and Associates, Burr Ridge, IL (United States); Lutz, R. [PWR Owners Group (PWROG); Paik, C. [Fauske and Associates, Burr Ridge, IL (United States); Plys, M. [Fauske and Associates, Burr Ridge, IL (United States); Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Rempe, J. [Rempe and Associates LLC, Idaho Falls, ID (United States); Robb, K. [Argonne National Lab. (ANL), Argonne, IL (United States); Wachowiak, R. [Electric Power Research Inst. (EPRI), Knovville, TN (United States)

    2015-01-31

    The overall objective of this study was to conduct a technology gap evaluation on accident tolerant components and severe accident analysis methodologies with the goal of identifying any data and/or knowledge gaps that may exist, given the current state of light water reactor (LWR) severe accident research, and additionally augmented by insights obtained from the Fukushima accident. The ultimate benefit of this activity is that the results can be used to refine the Department of Energy’s (DOE) Reactor Safety Technology (RST) research and development (R&D) program plan to address key knowledge gaps in severe accident phenomena and analyses that affect reactor safety and that are not currently being addressed by the industry or the Nuclear Regulatory Commission (NRC).

  17. The efficacy and safety of febuxostat for urate lowering in gout patients ≥65 years of age

    Directory of Open Access Journals (Sweden)

    Jackson Robert L

    2012-03-01

    Full Text Available Abstract Background The incidence of gout rises with increasing age. Management of elderly (≥65 years gout patients can be challenging due to high rates of comorbidities, such as renal impairment and cardiovascular disease, and concomitant medication use. However, there is little data specifically addressing the efficacy and safety of available urate-lowering therapies (ULT in the elderly. The objective of this post hoc analysis was to examine the efficacy and safety of ULT with febuxostat or allopurinol in a subset of elderly subjects enrolled in the CONFIRMS trial. Methods Hyperuricemic (serum urate [sUA] levels ≥ 8.0 mg/dL gout subjects were enrolled in the 6-month, double-blind, randomized, comparative CONFIRMS trial and randomized, 1:1:1, to receive febuxostat, 40 mg or 80 mg, or allopurinol (200 mg or 300 mg based on renal function once daily. Flare prophylaxis was provided throughout the study duration. Study endpoints were the percent of elderly subjects with sUA Results Of 2,269 subjects enrolled, 374 were elderly. Febuxostat 80 mg was significantly more efficacious (82.0% than febuxostat 40 mg (61.7%; p p p = 0.029. In subjects with mild-to-moderate renal impairment, significantly greater ULT efficacy was observed with febuxostat 40 mg (61.6%; p = 0.028 and febuxostat 80 mg (82.5%; p p p = 0.011 groups. Flare rates declined steadily in all treatment groups. Rates of AEs were low and comparable across treatments. Conclusions These data suggest that either dose of febuxostat is superior to commonly prescribed fixed doses of allopurinol (200/300 mg in subjects ≥65 years of age with high rates of renal dysfunction. In addition, in this high-risk population, ULT with either drug was well tolerated. Trial registration clinicaltrials.gov NCT#00430248

  18. Safety, Efficacy, and Exposure-Response of Voriconazole in Pediatric Patients With Invasive Aspergillosis, Invasive Candidiasis or Esophageal Candidiasis.

    Science.gov (United States)

    Martin, Judith M; Macias-Parra, Mercedes; Mudry, Peter; Conte, Umberto; Yan, Jean L; Liu, Ping; Capparella, M Rita; Aram, Jalal A

    2017-01-01

    Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited. Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored. Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established. Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.

  19. Pharmacokinetics, pharmacodynamics, tolerability, and safety of exenatide in Japanese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kothare, Prajakti A; Linnebjerg, Helle; Isaka, Yoshitaka; Uenaka, Kazunori; Yamamura, Ayuko; Yeo, Kwee Poo; de la Peña, Amparo; Teng, Choo Hua; Mace, Kenneth; Fineman, Mark; Shigeta, Hirofumi; Sakata, Yukikuni; Irie, Shin

    2008-12-01

    In this single-blind, parallel, placebo-controlled study, the pharmacokinetics, pharmacodynamics, tolerability, and safety of subcutaneous exenatide were evaluated in 40 Japanese patients with type 2 diabetes. Patients were allocated to 4 groups and randomized to receive exenatide (n = 8/group) or placebo (n = 2/group), with all receiving placebo on day 1. On day 2, patients received single-dose exenatide (2.5 microg [group A] or 5 microg [groups B, C, and D]) or placebo and then bid on days 3 to 5. On days 6 to 10, groups A and B continued on 2.5 and 5 microg bid; groups C and D received 10 and 15 microg bid, respectively. The last dose was given on the morning of day 10. All adverse events were mild or moderate in severity. Exenatide was generally well tolerated up to 10 microg. Exenatide was well absorbed with a median t(max) of 1.5 hours and mean t((1/2)) of 1.6 hours; exposure increased with dose. Up to 10 microg, exenatide reduced postprandial glucose concentrations in a dose-dependent fashion compared with placebo; decreases were similar for 10 and 15 microg. An E(max) model demonstrated that doses higher than 2.5 microg were necessary for adequate glycemic response. Based on tolerability and pharmacokinetic/pharmacodynamic relationships, 5 and 10 microg exenatide may be considered for further clinical development in Japanese patients with type 2 diabetes.

  20. Tolerance and safety of superficial chemical peeling with salicylic acid in various facial dermatoses

    Directory of Open Access Journals (Sweden)

    Iqbal Zafar

    2005-03-01

    Full Text Available BACKGROUND: Chemical peeling is a skin-wounding procedure that may have some potentially undesirable side-effects. AIMS: The present study is directed towards safety concerns associated with superficial chemical peeling with salicylic acid in various facial dermatoses. METHODS: The study was a non-comparative and a prospective one. Two hundred and sixty-eight patients of either sex, aged between 10 to 60 years, undergoing superficial chemical peeling for various facial dermatoses (melasma, acne vulgaris, freckles, post-inflammatory scars/pigmentation, actinic keratoses, plane facial warts, etc. were included in the study. Eight weekly peeling sessions were carried out in each patient. Tolerance to the procedure and any undesirable effects noted during these sessions were recorded. RESULTS: Almost all the patients tolerated the procedure well. Mild discomfort, burning, irritation and erythema were quite common but the incidence of major side-effects was very low and these too, were easily manageable. There was no significant difference in the incidence of side-effects between facial dermatoses (melasma, acne and other pigmentary disorders. CONCLUSION: Chemical peeling with salicylic acid is a well tolerated and safe treatment modality in many superficial facial dermatoses.

  1. Efficacy and safety of Camosunate for the treatment of uncomplicated malaria in the University of Benin Teaching Hospital, Benin City, Nigeria

    Directory of Open Access Journals (Sweden)

    Damien Uyagu

    2013-10-01

    Full Text Available In Nigeria, nearly 110 million clinical cases of malaria are diagnosed per year, thus being a major public health problem. The problems of resistance resulted in the introduction of the artemisinin based combinations (ACT by the WHO. Artesunate and amodiaquine (AS+AQ is at present the world’s second most widely used ACT. This study is an assessment of the efficacy and safety of Camosunate (a brand of AS+AQ; Geneith Pharmaceutical Ltd., Oshodi, Lagos in the treatment of uncomplicated malaria conducted at the University of Benin Teaching Hospital (UBTH. A cross-sectional assessment of the efficacy and safety of Camosunate was conducted over a period of one year using 120 patients selected after stratification, by random sampling technique. All recruited patients had slide-proven uncom- plicated malaria and were followed up for 28 days on commencement of Camosunate. Data was collected using a structured interviewer- administered questionnaire and was analysed using SPSS version 15. The overall efficacy of Camosunate was found to be 95.8%. Treatment was well tolerated as testified by the fact that there was no case withdrawal due to adverse drug reaction (ADR or treatment emergent signs and symptoms (TESS. Also no evidence of toxicity was recorded. Camosunate is highly efficacious and well tolerated in this area of Nigeria and justifies its use as a first line treatment for uncomplicated malaria.

  2. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

    Science.gov (United States)

    Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

    2016-01-01

    In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.

  3. Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer

    DEFF Research Database (Denmark)

    Tombal, Bertrand; Borre, Michael; Rathenborg, Per

    2015-01-01

    BACKGROUND: Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate...... cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density. TRIAL REGISTRATION: NCT01302041....... for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability. OBJECTIVE: To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single...

  4. Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: a randomized trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Kofoed, Poul-Erik; Rodrigues, Amabelia

    2011-01-01

    In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele,......, was routinely used. The present study compared the efficacy and tolerability of a double standard dose of chloroquine with the efficacy and tolerability of artemether-lumefantrine.......In 2008, Guinea-Bissau introduced artemether-lumefantrine for treatment of uncomplicated malaria. Previously, 3 times the standard dose of chloroquine, that was probably efficacious against Plasmodium falciparum with the resistance-associated chloroquine-resistance transporter (pfcrt) 76T allele...

  5. Hypothesis Testing of Inclusion of the Tolerance Interval for the Assessment of Food Safety.

    Directory of Open Access Journals (Sweden)

    Hungyen Chen

    Full Text Available In the testing of food quality and safety, we contrast the contents of the newly proposed food (genetically modified food against those of conventional foods. Because the contents vary largely between crop varieties and production environments, we propose a two-sample test of substantial equivalence that examines the inclusion of the tolerance intervals of the two populations, the population of the contents of the proposed food, which we call the target population, and the population of the contents of the conventional food, which we call the reference population. Rejection of the test hypothesis guarantees that the contents of the proposed foods essentially do not include outliers in the population of the contents of the conventional food. The existing tolerance interval (TI0 is constructed to have at least a pre-specified level of the coverage probability. Here, we newly introduce the complementary tolerance interval (TI1 that is guaranteed to have at most a pre-specified level of the coverage probability. By applying TI0 and TI1 to the samples from the target population and the reference population respectively, we construct a test statistic for testing inclusion of the two tolerance intervals. To examine the performance of the testing procedure, we conducted a simulation that reflects the effects of gene and environment, and residual from a crop experiment. As a case study, we applied the hypothesis testing to test if the distribution of the protein content of rice in Kyushu area is included in the distribution of the protein content in the other areas in Japan.

  6. Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Ashwinikumar A Raut

    2012-01-01

    Full Text Available Ashwagandha (Withania somnifera (WS, a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30 were enrolled. After baseline investigations, they received WS capsules (Rx (aqueous extract, 8:1 daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day x10 days, 1 000 mg/day x 10 days, 1 250 mg/day x 10 days. Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar′s test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.

  7. The use of ketamine in ECT anaesthesia: A systematic review and critical commentary on efficacy, cognitive, safety and seizure outcomes.

    Science.gov (United States)

    Gálvez, Verònica; McGuirk, Lucy; Loo, Colleen K

    2017-09-01

    This review will discuss ECT efficacy and cognitive outcomes when using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into account important moderator variables that have often not been considered to date. It will also include information on safety and other ECT outcomes (seizure threshold and quality). A systematic search through MEDLINE, PubMed, PsychINFO, Cochrane Databases and reference lists from retrieved articles was performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from 1995 to September 2016. Meta-analyses, randomised controlled trials, open-label and retrospective studies published in English of depressed samples receiving ECT with ketamine anaesthesia were included (n = 24). Studies were heterogeneous in the clinical populations included and ECT treatment and anaesthetic methods. Frequently, studies did not report on ECT factors (i.e., pulse-width, treatment schedule). Findings regarding efficacy were mixed. Tolerance from repeated use may explain why several studies found that ketamine enhanced efficacy early in the ECT course but not at the end. The majority of studies did not comprehensively examine cognition and adverse effects were not systematically studied. Only a minority of the studies reported on seizure threshold and expression. The routine use of ketamine anaesthesia for ECT in clinical settings cannot yet be recommended based on published data. Larger randomised controlled trials, taking into account moderator variables, specifically reporting on ECT parameters and systematically assessing outcomes are encouraged.

  8. Efficacy and Safety of Artemether in the Treatment of Chronic Fascioliasis in Egypt: Exploratory Phase-2 Trials

    Science.gov (United States)

    Keiser, Jennifer; Sayed, Hanan; El-Ghanam, Maged; Sabry, Hoda; Anani, Saad; El-Wakeel, Aly; Hatz, Christoph; Utzinger, Jürg; el-Din, Sayed Seif; El-Maadawy, Walaa; Botros, Sanaa

    2011-01-01

    Background Fascioliasis is an emerging zoonotic disease of considerable veterinary and public health importance. Triclabendazole is the only available drug for treatment. Laboratory studies have documented promising fasciocidal properties of the artemisinins (e.g., artemether). Methodology We carried out two exploratory phase-2 trials to assess the efficacy and safety of oral artemether administered at (i) 6×80 mg over 3 consecutive days, and (ii) 3×200 mg within 24 h in 36 Fasciola-infected individuals in Egypt. Efficacy was determined by cure rate (CR) and egg reduction rate (ERR) based on multiple Kato-Katz thick smears before and after drug administration. Patients who remained Fasciola-positive following artemether dosing were treated with single 10 mg/kg oral triclabendazole. In case of treatment failure, triclabendazole was re-administered at 20 mg/kg in two divided doses. Principal Findings CRs achieved with 6×80 mg and 3×200 mg artemether were 35% and 6%, respectively. The corresponding ERRs were 63% and nil, respectively. Artemether was well tolerated. A high efficacy was observed with triclabendazole administered at 10 mg/kg (16 patients; CR: 67%, ERR: 94%) and 20 mg/kg (4 patients; CR: 75%, ERR: 96%). Conclusions/Significance Artemether, administered at malaria treatment regimens, shows no or only little effect against fascioliasis, and hence does not represent an alternative to triclabendazole. The role of artemether and other artemisinin derivatives as partner drug in combination chemotherapy remains to be elucidated. PMID:21909440

  9. Safety and efficacy of health supplement (Pegaga based product

    Directory of Open Access Journals (Sweden)

    Firdaus Abd Rahman

    2016-01-01

    Conclusions: Most traditional products claim contained herbs and have many indication although not proven by evidence based. Hence, consumers must be more selective before buying any health products. MOH continuing demonstrate enforcement action and educating the public in this matter. More research also must be conducted to confirm the efficacy and the appropriate dose for a particular situation either for prevention or treatment of disease.

  10. Three in one: safety, efficacy, and patient acceptability of triple fixed-dose combination medicine in the management of hypertension

    Directory of Open Access Journals (Sweden)

    Taylor AA

    2012-08-01

    Full Text Available Addison A Taylor, Shawn RagbirDepartment of Medicine, Baylor College of Medicine, Houston, TX, USAAbstract: Hypertensive patients whose blood pressures are more than 20 mmHg above their goal will often require three or more medications. Careful selection of medications whose actions are complementary or have an improved adverse effect profile when combined can affect not only the blood pressure but also patient acceptance, thus improving persistence in taking the medications as prescribed. This review will highlight the three single-pill three-drug combinations currently available in the US and will address their efficacy, safety, and tolerability. All three include the dihydropyridine calcium-channel blocker, amlodipine, and the thiazide diuretic, hydrochlorothiazide. They each contain a different renin–angiotensin system blocker. One includes the angiotensin-receptor blocker, olmesartan, while another contains valsartan. The third combination includes the direct renin inhibitor, aliskiren. All three fixed-dose combinations (FDC at maximum doses of each component lowers the blood pressure of patients with stage II hypertension by 37 to 40 mmHg systolic and 21 to 25 mmHg diastolic, which is superior to any two of the components that comprise the three-drug FDC. These drugs are effective in males and females, the elderly, diabetics, minority populations, and patients with metabolic syndrome. Triple-drug FDCs are well tolerated with a low incidence of adverse effects, the most common being peripheral edema related to amlodipine. Extrapolation of data from two-drug FDC suggests that medication compliance (adherence and persistence should be better with these FDCs than with the individual components taken as separate medications, although additional studies are necessary to confirm this.Keywords: calcium-channel blockers, hypertension, patient tolerability, renin–angiotensin system antagonists, safety, triple-drug combinations

  11. Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis.

