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Sample records for efficacy safety tolerability

  1. 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.

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

    NARCIS (Netherlands)

    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. 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

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

    NARCIS (Netherlands)

    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

  5. 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.

  6. 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

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

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    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.

  8. 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.

  9. 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

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

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    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.

  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. 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.

  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. 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.

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    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

  15. 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.

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

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    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...

  17. 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.

  18. Sulfasalazine efficacy and tolerability in rheumatic diseases

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    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.

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

    DEFF Research Database (Denmark)

    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...

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

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    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.

  1. 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

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

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    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. 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.

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

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    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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. 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

  16. 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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. 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.

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

    Science.gov (United States)

    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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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....

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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

  19. 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.

  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. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  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. 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.

  11. 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

  12. 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/...

  13. 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 ...

  14. 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,

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

    Science.gov (United States)

    Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

    2013-08-01

    Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy.

    Science.gov (United States)

    Lattanzi, Simona; Brigo, Francesco; Cagnetti, Claudia; Verrotti, Alberto; Zaccara, Gaetano; Silvestrini, Mauro

    2018-01-01

    Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and

  2. 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 ...

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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)

  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. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Graff, J N; Baciarello, G; Armstrong, A J

    2016-01-01

    BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years......-resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged ... who received enzalutamide, an androgen receptor inhibitor, in the phase III PREVAIL trial. PATIENTS AND METHODS: PREVAIL was a randomised, double-blind, multinational study of oral enzalutamide 160 mg/day (N = 872) versus placebo (N = 845) in chemotherapy-naive men with metastatic castration...

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Efficacy and safety of icotinib in treating non-small cell lung cancer: a systematic evaluation and meta-analysis based on 15 studies.

    Science.gov (United States)

    Biaoxue, Rong; Hua, Liu; Wenlong, Gao; Shuanying, Yang

    2016-12-27

    Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study. The overall response rate (ORR) and disease control rate (DCR) of icotinib were 40.99% (95% CI: 33.77% to 48.22%) and 77.16% (95% CI: 51.43% to 82.31%). The pooled progression-free survival (PFS) and overall survival (OS) were 7.34 months (95% CI: 5.60 to 9.07) and 14.98 months (95% CI: 9.78 to 20.18). Patients with EGFR mutations exhibited better ORR (OR = 3.67, p Icotinib is an effective and well tolerated regimen for Chinese patients with advanced NSCLC. Further randomized trials with large population are required to provide stronger evidence for icotinib in treating NSCLC.

  17. 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...

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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)....

  6. 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

  7. 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

  8. 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

  9. Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

    Science.gov (United States)

    Hyun, M Y; Lee, Y; No, Y A; Yoo, K H; Kim, M N; Hong, C K; Chang, S E; Won, C H; Kim, B J

    2015-03-01

    Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds. © 2014 British Association of Dermatologists.

  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. 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...

  12. 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

  13. 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.

  14. 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

  15. 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.

  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. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. A randomized study of the efficacy and safety of transdermal granisetron in the control of nausea and vomiting induced by moderately emetogenic chemotherapy in Korean patients.

    Science.gov (United States)

    Kim, Jeong Eun; Hong, Yong Sang; Lee, Jae-Lyun; Kim, Kyu-Pyo; Park, Seong Joon; Sym, Sun Jin; Shin, Dong Bok; Lee, Jeeyun; Park, Young Suk; Ahn, Jin Seok; Kim, Tae Won

    2015-06-01

    The granisetron transdermal system (GTS) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting (CINV) during multiday chemotherapy. We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy (MEC). A total of 276 patients were randomized into GTS (n = 139, one patch on days 1-4) or control group (n = 137, intravenous on day 1 and oral on days 2-4). The primary endpoint was the percentage of patients achieving complete response (CR) from chemotherapy initiation until 24 h after the final administration. Out of 234 patients (112 in GTS and 122 in control group) included in the per protocol analysis, 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy. The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients; 74.6 % of the patients in the control group achieved CR (95 % confidence interval -10.73 to 11.55 %). The CR rate did not change after subgroup analyses by sex, age, and chemotherapy naivety and analysis per day and overall days of treatment. The GTS group showed sustained CR from day 1 to day 4. Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), showed no difference. Both treatments were well tolerated and safe. The GTS showed non-inferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of control group. The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC.

  3. 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...

  4. Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Salvatore Siena

    Full Text Available This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb to determine the response rate of lenalidomide plus cetuximab combination therapy. Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day and intravenous cetuximab (400 mg/m(2 followed by weekly 250 mg/m(2 in 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.

  5. 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...

  6. 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...

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Safety and clinical efficacy of golimumab in the treatment of arthritides

    Directory of Open Access Journals (Sweden)

    Ismail Simsek

    2010-09-01

    Full Text Available Ismail Simsek, Yusuf YaziciNew York University School of Medicine, NYU Hospital for Joint Diseases, New York, USAAbstract: Golimumab is a human anti-tumor necrosis factor (TNF-alpha monoclonal antibody that was recently approved for the treatment of patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This review covers the published clinical trial data on the use of golimumab for the approved indications mentioned above with respect to efficacy and safety. The various ongoing trials for golimumab have yielded promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with rheumatoid arthritis, as well as in patients who were previously treated with other anti-TNF agents. In addition, the efficacy of golimumab in psoriatic arthritis and ankylosing spondylitis has also been demonstrated. The real safety information will be available only once the drug has been used in many more patients, who frequently have comorbid conditions.Keywords: arthritis, rheumatoid, psoriatic arthritis, ankylosing spondylitis

  19. 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.

  20. 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

  1. 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. 

  2. 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.

  3. Transplantation Tolerance through Hematopoietic Chimerism: Progress and Challenges for Clinical Translation

    Directory of Open Access Journals (Sweden)

    Benedikt Mahr

    2017-12-01

    Full Text Available The perception that transplantation of hematopoietic stem cells can confer tolerance to any tissue or organ from the same donor is widely accepted but it has not yet become a treatment option in clinical routine. The reasons for this are multifaceted but can generally be classified into safety and efficacy concerns that also became evident from the results of the first clinical pilot trials. In comparison to standard immunosuppressive therapies, the infection risk associated with the cytotoxic pre-conditioning necessary to allow allogeneic bone marrow engraftment and the risk of developing graft-vs.-host disease (GVHD constitute the most prohibitive hurdles. However, several approaches have recently been developed at the experimental level to reduce or even overcome the necessity for cytoreductive conditioning, such as costimulation blockade, pro-apoptotic drugs, or Treg therapy. But even in the absence of any hazardous pretreatment, the recipients are exposed to the risk of developing GVHD as long as non-tolerant donor T cells are present. Total lymphoid irradiation and enriching the stem cell graft with facilitating cells emerged as potential strategies to reduce this peril. On the other hand, the long-lasting survival of kidney allografts, seen with transient chimerism in some clinical series, questions the need for durable chimerism for robust tolerance. From a safety point of view, loss of chimerism would indeed be favorable as it eliminates the risk of GVHD, but also complicates the assessment of tolerance. Therefore, other biomarkers are warranted to monitor tolerance and to identify those patients who can safely be weaned off immunosuppression. In addition to these safety concerns, the limited efficacy of the current pilot trials with approximately 40–60% patients becoming tolerant remains an important issue that needs to be resolved. Overall, the road ahead to clinical routine may still be rocky but the first successful long

  4. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

  7. 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 ...

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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...

  14. 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...

  15. Efficacy and safety of praziquantel in preschool-aged children in an area co-endemic for Schistosoma mansoni and S. haematobium.

    Directory of Open Access Journals (Sweden)

    Jean T Coulibaly

    Full Text Available In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied.We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians.Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR, 88.6%; egg reduction rate (ERR, 96.7% and S. haematobium (CR, 88.9%; ERR, 98.0%. POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%. Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation, were observed in four Schistosoma egg-negative children.Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  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. 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…

  3. 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.

  4. 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

  5. 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.)

  6. 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.

  7. [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.

  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. Efficacy and safety of escitalopram versus desvenlafaxine in the treatment of major depression: A preliminary 1-year prospective randomized open label comparative trial

    Directory of Open Access Journals (Sweden)

    Brij Mohan Gupta

    2016-01-01

    Full Text Available Aim and Objective: To compare efficacy and safety of escitalopram with desvenlafaxine in the treatment of major depression.Materials and Methods: A total of 60 patients of depression were randomized into two groups after meeting inclusion criterion. In the first 3 weeks, escitalopram 10 mg/day was given and then 20 mg/day for the next 3 weeks in group 1 (n = 30. Desvenlafaxine in the first 3 weeks was given 50 mg/day and 100 mg/day for the next 3 weeks in group 2 (n = 30. The parameters evaluated during the study were efficacy assessments byHamilton Scale of Rating Depression (HAM-D, Hamilton Rating Scale of Anxiety (HAM-A, and Clinical Global Impression (CGI. Safety assessments were done by UKU-scale. Results: Escitalopram and desvenlafaxine significantly (P < 0.001, reduced HAM-D, HAM-A, and CGI scores from their respective base lines. However, on comparison failed show any statistical difference at 3 and 6 weeks of treatment. Escitalopram and desvenlafaxine were both found to be safe and well-tolerated and there was not much difference between the two groups as evident from UKU Scale and their effect on various biochemical parameters. Conclusion: The present study demonstrated similar efficacy and safety in reducing depression and anxiety with both escitalopram and desvenlafaxine, but clinical superiority of one drug over the other cannot be concluded due to limitations of the small sample size.

  10. [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.

  11. 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

  12. 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

  13. A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yi [Yisheng Biopharma. Co., Ltd., Beijing (China); Zhang, Shoufeng [Academy of Military Medical Sciences, Changchun (China); Li, Wei [National Center for Safety Evaluation of Drugs, Beijing (China); Hu, Yuchi; Zhao, Jinyan [Beijing Institute for Drug Control, Beijing (China); Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu [Yisheng Biopharma. Co., Ltd., Beijing (China); Hu, Rongliang, E-mail: ronglianghu@hotmail.com [Academy of Military Medical Sciences, Changchun (China); Shao, Hui, E-mail: hui.shao@yishengbio.com [Yisheng Biopharma. Co., Ltd., Beijing (China); Li, Lietao, E-mail: lietao.li@gmail.com [Yisheng Biopharma. Co., Ltd., Beijing (China)

    2016-02-15

    Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

  14. A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

    International Nuclear Information System (INIS)

    Zhang, Yi; Zhang, Shoufeng; Li, Wei; Hu, Yuchi; Zhao, Jinyan; Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu; Hu, Rongliang; Shao, Hui; Li, Lietao

    2016-01-01

    Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

  15. 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.

  16. 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

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

    Science.gov (United States)

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

    2015-07-01

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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Efficacy and safety of extended- versus immediate-release pramipexole in Japanese patients with advanced and L-dopa-undertreated Parkinson disease: a double-blind, randomized trial.

    Science.gov (United States)

    Mizuno, Yoshikuni; Yamamoto, Mitsutoshi; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Kagimura, Tatsuro; Sarashina, Akiko; Rascol, Olivier; Schapira, Anthony H V; Barone, Paolo; Hauser, Robert A; Poewe, Werner

    2012-01-01

    To compare the efficacy, safety, tolerability, and trough plasma levels of pramipexole extended-release (ER) and pramipexole immediate-release (IR), and to assess the effects of overnight switching from an IR to an ER formulation, in L-dopa-treated patients with Parkinson disease (PD). After a 1- to 4-week screening/enrollment, 112 patients who had exhibited L-dopa-related problems or were receiving suboptimal L-dopa dosage were randomized in double-blind, double-dummy, 1:1 fashion to pramipexole ER once daily or pramipexole IR 2 to 3 times daily for 12 weeks, both titrated to a maximum daily dose of 4.5 mg. Successful completers of double-blind treatment were switched to open-label pramipexole ER, beginning with a 4-week dose-adjustment phase. Among the double-blind treatment patients (n = 56 in each group), Unified Parkinson's Disease Rating Scale Parts II+III total scores decreased significantly from baseline and to a similar degree with pramipexole ER and IR formulations. In each group, 47 double-blind patients (83.9%) reported adverse events (AEs), requiring withdrawal of 3 ER patients (5.4%) and 2 IR patients (3.6%). Trough plasma levels at steady state (at the same doses and dose-normalized concentrations) were also similar with both formulations. Among open-label treatment patients (n = 53 from IR to ER), 83% were successfully switched (no worsening of PD symptoms) to pramipexole ER. In L-dopa-treated patients, pramipexole ER and pramipexole IR demonstrated similar efficacy, safety, tolerability, and trough plasma levels. Patients can be safely switched overnight from pramipexole IR to pramipexole ER with no impact on efficacy.

  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. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

    Science.gov (United States)

    Schweizer, Anja; Dejager, Sylvie; Foley, James E; Kothny, Wolfgang

    2011-01-01

    Aim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies. PMID:21415917

  5. 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

  6. Safety and efficacy of dihydroartemisinin-piperaquine versus artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Zambian children

    Directory of Open Access Journals (Sweden)

    Mulenga Modest

    2011-02-01

    Full Text Available Abstract Background Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum. Objective The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia. Methods Between 2005 and 2006, 304 children (6-59 months old with uncomplicated P. falciparum were enrolled, randomized to AL (101 or DHA/PQP (203 and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Recurrent infections were genotyped to distinguish between recrudescence and new infection. Results No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p Conclusion DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia. Trial Registration ISRCTN16263443, at http://www.controlled-trials.com/isrctn

  7. 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.

  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. 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

  10. [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.

  11. 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....

  12. 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.

  13. 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.

  14. [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.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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...

  17. Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

    Directory of Open Access Journals (Sweden)

    Schweizer A

    2011-02-01

    Full Text Available Anja Schweizer1, Sylvie Dejager2, James E Foley3, Wolfgang Kothny31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharma SAS, Rueil-Malmaison, France; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs, of vildagliptin based on a large pooled database of Phase II and III clinical trials.Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks' duration. AE profiles of vildagliptin (50 mg bid; N = 6116 were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210. Absolute incidence rates were calculated for all AEs, serious AEs (SAEs, discontinuations due to AEs, and deaths.Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively, whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators. The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas.Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.Keywords: type 2 diabetes, dipeptidyl peptidase-4, edema, safety, vildagliptin

  18. A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia).

    Science.gov (United States)

    Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

    2017-01-01

    Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed ( Ambrosia artemisiifolia ) is on the rise throughout Europe, having a significant negative impact on the patients' and their family's quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

  19. 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

  20. 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 ...

  1. 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 ...

  2. Safety and efficacy evaluation of gelatin-based nanoparticles associated with UV filters.

    Science.gov (United States)

    Oliveira, Camila Areias de; Dario, Michelli Ferrera; Sarruf, Fernanda Daud; Mariz, Inês Fátima Afonso; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

    2016-04-01

    The safety and efficacy assessment of nanomaterials is a major concern of industry and academia. These materials, due to their nanoscale size, can have chemical, physical, and biological properties that differ from those of their larger counterparts. The encapsulation of natural ingredients can provide marked improvements in sun protection efficacy. This strategy promotes solubility enhancement of flavonoids and yields an improved active ingredient with innovative physical, physicochemical and functional characteristics. Rutin, a flavonoid, has chemical and functional stability in topical vehicles exerting a synergistic effect in association with ultraviolet (UV) filters. However, the solubility of rutin is a limiting factor. Additionally, this bioactive compound does not have tendency to permeate across the stratum corneum. As an alternative to common synthetic based sunscreens, rutin-entrapped gelatin nanoparticles were designed. The present study investigated the pre-clinical safety of gelatin nanoparticles (GNPs) using an in vitro method and also assessed the clinical safety and efficacy of the association of GNPs with three commonly used chemical UV filters (ethylhexyl dimethyl PABA, ethylhexyl methoxycinnamate and methoxydibenzoylmethane). The non-irritant and adequate safety profile under sun-exposed skin conditions of the nanomaterials and the emulsions qualified the products for clinical efficacy assays. The in vivo results indicated that the GNPs increased the antioxidant protection of the emulsions developed. However, the presence of rutin in the nanosized material did not enhance performance on the SPF test. In conclusion, these findings characterized the nanomaterials as an innovative platform for multifunctional bioactive sunscreens. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus and Impaired Renal Function: Interim Report from Post-marketing Surveillance.