    Science.gov (United States)

    Shoughy, Samir S; Jaroudi, Mahmoud O; Tabbara, Khalid F

    2016-01-01

    The objective of this study was to evaluate the efficacy and safety of topical low-dose tacrolimus (0.01%) solution in patients with vernal keratoconjunctivitis (VKC). A total of 62 consecutive patients with VKC refractory to conventional treatment were included retrospectively. Tacrolimus 0.01% ophthalmic solution was administered to patients twice daily after discontinuation of all previous topical medications. The duration of treatment ranged from 1 month to 29 months. The clinical symptoms of itching, redness, foreign body sensation, and discharge and the clinical signs of conjunctival hyperemia, conjunctival papillary hypertrophy, limbal infiltration, Trantas dots, and superficial punctate keratopathy were graded as 0 (normal), 1+ (mild), 2+ (moderate), or 3+ (severe). Assessment was carried out before initiation of therapy and on the last visit after treatment. There were 62 patients with VKC comprising 49 male and 13 female patients. The median age was 12 years (range: 5-47 years). The mean visual acuity improved from 20/30 to 20/25 following treatment. There was statistically significant improvement in symptoms of itching (P<0.001), redness (P<0.001), foreign body sensation (P<0.001), and discharge (P<0.001). Statistically significant improvement was also observed in clinical signs of conjunctival hyperemia (P<0.001), limbal infiltration (P<0.001), Trantas dots (P<0.001), superficial punctate keratopathy (P<0.001), and conjunctival papillary hypertrophy (P<0.001). The solution form of tacrolimus was well tolerated. None of the patients developed elevation of intraocular pressure, cataract, or infectious keratitis. Low-dose topical tacrolimus 0.01% solution is effective and safe in the management of patients with refractory VKC.

  12. Evaluation of safety and efficacy of a new multipurpose disinfecting solution on silicone hydrogel contact lenses☆

    Science.gov (United States)

    Pinto-Fraga, José; Blázquez Arauzo, Francisco; Urbano Rodríguez, Rubén; González-García, María J.

    2014-01-01

    Purpose To evaluate the safety and efficacy of a new multipurpose disinfecting solution (MPDS) with a formulation that includes aloe vera on its composition. Methods This is a prospective, randomized, double-masked clinical trial with a crossover design that included seven examinations. Two different MPDSs, Avizor Alvera® (study solution) and All Clean Soft® (control solution), each were used for 1 month. Comfilcon A silicone hydrogel contact lenses were used during the trial. The main outcome variables were corneal staining and deposits on the surfaces of the contact lenses. Other parameters including ocular surface response, contact lens wettability, user satisfaction, and adverse events, were analyzed according to the International Organization for Standardization (ISO) 11980:2010 guidance for clinical investigation. Results Twenty subjects (10 women, 10 men) (mean age, 27.7 ± 5.6 years; range, 20–41) were included. No differences between both MPDSs were found in the percentage of subjects with corneal staining >0 at day 30 (study: 35%, control: 50%; p = 0.46); neither in the percentage of subjects with deposits on the surface of the contact lens >0 at day 30 (study: 26.32%, control: 52.63%; p = 0.18). The study MPDS received higher rates in comfort (study: 8.14 ± 1.09, control: 7.94 ± 0.92; p = 0.56) and satisfaction at day 30 (study: 8.63 ± 0.91, control: 8.29 ± 0.80; p = 0.19), however the scores were not significantly different with the control MPDS. Conclusions The clinical trial showed that the study MPDS is safe, efficient, and has acceptable physiologic tolerance, according to the ISO 11980:2010 guidance for clinical investigation. PMID:25649640

  13. Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children.

    Science.gov (United States)

    Yanagida, Noriyuki; Sato, Sakura; Asaumi, Tomoyuki; Nagakura, Kenichi; Ogura, Kiyotake; Ebisawa, Motohiro

    2016-01-01

    The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities. © 2017 The Author(s) Published by S. Karger AG, Basel.

  14. Ciprofloxacin DPI: a randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis.

    Science.gov (United States)

    Dorkin, Henry L; Staab, Doris; Operschall, Elisabeth; Alder, Jeff; Criollo, Margarita

    2015-01-01

    Treatment of infective bronchitis involving Pseudomonas aeruginosa is a cornerstone of care in patients with cystic fibrosis (CF). This phase IIb, randomised, double-blind, placebo-controlled study assessed the efficacy and safety of ciprofloxacin dry powder for inhalation (DPI) in this population. Patients with CF, ≥12 years of age (N=286), were randomised to ciprofloxacin DPI (32.5 mg (n=93) or 48.75 mg (n=93)), or corresponding placebo (32.5 mg, n=65; 48.75 mg, n=35) twice daily for 28 days. The primary objective was the change in forced expiratory volume in 1 s (FEV1) from baseline (day 0) to end of treatment (day 29) in the intent-to-treat population for ciprofloxacin DPI compared with the corresponding placebo group. The primary effectiveness objective was not met; there were no significant differences in change in FEV1 between ciprofloxacin DPI and the corresponding placebo group for either dose (p=0.154). However, in pooled analyses, FEV1 decline from baseline to treatment end was significantly lower with ciprofloxacin DPI than with placebo (pooled data; p=0.02). Ciprofloxacin DPI showed positive effects on sputum bacterial load and quality of life, but these effects were not maintained at the 4-week follow-up. Ciprofloxacin DPI was well tolerated and there were no significant differences in type/incidence of treatment-emergent adverse events by treatment group (p=0.115). Further investigations are needed to determine the full scope of the beneficial effects of ciprofloxacin DPI for patients with CF. Clinicaltrials.gov NCT00645788; EudraCT 2008-008314-40.

  15. Efficacy and Safety of Prolonged Rituximab Treatment in Patients with Systemic Juvenile Idiopathic Arthritis

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2013-01-01

    Full Text Available Aim: to assess efficacy and safety of rituximab treatment in children with systemic juvenile idiopathic arthritis under prolonged follow-up. Patients and methods: results of treatment of 60 children (33 girls and 27 boys with systemic variant of juvenile idiopathic arthritis being followed-up in rheumatology department of the Federal State Institution «Scientific Centre of Children Health» of RAMS (FSI «SCCH» RAMS were analyzed. The mean age of children was 8,7 years. The mean duration of disease course at the moment of first rituximab administration was 5,3 years. At the beginning of rituximab therapy all children had active articular syndrome, severe systemic manifestations and significantly increased laboratory markers of activity. As the signs of improvement the authors used pediatric criteria of the American College of Rheumatology. The treatment was approved by the local ethic committee of the FSI «SCCH» RAMS; the patients’ representatives and patients older than 14 years old had signed informed agreement. Results: remission was induced in 26 of 60 (43% patients: in 9 of them after the 1st course of treatment, in 8 — after the 2nd, in 6 — after the 3d and in 3 — after the 4th. The maximal duration of remission was 5 years 4 months, minimal — 6 months. Other genetically engineered drugs were administered to 34 (57% of the patients: due to the primary inefficiency in 15, secondary inefficiency — in 10; due to partial inefficiency — in 9 children. The drug was well-tolerated in most of the patients. Undesirable effects were represented by transfusional reactions to the rituximab infusion, infections with different severity and granulocytopenia. Conclusions: rituximab has high efficiency in patients with severe systemic variant of juvenile idiopathic arthritis. The drug induced remission in patients who had been considered almost incurable, with low status of physical and social adaptation.

  16. Sequential antimicrobial treatment with linezolid for neurosurgical infections: efficacy, safety and cost study.

    Science.gov (United States)

    Martín-Gandul, Cecilia; Mayorga-Buiza, M J; Castillo-Ojeda, E; Gómez-Gómez, M J; Rivero-Garvía, M; Gil-Navarro, M V; Márquez-Rivas, F J; Jiménez-Mejías, M E

    2016-10-01

    Evidence for the effectiveness of linezolid in neurosurgical infections (NSIs) is growing. The comfortable oral dosage and tolerance of linezolid opens the possibility for sequential antimicrobial treatment (SAT) in stable patients after a period of intravenous treatment. To evaluate the efficacy and safety of SAT with oral linezolid in patients with NSI and to analyse the cost implications, an observational, non-comparative, prospective cohort study was conducted on clinically stable consecutive adult patients at the Neurosurgical Service. Following intravenous treatment, patients were discharged with SAT with oral linezolid. A total of 77 patients were included. The most common NSIs were: 41 surgical wound infections, 20 subdural empyemas, 18 epidural abscesses, and 16 brain abscesses. Forty-four percent of patients presented two or more concomitant NSIs. Aetiological agents commonly isolated were: Propionibacterium acnes (36 %), Staphylococcus aureus (23 %), Staphylococcus epidermidis (21 %) and Streptococcus spp. (13 %). The median duration of the SAT was 15 days (range, 3-42). The SAT was interrupted in five cases due to adverse events. The remainder of the patients were cured at the end of the SAT. A total of 1,163 days of hospitalisation were saved. An overall cost reduction of €516,188 was attributed to the SAT. Eight patients with device infections did not require removal of the device, with an additional cost reduction of €190,595. The mean cost saving per patient was €9,179. SAT with linezolid was safe and effective for the treatment of NSI. SAT reduces hospitalisation times, which means significant savings of health and economic resources.

  17. Efficacy and safety of rosuvastatin every other day compared with once daily in patients with hypercholesterolemia.

    Science.gov (United States)

    Wongwiwatthananukit, Supakit; Sansanayudh, Nakarin; Dhummauppakorn, Rawadee; Kitiyadisai, Chutiporn

    2006-11-01

    Although most patients with hypercholesterolemia require life-long therapy with statins, these drugs are underused due to high costs. Every-other-day therapy could be one strategy to resolve this problem. To compare the efficacy and safety of rosuvastatin 10 mg administered every other day versus once daily. An 8 week, randomized, open-label, parallel trial was conducted at the outpatient department of Phramongkutklao Hospital in Bangkok, Thailand. Eighty patients with primary hypercholesterolemia were equally randomized to receive rosuvastatin 10 mg once daily or every other day; 76 patients completed the study. Laboratory data were assessed at baseline and at the end of the study. Low-density lipoprotein cholesterol (LDL-C) levels were reduced by 48% and 39% in the once-daily and every-other-day groups, respectively (p = 0.011). The percentage of patients who achieved LDL-C goals according to National Cholesterol Education Program-Adult Treatment Panel III guidelines was not significantly different between the once-daily (85%) and every-other-day (70%) groups (p = 0.180). In addition, both regimens were well tolerated, with no patient developing an elevation of more than 3 times baseline levels of aspartate aminotransferase or alanine aminotransferase or 10 times that of creatine kinase. As expected, the monthly cost per percent LDL-C reduction of the once-daily (0.72 dollars) regimen was about 38% higher than that of the every-other-day (0.44 dollars) regimen. Every-other-day dosing of rosuvastatin may be an alternative regimen for cost savings, without a major decrease in therapeutic benefit or increase in adverse events, in patients with hypercholesterolemia. The number of patients achieving their LDL-C goal using the every-other-day regimen is comparable with the number using the once-daily regimen, especially in the low-risk patient category.

  18. Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

    Science.gov (United States)

    Pieri, Lisa; Paoli, Chiara; Arena, Umberto; Marra, Fabio; Mori, Fabio; Zucchini, Mery; Colagrande, Stefano; Castellani, Alessandro; Masciulli, Arianna; Rosti, Vittorio; De Stefano, Valerio; Betti, Silvia; Finazzi, Guido; Ferrari, Maria Luisa; Rumi, Elisa; Ruggeri, Marco; Nichele, Ilaria; Guglielmelli, Paola; Fjerza, Rajmonda; Mannarelli, Carmela; Fanelli, Tiziana; Merli, Lucia; Corbizi Fattori, Giuditta; Massa, Margherita; Cimino, Giuseppe; Rambaldi, Alessandro; Barosi, Giovanni; Cazzola, Mario; Barbui, Tiziano; Vannucchi, Alessandro M

    2017-02-01

    Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms. © 2016 Wiley Periodicals, Inc.

  19. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

  20. Evaluation of safety and efficacy of a new multipurpose disinfecting solution on silicone hydrogel contact lenses.

    Science.gov (United States)

    Pinto-Fraga, José; Blázquez Arauzo, Francisco; Urbano Rodríguez, Rubén; González-García, María J

    2015-01-01

    To evaluate the safety and efficacy of a new multipurpose disinfecting solution (MPDS) with a formulation that includes aloe vera on its composition. This is a prospective, randomized, double-masked clinical trial with a crossover design that included seven examinations. Two different MPDSs, Avizor Alvera® (study solution) and All Clean Soft® (control solution), each were used for 1 month. Comfilcon A silicone hydrogel contact lenses were used during the trial. The main outcome variables were corneal staining and deposits on the surfaces of the contact lenses. Other parameters including ocular surface response, contact lens wettability, user satisfaction, and adverse events, were analyzed according to the International Organization for Standardization (ISO) 11980:2010 guidance for clinical investigation. Twenty subjects (10 women, 10 men) (mean age, 27.7±5.6 years; range, 20-41) were included. No differences between both MPDSs were found in the percentage of subjects with corneal staining >0 at day 30 (study: 35%, control: 50%; p=0.46); neither in the percentage of subjects with deposits on the surface of the contact lens >0 at day 30 (study: 26.32%, control: 52.63%; p=0.18). The study MPDS received higher rates in comfort (study: 8.14±1.09, control: 7.94±0.92; p=0.56) and satisfaction at day 30 (study: 8.63±0.91, control: 8.29±0.80; p=0.19), however the scores were not significantly different with the control MPDS. The clinical trial showed that the study MPDS is safe, efficient, and has acceptable physiologic tolerance, according to the ISO 11980:2010 guidance for clinical investigation. Copyright © 2014 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

  1. Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial.

    Science.gov (United States)

    Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Karlsson, Maria; Silberg, Debra G

    2013-09-01

    Lesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase IIb study was performed to assess the efficacy and safety of lesogaberan as an add-on to proton pump inhibitor (PPI) therapy in patients with GERD who are partially responsive to PPI therapy (ClinicalTrials.gov reference: NCT01005251). In total, 661 patients were randomised to receive 4 weeks of placebo or 60, 120, 180 or 240 mg of lesogaberan twice daily, in addition to ongoing PPI therapy. Symptoms were measured using the Reflux Symptom Questionnaire electronic Diary. Response to treatment was defined as having an average of ≥ 3 additional days per week of not more than mild GERD symptoms during treatment compared with baseline. In the primary analysis, 20.9%, 25.6%, 23.5% and 26.2% of patients responded to the 60, 120, 180 and 240 mg twice daily lesogaberan doses, respectively, and 17.9% responded to placebo. The response to the 240 mg twice daily dose was statistically significantly greater than the response to placebo using a one-sided test at the predefined significance level of p < 0.1. However, the absolute increases in the proportions of patients who responded to lesogaberan compared with placebo were low. Lesogaberan was generally well tolerated, although six patients receiving lesogaberan developed reversible elevated alanine transaminase levels. In patients with GERD symptoms partially responsive to PPI therapy, lesogaberan was only marginally superior to placebo in achieving an improvement in symptoms.