    Science.gov (United States)

    Haneda, Masakazu; Kadowaki, Takashi; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Ishii, Manabu; Matsukawa, Miyuki; Ueno, Makoto

    2018-06-01

    Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from

  4. An open-label Optional Titration Trial to Evaluate the Efficacy ...

    African Journals Online (AJOL)

    An eight-week open-label optional titration trial to evaluate the efficacy, tolerability and safety of Valsartan 80 mg/ & 160 mg once daily was carried out in patients with mild to moderate essential hypertension at the Lagos University Teaching Hospital. There was a significant reduction in both systolic and diastolic blood ...

  5. A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Woo, Vincent C

    2017-08-01

    The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  6. 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

  7. 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....

  8. 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.

  9. 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

  10. Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia.

    Science.gov (United States)

    Amarapurkar, Deepak N; Rane, Priya

    2004-12-01

    Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly used in the management of functional dyspepsia. However, in a recently conducted international, multicentric study, efficacy of 3 different regimens of mosapride was shown to be comparable to placebo. The objective of this phase 4 randomised, double blind, prospective study was to compare the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia among patients attending the gastroenterology outpatient department of a tertiary care hospital. Ganaton 50 mg or mosapride citrate 5 mg three times daily before meals for a period of 2 weeks was administered orally. Thirty functional dyspepsia patients in each group (total = 60) were randomised to receive itopride hydrochloride or mosapride citrate treatment for 2 weeks. In itopride versus mosapride groups, global efficacy as judged by patients was excellent in 17 versus 9 (p itopride versus mosapride group global efficacy as judged by physician was excellent in 24 (80%) versus 15 (50%) and poor in 0 (0%) versus 3 (10%) patients respectively. The global efficacy was rated as excellent to good in significantly (p itopride (93.3%) group as compared to mosapride (63.33 %) group. None of the patients reported any adverse events with itopride treatment. In the mosapride group 5 patients (16.7%) reported adverse events. Two patients (6.7%) were withdrawn from mosapride treatment due to adverse events. The physician rated global tolerability ofitopride versus mosapride treatment as excellent in 23 (76.7%) versus 8 (26.7%) (p itopride hydrochloride) is superior in efficacy and safety over mosapride citrate in the management of functional dyspepsia.

  11. 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.

  12. The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other Chronic Pain Disorders.

    Science.gov (United States)

    Patten, Denise K; Schultz, Bob G; Berlau, Daniel J

    2018-03-01

    Chronic inflammatory diseases are complex to treat and have an impact on a large number of patients. Due to the difficulty of treating these diseases and the great impact on quality of life, patients often seek off-label, complimentary, or alternative medicines to gain relief from symptoms. Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the U.S. Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block Toll-like receptor 4, resulting in an analgesic and antiinflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy. © 2018 Pharmacotherapy Publications, Inc.

  13. 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.

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

    Science.gov (United States)

    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

  15. 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

  16. 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

  17. 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.

  18. Brief Report: Efficacy and Safety of Switching to Coformulated Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide (E/C/F/TAF) in Virologically Suppressed Women.

    Science.gov (United States)

    Hodder, Sally; Squires, Kathleen; Kityo, Cissy; Hagins, Debbie; Avihingsanon, Anchalee; Kido, Anna; Jiang, Shuping; Kulkarni, Rima; Cheng, Andrew; Cao, Huyen

    2018-06-01

    The integrase inhibitor regimen [elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (TDF)] demonstrated superior efficacy when compared with a protease inhibitor regimen [ritonavir-boosted atazanavir (ATV + RTV) and FTC/TDF] in 575 treatment-naive women at week 48. We investigated the efficacy, safety, and tolerability of switching to a TAF-based, single-tablet regimen containing elvitegravir, cobicistat, FTC, and tenofovir alafenamide (E/C/F/TAF) versus remaining on ATV + RTV plus FTC/TDF. After completing the initial randomized, blinded phase, virologically suppressed (HIV-1 RNA TAF versus remaining on their current regimen. The primary end point was proportion of participants with plasma HIV-1 RNA TAF and 53 to remain on ATV + RTV plus FTC/TDF. At week 48, virologic suppression was maintained in 150 (94%) of women on E/C/F/TAF and 46 (87%) on ATV + RTV plus FTC/TDF [difference 7.5% (95% confidence interval -1.2% to 19.4%)], demonstrating noninferiority of E/C/F/TAF to ATV + RTV and FTC/TDF. Incidence of AEs was similar between groups; study drug-related AEs were more common with E/C/F/TAF (11% versus 4%). Switching to E/C/F/TAF was noninferior to continuing ATV + RTV plus FTC/TDF in maintaining virologic suppression and was well tolerated at 48 weeks.

  19. Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder

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    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

  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. Systematic review to evaluate the safety, efficacy and economical outcomes of the Vibrant Soundbridge for the treatment of sensorineural hearing loss.

    Science.gov (United States)

    Bruchhage, Karl-Ludwig; Leichtle, Anke; Schönweiler, Rainer; Todt, Ingo; Baumgartner, Wolf-Dieter; Frenzel, Henning; Wollenberg, Barbara

    2017-04-01

    Introduced in the late 90s, the active middle ear implant Vibrant Soundbridge (VSB) is nowadays used for hearing rehabilitation in patients with mild to severe sensorineural hearing loss (SNHL) unable to tolerate conventional hearing aids. In experienced hands, the surgical implantation is fast done, safe and highly standardized. Here, we present a systematic review, after more than 15 years of application, to determine the efficacy/effectiveness and cost-effectiveness, as well as patient satisfaction with the VSB active middle ear implant in the treatment of mild to severe SNHL. A systematic search of electronic databases, investigating the safety and effectiveness of the VSB in SNHL plus medical condition resulted in a total of 1640 papers. After removing duplicates, unrelated articles, screening against inclusion criteria and after in-depth screening, the number decreased to 37 articles. 13 articles were further excluded due to insufficient outcome data. 24 studies remained to be systematically reviewed. Data was searched on safety, efficacy and economical outcomes with the VSB. Safety-oriented outcomes included complication/adverse event rates, damage to the middle/inner ear, revision surgery/explant rate/device failure and mortality. Efficacy outcomes were divided into audiological outcomes, including hearing thresholds, functional gain, speech perception in quiet and noise, speech recognition thresholds, real ear insertion gain and subjective outcomes determined by questionnaires and patient-oriented scales. Data related to quality of life (QALY, ICER) were considered under economical outcomes. The VSB turns out to be a highly reliable and a safe device which significantly improves perception of speech in noisy situations with a high sound quality. In addition, the subjective benefit of the VSB was found to be mostly significant in all studies. Finally, implantation with the VSB proved to be a cost-effective and justified health care intervention.

  2. 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

  3. 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

  4. Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis.

    Science.gov (United States)

    Rudroju, Neelima; Bansal, Dipika; Talakokkula, Shiva Teja; Gudala, Kapil; Hota, Debasish; Bhansali, Anil; Ghai, Babita

    2013-01-01

    Anticonvulsants and antidepressants are mostly used in management of painful diabetic neuropathy (PDN). However there are few direct comparisons between drugs of these classes, making evidence-based decision-making in the treatment of painful diabetic neuropathy difficult. This study aimed to perform a network meta-analysis and benefit-risk analysis to evaluate the comparative efficacy and safety of these drugs in PDN treatment. Comparative effectiveness study. Medical Education and Research facility in India. A comprehensive data search was done in PubMed, Cochrane, and Embase up to August 2012. We then systematically reviewed the studies which compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations. We performed a random-effects network meta-analysis to rank treatments in terms of efficacy and safety. We chose the number of patients experiencing = 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, taking efficacy outcome as benefit and safety outcome as risk. Analysis was intention-to-treat. We included 21 published trials in the analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be significantly efficacious compared to placebo with odds ratios (OR) of 2.12, 3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused more withdrawals than gabapentin. The ranking order of efficacy was gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin, duloxetine, amitriptyline, and placebo and the ranking order of safety was placebo, gabapentin, pregabalin, venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin, duloxetine

  5. 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

  6. Three in one: safety, efficacy, and patient acceptability of triple fixed-dose combination medicine in the management of hypertension

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    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

  7. 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.

  8. 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.

  9. Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders

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    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

  10. 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.

  11. [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.