  2. Evaluation of the Safety and Tolerability of Conjunctival Ring for Posterior Segment of the Eye.

    Science.gov (United States)

    Kinoshita, Satoshi; Ohguchi, Takeshi; Noda, Kousuke; Murata, Miyuki; Yasueda, Shin-Ichi; Obata, Haruka; Matsunaga, Toru; Fukushima, Tsutomu; Kanda, Atsuhiro; Ishida, Susumu

    2017-08-01

    To evaluate the safety and tolerability of conjunctival rings (CRs), a novel device for drug delivery to the posterior segment of the eye. In animal studies, CRs containing 5% dexamethasone sodium phosphate (DSP) or vehicle solution were placed on the right and left eyes of C57BL/6J mice, respectively. Contact lenses (CLs) containing vehicle solution were used as a control. Twenty-four hours after placement of the CRs, corneal fluorescein staining was graded based on the McDonald-Shadduck scoring system, ranging from 0 to 4. In humans, CRs containing vehicle solution were placed on the right eye of healthy volunteers for 9 hours. The corneal curvature, corneal thickness, intraocular pressure, visual acuity, tear production (Schirmer I test), tear film break-up time and fluorescein staining scores of the cornea (scores ranging from 0 to 3) and conjunctiva (scores ranging from 0 to 6) were assessed before and after wearing the CRs. The release characteristics of DSP from CRs were also evaluated. In animal experiments, corneal fluorescein staining scores were 1 or less in all the groups, and there was no significant difference between the CR group and the CL group. In the preclinical safety evaluation of CR for humans, ophthalmic examination revealed that CR caused no significant changes in all the parameters investigated including corneal curvature (p = 0.77), corneal thickness (p = 0.96), intraocular pressure (p = 0.59), visual acuity (p = 0.14), Schirmer I test results (p = 0.76), tear film break-up time (p = 0.68), corneal fluorescein staining scores (p = 0.64), and conjunctival fluorescein staining scores (p = 0.52). The DSP release from CRs occurs within a few hours, which is similar to the drug-release property of medicated CL, as reported previously. The current data showed the safety and tolerability of CR as a drug delivery device for the treatment of posterior segment diseases.

  3. Tolerability and safety of Souvenaid in patients with mild Alzheimer's disease: results of multi-center, 24-week, open-label extension study.

    Science.gov (United States)

    Olde Rikkert, Marcel G M; Verhey, Frans R; Blesa, Rafael; von Arnim, Christine A F; Bongers, Anke; Harrison, John; Sijben, John; Scarpini, Elio; Vandewoude, Maurits F J; Vellas, Bruno; Witkamp, Renger; Kamphuis, Patrick J G H; Scheltens, Philip

    2015-01-01

    The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to improve synapse formation and function in patients with Alzheimer's disease (AD). Two double-blind randomized controlled trials (RCT) with Souvenaid of 12 and 24 week duration (Souvenir I and Souvenir II) showed that memory performance was improved in drug-naïve mild AD patients, whereas no effects on cognition were observed in a 24-week RCT (S-Connect) in mild to moderate AD patients using AD medication. Souvenaid was well-tolerated in all RCTs. In this 24-week open-label extension (OLE) study to the 24-week Souvenir II RCT, long-term safety and intake adherence of the medical food Souvenaid was evaluated. Patients with mild AD (n = 201) received Souvenaid once-daily during the OLE. Main outcome parameters were safety and product intake adherence. The memory domain z-score from a revised neuropsychological test battery was continued as exploratory parameter. Compared to the RCT, a similar (low) incidence and type of adverse events was observed, being mainly (68.3%) of mild intensity. Pooled data (RCT and OLE) showed that 48-week use of Souvenaid was well tolerated with high intake adherence (96.1%). Furthermore, a significant increase in the exploratory memory outcome was observed in both the active-active and control-active groups during Souvenaid intervention. Souvenaid use for up to 48-weeks was well tolerated with a favorable safety profile and high intake adherence. The findings in this OLE study warrant further investigation toward the long-term safety and efficacy of Souvenaid in a well-controlled, double-blind RCT.

  4. THE EFFICACY AND SAFETY OF OXCARBAZEPINE AS ADD-ON THERAPY IN INTRACTABLE EPILEPSY IN CHILDREN

    OpenAIRE

    Azita TAVASSOLI; Mohammad GHOFRANI; Mohsen ROUZROKH; Eznollah AZARGASHB

    2010-01-01

    Objective1-3% of the population suffer from epilepsy. Up to 30% of them develop refractory epilepsy and their seizures occur more than once per month despite receiving at least 2 first line antiepileptic drugs. In  this group, more efficacious antiepileptics are needed. This study was undertaken to evaluate the efficacy and safety of Oxcarbazepine as an adjunction therapy in children with refractory epilepsy.Materials & MethodsFrom Feb 2004 until Sep 2006, 30 patients with refractory epilepsy...

  5. Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.

    Science.gov (United States)

    Biton, Victor; Gil-Nagel, Antonio; Brodie, Martin J; Derossett, Sarah E; Nohria, Virinder

    2013-11-01

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Exercise Self-Efficacy Moderates the Relation between Anxiety Sensitivity and Body Mass Index and Exercise Tolerance in Treatment-Seeking Smokers

    Science.gov (United States)

    Farris, Samantha G.; Davis, Michelle L.; Rosenfield, David; Kauffman, Brooke Y.; Baird, Scarlett O.; Powers, Mark B.; Otto, Michael W.; Marcus, Bess H.; Church, Timothy S.; Smits, Jasper A. J.; Zvolensky, Michael J.

    2016-01-01

    There is little known about factors that contribute to the comorbidity of cigarette smoking and obesity. The current study sought to test whether exercise self-efficacy moderated the relation between anxiety sensitivity (fear of internal sensations) and BMI and exercise tolerance among cigarette smokers. Smokers (n = 72; 50% female; Mcpd = 19.3, SD = 10.65) were recruited to participate in a smoking cessation treatment trial. During medical screen, we measured weight, height, and exercise tolerance (functional capacity) employing a standardized maximal exercise testing protocol. After adjusting for participant sex and cigarettes per day, exercise self-efficacy moderated the association between anxiety sensitivity and BMI, such that the positive association between anxiety sensitivity and BMI was significantly stronger when exercise self-efficacy was low. The same pattern of results emerged for exercise tolerance. Exercise self-efficacy moderated the association between anxiety sensitivity and exercise tolerance, such that the negative association between anxiety sensitivity and exercise tolerance was significantly stronger when exercise self-efficacy was low. Among smokers, anxiety sensitivity may be a risk variable that, directly and indirectly in the context of low self-efficacy for exercise, causes or maintains higher body weight and lower exercise tolerance. PMID:27725844

  7. Safety and efficacy of personal care products containing colloidal oatmeal

    OpenAIRE

    Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

    2012-01-01

    Maryline Criquet,1 Romain Roure,1 Liliane Dayan,2 Virginie Nollent,1 Christiane Bertin11Johnson & Johnson Santé Beauté France, Issy les Moulineaux, 2Independent consultant dermatologist, Paris, FranceBackground: Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vu...

  8. Efficacy and Safety of Pomegranate Medicinal Products for Cancer

    Science.gov (United States)

    Vlachojannis, Christian

    2015-01-01

    Preclinical in vitro and in vivo studies demonstrate potent effects of pomegranate preparations in cancer cell lines and animal models with chemically induced cancers. We have carried out one systematic review of the effectiveness of pomegranate products in the treatment of cancer and another on their safety. The PubMed search provided 162 references for pomegranate and cancer and 122 references for pomegranate and safety/toxicity. We identified 4 clinical studies investigating 3 pomegranate products, of which one was inappropriate because of the low polyphenol content. The evidence of clinical effectiveness was poor because the quality of the studies was poor. Although there is no concern over safety with the doses used in the clinical studies, pomegranate preparations may be harmful by inducing synthetic drug metabolism through activation of liver enzymes. We have analysed various pomegranate products for their content of anthocyanins, punicalagin, and ellagic acid in order to compare them with the benchmark doses from published data. If the amount of coactive constituents is not declared, patients risk not benefiting from the putative pomegranate effects. Moreover, pomegranate end products are affected by many determinants. Their declaration should be incorporated into the regulatory guidance and controlled before pomegranate products enter the market. PMID:25815026

  9. Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder

    Directory of Open Access Journals (Sweden)

    Hoffmann Vicki

    2010-11-01

    Full Text Available Abstract Background To examine potential differences in efficacy and safety of treatment with olanzapine in patients with schizophrenia of white and black descent. Methods A post-hoc, pooled analysis of 6 randomized, double-blind trials in the treatment of schizophrenia, schizophreniform disorder, or schizoaffective disorder compared white (N = 605 and black (N = 375 patients treated with olanzapine (5 to 20 mg/day for 24 to 28 weeks. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS total score; and positive, negative, and general psychopathology scores; and the Clinical Global Impression of Severity (CGI-S scores at 6 months. Safety measures included differences in the frequencies of adverse events along with measures of extrapyramidal symptoms, weight, glucose, and lipid changes over time. Results 51% of black patients and 45% of white patients experienced early study discontinuation (P = .133. Of those who discontinued, significantly more white patients experienced psychiatric worsening (P = .002 while significantly more black patients discontinued for reasons other than efficacy or tolerability (P = .014. Discontinuation for intolerability was not different between groups (P = .320. For the estimated change in PANSS total score over 6 months, there was no significant difference in efficacy between white and black patients (P = .928, nor on the estimated PANSS positive (P = .435, negative (P = .756 or general psychopathology (P = .165 scores. Overall, there was no significant difference in the change in CGI-S score between groups from baseline to endpoint (P = .979. Weight change was not significantly different in white and black patients over 6 months (P = .127. However, mean weight change was significantly greater in black versus white patients at Weeks 12 and 20 only (P = .028 and P = .026, respectively. Additionally, a significantly greater percentage of black patients experienced clinically significant

  10. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal

    Directory of Open Access Journals (Sweden)

    Lemoine P

    2011-07-01

    Full Text Available Patrick Lemoine1, Doron Garfinkel2, Moshe Laudon3, Tali Nir3, Nava Zisapel3,41The Clinique Lyon-Lumière, Meyzieu, France; 2Geriatric-Palliative Department, Shoham Geriatric Medical Center, Pardes Hanna, Israel; 3Neurim Pharmaceuticals Ltd, Tel-Aviv, Israel; 4Department of Neurobiology Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelBackground: Prolonged-release melatonin (PRM 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18–80 and lack of withdrawal and rebound symptoms upon discontinuation.Objective: To investigate the efficacy, safety, and withdrawal phenomena associated with 6–12 months PRM treatment.Methods: Data from a prospective 6–12-month open-label study of 244 community dwelling adults with primary insomnia, who had participated in a placebo-controlled, double-blind dose-ranging trial of PRM. Patients received PRM nightly, followed by a 2-week withdrawal period. Main outcome measures were patient-reported sleep quality ratings (diary, adverse events, vital signs, and laboratory tests recorded at each visit, and withdrawal symptoms (CHESS-84 [Check-list Evaluation of Somatic Symptoms]. Nocturnal urinary 6-sulfatoxymelatonin excretion, a measure of the endogenous melatonin production, was assessed upon discontinuing long-term PRM.Results: Of the 244 patients, 36 dropped out, 112 completed 6 months of treatment, and the other 96 completed 12 months of treatment. The mean number of nights by which patients reported sleep quality as "good" or "very good" was significantly higher during PRM than before treatment. There was no evidence of tolerance to PRM. Discontinuation of PRM was not associated with rebound insomnia or withdrawal symptoms; on the contrary, residual benefit was observed. PRM was well tolerated, and there was no suppression of endogenous melatonin production

  11. Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

    Science.gov (United States)

    Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

    2016-06-01

    According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the

  12. [Prospective, monocentric, uncontrolled study of efficacy, tolerance and adherence of cyclosporin 0.1 % for severe dry eye syndrome].

    Science.gov (United States)

    Boujnah, Y; Mouchel, R; El-Chehab, H; Dot, C; Burillon, C; Kocaba, V

    2018-02-01

    To evaluate the efficacy, tolerability and treatment adherence of Ikervis ® (Santen, SAS) (ciclosporine 0.1 %) for first line therapy or following treatment with Restasis ® (Allergan, Inc.) (ciclosporine 0.05 %) for severe dry eye syndrome. A prospective, monocentric, uncontrolled study was conducted between January 2012 and March 2015 on 110 eyes of 55 patients with severe dry eye on first line therapy or previously treated with Restasis ® who required the introduction of Ikervis ® . Patients' quality of life was assessed before and after treatment was started using a standardized questionnaire (Ocular Surface Disease Index © [OSDI]), clinical efficacy was quantified at the slit lamp, by measurement of the Break Up time Test (BUT) and the Oxford classification. Tolerability and adherence to treatment were measured using a simple questionnaire. A total of 72 eyes of 37 patients were included. Etiologies of dry eye syndrome were dominated by Sjögren syndrome (32 %) and severe ocular surface conditions (48 %). The mean age was 57.7 years (±17.45) and mean follow-up was 458 days (±292). The mean BUT increased by 2.043seconds [1.522-2.563] (Pdry eye. Its indications tend to evolve towards less severe dry eye. However, the tolerability profile remains poor, and an improvement in this would be desirable. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. The Tolerability and Efficacy of Oral Isotonic Solution versus Plain Water in Dengue Patients: A Randomized Clinical Trial.

    Science.gov (United States)

    Nainggolan, Leonard; Bardosono, Saptawati; Ibrahim Ilyas, Ermita I

    2018-01-01

    Plasma leakage plays an important role in dengue infection, and this condition can lead to hemoconcentration, hypovolemia, and shock. Fluid replacement is the main treatment for dengue. There is a lack of evidence to support certain oral fluid therapy as a treatment for dengue patients. The objective of this study is to evaluate tolerability and efficacy of oral isotonic solution (OIS) compared to plain water as a fluid replacement in dengue patients. A randomized, clinical trial with single-blinded groups was conducted to compare tolerability and efficacy of OIS and plain water in dengue patients. We evaluated gastrointestinal disturbances (nausea, vomiting, and bloating), body temperature, mean arterial pressure (MAP), fluid balance, hematocrit, Na + , and K + levels. Data were analyzed with SPSS 20.0, and figures were made with GraphPad Prism version 5.01. Twenty four subjects were included and divided equally into two groups. Our results showed that there are no significant differences but indicate several noteworthy trends. The intervention group (OIS) experienced less nausea, less vomiting, had positive fluid balance and higher MAP, and became afebrile faster compared to the control group (plain water). Although not statistically significant, this study shows the trend that OIS is well-tolerated and effective for dengue patients compared to plain water.

  14. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per S; Lisby, Steen; Grove, Richard

    2014-01-01

    OBJECTIVES: We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple sclerosis (RRMS). METHODS: In this randomized, double-blind, placebo-controlled study, patients received 2 ofatumumab infusions (100 mg, 300 mg......, or 700 mg) or placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety and efficacy were assessed. RESULTS: Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients in the 300-mg group...