  12. 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

  13. Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.

    Science.gov (United States)

    García-Ara, Carmen; Pedrosa, María; Belver, María Teresa; Martín-Muñoz, María Flor; Quirce, Santiago; Boyano-Martínez, Teresa

    2013-04-01

    Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE 17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. 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

  15. Safety-efficacy balance of S-ketamine and S-norketamine in acute and chronic pain

    OpenAIRE

    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 anesthetic. Recently there has been a renewed interest for the treatment of therapy-resistant chronic pain with subanesthetic doses of ketamine. This thesis describes the effects of S-ketamine in pa...

  16. 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.

  17. 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...

  18. 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

  19. A review of the pharmacology and clinical efficacy of brivaracetam

    Directory of Open Access Journals (Sweden)

    Klein P

    2018-01-01

    Full Text Available Pavel Klein,1 Anyzeila Diaz,2 Teresa Gasalla,3 John Whitesides4 1Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA; 2Neurology Patient Value Unit, UCB Pharma, Smyrna, GA, USA; 3Neurology Patient Value Unit, UCB Pharma, Monheim am Rhein, Germany; 4Asset Development, UCB Pharma, Raleigh, NC, USA Abstract: Brivaracetam (BRV; Briviact is a new antiepileptic drug (AED approved for adjunctive treatment of focal (partial-onset seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg and multiple (200–800 mg/day oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV. Keywords: brivaracetam, efficacy

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

    Science.gov (United States)

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

    2012-04-01

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

  2. 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...

  3. Simultaneous sequential monitoring of efficacy and safety led to masking of effects.

    Science.gov (United States)

    van Eekelen, Rik; de Hoop, Esther; van der Tweel, Ingeborg

    2016-08-01

    Usually, sequential designs for clinical trials are applied on the primary (=efficacy) outcome. In practice, other outcomes (e.g., safety) will also be monitored and influence the decision whether to stop a trial early. Implications of simultaneous monitoring on trial decision making are yet unclear. This study examines what happens to the type I error, power, and required sample sizes when one efficacy outcome and one correlated safety outcome are monitored simultaneously using sequential designs. We conducted a simulation study in the framework of a two-arm parallel clinical trial. Interim analyses on two outcomes were performed independently and simultaneously on the same data sets using four sequential monitoring designs, including O'Brien-Fleming and Triangular Test boundaries. Simulations differed in values for correlations and true effect sizes. When an effect was present in both outcomes, competition was introduced, which decreased power (e.g., from 80% to 60%). Futility boundaries for the efficacy outcome reduced overall type I errors as well as power for the safety outcome. Monitoring two correlated outcomes, given that both are essential for early trial termination, leads to masking of true effects. Careful consideration of scenarios must be taken into account when designing sequential trials. Simulation results can help guide trial design. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Clinical efficacy and safety of fluoxetine in generalized anxiety disorder in Chinese patients

    Directory of Open Access Journals (Sweden)

    Zou C

    2013-11-01

    Full Text Available Chuan Zou,1 Xiang Ding,1 Joseph H Flaherty,2 Birong Dong1 1The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu, People's Republic of China; 2St Louis University, St Louis, MO, USA Background: Generalized anxiety disorder (GAD is a prevalent, disabling disease and is highly comorbid with other psychiatric disorders both in Western countries and the People's Republic of China. Fluoxetine, a selective inhibitor of serotonin reuptake (SSRI, is widely utilized in the management of GAD in clinical practice despite the lack of strong evidence. This article reviews fluoxetine trials to investigate fluoxetine's efficacy and tolerability in Chinese patients with GAD. Methods: A literature review was conducted using the following databases up to and including April 2013: Chinese BioMedical Literature, China National Knowledge Infrastructure, EMBASE, MEDLINE, and PsycINFO. We selected clinical studies that utilized fluoxetine for GAD in which all participants were Chinese. Results: Fifteen open-label, non-placebo trials were identified and analyzed; eleven anxiolytics were compared with fluoxetine separately. Short-term efficacy of fluoxetine had been established in these open-label, head-to-head controlled trials. Fluoxetine had rapid onset of action (approximately 1–2 weeks and seemed to be effective in maintenance treatment. Fluoxetine was generally well-tolerated with the most common side effect of dry month and nausea. Compared to other anxiolytic agents, fluoxetine was equivalent with all of the comparative anxiolytics in terms of efficacy except mirtazapine which showed conflicting results with fluoxetine in two studies. In terms of side effects, fluoxetine was better tolerated than diazepam, doxepine, and amitriptyline, less tolerated than escitalopram, and had similar tolerability with duloxetine as well as alprazolam. Conclusion: Given the high risk of bias of the included studies, the overall small sample

  5. 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

  6. Efficacy and safety of an adjunctive mGlu2 receptor positive allosteric modulator to a SSRI/SNRI in anxious depression.

    Science.gov (United States)

    Kent, Justine M; Daly, Ella; Kezic, Iva; Lane, Rosanne; Lim, Pilar; De Smedt, Heidi; De Boer, Peter; Van Nueten, Luc; Drevets, Wayne C; Ceusters, Marc

    2016-06-03

    This phase 2a, randomized, multicenter, double-blind, proof-of-concept study was designed to evaluate, efficacy, safety and tolerability of JNJ-40411813/ADX71149, a novel metabotropic glutamate 2 receptor positive allosteric modulator as an adjunctive treatment for major depressive disorder (MDD) with significant anxiety symptoms. Eligible patients (18-64 years) had a DSM-IV diagnosis of MDD, Hamilton Depression Rating Scale-17 (HDRS17) score of ≥ 18, HDRS17 anxiety/somatization factor score of ≥ 7, and an insufficient response to current treatment with a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor. The doubly-randomized, 8-week double-blind treatment phase was comprised of two 4-week periods, from which a combined test statistic was generated, with pre-determined weights assigned to each of the 2 treatment periods. Period 1: patients (n=121) were randomly assigned (1:1) to JNJ-40411813 (n=62; 50mg to 150 mg b.i.d, flexibly dosed) or placebo (n=59); Period 2: placebo-treated patients (n=22) who continued to meet entry severity criteria were re-randomized (1:1) to JNJ-40411813 or placebo, while other patients underwent sham re-randomization and continued on their same treatment. Of 121 randomized patients, 100 patients (82.6%) were completers. No efficacy signal was detected on the primary endpoint, the 6-item Hamilton Anxiety Subscale (HAM-A6, p=0.51). Efficacy signals (based on prespecified 1-sided pdepression (HDRS17 total score, 6-item subscale of HDRS17 assessing core depressive symptoms [HAM-D6], and Inventory of Depressive Symptomatology [IDS-C30]) and anxiety (HDRS17 anxiety/somatization factor, IDS-C30 anxiety subscale). Although well-tolerated, the results do not suggest efficacy for JNJ-40411813 as an adjunctive treatment for patients with MDD with significant anxious symptoms in the dose range studied. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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

  8. 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 ...

  9. Viral Infection: A Potent Barrier to Transplantation Tolerance

    Directory of Open Access Journals (Sweden)

    David M. Miller

    2008-01-01

    Full Text Available Transplantation of allogeneic organs has proven to be an effective therapeutic for a large variety of disease states, but the chronic immunosuppression that is required for organ allograft survival increases the risk for infection and neoplasia and has direct organ toxicity. The establishment of transplantation tolerance, which obviates the need for chronic immunosuppression, is the ultimate goal in the field of transplantation. Many experimental approaches have been developed in animal models that permit long-term allograft survival in the absence of chronic immunosuppression. These approaches function by inducing peripheral or central tolerance to the allograft. Emerging as some of the most promising approaches for the induction of tolerance are protocols based on costimulation blockade. However, as these protocols move into the clinic, there is recognition that little is known as to their safety and efficacy when confronted with environmental perturbants such as virus infection. In animal models, it has been reported that virus infection can prevent the induction of tolerance by costimulation blockade and, in at least one experimental protocol, can lead to significant morbidity and mortality. In this review, we discuss how viruses modulate the induction and maintenance of transplantation tolerance.