  15. Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

    Energy Technology Data Exchange (ETDEWEB)

    Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com [Genentech, Inc., South San Francisco, CA (United States); Flagella, Kelly; Beyer, Joseph [Genentech, Inc., South San Francisco, CA (United States); Tibbitts, Jay [UCB, Brussels (Belgium); Kaur, Surinder; Saad, Ola; Yi, Joo-Hee; Girish, Sandhya; Dybdal, Noel; Reynolds, Theresa [Genentech, Inc., South San Francisco, CA (United States)

    2013-12-01

    Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeys and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic

  16. Safety and efficacy of personal care products containing colloidal oatmeal.

    Science.gov (United States)

    Criquet, Maryline; Roure, Romain; Dayan, Liliane; Nollent, Virginie; Bertin, Christiane

    2012-01-01

    Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized. In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions) by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin. We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation. Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period.

  17. Safety and efficacy of personal care products containing colloidal oatmeal

    Directory of Open Access Journals (Sweden)

    Criquet M

    2012-11-01

    Full Text Available Maryline Criquet,1 Romain Roure,1 Liliane Dayan,2 Virginie Nollent,1 Christiane Bertin11Johnson & Johnson Santé Beauté France, Issy les Moulineaux, 2Independent consultant dermatologist, Paris, FranceBackground: Colloidal oatmeal is a natural ingredient used in the formulation of a range of personal care products for relief of skin dryness and itchiness. It is also used as an adjunctive product in atopic dermatitis. The safety of personal care products used on vulnerable skin is of particular importance and the risk of developing further skin irritations and/or allergies should be minimized.Methods: In a series of studies, we tested the safety of personal care products containing oatmeal (creams, cleansers, lotions by assessing their irritant/allergenic potential on repeat insult patch testing, in safety-in-use and ocular studies using subjects with nonsensitive and sensitive skin. We also tested the skin moisturizing and repair properties of an oatmeal-containing skin care product for dry skin.Results: We found that oatmeal-containing personal care products had very low irritant potential as well as a very low allergenic sensitization potential. Low-level reactions were documented in 1.0% of subjects during the induction phase of repeat insult patch testing; one of 2291 subjects developed a persistent but doubtful low-level reaction involving edema during the challenge phase in repeat insult patch testing. No allergies were reported by 80 subjects after patch testing after in-use application. Sustained skin moisturizing was documented in subjects with dry skin that lasted up to 2 weeks after product discontinuation.Conclusion: Our results demonstrate that colloidal oatmeal is a safe and effective ingredient in personal care products. No allergies were reported by consumers of 445,820 products sold during a 3-year period.Keywords: Avena sativa, colloids, protective agents, atopic dermatitis, irritant dermatitis, allergenic dermatitis, skin

  18. Safety and efficacy of levetiracetam for the treatment of partial onset seizures in children from one month of age

    Directory of Open Access Journals (Sweden)

    Cormier J

    2013-02-01

    Full Text Available Justine Cormier, Catherine J ChuMassachusetts General Hospital, Department of Neurology, Programs in Child Neurology and Neurophysiology, Boston, MA, USAAbstract: Epilepsy is a common neurological disorder in the pediatric population, affecting up to one percent of children, and for which the mainstay of treatment is anticonvulsant medication. Despite the frequent use of anticonvulsant drugs, remarkably little is known about the safety and efficacy of most of these medications in the pediatric epilepsy population. Of 34 anticonvulsants currently approved for use by the US Food and Drug Administration (FDA, only 13 have been approved for use in children. Although infants and young children are disproportionately affected by epilepsy, there are currently only three anticonvulsant medications that have been specifically evaluated and approved for use in children younger than 2 years of age. In 2012, the FDA approved levetiracetam as an adjunctive treatment for partial onset seizures in infants and children from one month of age. Here we review the available data on levetiracetam in the pediatric epilepsy population. We first discuss the pharmacological profile of levetiracetam, including its mechanism of action, formulations and dosing, and pharmacokinetics in children. We then review the available efficacy, safety, and tolerability data in children from one month of age with partial onset seizures. We conclude that the current data leading to the approval of levetiracetam for use in infants and children with partial onset seizures is encouraging, although more work needs to be done before definitive conclusions can be drawn about the efficacy of levetiracetam across different pediatric age groups.Keywords: levetiracetam, anticonvulsant drug, partial seizures, pediatric epilepsy

  19. [Safety and efficacy of a new preservative-free levocabastine ophthalmic solution (Levofree®) using the conjunctival provocation test].

    Science.gov (United States)

    Allaire, C; Siou-Mermet, R; Bassols, A

    2012-09-01

    To evaluate the safety and efficacy of preservative-free levocabastine 0.05 % ophthalmic solution compared to placebo (vehicle) and to preserved levocabastine 0.05 % ophthalmic suspension in the prevention of allergic conjunctivitis induced by a conjunctival provocation test. Ninety-two subjects (18-50 years) with a previous history of allergic conjunctivitis to pollen were randomised to receive either preservative-free levocabastine solution in one eye and preserved levocabastine suspension in the fellow eye (n=69), or preservative-free levocabastine in one eye and placebo in the fellow eye (n=23). One drop of each product was administered 10 minutes (visit 3) and 4 hours (visit 4) prior to the provocation test. The primary efficacy criterion was the sum of the itching and conjunctival hyperemia scores assessed at 3, 5 and 10 minutes after the provocation test. The safety evaluation included adverse events, visual acuity, intra-ocular pressure and study drug drop sensation. The efficacy of the preservative-free solution was significantly higher than that of placebo at all time points (P≤0.01) with one exception at visit 4 (3 minutes after the provocation test). It was significantly higher than that of the preserved suspension at visit 3, and equivalent at visit 4. The incidence of adverse events was lower with the preservative-free solution than with the preserved suspension. 94.2 % and 95.7 % subjects rated preservative-free levocabastine drop sensation as "good" or "very good" at visits 3 and 4 respectively, whereas these rates were 68.1 % and 63.8 % with preserved levocabastine. This difference between the two formulations was highly statistically significant (Ppreservative-free levocabastine was superior to that of the placebo and of the preserved suspension at visit 3, at least as effective as the preserved suspension at visit 4, and better tolerated at each visit. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  20. Safety and efficacy of transarterial chemoembolization plus sorafenib for hepatocellular carcinoma with portal venous tumour thrombus

    International Nuclear Information System (INIS)

    Pan, T.; Li, X.-S.; Xie, Q.-K.; Wang, J.-P.; Li, W.; Wu, P.-H.; Zhao, M.

    2014-01-01

    Aim: To evaluate the safety and efficacy of combined therapy with transarterial chemoembolization (TACE) and sorafenib for hepatocellular carcinoma (HCC) with portal venous tumour thrombus (PVTT). Materials and methods: This study was approved by the institutional review board. From May 2009 to May 2012, 170 consecutive patients were newly diagnosed with advanced-stage HCC and treated with TACE plus sorafenib. Among them, 41 patients with PVTT were retrospectively enrolled in the study. The adverse events (AEs), overall survival (OS), time to progression (TTP), and prognostic factors were analysed. Statistical analysis was performed with the Kaplan–Meier method using the log-rank test and Cox regression models. Results: The most common AEs were hand–foot skin reaction related to sorafenib and fever related to TACE. Procedure-related mortality and grade 4 AEs were not observed. Grade 3 AEs were observed in five patients. During the median follow-up period of 13.5 months (range 1.4–45 months), the 6-month and 1-year survival rates were 87.7% and 53.6%, respectively. The median OS was 13 months (range 1.4–44.8 months), and the median TTP was 7 months (range 1–18.6 months). The Child–Pugh class (p = 0.022), extrahepatic metastasis (p = 0.009), and gross morphological type (nodular type versus diffuse type; p = 0.008) were prognostic factors related to OS in the multivariate analysis. Conclusion: TACE plus sorafenib in an interrupted therapeutic scheme was well tolerated and might improve OS for HCC patients with PVTT, especially in those with Child–Pugh class A, no extrahepatic metastasis, or nodular-type HCC. - Highlights: • We introduce the safety of TACE plus sorafenib for patients with advanced HCC and PVTT. • We suggest that the combined therapy might prolong the TTP and OS than sorafenib alone. • Clinic benefit determinations with the Child-Pugh class, extrahepatic metastasis or gross type

  1. Early safety and efficacy of fingolimod treatment in Denmark

    DEFF Research Database (Denmark)

    Voldsgaard, A; Koch-Henriksen, N; Magyari, M

    2017-01-01

    BACKGROUND: Initiation of fingolimod treatment is associated with a transient decrease of heart rate, and atrioventricular (AV) conduction block may occur. OBJECTIVE: To evaluate the therapeutic effect and safety of fingolimod treatment in MS patients in Denmark with focus on cardiac and pulmonary...... to bradycardia and/or second-degree AV block type I. All patients recovered spontaneously. Two patients discontinued fingolimod. Eleven (5.4%) patients reported respiratory complaints and two of these patients discontinued treatment. CONCLUSIONS: Fingolimod appears to be safe and effective in MS patients...

  2. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.

    Science.gov (United States)

    Mash, D C; Kovera, C A; Pablo, J; Tyndale, R F; Ervin, F D; Williams, I C; Singleton, E G; Mayor, M

    2000-09-01

    Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

  3. Safety and Tolerability of Hyperbaric Oxygen Therapy in Cats and Dogs.

    Science.gov (United States)

    Birnie, Gemma L; Fry, Darren R; Best, Matthew P

    2018-05-14

    This prospective clinical trial was designed to evaluate the safety of hyperbaric oxygen therapy (HBOT) in a population of cats and dogs with a variety of naturally occurring diseases. Seventy-eight dogs and twelve cats with various naturally occurring disease conditions, who had the potential to benefit from HBOT, were enrolled in the study. These patients were treated with HBOT in a monoplace hyperbaric oxygen chamber at 2 air pressure absolute for a treatment length of either 45 min or 60 min. There were 230 hyperbaric oxygen treatments performed during the study period. No major adverse effects were observed. There were 76 minor adverse effects recorded, which were not considered to be of clinical significance. Hyperbaric oxygen therapy was well tolerated and there were no major adverse effects recorded during treatment.

  4. Review of the Safety and Efficacy of Moringa oleifera.

    Science.gov (United States)

    Stohs, Sidney J; Hartman, Michael J

    2015-06-01

    Moringa oleifera leaves, seeds, bark, roots, sap, and flowers are widely used in traditional medicine, and the leaves and immature seed pods are used as food products in human nutrition. Leaf extracts exhibit the greatest antioxidant activity, and various safety studies in animals involving aqueous leaf extracts indicate a high degree of safety. No adverse effects were reported in association with human studies. Five human studies using powdered whole leaf preparations of M. oleifera have been published, which have demonstrated anti-hyperglycemic (antidiabetic) and anti-dyslipidemic activities. These activities have been confirmed using extracts as well as leaf powders in animal studies. A rapidly growing number of published studies have shown that aqueous, hydroalcohol, or alcohol extracts of M. oleifera leaves possess a wide range of additional biological activities including antioxidant, tissue protective (liver, kidneys, heart, testes, and lungs), analgesic, antiulcer, antihypertensive, radioprotective, and immunomodulatory actions. A wide variety of polyphenols and phenolic acids as well as flavonoids, glucosinolates, and possibly alkaloids is believed to be responsible for the observed effects. Standardization of products is an issue. However, the results of published studies to date involving M. oleifera are very promising. Additional human studies using standardized extracts are highly desirable. © 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

  5. Efficacy and tolerability of the dietary supplement Testostam in patients with erectile dysfunction

    OpenAIRE

    Горпинченко, І. І.; Ситенко, А. М.

    2017-01-01

    The objective: assessment of tolerability and effect of dietary supplement (DS) Testers on the parameters of erectile function provided that within 30 days, 2 capsules per day. Patients and methods. An open study of the effectiveness and tolerability of the DS Testostam (1 capsule of 500 mg: 350 mg of the Tribulus terrestri extract / 150 mg of the Pausinystalia yohimbe extract), ingested 1 capsule twice a day for 30 days, in 30 patients aged 53±5 years with moderate erectile dysfunction (i...

  6. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    International Nuclear Information System (INIS)

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-01-01

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  7. Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF

    Science.gov (United States)

    Jhund, Pardeep S.; Fu, Michael; Bayram, Edmundo; Chen, Chen-Huan; Negrusz-Kawecka, Marta; Rosenthal, Arvo; Desai, Akshay S.; Lefkowitz, Martin P.; Rizkala, Adel R.; Rouleau, Jean L.; Shi, Victor C.; Solomon, Scott D.; Swedberg, Karl; Zile, Michael R.; McMurray, John J.V.; Packer, Milton

    2015-01-01

    Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF). Methods In PARADIGM-HF, 8399 patients aged 18–96 years and in New York Heart Association functional class II–IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 (n = 1624), 55–64 (n = 2655), 65–74 (n = 2557), and ≥75 (n = 1563). Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories (P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories. Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit–risk profile in all age groups. PMID:26231885

  8. A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.

    Science.gov (United States)

    Harris, Jeffrey M; Maciuca, Romeo; Bradley, Mary S; Cabanski, Christopher R; Scheerens, Heleen; Lim, Jeremy; Cai, Fang; Kishnani, Mona; Liao, X Charlene; Samineni, Divya; Zhu, Rui; Cochran, Colette; Soong, Weily; Diaz, Joseph D; Perin, Patrick; Tsukayama, Miguel; Dimov, Dimo; Agache, Ioana; Kelsen, Steven G

    2016-03-18

    Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. ClinicalTrials.gov NCT01582503.

  9. Paracetamol (acetaminophen) efficacy and safety in the newborn.

    Science.gov (United States)

    Cuzzolin, Laura; Antonucci, Roberto; Fanos, Vassilios

    2013-02-01

    Neonates can perceive pain, therefore an adequate analgesic therapy is a major issue not only from an ethical perspective but also to improve short- and long-term outcome. Fever during the neonatal period requires hospitalization and needs a treatment with an antipyretic agent because of the high risk of severe complications. Paracetamol (acetaminophen), the most commonly prescribed drug in paediatric patients for its analgesic and antipyretic effects, is the only agent recommended for use as an antipyretic in the newborn and has been recently proposed as a supplement therapy to opioids for postoperative analgesia. This article aims to give an updated overview on the use of paracetamol in newborns by presenting its pharmacological profile (mechanism of action, pharmacokinetics), recommendations for dosing regimens (oral or rectal administration: 25-30 mg/kg/day in preterm neonates of 30 weeks' gestation, 45 mg/kg/day in preterm neonates of 34 weeks' gestation, 60 mg/kg/day in term neonates; i.v. administration: indicatively 20-40 mg/kg/day depending on gestational age, with some differences among various guidelines) and clinical uses (more commonly as analgesic/antipyretic by oral or rectal route, but also i.v. in anaesthesia for postoperative analgesia and painful procedures in Neonatal Intensive Care Units). Moreover, drug tolerability is discussed in the light of its potential hepatotoxicity and the unique characteristics of the newborn patient. By analyzing the available literature and the dosing guidelines, a mismatch exists between the current clinical use of paracetamol and the recommendations, suggesting a cautious approach particularly in extremely preterm neonates.

  10. Assessment of topiramate′s efficacy and safety in epilepsy

    Directory of Open Access Journals (Sweden)

    Prem P Gupta

    2014-01-01

    Full Text Available Objective: To study the significance of topiramate (TPM addition on seizure control in treatment of epilepsy. Design: A prospective open label add-on trial of TPM addition in patients with epilepsy was done. The events of baseline phase of 12 weeks followed by titration and maintenance phases were recorded. Assessment of the number of seizure and emergent adverse effects was done by a monthly visit for each case. Main Outcome Measures: Reduction of more than 50% mean seizure frequency or response ratio of 0.33 was taken as the criteria for responders. Statistical Analysis: Normal Z-test for significance of differences between two proportions and Chi-square test for presence of association was applied and mean age, median duration, sex ratio, percentage prevalence were depicted. Results: Significant responses to TPM in both partial as well as generalized seizures were observed (Z = 6.66, P < 0.001 and Z = 4.185, P < 0.01. The effect was more pronounced in patients with partial seizures. However, the overall response was highly significant (Z = 7.839, P < 0.001. The best response was noted at the dose of 200-300 mg/day (Z = 6.708, P < 0.001. More than 35% cases of partial and generalized seizures reported more than 75% reduction levels. The drug was well tolerated in more than 65% cases for side effects on psychosis, giddiness, and anorexia. Mild side effects were seen only in about less than 35% cases. Conclusions: TPM was found as a significantly effective add-on anticonvulsant with some limitation or mild side effects.

  11. Golimumab in the treatment of psoriatic arthritis: efficacy and safety

    Directory of Open Access Journals (Sweden)

    Tatiana Viktorovna Korotaeva

    2015-01-01

    Full Text Available Tumor necrosis factor-α (TNF-α holds a central position in the pathogenesis of autoimmune inflammatory diseases of the locomotor apparatus. A separate class of drugs, namely, TNF-α inhibitors, that are effective against multicomponent diseases, such as psoriatic arthritis (PsA, is now available to physicians. The paper reviews the results of clinical trials of the TNF-α inhibitor golimumab, a human TNF-α monoclonal antibody. Golimumab exerts a positive effect on all manifestations of PsA: arthritis, psoriatic skin and nail lesions, dactylitis, enthesitis, and quality of life. The drug is noted for its convenient route of administration – its standard dose is 50 mg injected subcutaneously once a month and for its low molecular immunogenicity. Recent data suggest that golimumab is an effective drug with a safety profile similar to that of the entire class of TNF-α inhibitors.

  12. Safety, efficacy, and patient acceptability of rifaximin for hepatic encephalopathy

    DEFF Research Database (Denmark)

    Kimer, Nina; Krag, Aleksander; Gluud, Lise L

    2014-01-01

    Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production of ...... and safety of long-term treatment with rifaximin and evaluate effects of combination therapy with lactulose and branched-chain amino acids for patients with liver cirrhosis and hepatic encephalopathy.......Hepatic encephalopathy is a complex disease entity ranging from mild cognitive dysfunction to deep coma. Traditionally, treatment has focused on a reduction of ammonia through a reduced production, absorption, or clearance. Rifaximin is a nonabsorbable antibiotic, which reduces the production...... of ammonia by gut bacteria and, to some extent, other toxic derivatives from the gut. Clinical trials show that these effects improve episodes of hepatic encephalopathy. A large randomized trial found that rifaximin prevents recurrent episodes of hepatic encephalopathy. Most patients were treated...

  13. Efficacy and Safety of Leucine Supplementation in the Elderly.

    Science.gov (United States)

    Borack, Michael S; Volpi, Elena

    2016-12-01

    Leucine supplementation has grown in popularity due to the discovery of its anabolic effects on cell signaling and protein synthesis in muscle. The current recommendation is a minimum intake of 55 mg ⋅ kg -1 . d -1 Leucine acutely stimulates skeletal muscle anabolism and can overcome the anabolic resistance of aging. The value of chronic leucine ingestion for muscle growth is still unclear. Most of the research into leucine consumption has focused on efficacy. To our knowledge, very few studies have sought to determine the maximum safe level of intake. Limited evidence suggests that intakes of ≤1250 mg ⋅ kg -1 . d -1 do not appear to have any health consequences other than short-term elevated plasma ammonia concentrations. Similarly, no adverse events have been reported for the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), although no studies have tested HMB toxicity in humans. Therefore, future research is needed to evaluate leucine and HMB toxicity in the elderly and in specific health conditions. © 2016 American Society for Nutrition.

  14. Safety and efficacy of low-dose, subacute exposure of mature ewes to sodium chlorate

    Science.gov (United States)

    The objective was to determine the safety and efficacy of low-dose, subacute exposure of mature ewes to NaClO3 in the drinking water. Twenty-five ewes (BW = 62.5 ± 7.3 kg) were placed indoors in individual pens with ad libitum access to water and feed. After 7 d of adaptation, ewes were assigned ran...

  15. Safety and protective efficacy of porcine reproductive and respiratory syndrome recombinant virus vaccines in young pigs.

    NARCIS (Netherlands)

    Verheije, M.H.; Kroese, M.V.; Linden, van der I.F.A.; Boer-Luijtze, de E.A.; Rijn, van P.A.; Pol, J.M.A.; Meulenberg, J.J.M.; Steverink, P.J.G.M.

    2003-01-01

    Three porcine reproductive and respiratory syndrome virus (PRRSV) recombinants, generated by mutagenesis of an infectious cDNA clone of the Lelystad virus (LV) isolate, were tested for their safety and protective efficacy as potential PRRSV vaccines in pigs. Recombinant vABV688 contains two amino

  16. Assessment of efficacy and safety of praziquantel in the treatment of ...

    African Journals Online (AJOL)

    This study assessed the efficacy and safety of PZQ in school-aged children in four ... All pupils were also treated with a single dose of PZQ at 40 mg/kg. ... The presence of S. haematobium was neither age nor sex dependent (p>0.05).

  17. Efficacy and Safety of Canagliflozin in Patients with Type 2 Diabetes and Stage 3 Nephropathy

    NARCIS (Netherlands)

    Yamout, Hala; Perkovic, Vlado; Davies, Melanie; Woo, Vincent; de Zeeuw, Dick; Mayer, Cristiana; Vijapurkar, Ujjwala; Kline, Irina; Usiskin, Keith; Meininger, Gary; Bakris, George

    2014-01-01

    Background/Aims: Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of >= 45 ml/mm/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT(2)

  18. Safety and efficacy of Profermin(R) to induce remission in ulcerative colitis

    DEFF Research Database (Denmark)

    Krag, Aleksander; Israelsen, Hans; von Ryberg, Bjørn

    2012-01-01

    AIM: To test the efficacy and safety of Profermin(R) in inducing remission in patients with active ulcerative colitis (UC). METHODS: The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index (SCCAI) > 4 and < 12 (median: 7.5), who were treated ope...

  19. Neonatal pearls : safety and efficacy of medication use in fetus and neonate

    NARCIS (Netherlands)

    Lugt, Neeltje Margaretha van der

    2013-01-01

    Neonatal health care is provided with medication and protocols for almost all morbidities. Before the use of these medicines is allowed, they are extensively studied and tested for efficacy and safety. As patient population and knowledge on specific diseases changes with time, repeated evaluation

  20. A meta-analysis of the efficacy of preoperative surgical safety ...

    African Journals Online (AJOL)

    A meta-analysis of the efficacy of preoperative surgical safety checklists to improve perioperative outcomes. BM Biccard, RN Rodseth, L Cronje, P Agaba, E Chikumba, L du Toit, Z Farina, S Fischer, PD Gopalan, K Govender, J Kanjee, AC Kingwill, F Madzimbamuto, D Mashava, B Mrara, M Mudely, E Ninise, J Swanevelder, ...

  1. Clinical assessment of the efficacy and safety of T-Angelica Herbal ...

    African Journals Online (AJOL)

    The safety, efficacy, and acceptability of T-Angelica Herbal Tonic (THAT), a phytomedicinal beverage was studied over a period of one week in ten healthy volunteers for regulatory purposes. The study started after an overnight fast with each subject drinking 150ml of the beverage every night and every morning for a period ...

  2. Efficacy and safety of ursodeoxycholic acid versus cholestyramine in intrahepatic cholestasis of pregnancy

    NARCIS (Netherlands)

    Kondrackiene, Jurate; Beuers, Ulrich; Kupcinskas, Limas

    2005-01-01

    BACKGROUND & AIMS: Treatment of intrahepatic cholestasis of pregnancy with ursodeoxycholic acid appears promising, but data are limited so far. The aim of this randomized study was to evaluate the efficacy and safety of ursodeoxycholic acid in comparison with cholestyramine. METHODS: Eighty-four

  3. Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease

    NARCIS (Netherlands)

    Holvast, A; Huckriede, A; Wilschut, J; Horst, G; De Vries, JJC; Benne, CA; Kallenberg, CGM; Bijl, M

    Objective: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. Methods: SLE patients (n = 56) and healthy controls (n = 18) were studied. All patients had

  4. Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma

    DEFF Research Database (Denmark)

    Pedersen, Søren; Engelstätter, Renate; Weber, Hans-Jochen

    2009-01-01

    BACKGROUND: Ciclesonide is a new inhaled corticosteroid (ICS). Information about its clinical efficacy and safety in relation to other ICS in children is needed for clinical positioning. OBJECTIVE: This 12-week, randomized, double-blind, double-dummy, three-arm, parallel-group study compared the ...

  5. Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

    NARCIS (Netherlands)

    Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

    2012-01-01

    Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

  6. Efficacy and safety of raltegravir for treatment of HIV for 5 years in the BENCHMRK studies

    DEFF Research Database (Denmark)

    Eron, Joseph J; Cooper, David A; Steigbigel, Roy T

    2013-01-01

    Two randomised, placebo-controlled trials-BENCHMRK-1 and BENCHMRK-2-investigated the efficacy and safety of raltegravir, an HIV-1 integrase strand-transfer inhibitor. We report final results of BENCHMRK-1 and BENCHMRK-2 combined at 3 years (the end of the double-blind phase) and 5 years (the end ...

  7. Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders?

    Science.gov (United States)

    2014-01-01

    Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached. PMID:24444292

  8. Safety and Efficacy of Ferric Carboxymaltose in Anemic Pregnant Women: A Retrospective Case Control Study

    NARCIS (Netherlands)

    Pels, Anouk; Ganzevoort, Wessel

    2015-01-01

    Background. Anemia during pregnancy is commonly caused by iron deficiency and can have severe consequences for both the mother and the developing fetus. The aim of this retrospective study was to assess the safety and efficacy of intravenous ferric carboxymaltose (FCM) in pregnant women. Methods.

  9. Gamma-Knife surgery (GKS) in patients with acromegaly: safety and efficacy

    International Nuclear Information System (INIS)

    Katz, D.; Miragaya, K.; Tenca, E.; Margni, A.; Artes, C.; Antico, J.

    2007-01-01

    The acromegaly is associated with increased morbidity and mortality than the general population. Since the surgical and pharmacological treatment for acromegaly have specific limitations, the GKS has been used as a therapeutic option in selected patients. The object is to evaluate the efficacy and safety of GKS in patients with acromegaly [es

  10. Safety and efficacy of anticoagulation for secondary stroke prevention in atrial fibrillation patients: The AMADEUS trial

    NARCIS (Netherlands)

    Lane, D.A.; Kamphuisen, P.W.; Minini, P.; Buller, H.R.; Lip, G.Y.H.

    2010-01-01

    ackground: Patients with atrial fibrillation (AF) and previous ischemic stroke are at high risk of recurrent stroke, but are also perceived to be at increased bleeding risk while treated with anticoagulants. Methods: Post-hoc analyses examined the efficacy and safety of anticoagulation of 4576 AF

  11. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt

    2017-01-01

    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  12. Efficacy and Safety of Lisdexamfetamine Dimesylate in Adolescents with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Findling, Robert L.; Childress, Ann C.; Cutler, Andrew J.; Gasior, Maria; Hamdani, Mohamed; Ferreira-Cornwell, M. Celeste; Squires, Liza

    2011-01-01

    Objective: To examine lisdexamfetamine dimesylate (LDX) efficacy and safety versus placebo in adolescents with attention-deficit/hyperactivity disorder (ADHD). Method: Adolescents (13 through 17) with at least moderately symptomatic ADHD (ADHD Rating Scale IV: Clinician Version [ADHD-RS-IV] score greater than or equal to 28) were randomized to…

  13. Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders

    Directory of Open Access Journals (Sweden)

    Cox JH

    2016-06-01

    Full Text Available Joanna H Cox,1 Stefano Seri,2,3 Andrea E Cavanna,2,4,5 1Heart of England NHS Foundation Trust, 2School of Life and Health Sciences, Aston Brain Centre, Aston University, 3Children’s Epilepsy Surgery Programme, The Birmingham Children’s Hospital NHS Foundation Trust, 4Department of Neuropsychiatry, Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, 5Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology and UCL, London, UK Abstract: Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown to be effective for tic control, but are also associated with poor tolerability because of their adverse effects. The newer antipsychotic medication aripiprazole is characterized by a unique mechanism of action (D2 partial agonism, and over the last decade has increasingly been used for the treatment of tics. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders (age range: 4–18 years. Our search identified two randomized controlled trials (involving 60 and 61 participants and ten open-label studies (involving between six and 81 participants. The majority of these studies used two validated clinician-rated instruments (Yale Global Tic Severity Scale and Clinical Global Impression scale as primary outcome measures. The combined results from randomized controlled trials and open-label studies showed that aripiprazole is an

  14. Comparative efficacy and safety of approved treatments for macular oedema secondary to branch retinal vein occlusion

    DEFF Research Database (Denmark)

    Regnier, Stephane A; Larsen, Michael; Bezlyak, Vladimir

    2015-01-01

    OBJECTIVE: To compare the efficacy and safety of approved treatments for macular oedema secondary to branch retinal vein occlusion (BRVO). DESIGN: Randomised controlled trials (RCTs) evaluating the efficacy and safety of approved treatments for macular oedema secondary to BRVO were identified from...... an updated systematic review. SETTING: A Bayesian network meta-analysis of RCTs of treatments for macular oedema secondary to BRVO. INTERVENTIONS: Ranibizumab 0.5 mg pro re nata, aflibercept 2 mg monthly (2q4), dexamethasone 0.7 mg implant, laser photocoagulation, ranibizumab+laser, or sham intervention...... pressure (IOP)/ocular hypertension (OH). RESULTS: 8 RCTs were identified for inclusion with 1743 adult patients. The probability of being the most efficacious treatment at month 6 or 12 based on letters gained was 54% for ranibizumab monotherapy, 30% for aflibercept, 16% for ranibizumab plus laser...

  15. Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: A network meta-analysis.