  10. Long-term efficacy and safety of anastrozole for adjuvant treatment of early breast cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Sharath Gangadhara

    2009-04-01

    Full Text Available Sharath Gangadhara, Gianfilippo BertelliSouth West Wales Cancer Institute, Singleton Hospital, Swansea, UKAbstract: For more than 20 years, tamoxifen has been the gold standard for the adjuvant treatment of postmenopausal women with hormone-responsive early breast cancer. However, recent randomized trials have shown efficacy and tolerability benefits with the third-generation aromatase inhibitor anastrozole, resulting in an increased use of this agent in the adjuvant setting. Data on anastrozole’s long-term efficacy and tolerability are therefore of interest in clinical practice and will be reviewed here, especially in the light of the 100-month analysis of the ATAC (Anastrozole, Tamoxifen Alone or in Combination trial.Keywords: anastrozole, aromatase inhibitors, breast cancer, adjuvant therapy 

  11. 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.

  12. 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

  13. 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.

  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. 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.

  16. 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.

  17. 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...

  18. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

    Science.gov (United States)

    2013-01-01

    Background Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. Methods Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. Results Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. Conclusion Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However

  19. [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.

  20. 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

  1. Long-term safety and efficacy of adalimumab for intestinal Behçet's disease in the open label study following a phase 3 clinical trial

    Directory of Open Access Journals (Sweden)

    Nagamu Inoue

    2017-07-01

    Full Text Available Background/Aims: Intestinal Behçet's disease (BD is an immune-mediated inflammatory disorder. We followed up the patients and evaluated safety profile and effectiveness of adalimumab for the treatment of intestinal BD through 100 weeks rolled over from the 52 week clinical trial (NCT01243671.Methods: Patients initiated adalimumab therapy at 160 mg at week 0, followed by 80 mg at week 2, followed by 40 mg every other week until the end of the study. Long-term safety and all adverse events (AEs were examined. The efficacy was assessed on the basis of marked improvement (MI and complete remission (CR using a composite efficacy index, which combined global gastrointestinal symptoms and endoscopic assessments.Results: Twenty patients were enrolled in this study; 15 patients received adalimumab treatment until study completion. The incidence of AEs through week 100 was 544.4 events/100 person-years, which was comparable to the incidence through week 52 (560.4 events/100 person-years. No unexpected trend was observed and adalimumab was well tolerated. At weeks 52 and 100, 60.0% and 40.0% of patients showed MI, respectively, and 20.0% and 15.0% of patients showed CR, respectively.Conclusions: This report demonstrates 2 years safety and effectiveness of adalimumab in intestinal BD patients. Patients with intestinal BD refractory to conventional treatment receiving up to 2 years of adalimumab treatment demonstrated safety outcomes consistent with the known profile of adalimumab, and the treatment led to sustained reduction of clinical and endoscopic disease activity.

  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. 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.

  4. 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, ...

  5. 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.

  6. 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.

  7. Safety and anti-hyperglycemic efficacy of various tea types in mice

    Science.gov (United States)

    Han, Manman; Zhao, Guangshan; Wang, Yijun; Wang, Dongxu; Sun, Feng; Ning, Jingming; Wan, Xiachun; Zhang, Jinsong

    2016-01-01

    Tea, a beverage consumed worldwide, has proven anti-hyperglycemic effects in animal models. Better efficacies of tea beverages are frequently associated with high-dose levels, whose safety attracts considerable attention. Based on the inherent nature of tea catechin oxidation, fresh tea leaves are manufactured into diverse tea types by modulating the oxidation degree of catechins. The present study aimed to assess various tea types for their safety properties and anti-hyperglycemic effects. Mice were allowed free access to tea infusion (1:30, w/v) for one week, and the rare smoked tea caused salient adverse reactions, including hepatic and gastrointestinal toxicities; meanwhile, the widely-consumed green and black teas, unlike the rare yellow tea, suppressed growth in fast-growing healthy mice. When mice were fed a high-fat diet and allowed free access to tea infusion (1:30, w/v) for 25 days, only yellow tea significantly reduced blood glucose. Therefore, various teas showed different safety profiles as well as anti-hyperglycemic efficacy strengths. To achieve an effective and safe anti-hyperglycemic outcome, yellow tea, which effectively suppressed high-fat diet-induced early elevation of hepatic thioredoxin-interacting protein, is an optimal choice. PMID:27531374

  8. 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.

  9. 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

  10. 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)

  11. Clinical efficacy and tolerability of praziquantel for intestinal and urinary schistosomiasis-a meta-analysis of comparative and non-comparative clinical trials.

    Directory of Open Access Journals (Sweden)

    Julien Zwang

    Full Text Available Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo. Most studied were in school-aged children (64%, S. mansoni (58%, and the 40 mg/kg dose (56%; 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017 and egg reduction rate (ERR, n=13,007; safety as adverse events (AE incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0 for S. japonicum, 77.1% (68.4-85.1 for S. haematobium, 76.7% (95%CI 71.9-81.2 for S. mansoni, and 63.5% (95%CI 48.2-77.0 for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects. On average, 56.9% (95%CI 47.4-67.9 of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.

  12. 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.

  13. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

    Science.gov (United States)

    Heal, D J; Cheetham, S C; Smith, S L

    2009-12-01

    Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

  14. The safety of phosphodiesterase type 5 inhibitors for erectile dysfunction.

    Science.gov (United States)

    Ventimiglia, Eugenio; Capogrosso, Paolo; Montorsi, Francesco; Salonia, Andrea

    2016-01-01

    Phosphodiesterase type 5 inhibitors (PDE5Is) are the leading drugs for the treatment of erectile dysfunction (ED), being recommended as a first line treatment by both the European and US urological guidelines. PDE5Is are highly effective as compared to placebo, well tolerated and have a very low, though not negligible, rate of severe treatment-related adverse events. This paper reviews the safety profile of currently available PDE5Is, comparing them in a broad spectrum ED population and outlining a number of real-life aspects of importance in the real-life everyday clinical setting. Guidelines unanimously agree in considering PDE5Is as first line treatments for ED when well-tolerated and not contraindicated. Despite the fact that no high-grade evidence comparing the efficacy and the safety for PDE5Is is currently available, published data seem to suggest that there are no major differences in their safety profiles. Moreover, although oral PDE5Is were shown to cause more AEs than placebo, they were generally mild and well tolerated.

  15. 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

  16. Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

    Science.gov (United States)

    Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

    2012-09-01

    A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study

  17. Safety and efficacy of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice: interim results of the STELLA-LONG TERM post-marketing surveillance study.

    Science.gov (United States)

    Nakamura, Ichiro; Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Uno, Satoshi

    2018-02-01

    Data regarding the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in the real-world setting in Japan are limited. The STELLA-LONG TERM study is an ongoing 3-year post-marketing surveillance study of ipragliflozin in type 2 diabetes (T2D) patients. Here, we report the interim results (including 3-, 12-, and 24-month data). All Japanese patients with T2D who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015 at participating centers in Japan were registered in STELLA-LONG TERM. At 3, 12, and 24 months, the safety analysis set comprised 11,053, 5475, and 138 patients, respectively; the efficacy analysis set comprised 8757 patients. Ipragliflozin treatment resulted in statistically significant improvements versus baseline in hemoglobin A1c, fasting plasma glucose concentration, body weight, blood pressure, heart rate, and serum concentrations of low-density lipoprotein cholesterol and triglycerides. The adverse drug reaction incidence rate was 10.71%, the most common reactions being renal and urinary disorders (5.06%), infections and infestations (1.24%), and skin and subcutaneous tissue disorders (1.14%). Ipragliflozin was well tolerated and effective in Japanese patients with T2D; no new safety issues were identified.