    Science.gov (United States)

    Bai, Zhihua; Wang, Guoqiang; Cai, Shangli; Ding, Xindi; Liu, Weiwei; Huang, Depei; Shen, Weidi; Zhang, Juncheng; Chen, Kui; Yang, Yuqing; Zhang, Lili; Zhao, Xiaochen; Ouyang, Qiong; Zhao, Jingping; Lu, Huafei; Hao, Wei

    2017-07-01

    We aimed to create hierarchies of the efficacy, acceptability and tolerability of eight atypical antipsychotics in the treatment of Chinese patients with acute schizophrenia. We systematically searched for RCT articles published between January 1st 2005 and December 31st 2014 in electronic databases (Medline, Pubmed, Embase, the Cochrane Library and ClinicalTrial.gov for studies in English and the China National Knowledge Infrastructure, Wan Fang, and VIP Information/Chinese Scientific Journals Database for studies in Chinese). The primary outcome was efficacy, as measured by the change of PANSS total score. Pairwise comparisons were performed using random-effects model by the Dersimonian-Laird method and network meta-analyses were performed in a Bayesian set. Sixty high-quality RCTs with 6418 participants were included. A pattern of superiority from olanzapine, paliperidone and amisulpride was seen in the primary outcome. Only paliperidone was found better than aripiprazole (odds ratio, 0.49 [95% credible intervals, 0.25 to 0.99]), ziprasidone (0.42 [0.21 to 0.85]) and quetiapine (0.36 [0.13 to 0.93]) in terms of all-cause discontinuation. The best and worst drugs in terms of weight gain, EPS and somnolence were aripiprazole and olanzapine, clozapine and amisulpride, aripiprazole and clozapine, respectively. The rank of efficacy did not change substantially in sensitivity analyses or in meta-regressions. Our findings provided the hierarchies of eight antipsychotics in efficacy, acceptability and tolerability. These findings are expected to help Chinese clinicians to select the appropriate antipsychotic drug for their patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

    Science.gov (United States)

    Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola

    2016-01-02

    Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (pvaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (pvaccine administration (pchildren, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Safety and efficacy assessment of standardized herbal formula PM012

    Science.gov (United States)

    2012-01-01

    Background This study was conducted to evaluate the efficacy of the herbal formula PM012 on an Alzheimer's disease model, human presenilin 2 mutant transgenic mice (hPS2m), and also to evaluate the toxicity of PM012 in Sprague-Dawely rats after 4 or 26 weeks treatment with repeated oral administration. Methods Spatial learning and memory capacities of hPS2m transgenic mice were evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly administered orally to male and female SD rats (15/sex/group) at doses of 0 (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate the recovery potential, 5 animals of each sex were assigned to vehicle control and 2,000 mg/kg/day groups during the 4-week recovery period. Results The results showed that PM012-treated hPS2m transgenic mice showed significantly reduced escape latency when compared with the hPS2m transgenic mice. The repeated oral administration of PM012 over 26 weeks in male and female rats induced an increase and increasing trend in thymus weight in the female treatment groups (main and recovery groups), but the change was judged to be toxicologically insignificant. In addition, the oral administration of the herbal medicine PM012 did not cause adverse effects as assessed by clinical signs, mortality, body weight, food and water consumption, ophthalmology, urinalysis, hematology, serum biochemistry, blood clotting time, organ weights and histopathology. The No Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for both sexes, and the target organ was not identified. Conclusion These results suggest that PM012 has potential for use in the treatment of the Alzheimer's disease without serious adverse effects. PMID:22458507

  18. Efficacy and safety of Saccharomyces boulardii for acute diarrhea.

    Science.gov (United States)

    Feizizadeh, Sahar; Salehi-Abargouei, Amin; Akbari, Vajihe

    2014-07-01

    The efficacy of Saccharomyces boulardii for treatment of childhood diarrhea remains unclear. Our objective was to systematically review data on the effect of S. boulardii on acute childhood diarrhea. Our data sources included Medline, Embase, CINAHL, Scopus, and The Cochrane Library up to September 2013 without language restrictions. Randomized controlled trials and non-randomized trials that evaluated effectiveness of S. boulardii for treatment of acute diarrhea in children were included. Two reviewers independently evaluated studies for eligibility and quality and extracted the data. In total, 1248 articles were identified, of which 22 met the inclusion criteria. Pooling data from trials showed that S. boulardii significantly reduced the duration of diarrhea (mean difference [MD], -19.7 hours; 95% confidence interval [CI], -26.05 to -13.34), stool frequency on day 2 (MD, -0.74; 95% CI, -1.38 to -0.10) and day 3 (MD, -1.24; 95% CI, -2.13 to -0.35), the risk for diarrhea on day 3 (risk ratio [RR], 0.41; 95% CI, 0.27 to 0.60) and day 4 (RR, 0.38; 95% CI, 0.24 to 0.59) after intervention compared with control. The studies included in this review were varied in the definition of diarrhea, the termination of diarrhea, inclusion and exclusion criteria, and their methodological quality. This review and meta-analysis show that S. boulardii is safe and has clear beneficial effects in children who have acute diarrhea. However, additional studies using head-to-head comparisons are needed to define the best dosage of S. boulardii for diarrhea with different causes. Copyright © 2014 by the American Academy of Pediatrics.

  19. An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

    Directory of Open Access Journals (Sweden)

    Pandina Gahan

    2012-06-01

    Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

  20. Safety-efficacy balance of S-ketamine and S-norketamine in acute and chronic pain

    NARCIS (Netherlands)

    Noppers, Ingeborg Marieke

    2011-01-01

    The balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and efficacy need to be performed. Ketamine is a relatively ‘old’ drug and used for almost 50 years as an

  1. 78 FR 60290 - Availability of Masked and De-identified Non-Summary Safety and Efficacy Data; Reopening of...

    Science.gov (United States)

    2013-10-01

    ..., 2013, on the following topics: (1) What factors should be considered in masking study data (e.g., data...] Availability of Masked and De-identified Non-Summary Safety and Efficacy Data; Reopening of Comment Period... of Masked and De- identified Non-Summary Safety and Efficacy Data; Request for Comments,'' which...

  2. Efficacy and safety of sotagliflozin in treating diabetes type 1.

    Science.gov (United States)

    Rendell, Marc S

    2018-02-01

    Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes. Areas covered: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials. Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety issue arises from the as yet unknown potential risks in women of child bearing potential in whom DKA is of utmost concern. The sotagliflozin development program has now been extended to trials in Type 2 diabetes, and long term studies will be needed to assess the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.

  3. Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders.

    Science.gov (United States)

    Cox, Joanna H; Seri, Stefano; Cavanna, Andrea E

    2016-01-01

    Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown to be effective for tic control, but are also associated with poor tolerability because of their adverse effects. The newer antipsychotic medication aripiprazole is characterized by a unique mechanism of action (D2 partial agonism), and over the last decade has increasingly been used for the treatment of tics. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders (age range: 4-18 years). Our search identified two randomized controlled trials (involving 60 and 61 participants) and ten open-label studies (involving between six and 81 participants). The majority of these studies used two validated clinician-rated instruments (Yale Global Tic Severity Scale and Clinical Global Impression scale) as primary outcome measures. The combined results from randomized controlled trials and open-label studies showed that aripiprazole is an effective, safe, and well-tolerated medication for the treatment of tics. Aripiprazole-related adverse effects (nausea, sedation, and weight gain) were less frequent compared to other antidopaminergic medications used for tic management and, when present, were mostly transient and mild. The reviewed studies were conducted on small samples and had relatively short follow-up periods, thus highlighting a need for further trials to assess the long-term use of aripiprazole in pediatric patients with Tourette syndrome

  4. Efficacy and Safety of Injectable Robenacoxib for the Treatment of Pain Associated With Soft Tissue Surgery in Dogs.

    Science.gov (United States)

    Friton, G; Thompson, C; Karadzovska, D; King, S; King, J N

    2017-05-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a cyclooxygenase-2 selective NSAID. Assess the clinical efficacy and safety of an injectable formulation of robenacoxib in dogs undergoing surgery. Three hundred and seventeen client-owned dogs (N = 159 robenacoxib or N = 158 placebo). In this prospective, multicenter, randomized, masked, placebo-controlled, parallel-group study, dogs received a SC injection of either robenacoxib, at a target dose of 2.0 mg/kg, or placebo once prior to surgery and for 2 additional days postoperatively. Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale (CMPS-SF). The primary efficacy variable was treatment success/failure, with failure defined as the need for rescue therapy to control pain or withdrawal of the dog from the study due to an adverse event. Significantly (P = .006) more dogs administered robenacoxib were considered treatment successes (108 of 151, 73.7%) compared to dogs given placebo (85 of 152, 58.1%). Total pain scores (P dogs receiving robenacoxib versus placebo. Robenacoxib administered by SC injection prior to surgery and for 2 additional days postoperatively was effective and well tolerated in the control of postoperative pain and inflammation associated with soft tissue surgery in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Repeated Artemisinin-Based Combination Therapies in a Malaria Hyperendemic Area of Mali: Efficacy, Safety, and Public Health Impact

    Science.gov (United States)

    Sagara, Issaka; Fofana, Bakary; Gaudart, Jean; Sidibe, Bakary; Togo, Amadou; Toure, Sekou; Sanogo, Kassim; Dembele, Demba; Dicko, Alassane; Giorgi, Roch; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

    2012-01-01

    Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria. PMID:22764291

  6. Efficacy and Safety of Minoxidil 5% Foam in Combination With a Botanical Hair Solution in Men With Androgenic Alopecia.

    Science.gov (United States)

    Keaney, Terrence C; Pham, Hanh; von Grote, Erika; Meckfessel, Matthew H

    2016-04-01

    Androgenic alopecia (AGA) is the most common type of hair loss in men, characterized by hair miniaturization, hairline recession, and vertex balding. It affects approximately 50% of men, negatively affecting self-esteem and sociability. Topical minoxidil formulations are approved up to a 5% concentration for men, but patient adherence to treatment is challenged by gradual results that may be perceived as a lack of initial benefit. Herbal extracts, which are also believed to promote healthier-looking hair, have a long history of use in hair care formulations. The safety and efficacy of a twice-daily regimen of 5% minoxidil foam used in combination with a novel botanical hair solution was evaluated in a 12-week, multicenter, single-arm, open label study in 56 subjects with mild to moderate AGA. Assessments included investigator ratings of improvement and subject self-ratings of satisfaction. Investigator ratings indicated significant improvement in scalp hair coverage and perception of overall treatment benefit in as early as 4 weeks (P<.001). Subject self-ratings were significant for improved hair growth and hair appearance in as few as 4 weeks (P<.05). The regimen was well tolerated, and subjects indicated a high degree of satisfaction. Investigator and subject-assessed efficacy and subject satisfaction with this novel regimen provide clinicians with an effective treatment option for AGA that also provides a high level of patient satisfaction, which may help promote patient adherence to long-term treatment.

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

    Science.gov (United States)

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

    2016-03-01

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

  8. Safety and efficacy of erenumab for preventive treatment of chronic migraine

    DEFF Research Database (Denmark)

    Tepper, Stewart; Ashina, Messoud; Reuter, Uwe

    2017-01-01

    BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is important in migraine pathophysiology. We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine. METHODS: This was a phase 2, randomised, double...... assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of double-blind treatment (weeks 9-12). Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-erenumab antibodies. The efficacy analysis set included patients who...... received at least one dose of investigational product and completed at least one post-baseline monthly measurement. The safety analysis set included patients who received at least one dose of investigational product. The study is registered with ClinicalTrials.gov, number NCT02066415. FINDINGS: From April...

  9. Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant : Safety and Tolerability

    NARCIS (Netherlands)

    Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

    2016-01-01

    BACKGROUND AND OBJECTIVES: QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and

  10. Efficacy and safety of febuxostat in the treatment of hyperuricemia in stable kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Sofue T

    2014-02-01

    Full Text Available Tadashi Sofue,1 Masashi Inui,2 Taiga Hara,1 Yoko Nishijima,1 Kumiko Moriwaki,1 Yushi Hayashida,3 Nobufumi Ueda,3 Akira Nishiyama,4 Yoshiyuki Kakehi,3 Masakazu Kohno1 1Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Kagawa University, Kagawa, 2Department of Urology, Tokyo Women's Medical University, Tokyo, 3Department of Urology, 4Department of Pharmacology, Kagawa University, Kagawa, Japan Background: Post-transplant hyperuricemia (PTHU, defined as serum uric acid concentration ≥7.0 mg/dL or need for treatment with allopurinol or benzbromarone, reduces long-term allograft survival in kidney transplant recipients. Febuxostat, a new nonpurine selective xanthine oxidase inhibitor, is well tolerated in patients with moderate renal impairment. However, its efficacy and safety in kidney recipients with PTHU is unclear. We therefore assessed the efficacy and safety of febuxostat in stable kidney transplant recipients with PTHU. Methods: Of 93 stable adult kidney transplant recipients, 51 were diagnosed with PTHU (PTHU group and 42 were not (NPTHU group. Of the 51 patients with PTHU, 26 were treated with febuxostat (FX group and 25 were not (NFX group, at the discretion of each attending physician. One-year changes in serum uric acid concentrations, rates of achievement of target uric acid (<6.0 mg/dL, estimated glomerular filtration rates in allografts, and adverse events were retrospectively analyzed in the FX, NFX, and NPTHU groups. Results: The FX group showed significantly greater decreases in serum uric acid (-2.0±1.1 mg/dL versus 0.0±0.8 mg/dL per year, P<0.01 and tended to show a higher rate of achieving target uric acid levels (50% versus 24%; odds ratio 3.17 [95% confidence interval 0.96–10.5], P=0.08 than the NFX group. Although baseline allograft estimated glomerular filtration rates tended to be lower in the FX group than in the NFX group (40±14 mL/min/1.73 m2 versus 47±19 mL/min/1.73 m2

  11. Evidences of safety and tolerability of the zoledronic acid 5 mg yearly in the post-menopausal osteoporosis: the HORIZON project

    Directory of Open Access Journals (Sweden)

    F. Bertoldo

    2011-06-01

    Full Text Available Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Despite evidence supporting the anti-fracture efficacy of aminobisphosphonates approximately 50% of patients do not follow their prescribed treatment regimen and/or discontinue treatment within the first year. Poor compliance is associated with negative outcomes, including increased fracture risk. Tolerability and safety are among the causes of poor compliance. Intravenous bisphosphonates avoids the gastrointestinal intolerance and the complex dosing instruction of the oral route ensuring full compliance which may provide improved efficacy. However, there are some concerns regarding potent intravenous bisphosphonates as zoledronic acid with respect to tolerability, mainly the acute phase response and to safety, mainly a theoretical risk of over suppression of bone turnover, renal toxicity and osteonecrosis of the jaw. In the HORIZON study, 152 patients on active treatment (82 or placebo (70 underwent to a bone biopsy after double tetracycline labeling. Bone biopsies (iliac crest were obtained at the final visit at month 36, 1 year after the last infusion. The biopsies were analyzed by histomorphometry on bone sections and by micro-CT (μCT analysis. 143 biopsies (76 zoledronic acid, 67 placebo had at least one μCT parameter measured and 111 were available for quantitative histomorphometry (59 zoledronic acid, 52 placebo. Micro-CT analysis of bone structure revealed higher trabecular bone volume (BV/TV, decreased trabecular separation (Tb.Sp, and a strong trend towards improvement in connectivity density in biopsies obtained from patients treated with zoledronic acid, indicating preservation of trabecular bone structure with respect to placebo. Histomorphometric analysis obtained from patients treated with zoledronic acid exhibited reduction of bone turnover, as suggested by decreased activation frequency (Ac.F by 63%, mineralizing surface (MS

  12. Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy.

    Science.gov (United States)

    Wang, Julie; Jones, Stacie M; Pongracic, Jacqueline A; Song, Ying; Yang, Nan; Sicherer, Scott H; Makhija, Melanie M; Robison, Rachel G; Moshier, Erin; Godbold, James; Sampson, Hugh A; Li, Xiu-Min

    2015-10-01

    Food Allergy Herbal Formula-2 (FAHF-2) is a 9-herb formula based on traditional Chinese medicine that blocks peanut-induced anaphylaxis in a murine model. In phase I studies FAHF-2 was found to be safe and well tolerated. We sought to evaluate the safety and effectiveness of FAHF-2 as a treatment for food allergy. In this double-blind, randomized, placebo-controlled study 68 subjects aged 12 to 45 years with allergies to peanut, tree nut, sesame, fish, and/or shellfish, which were confirmed by baseline double-blind, placebo-controlled oral food challenges (DBPCFCs), received FAHF-2 (n = 46) or placebo (n = 22). After 6 months of therapy, subjects underwent DBPCFCs. For those who demonstrated increases in the eliciting dose, a repeat DBPCFC was performed 3 months after stopping therapy. Treatment was well tolerated, with no serious adverse events. By using intent-to-treat analysis, the placebo group had a higher eliciting dose and cumulative dose (P = .05) at the end-of-treatment DBPCFC. There was no difference in the requirement for epinephrine to treat reactions (P = .55). There were no significant differences in allergen-specific IgE and IgG4 levels, cytokine production by PBMCs, or basophil activation between the active and placebo groups. In vitro immunologic studies performed on subjects' baseline PBMCs incubated with FAHF-2 and food allergen produced significantly less IL-5, greater IL-10 levels, and increased numbers of regulatory T cells than untreated cells. Notably, 44% of subjects had poor drug adherence for at least one third of the study period. FAHF-2 is a safe herbal medication for subjects with food allergy and shows favorable in vitro immunomodulatory effects; however, efficacy for improving tolerance to food allergens is not demonstrated at the dose and duration used. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  13. THE STUDY THE EFFICACY AND SAFETY OF ANTIMICROBIAL AGENTS

    Directory of Open Access Journals (Sweden)

    V. V. Bagaeva

    2015-01-01

    Full Text Available Abstract:Effective treatment of patients with infectious and inflammatory diseases of the skin and mucous membranes often involves the use of antimicrobial agents.The purpose of the study was an in vitro estimation of cytotoxicity and the efficiency of national resources for local use: gel with bacteriophages («Otofag», «Fagogin», «Fagoderm», «Fagodent» and antiseptic — «Сhlorhexidine» and «Miramistin».Materials and Methods. To study the effectiveness of antimicrobial agents they used to provide crop strains of Staphylococcus aureus and Streptococcus pyogenes as one of the most common representatives of pathogens. The study of cell viability and cytotoxicity antimicrobials performed on cell lines KB — epidermoid carcinoma of the oral cavity of a human. For this purpose we use mikrotetrazoly test, which is widely used in the assessment of the effects on the cells of toxins, pharmaceuticals, adverse environmental factors, allowing to evaluate the toxicity of investigational drugs in vitro.The results showed that the efficacy against pathogens Staphylococcus aureus and Streptococcus pyogenes, has even a 10‑fold dilution of «Сhlorhexidine» 0.05% and gels with bacteriophages. Antiseptic «Miramistin» is effective only on the initial concentration. The study of cytotoxicity showed that the processing of epidermoid carcinoma cells with «Chlorhexidine» and «Мiramistin» invokes the irreversible reactions, while the composition processing of gels based on bacteriophages not further affect cell viability.Conclusions The results of the experiment confirmed the significant toxicity of tools such as «Сhlorhexidine» and «Miramistin» in proposed concentrations in the pharmacy network. Despite the high efficiency of these vehicles with regard to the studied pathogens, their long-term use in treatment of inflammatory diseases of the skin and mucous membranes can cause a slowing of repair processes. Gel means with bacteriophages

  14. Safety and efficacy of a new tourniquet system

    Directory of Open Access Journals (Sweden)

    Sato Junko

    2012-08-01

    Full Text Available Abstract Background In upper limb surgery, the pneumatic tourniquet is an essential tool to provide a clean, bloodless surgical field, improving visualization of anatomical structures and preventing iatrogenic failure. Optimal inflation pressure to accomplish these objects without injuring normal tissue and inducing complications is not yet established. Use of the minimum tourniquet pressure necessary to produce a bloodless surgical field is preferable in order to prevent injury to normal tissue. Various methods have been implemented in an effort to lower effective cuff pressure. The purpose of this study is to report clinical experience with a new tourniquet system in which pressure is synchronized with systolic blood pressure (SBP using a vital information monitor. Methods We routinely used the tourniquet system in 120 consecutive upper limb surgeries performed under general anaesthesia in our operating room instead of our clinic. Cuff pressure was automatically regulated to additional 100 mmHg based on the SBP and was renewed every 2.5 minutes intervals. Results An excellent bloodless field was obtained in 119 cases, with the exception of one case of a 44-year-old woman who underwent internal screw fixation of metacarpal fracture. No complications, such as compartment syndrome, deep vein disorder, skin disorder, paresis, or nerve damage, occurred during or after surgery. Conclusions This new tourniquet system, synchronized with SBP, can be varied to correspond with sharp rises or drops in SBP to supply adequate pressure. The system reduces labor needed to deflate and re-inflate to achieve different pressures. It also seemed to contribute to the safety in upper limb surgery, in spite of rare unexpected oozing mid-surgery, by reducing tissue pressure.

  15. CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

    Science.gov (United States)

    Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso

    2017-03-01

    Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.

  16. Tolerability and efficacy of paliperidone ER compared to olanzapine in the treatment of schizophrenia: A randomized, double-blind, multicentric trial

    Directory of Open Access Journals (Sweden)

    Sandip Shah

    2011-01-01

    Full Text Available Background: Paliperidone is an active metabolite of risperidone and actss through a combination of central dopamine Type 2 (D2 and serotonin Type 2 (5HT2A receptor antagonism. Aim: The present randomized, double-blind, multicentric trial was designed to determine the safety and efficacy of paliperidone extended release (ER compared to olanzapine in the treatment of acute schizophrenia. Materials and Methods: A total of 214 patients with diagnosis of schizophrenia were randomized to paliperidone ER (n=109 and olanzapine (n=106 treatment groups. Totally 206 patients were evaluated for efficacy parameters using Positive and negative syndrome scale (PANSS score and Clinical Global Impression-severity of illness (CGI-S and Clinical Global Impression-improvement of illness (CGI-I scales. Safety was assessed by treatment-emergent adverse events and movement disorders. Results: All patients showed significant reduction in PANSS scores at the end of treatment. However, the results were comparable and there was no significant difference at the end of the trial between paliperidone ER group and olanzapine group. Both the treatment groups showed decrease in the severity of illness and improvement in symptomatology. The most common adverse events reported in paliperidone ER versus olanzapine group were Extra Pyramidal Syndrome (EPS (13.7% vs. 15.6%, headache (12.7% vs. 8.9%, increased appetite (8.8% vs. 10.0% and drowsiness (4.9% vs. 303%. There was no clinically relevant difference in change from baseline to the end of the trial in abnormal involuntary movement scale (AIMS and barnes akathisia rating scale (BARS total scores between both the groups. Conclusion: Paliperidone ER is effective in controlling schizophrenic symptoms as well as exhibits comparable tolerability profile. Thus, paliperidone ER has the potential to be a useful new treatment option for patients with schizophrenia.

  17. Clinical pharmacokinetics, safety, and preliminary efficacy evaluation of icotinib in patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Liu, Dongyang; Zhang, Li; Wu, Yiwen; Jiang, Ji; Tan, Fenlai; Wang, Yingxiang; Liu, Yong; Hu, Pei

    2015-09-01

    To receive pharmacokinetics, safety, and anti-tumor activity of icotinib, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), in patients with advanced non-small-cell lung cancer (NSCLC). Patients (n=40) with advanced NSCLC were enrolled to receive escalating doses of icotinib, which was administrated on Day 1 followed by 28-day continuous dosing starting from Day 4. Four dosing regimens, 100mg b.i.d., 150 mg b.i.d., 125 mg t.i.d., and 200mg b.i.d. were studied. Pharmacokinetics (PK), safety, and efficacy of icotinib were evaluated. Icotinib was well tolerated in Chinese patients with refractory NSCLC. No toxicity with >3 grades were reported in more than 2 patients under any dose levels. One complete response (3%) and 9 partial responses (23%) were received. Total disease control rate could reach at 73% and median progress-free survival (range) was 154 (17-462) days. PK exposure of icotinib increased with increase of dose in NSCLC patients. Food was suggested to increase PK exposure by ∼30%. Mean t1/2β was within 5.31-8.07 h. No major metabolite (>10% plasma exposure of icotinib) was found in NSCLC patients. Icotinib with up to 400 mg/day exhibited good tolerance and preliminary antitumor activity in Chinese NSCLC patients. Pharmacokinetics of icotinib and 5 major metabolites were fully investigated in NSCLC patients. Optimized biologic dose (OBD) was finally recommended to be 125 mg t.i.d. for the later clinical study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.

    Science.gov (United States)

    Sawant, Prabha; Das, H S; Desai, Nutan; Kalokhe, S; Patil, S

    2004-08-01

    Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride in patients of NUD and compare it with domperidone. Fifty-six patients who fulfilled the inclusion and exclusion criteria were enrolled in the study. Patients underwent upper gastrointestinal endoscopy to rule out organic pathology as a cause for their symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the beginning of treatment and at the end of Week-one and Week-two Patients were randomly allocated to receive either one tablet of itopride hydrochloride 50mg three times daily or one tablet of domperidone 10mg three times daily for two weeks. Pre-treatment and post-treatment hemogram, liver function and renal function tests, prolactin level and ECG were done in all patients. The response to therapy was evaluated by assessing the relief of symptoms at the end of two weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t-test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square test as applicable. Of the fifty-five patients enrolled in the study (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were females. They had a median duration of symptoms for 4 weeks. Twenty-seven patients received itopride and 28 received domperidone. One patient did not follow up in the domperidone group, thus 54 patients were evaluable for analysis. Moderate to complete symptomatic relief was observed in 22 (81%) patients in the itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS). Both the drugs were well tolerated and neither caused prolongation of QT interval nor any abnormality in any serum biochemistry values. Therapy with itopride resulted in good symptomatic relief, was safe, well tolerated and comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue of its efficacy and

  19. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies

    Energy Technology Data Exchange (ETDEWEB)

    Balassy, Csilla [Medical University of Vienna, Vienna General Hospital, Department of Radiology, Division of General and Pediatric Radiology, Vienna (Austria); Roberts, Donna [Medical University of South Carolina, Department of Radiology, Charleston, SC (United States); Miller, Stephen F. [LeBonheur Children' s Hospital, Department of Radiology, Memphis, TN (United States)

    2015-11-15

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children. (orig.)

  20. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies.

    Science.gov (United States)

    Balassy, Csilla; Roberts, Donna; Miller, Stephen F

    2015-11-01

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children.

  1. Safety and efficacy of gadoteric acid in pediatric magnetic resonance imaging: overview of clinical trials and post-marketing studies

    International Nuclear Information System (INIS)

    Balassy, Csilla; Roberts, Donna; Miller, Stephen F.

    2015-01-01

    Gadoteric acid is a paramagnetic gadolinium macrocyclic contrast agent approved for use in MRI of cerebral and spinal lesions and for body imaging. To investigate the safety and efficacy of gadoteric acid in children by extensively reviewing clinical and post-marketing observational studies. Data were collected from 3,810 children (ages 3 days to 17 years) investigated in seven clinical trials of central nervous system (CNS) imaging (n = 141) and six post-marketing observational studies of CNS, musculoskeletal and whole-body MR imaging (n = 3,669). Of these, 3,569 children were 2-17 years of age and 241 were younger than 2 years. Gadoteric acid was generally administered at a dose of 0.1 mmol/kg. We evaluated image quality, lesion detection and border delineation, and the safety of gadoteric acid. We also reviewed post-marketing pharmacovigilance experience. Consistent with findings in adults, gadoteric acid was effective in children for improving image quality compared with T1-W unenhanced sequences, providing diagnostic improvement, and often influencing the therapeutic approach, resulting in treatment modifications. In studies assessing neurological tumors, gadoteric acid improved border delineation, internal morphology and contrast enhancement compared to unenhanced MR imaging. Gadoteric acid has a well-established safety profile. Among all studies, a total of 10 children experienced 20 adverse events, 7 of which were thought to be related to gadoteric acid. No serious adverse events were reported in any study. Post-marketing pharmacovigilance experience did not find any specific safety concern. Gadoteric acid was associated with improved lesion detection and delineation and is an effective and well-tolerated contrast agent for use in children. (orig.)

  2. Efficacy and Safety Evaluation of Myostaal Forte, a Polyherbal Formulation, in Treatment of Knee Osteoarthritis: A Randomised Controlled Pilot Study

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    Raakhi K Tripathi

    2017-10-01

    Full Text Available Introduction: Myostaal Forte, a proprietary poly-herbal formulation, is mixture of nine herbal plant extracts which possess analgesic, anti-inflammatory and chondroprotective properties. Aim: A prospective, randomised, active controlled, 2-arm, parallel group, assessor blind study was planned to evaluate clinical efficacy and safety of Myostaal Forte in patients of knee osteoarthritis. Materials and Methods: Idiopathic knee osteoarthritis cases as per American College of Rheumatology (ACR clinical criteria were screened and recruited. A total of sixty patients were assigned to receive Myostaal Forte TDS (n=30 or Paracetamol 650 mg TDS (n=30 for six weeks. Naproxen was rescue analgesia. Modified Western Ontario and McMaster Universities Arthritis Index (WOMAC, Visual Analogue Scale (VAS, global assessment scores determined by orthopaedic physician at baseline, two, four, six weeks and telephonically at eight weeks. Safety was assessed through laboratory investigations at baseline and six weeks, adverse events and tolerability. Data were expressed as Mean±SD and analysed by Chi-square and unpaired t-test. p0.05. No significant adverse events, changes in the laboratory parameters and excellent compliance to treatment were seen in both the groups. Conclusion: Earlier onset analgesic effect with sustained chondroprotection after treatment cessation makes Myostaal Forte, a safe and effective alternative for treatment of knee osteoarthritis.

  3. Efficacy and safety of creatine supplementation in juvenile dermatomyositis: A randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    Solis, Marina Yazigi; Hayashi, Ana Paula; Artioli, Guilherme Giannini; Roschel, Hamilton; Sapienza, Marcelo Tatit; Otaduy, Maria Concepción; De Sã Pinto, Ana Lucia; Silva, Clovis Artur; Sallum, Adriana Maluf Elias; Pereira, Rosa Maria R; Gualano, Bruno

    2016-01-01

    It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter. © 2015 Wiley Periodicals, Inc.

  4. Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

    Science.gov (United States)

    Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

    2015-04-01

    To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  5. Efficacy and Tolerability of Steroid-Free, Over-the-Counter Treatment Formulations in Infants and Children With Atopic Dermatitis

    Science.gov (United States)

    Weber, Teresa M.; Herndon, James H.; Ewer, Melissa; Stephens, Thomas J.; Flick, Iris; Filbry, Alexander; Neufang, Gitta; Schoelermann, Andrea M.