  18. Pharmacokinetics, Safety, and 48-Week Efficacy of Oral Raltegravir in HIV-1–Infected Children Aged 2 Through 18 Years

    Science.gov (United States)

    Nachman, Sharon; Zheng, Nan; Acosta, Edward P.; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fenton, Terence; Xu, Xia; Wenning, Larissa; Spector, Stephen A.; Frenkel, Lisa M.; Alvero, Carmelita; Worrell, Carol; Handelsman, Edward; Wiznia, Andrew; Moultrie, Harry; Kindra, Gurpreet; Sanders, Margaret Ann; Williams, Ruth; Jensen, Jennifer; Acevedo, Midnela; Fabregas, Lizbeth; Jurgrau, Andrea; Foca, Marc; Higgins, Alice; Deville, Jaime G.; Nielsen-Saines, Karin; Carter, Michele F.; Swetnam, John; Wilson, Joan; Donnelly, Margaret; Akleh, Siham; Rigaud, Mona; Kaul, Aditya; Patel, Nehali; Gaur, Aditya; Utech, L. Jill; Cardoso, Edmundo; Moreira, Ana Maria; Santos, Breno; Bobat, Raziya; Mngqibisa, Rosie; Burey, Marlene; Abadi, Jacob; Rosenberg, Michael; Luzuriaga, Katherine; Picard, Donna; Pagano-Therrien, Jessica; Dittmer, Sylvia; Ndiweni, Hilda Ntatule; Patel, Amisha; DelRey, Michelle; McMullen-Jackson, Chivon; Paul, Mary E.; Melvin, Ann; Venema-Weiss, Corry; Lane, Jenna; Beneri, Christy; Ferraro, Denise; Infanzon, Erin; McAuley, James B; Aziz, Mariam; McNichols, Maureen; Pelton, Stephen; McLaud, Deb; Clarke, Diana; Zeichner, Steven; Akar, Arezou; Thompson, Deidre; Douglas, Steven D.; Rutstein, Richard M.; Vincent, Carol A.; Vachon, Mary Elizabeth; Cavallo, Martha; Purswani, Murli Udharam; Masheto, Gaerolwe; Ogwu, Anthony; Kakhu, Tebogo; Viani, Rolando M.; Darcey, Anita,; Norris, Kimberly; Burchett, Sandra K.; Kneut, Catherine; Karthas, Nancy; Casey, Denise; Emmanuel, Patricia; Lujan-Zilbermann, Jorge; Rana, Sohail; Houston, Patricia; Mengistab, Mulu; Rathore, Mobeen; Mirza, Ayesha; Gayton, Tabetha; Barr, Emily; Dunn, Jennifer; Hahn, Kerry; Eysallenne, Zulma; Howard, F. Sholar; Graham, Kathleen; Negra, Marinella Della; Queiroz, Wladimir; Lian, Yu Ching; Wara, Diane; Ruel, Ted; VanDyke, Russell; Reilly, Patricia; Bradford, Sheila; van Rensburg, Anita Janse; Dobbels, Els; Bester, Marietjie; Bamji, Mahrukh; Paul, Santa; Sarza, Mirala; Kovacs, Andrea; Homans, James; Spencer, LaShonda; Hofer, Cristna; Abreu, Thalita; Oliveira, Ricardo; Joao, Esau C.; Pinto, Jorge; Ferreira, Flavia; Kakehasi, Fabiana; Cervi, Maria Celia; Isaac, Marcia De Lima; Losso, Marcelo H.; Stankievich, Erica; Foradori, Irene; Tucker, Diane; Church, Joseph; Belzer, Marvin; Hopkins, Johns; Ellen, Jonathan; Agwu, Allison; Laurel, Borkovic

    2014-01-01

    Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)–infected youth. Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24. Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/µL (4.6%). Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses. Clinical Trials Registration NCT00485264. PMID:24145879

  19. 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)

  20. Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature.

    Science.gov (United States)

    Sousa, Sandra; Duarte, Ana Catarina; Cordeiro, Inês; Ferreira, Joana; Gonçalves, Maria João; Meirinhos, Tiago; Rocha, Teresa Martins; Romão, Vasco C; Santos, Maria José

    2017-01-01

    Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD). A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014), complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion) and safety (reactions to vaccine and relapse of rheumatic disease) outcomes were extracted and summarized according to the type of vaccine. Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy. Existing literature demonstrates that vaccines are generally well

  1. Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Sandra Sousa

    2017-01-01

    Full Text Available Introduction: Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. Objectives: To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD. Methods: A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014, complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion and safety (reactions to vaccine and relapse of rheumatic disease outcomes were extracted and summarized according to the type of vaccine. Results: Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy

  2. GOLIMUMAB — A NEW TNF α-BLOCKER. THE REVIEW OF THE EFFICACY AND SAFETY EVALUATION RESULTS

    Directory of Open Access Journals (Sweden)

    R. V. Denisova

    2012-01-01

    Full Text Available The article represents the results of efficacy and safety evaluation of the human monoclonal antibodies — golimumab, according to the data of international multicenter randomized double-blind placebo-controlled trials, including patients with active stage of rheumatoid arthritis. It was shown, that golimumab was reliably more effective than placebo both when administered hypodermic and intravenous. The safety profile of golimumab is comparable to that of the other tumor necrosis factor alpha blockers. The review also contains information on the 3d phase of golimumab efficacy and safety research in patients with juvenile idiopathic arthritis.

  3. Dopamine serotonin stabilizer RP5063: A randomized, double-blind, placebo-controlled multicenter trial of safety and efficacy in exacerbation of schizophrenia or schizoaffective disorder.

    Science.gov (United States)

    Cantillon, Marc; Prakash, Arul; Alexander, Ajay; Ings, Robert; Sweitzer, Dennis; Bhat, Laxminarayan

    2017-11-01

    The study objectives were to evaluate the efficacy, safety, tolerability, and pharmacokinetics of RP5063 versus placebo. The study was conducted in adults with acute exacerbation of schizophrenia or schizoaffective disorder. This 28-day, multicenter, placebo-controlled, double-blind study randomized 234 subjects to RP5063 15, 30, or 50mg; aripiprazole; or placebo (3:3:3:1:2) once daily. The aripiprazole arm was included solely to show assay sensitivity and was not powered to show efficacy. The primary endpoint was change from baseline to Day 28/EOT (End-of-Treatment) in Positive and Negative Syndrome Scale (PANSS) total score; secondary endpoints included PANSS subscales, improvement ≥1 point on the Clinical Global Impressions-Severity (CGI-S), depression and cognition scales. The primary analysis of PANSS Total showed improvement by a mean (SE) of -20.23 (2.65), -15.42 (2.04), and -19.21 (2.39) in the RP5063 15, 30, and 50mg arms, versus -11.41 (3.45) in the placebo arm. The difference between treatment and placebo reached statistical significance for the 15mg (p=0.021) and 50mg (p=0.016) arms. Improvement with RP5063 was also seen for multiple secondary efficacy outcomes. Discontinuation for any reason was much lower for RP5063 (14%, 25%, 12%) versus placebo (26%) and aripiprazole (35%). The most common treatment-emergent adverse events (TEAE) in the RP5063 groups were insomnia and agitation. There were no significant changes in body weight, electrocardiogram, or incidence of orthostatic hypotension; there was a decrease in blood glucose, lipid profiles, and prolactin levels. In conclusion, the novel dopamine serotonin stabilizer, RP5063 is an efficacious and well-tolerated treatment for acute exacerbation of schizophrenia or schizoaffective disorder. Copyright © 2017. Published by Elsevier B.V.

  4. 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).

  5. Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

    Science.gov (United States)

    Leyden, James J; Sniukiene, Vilma; Berk, David R; Kaoukhov, Alexandre

    2018-03-01

    There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other

  6. 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.

  7. [Fixed-dose combination fluticasone propionate/formoterol for the treatment of asthma: a review of its pharmacology, efficacy and tolerability].

    Science.gov (United States)

    Quintano Jiménez, J A; Ginel Mendoza, L; Entrenas Costa, L M; Polo García, J

    2016-02-01

    The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

  8. 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.

  9. 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 ...

  10. 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

  11. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

    Science.gov (United States)

    Stamp, Lisa K; Chapman, Peter T; Barclay, Murray L; Horne, Anne; Frampton, Christopher; Tan, Paul; Drake, Jill; Dalbeth, Nicola

    2017-09-01

    To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was gout. Allopurinol dose escalation is well tolerated. ANZCTR12611000845932; Results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies.