    2015-01-01

    ABSTRACT Background Two steroid-free, over-the-counter skin protectant products have been developed for the care and treatment of atopic dermatitis (AD)—Eucerin Eczema Relief Body Crème (Body Cream) for daily skin moisturization and Eucerin Eczema Relief Instant Therapy cream (Instant Therapy) for treatment of AD flare-ups. We tested the efficacy and tolerability of these formulations in infants and children with AD. Methods Study 1: Body Cream was applied twice daily to the lower legs of 64 children with a history of AD (aged 3 months to 12 years) for 14 days. Study 2: Instant Therapy was applied to active lesions and surrounding skin of 29 children (aged 3 months to 12 years) with active atopic lesions. Assessments were performed at baseline and Days 7 and 14. Symptoms were assessed using the Atopic Dermatitis Severity Index in Study 2. Results Body Cream significantly improved skin hydration and reduced itching, burning/stinging, erythema, and tactile roughness. Instant Therapy significantly improved skin hydration and AD symptoms, notably pruritus, erythema, and lichenification. Both products were safe and well tolerated. Discussion Body Cream and Instant Therapy were effective and well tolerated in the treatment of AD in children. These products provide steroid-free, nonprescription therapy for the maintenance and treatment of acute eczema and were proven effective and safe in infants as young as 3 months. PMID:25699134

  6. Safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus: a 1-year post-marketing surveillance in Japan.

    Science.gov (United States)

    Goda, Maki; Yamakura, Tomoko; Sasaki, Kazuyo; Tajima, Takumi; Ueno, Makoto

    2018-02-01

    To evaluate the safety and efficacy of canagliflozin in elderly patients with type 2 diabetes mellitus (T2DM) in clinical settings. The authors conducted a 1-year post-marketing surveillance (PMS) of canagliflozin in almost all the elderly patients (≥65 years old) with T2DM who began taking canagliflozin during the first 3 months after its launch in Japan. The main outcomes included the incidences of adverse drug reactions (ADRs), serious ADRs, and the changes of laboratory tests as well as efficacy variables. An ADR was reported in 9.09% (125 of 1375 patients) in the safety analysis set. The main ADRs were dehydration, constipation, thirst, pollakiuria, dizziness, cystitis, eczema, pruritus, and rash. The incidence of serious ADRs was 1.02% (14 patients), which included urinary tract infection, dehydration, hypoglycemia, and cerebral infarction (two patients each). ADRs of special interest that had been reported in clinical trials of SGLT2 inhibitors, such as hypoglycemia, volume depletion-related events, genital/urinary tract infection, polyuria/pollakiuria, and ketone body increased were also observed in this PMS. The safety profiles were similar to the results of a previous clinical study of canagliflozin, and new safety concerns were not identified in this survey. The mean change in HbA1c was -0.77% after 12 months of treatment in the efficacy analysis set. In this PMS, the safety and efficacy profiles of canagliflozin in elderly patients with T2DM were obtained in the clinical settings in Japan and the drug was well tolerated and effective in improving glycemic control.

  7. Efficacy and tolerability of vilazodone for major depressive disorder: evidence from phase III/IV randomized controlled trials

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    Shi LG

    2016-11-01

    Full Text Available Ligen Shi,1,2 Jingyi Wang,1 Shenbin Xu,2 Yunrong Lu1 1Department of Psychiatry, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, 2Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Vilazodone is a new molecule approved for major depressive disorder (MDD. This report focuses on the efficacy and tolerability of vilazodone for MDD. MEDLINE, EMBASE, and Cochrane Library were searched. A total of 1,930 patients from four trials were included. A significant improvement in the Montgomery–Asberg Depression Rating Scale (MADRS total score was seen as early as week 2 (P<0.01 in vilazodone-treated patients. The results showed a higher rate of MADRS response with vilazodone compared with placebo (P<0.001. There were also greater improvements in the Hamilton Rating Scale for Anxiety as well as the Clinical Global Impressions (severity of illness and improvement of illness scores from baseline in vilazodone-treated patients compared to placebo patients (P<0.001. Discontinuation rates due to adverse events were higher with vilazodone than placebo (P=0.0002. The most common adverse events of vilazodone were vomiting, nausea, diarrhea, insomnia, somnolence, dizziness, and dry mouth (P<0.05. Treatment-related effects on sexual function were mild compared to placebo in men (P=0.03. In conclusion, 40 mg/day of vilazodone had a rapid onset of response and showed good improvement in anxiety symptoms as well as good tolerability during short-term treatment (8–10 weeks for MDD. Further studies should focus on the efficacy and tolerability of vilazodone over a longer duration and should utilize active comparators. Keywords: vilazodone, major depressive disorder, sexual dysfunction, anxiety

  8. Safety, tolerability, and biomarkers of the treatment of mice with aerosolized toll-like receptor ligands

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    Victoria eAlfaro

    2014-02-01

    Full Text Available We have previously discovered a synergistically therapeutic combination of two Toll-like receptor (TLR ligands, an oligodeoxynucleotide (ODN and Pam2CSK4. Aerosolization of these ligands stimulates innate immunity within the lungs to prevent pneumonia from bacterial and viral pathogens. Here we examined the safety and tolerability of this treatment in mice, and characterized the expression of biomarkers of innate immune activation. We found that neutrophils appeared in lung lavage fluid 4 hours after treatment, reached a peak at 48 hours, and resolved by 7 days. The peak of neutrophil influx was accompanied by a small increase in lung permeability. Despite the abundance of neutrophils in lung lavage fluid, only rare neutrophils were visible histopathologically in the interstitium surrounding bronchi and veins and none were visible in alveolar airspaces. The cytokines IL-6, TNF and CXCL2 rose several hundred-fold in lung lavage fluid 4 hours after treatment in a dose-dependent and synergistic manner, providing useful biomarkers of lung activation. IL-6 rose five-fold in serum with delayed kinetics compared to its rise in lavage fluid, and might serve as a systemic biomarker of immune activation of the lungs. The dose-response relationship of lavage fluid cytokines was preserved in mice that underwent myeloablative treatment with cytosine arabinoside to model the treatment of hematologic malignancy. There were no overt signs of distress in mice treated with ODN/Pam2CSK4 in doses up to 8-fold the therapeutic dose, and no changes in temperature, respiratory rate, or behavioral signs of sickness including sugar water preference, food disappearance, cage exploration or social interaction, though there was a small degree of transient weight loss. We conclude that treatment with aerosolized ODN/Pam2CSK4 is well tolerated in mice, and that innate immune activation of the lungs can be monitored by the measurement of inflammatory cytokines in lung lavage

  9. Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months.

    Science.gov (United States)

    Ziesenitz, Victoria C; Zutter, Andreas; Erb, Thomas O; van den Anker, Johannes N

    2017-08-01

    Ibuprofen is a non-steroidal anti-inflammatory drug frequently administered to children of various ages for relief of fever and pain and is approved as an over-the-counter medication in many countries worldwide. Although there are extensive data on its efficacy and safety in children and adults, there are divergent dosing recommendations for analgesia and treatment of fever in infants, especially in the age group between 3 and 6 months of age. In this article, we have assessed the safety and efficacy of ibuprofen use in infants in an attempt to find the optimal method of pain and fever management in this specific age group. Based on the current evidence, short-term use of ibuprofen is considered safe in infants older than 3 months of age having a body weight above 5-6 kg when special attention is given to the hydration of the patient. Ibuprofen should be prescribed based on body weight using a dose of 5-10 mg/kg. This dose can be administered 3-4 times a day resulting in a maximum total daily dose of 30-40 mg/kg. The rectal route has been shown to be less reliable because of erratic absorption, especially in young infants. Since most efficacy and safety data have been derived from trials in infants with fever, future studies should focus on the efficacy of ibuprofen in young infants with pain.

  10. Efficacy and safety of low-dose topical tacrolimus in vernal keratoconjunctivitis

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    Shoughy SS

    2016-04-01

    Full Text Available Samir S Shoughy,1 Mahmoud O Jaroudi,1 Khalid F Tabbara1–3 1The Eye Center and The Eye Foundation for Research in Ophthalmology, 2Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 3Wilmer Ophthalmological Institute of the Johns Hopkins University School of Medicine, Baltimore, MD, USA Objective: The objective of this study was to evaluate the efficacy and safety of topical low-dose tacrolimus (0.01% solution in patients with vernal keratoconjunctivitis (VKC. Patients and methods: A total of 62 consecutive patients with VKC refractory to conventional treatment were included retrospectively. Tacrolimus 0.01% ophthalmic solution was administered to patients twice daily after discontinuation of all previous topical medications. The duration of treatment ranged from 1 month to 29 months. The clinical symptoms of itching, redness, foreign body sensation, and discharge and the clinical signs of conjunctival hyperemia, conjunctival papillary hypertrophy, limbal infiltration, Trantas dots, and superficial punctate keratopathy were graded as 0 (normal, 1+ (mild, 2+ (moderate, or 3+ (severe. Assessment was carried out before initiation of therapy and on the last visit after treatment. Results: There were 62 patients with VKC comprising 49 male and 13 female patients. The median age was 12 years (range: 5–47 years. The mean visual acuity improved from 20/30 to 20/25 following treatment. There was statistically significant improvement in symptoms of itching (P<0.001, redness (P<0.001, foreign body sensation (P<0.001, and discharge (P<0.001. Statistically significant improvement was also observed in clinical signs of conjunctival hyperemia (P<0.001, limbal infiltration (P<0.001, Trantas dots (P<0.001, superficial punctate keratopathy (P<0.001, and conjunctival papillary hypertrophy (P<0.001. The solution form of tacrolimus was well tolerated. None of the patients developed elevation of intraocular pressure

  11. Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma.

    Science.gov (United States)

    Pereira Barbosa, M; Bugalho de Almeida, A; Pereira, C; Chen, C-W; Georgiou, P; Peachey, G

    2015-01-01

    The real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. The methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. Of the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). The findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study. Copyright © 2014 Sociedade Portuguesa de Pneumologia

  12. Efficacy and safety of olmesartan medoxomil and hydrochlorothiazide compared with benazepril and amlodipine besylate.

    Science.gov (United States)

    Kereiakes, Dean J; Neutel, Joel M; Punzi, Henry A; Xu, Jianbo; Lipka, Leslie J; Dubiel, Robert

    2007-01-01

    Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg butor=160 mm Hg but or=100 mm Hg butor=95 mm Hg and145 mm Hg andbenazepril (10 mg/day for 2 weeks; then 20 mg/day for 2 weeks; then benazepril 20 mg/day plus amlodipine besylate 5 mg/day for 4 weeks; then benazepril 20 mg/day plus amlodipine besylate 10 mg/day for 4 weeks). The primary endpoint was change from baseline in mean SBP at the end of week 12 (end of study). Secondary endpoints included DBP after completion of monotherapy and combination therapy at the end of weeks 4 and 12, SBP at the end of week 4, and percentage of patients attaining BP goals ofbenazepril plus amlodipine besylate (least square [LS] mean change: -32.5 vs -26.5 mm Hg, p=0.024; LS mean treatment difference -6.0 mm Hg; 95% CI -11.1, -0.8 mm Hg). The LS mean change for reduction in DBP approached statistical significance with olmesartan medoxomil/HCTZ compared with the benazepril-based regimen (p=0.056) at week 12 (end of study). BP reductions showed statistically significant differences between treatment groups favoring olmesartan medoxomil/HCTZ in both SBP and DBP at week 8. The percentage of patients achieving goal rates at the end of the study for olmesartan medoxomil/HCTZ and benazepril plus amlodipine besylate, respectively, were 66.3% versus 44.7% (p=0.006) forbenazepril plus amlodipine besylate 20/5 and 20

  13. A randomized, comparative, open-label study of efficacy and tolerability of alfuzosin, tamsulosin and silodosin in benign prostatic hyperplasia.

    Science.gov (United States)

    Manjunatha, R; Pundarikaksha, H P; Madhusudhana, H R; Amarkumar, J; Hanumantharaju, B K

    2016-01-01

    Benign prostatic hyperplasia (BPH) is a common and progressive disease affecting elderly males, often associated with lower urinary tract symptoms (LUTS). α1-blockers are the mainstay in symptomatic therapy of BPH. Because of their greater uroselectivity and minimal hemodynamic effects, alfuzosin, tamsulosin, and silodosin are generally preferred. The aim of this study was to compare the efficacy and tolerability of alfuzosin, tamsulosin, and silodosin in patients with BPH and LUTS. Ninety subjects with BPH and LUTS were randomized into three groups of thirty in each, to receive alfuzosin sustained release (SR) 10 mg, tamsulosin 0.4 mg, or silodosin 8 mg for 12 weeks. The primary outcome measure was a change in the International Prostate Symptom Score (IPSS), and the secondary outcome measures were changes in individual subjective symptom scores, quality of life score (QLS), and peak flow rate (Qmax) from baseline. The treatment response was monitored at 2, 4, 8, and 12 weeks. IPSS improved by 88.18%, 72.12%, and 82.23% in alfuzosin SR, tamsulosin and silodosin groups (P 75% in all the three groups (P tamsulosin (P = 0.025 and P tamsulosin (three subjects). Alfuzosin, tamsulosin, and silodosin showed similar efficacy in improvement of LUTS secondary to BPH, with good tolerability, acceptability, and minimum hemodynamic adverse effects. Alfuzosin, tamsulosin, and silodosin are comparable in efficacy in symptomatic management of BPH. The occurrence of QTc prolongation in three subjects with tamsulosin in the present study is an unexpected adverse event as there are no reports of QTc prolongation with tamsulosin in any of the previous studies.

  14. Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study.

    Science.gov (United States)

    Hanke, A A; Joch, C; Görlinger, K

    2013-05-01

    The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996-March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. Since receiving marketing authorization (February 21, 1996), ~647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ~31 000) is in line with the incidence observed with other four-factor PCCs. In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.

  15. Safety and efficacy of atovaquone and proguanil hydrochloride for the prophylaxis of Plasmodium falciparum malaria in South Africa.

    Science.gov (United States)

    van der Berg, J D; Duvenage, C S; Roskell, N S; Scott, T R

    1999-04-01

    The objective of this study was to determine the safety and efficacy of atovaquone and proguanil hydrochloride combination therapy for the prophylaxis of Plasmodium falciparum malaria in at-risk nonimmune subjects in South Africa. This open-label trial was conducted at research sites in South Africa during the main malaria transmission season, February through July. The study volunteers were temporarily living in, or traveling to, a malaria-endemic area. They received I tablet of 250 mg atovaquone and 100 mg proguanil hydrochloride once daily for up to 10 weeks. Subjects were monitored using sequential clinical and laboratory assessments. Thick blood smears were stained and evaluated by a central laboratory. An immunochromatographic test for P. falciparum was also used for on-site patient management. Prophylactic success was summarized using a 95% confidence interval for the proportion of subjects who did not develop parasitemia or who withdrew due to a treatment-related adverse event. A total of 175 subjects (15% women) were enrolled in the trial. The mean duration of drug exposure was 8.9 weeks. The combination of atovaquone and proguanil hydrochloride was well tolerated. The most frequently reported adverse events considered possibly related to study treatment were headache (7%), abdominal pain (2%), increased cough (2%), and skin disorder (2%). No serious adverse events were reported, and no treatment-emergent effects were noted for any laboratory variables. One subject who was noncompliant with therapy developed parasitemia, and 3 subjects withdrew due to a treatment-related adverse event (2 subjects with headache and 1 with nausea and dizziness). The prophylaxis success rate was 97%. In this study, atovaquone and proguanil hydrochloride combination therapy had an excellent safety and efficacy profile for prophylaxis of P. falciparum malaria in nonimmune subjects.

  16. A prospective case series evaluating the safety and efficacy of the Klox BioPhotonic System in venous leg ulcers

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