    Science.gov (United States)

    Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H; Keystone, Edward

    2016-12-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies. © 2016 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  13. A prospective case series evaluating the safety and efficacy of the Klox BioPhotonic System in venous leg ulcers

    Directory of Open Access Journals (Sweden)

    Nikolis A

    2016-09-01

    Full Text Available Andreas Nikolis,1 Doria Grimard,2 Yves Pesant,3 Giovanni Scapagnini,4 Denis Vézina5 1Division of Plastic Surgery, Victoria Park Research Centre, Montreal, 2Q&T Research Chicoutimi, Chicoutimi, 3St-Jerome Medical Research Inc., St-Jerome, Quebec, Canada; 4Department of Medicine and Health Sciences, School of Medicine, University of Molise, Campobasso, Italy; 5Klox Technologies, Laval, Quebec, Canada Purpose: To investigate the safety and efficacy of the BioPhotonic System developed by Klox Technologies in a case series of ten patients with venous leg ulcers.Patients and methods: Ten patients with chronic venous leg ulcers, having failed on at least one previous therapy, were enrolled into this case series.Results: Nine patients were evaluable for efficacy. A response (defined as decrease in wound surface area was observed in seven patients (77.8%. Of these, four patients (44.4% achieved wound closure on average 4 months (127.5 days following the beginning of the treatment. Two patients did not respond to the investigational treatment. Quality of life improved over time throughout the study. Compliance was excellent, with 93.2% of visits completed as per protocol. Safety was unremarkable, with only four treatment-emergent-related adverse events, for which no specific intervention was required.Conclusion: The BioPhotonic System was shown to be safe and extremely well tolerated. It also demonstrated potential in terms of wound closure, wound surface area decrease, and wound bed preparation. Keywords: biophotonics, light, photobiomodulation, venous leg ulcers

  14. Relationship between knowledge, attitude, behavior, and self-efficacy on the radiation safety management of radiation workers in medical institutions

    International Nuclear Information System (INIS)

    Han, Eun Ok

    2007-01-01

    Radiation safety managements in medical institutions are needed to protect certain radiation damages as a part of National Coalition. This study investigates the characteristics of self-efficacy that become the major factor on the knowledge, attitude, and behavior on the radiation safety management of radiation workers as an approach of educational aspects and analyzes the relationship between such factors to provide basic materials for improving the activity level of radiation safety managements. In order to implement the goal of this study, a survey was performed for 1,200 workers who were engaged in radiation treatments in medical centers, such as general hospital, university hospital, private hospital, and public health center for 42 days from July 23, 2006. Then, the results of the analysis can be summarized as follows: 1. Average scores on knowledge, attitude, and behavior in the radiation safety management were presented as 75.76±11.20, 90.55±8.59, 80.58±11.70, respectively. Also, the average score of self-efficacy was recorded as 73.55±9.82. 2. Knowledge levels in the radiation safety management showed significant differences according to the sex, age, marriage, education, and experience. Also, males of married, older, highly educated, and largely experienced represented high knowledge levels. Attitude levels in the radiation safety management showed certain significant differences according to the type of medical centers in which private hospitals showed a relatively low level compared to that of high levels in university hospitals. Behavior levels in the radiation safety management also represented significant differences according to the age, marriage, education, experience, and types of medical centers. Factors in married, general hospital, older, highly educated, and largely experienced showed high behavior levels. In addition, the self-efficacy showed certain differences according to the marriage and types of medical centers. Factors in married

  15. Relationship between knowledge, attitude, behavior, and self-efficacy on the radiation safety management of radiation workers in medical institutions

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Ok [Daegu Health College, Daegu (Korea, Republic of)

    2007-06-15

    Radiation safety managements in medical institutions are needed to protect certain radiation damages as a part of National Coalition. This study investigates the characteristics of self-efficacy that become the major factor on the knowledge, attitude, and behavior on the radiation safety management of radiation workers as an approach of educational aspects and analyzes the relationship between such factors to provide basic materials for improving the activity level of radiation safety managements. In order to implement the goal of this study, a survey was performed for 1,200 workers who were engaged in radiation treatments in medical centers, such as general hospital, university hospital, private hospital, and public health center for 42 days from July 23, 2006. Then, the results of the analysis can be summarized as follows: 1. Average scores on knowledge, attitude, and behavior in the radiation safety management were presented as 75.76{+-}11.20, 90.55{+-}8.59, 80.58{+-}11.70, respectively. Also, the average score of self-efficacy was recorded as 73.55{+-}9.82. 2. Knowledge levels in the radiation safety management showed significant differences according to the sex, age, marriage, education, and experience. Also, males of married, older, highly educated, and largely experienced represented high knowledge levels. Attitude levels in the radiation safety management showed certain significant differences according to the type of medical centers in which private hospitals showed a relatively low level compared to that of high levels in university hospitals. Behavior levels in the radiation safety management also represented significant differences according to the age, marriage, education, experience, and types of medical centers. Factors in married, general hospital, older, highly educated, and largely experienced showed high behavior levels. In addition, the self-efficacy showed certain differences according to the marriage and types of medical centers. Factors in

  16. Efficacy and safety of pentavalent rotavirus vaccine in Japan: a randomized, double-blind, placebo-controlled, multicenter trial.

    Science.gov (United States)

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-08-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; pvaccine. The observed cases of RVGE included rotavirus types G1 (n=19), G3 (n=9), G9 (n=5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs.

  17. 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.

  18. The Safety and Efficacy of Methylphenidate and Dexmethylphenidate in Adults with Attention Deficit/Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Michael A. Sopko

    2010-01-01

    Full Text Available Objective To review the literature on the safety and efficacy of methylphenidate, OROS-methylphenidate, methylphenidate ER, and dexmethylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD. To analyze the effects of different doses of methylphenidate, it's various formulations, and methylphenidate on efficacy and safety in this population. Data Sources Literature retrieval was performed through Pubmed/MEDLINE (Up to May 2010 using the terms methylphenidate, dexmethylphenidate, and attention-deficit hyperactivity disorder. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction Double-blinded, placebo-controlled clinical trials, as well as crossover and open-label trials found using the search criteria listed above were included for review. Case reports were not included in this review. Data Synthesis Attention-deficit/hyperactivity disorder (ADHD is a psychiatric condition that is commonly seen in children and adolescents, that persists into adulthood for about 50% of patients. Methylphenidate and dexmethylphenidate are often prescribed to treat the symptoms associated with ADHD. The literature validating the safety and efficacy of methylphenidate and dexmethylphenidate in children and adolescents with ADHD is substantial. However, the literature specifically addressing the safety and efficacy of these medications in the adult population is less extensive and prescribing is often anecdotal based on child and adolescent data. Understanding the literature regarding methylphenidate and dexmethylphenidate and its effects in adults can enhance evidence-based medicine (EBM and improve treatment outcomes Conclusion Methylphenidate and dexmethylphenidate are safe and effective medications to treat the symptoms of ADHD in adults. Based on the literature, increased doses are associated with better treatment response with moderate safety concerns. The different dosage forms

  19. Assessment of the tolerability profile of an ophthalmic solution of 5% glycyrrhizin and copolymer PEG/PPG on healthy volunteers and evaluation of its efficacy in the treatment of moderate to severe blepharitis

    Directory of Open Access Journals (Sweden)

    Mencucci R

    2013-07-01

    Full Text Available Rita Mencucci, Eleonora Favuzza, Ugo MenchiniDepartment of Surgery and Translational Medicine – Eye Clinic, University of Florence, Florence, ItalyPurpose: To evaluate the tolerability on healthy volunteers and the efficacy on subjects affected by chronic moderate/severe blepharitis of a 5% glycyrrhizin and copolymer poly(ethylene glycol/poly(propylene glycol(PEG/PPG ophthalmic solution.Methods: The study was a randomized, controlled, open label, intra-patient monocentric study. It consisted of two different phases, the assessment of tolerability phase on 20 healthy volunteers, and the evaluation of the efficacy on 21 subjects affected by chronic moderate/severe blepharitis; the treatment period was 2 weeks, followed by 1-week of follow-up. In the efficacy phase, in both eyes, eyelid hygiene was also performed. At day 0, 3, 7, 14, and 21 a complete ophthalmological examination was performed. In the tolerability phase, signs of clinical toxicity were recorded and subject-reported symptoms were collected using a questionnaire. In the efficacy phase, global signs and symptoms of blepharitis scores were collected using standardized photographic scales and questionnaire. The statistical analysis was performed using the Wilcoxon signed-rank test. Results: No ocular signs of drug toxicity were reported. During the treatment period for tolerability phase, there were statistically significant higher scores of tearing and ocular discomfort in the tolerability study group versus the tolerability control group. In the efficacy phase, differences between global scores of the two groups were statistically significant at day 0 (score of the efficacy study group was higher than the efficacy control group; P = 0.005 and at day 21 (score of the efficacy study group was lower than the efficacy control group (P ≤ 0.001.The difference of global scores at day 3, 7, 14, and 21 versus day 0 was statistically significant in both groups. No serious adverse events

  20. The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Fan JS

    2018-03-01

    Full Text Available Junsheng Fan,1,2,* Zengfei Xia,1,* Xiaoli Zhang,1,* Yuqing Chen,1 Ruolan Qian,1 Sihan Liu,1 Danming You,1 Jian Zhang,1 Peng Luo1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China; 2Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China *These authors contributed equally to this work Background: Alectinib is a second-generation anaplastic lymphoma kinase (ALK inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib. Methods: A search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR, disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety. Results: A total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%, disease control rate 88% (95% CI: 82% to 94%, progression-free survival 9.36 months (95% CI: 7.38% to 11.34%, and intracranial ORR 52% (95% CI: 45% to 59%. ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%, and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%. The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18% and anemia (25%, were even higher than with the first-generation ALK inhibitor

  1. 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).

  2. 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).

  3. 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.

  4. Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility

    Directory of Open Access Journals (Sweden)

    Witkiewitz K

    2012-02-01

    Full Text Available Katie Witkiewitz, Kimber Saville, Kacie HamreusDepartment of Psychology, Washington State University Vancouver, Vancouver, WA, USAAbstract: Acamprosate, or N-acetyl homotaurine, is an N-methyl-D-aspartate receptor modulator approved by the Food and Drug Administration (FDA as a pharmacological treatment for alcohol dependence. The exact mechanism of action of acamprosate is still under investigation, but the drug appears to work by promoting a balance between the excitatory and inhibitory neurotransmitters, glutamate and gamma-aminobutyric acid, respectively, and it may help individuals with alcohol dependence by reducing withdrawal-associated distress. Acamprosate has low bioavailability, but also has an excellent tolerability and safety profile. In comparison with naltrexone and disulfiram, which are the other FDA-approved treatments for alcohol dependence, acamprosate is unique in that it is not metabolized by the liver and is also not impacted by alcohol use, so can be administered to patients with hepatitis or liver disease (a common comorbid condition among individuals with alcohol dependence and to patients who continue drinking alcohol. Acamprosate has demonstrated its efficacy in more than 25 placebo-controlled, double-blind trials for individuals with alcohol dependence, and has generally been found to be more efficacious than placebo in significantly reducing the risk of returning to any drinking and increasing the cumulative duration of abstinence. However, acamprosate appears to be no more efficacious than placebo in reducing heavy drinking days. Numerous trials have found that acamprosate is not significantly more efficacious than naltrexone or disulfiram, and the efficacy of acamprosate does not appear to be improved by combining acamprosate with other active medications (eg, naltrexone or with psychosocial treatment (eg, cognitive-behavioral therapy. In this review, we present the data on acamprosate, including its pharmacology

  5. 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...

  6. 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.

  7. Evaluation of long-term safety and efficacy of omalizumab in elderly patients with uncontrolled allergic asthma.

    Science.gov (United States)

    Tat, Tugba Songul; Cilli, Aykut

    2016-11-01

    Severe asthma management in elderly patients may be difficult because of increased comorbid conditions, polypharmacy, physiologic changes that occur with aging, incorrect use of inhaler devices, and poor adherence. To evaluate the long-term safety and efficacy of the anti-IgE antibody omalizumab in elderly (aged ≥65 years) patients with uncontrolled allergic asthma. The efficiency and adverse effects of omalizumab treatment were evaluated based on data extracted from medical records. Patients were evaluated monthly for efficacy and adverse reactions. Treatment efficacy was evaluated by level of asthma symptom control, using the Global Initiative for Asthma guideline. Nineteen consecutive elderly patients with asthma (female to male ratio, 14:5) formed our cohort. The mean (SD) age, disease duration, and total IgE level were 69.3 (5.8) years, 19.4 (8.6) years, and 299.1 (197.2) IU/mL, respectively. The mean (SD) duration of omalizumab treatment was 35.6 (17.8) months (range, 9-66 months). All the patients had at least 1 perennial inhalant allergen sensitivity and had uncontrolled allergic asthma. Elderly patients experienced no significantly important adverse reaction considered to be related to omalizumab treatment. Only 1 patient had a local adverse reaction and 1 had myalgia that was considered to be drug related. After omalizumab treatment, asthma symptoms were well controlled in 9 patients (47.4%) and partly controlled in 8 patients (42.1%). Two of the patients (10.5%) still had uncontrolled asthma. Our study found that omalizumab is a well-tolerated and effective therapy for elderly patients with uncontrolled asthma. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  10. Efficacy and tolerability of short-term specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A (MPL) for children and adolescents.

    Science.gov (United States)

    Drachenberg, K J; Heinzkill, M; Urban, E; Woroniecki, S R

    2003-01-01

    Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.

  11. 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

  12. 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.

  13. Antihypertensive efficacy and tolerability of lercanidipine in daily clinical practice. The ELYPSE Study. Eficacia de Lercanidipino y su Perfil de Seguridad.

    Science.gov (United States)

    Barrios, Vivencio; Navarro, Angel; Esteras, Antonio; Luque, Manuel; Romero, Joaquima; Tamargo, Juan; Prieto, Luis; Carrasco, Jose Luis; Herranz, Inmaculada; Navarro-Cid, Josefa; Ruilope, Luis M

    2002-01-01

    Lercanidipine, a long-acting dihydropyridine with a good antihypertensive efficacy and tolerability in clinical use. With the aim to determine the efficacy and tolerability of this drug in usual clinical practice we performed the ELYPSE trial. Grade 1 or 2 essential hypertensive patients in whom their physicians considered to prescribe a dihydropyridine were conferred to Lercanidipine 10 mg once daily with a 3-month follow-up; 9059 patients were included (age: 63 +/- 11 years; 58% women, 60% over 60 years, 56% grade 2 hypertensives and 69% previously treated with other antihypertensive drugs). A subgroup of 1267 patients (14%) who were included in the study had experienced adverse reactions with other drugs. Electronic case-report forms and a central database (Internet) were used in this trial. At baseline, blood pressure (BP) was 160.1 +/- 10.2/95.6 +/- 6.6 mmHg; and heart rate (HR) 77.3 +/- 9.3 beats/min. Significant reductions in both systolic and diastolic BP were attained at 1 month with slight additional decreases 2 months later. At 3 months, BP was 141.4 +/- 11.3/ 83.1 +/- 6.9 mmHg, and HR 75.2 +/- 8.2 beats/min (p < 0.001 versus baseline). At the study end. 64% of the patients achieved a diastolic BP < 90 mmHg, BP control (< 140/90 mmHg) was attained in 32%. In the subgroup of diabetics (n = 1269) an adequate BP control (< 130/85) was attained in only 16.4%. The overall incidence of adverse events was 6.5%, of which the most frequent were headache (2.9%), ankle oedema (1.2%), flushing (1.1%) and palpitations (0.6%). Withdrawal rate was < 1%. The efficacy and tolerability in the subgroup of patients included in the study due to adverse events with other drugs were similar to the whole study group. In this study Lercanidipine has shown a good efficacy and tolerability in daily clinical practice. These findings are concordant with those reported in randomized controlled trials.

  14. Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

    Directory of Open Access Journals (Sweden)

    Shoumariyeh K

    2014-09-01

    Full Text Available Khalid Shoumariyeh, Nikolas von BubnoffDepartment of Hematology, Oncology and Stem Cell Transplantation, University Hospital Freiburg, Freiburg, Germany Abstract: Treatment of chronic myeloid leukemia (CML has undergone dramatic changes in the last decade. Dissecting the molecular pathways that lead to the development of this disease resulted in the development of targeted therapy against the molecular driver of CML, namely the aberrantly activated tyrosine kinase BCR-ABL1. By introducing the tyrosine kinase inhibitor imatinib to the treatment repertoire, the natural course of the disease has been dramatically altered and overall survival of patients with CML prolonged substantially. Nevertheless, a significant number of patients are primarily resistant, acquire resistance during the course of their disease, or do not tolerate the intake of imatinib due to adverse effects. Second-generation tyrosine kinase inhibitors were developed in an attempt to overcome these problems. Dasatinib is a potent oral kinase inhibitor that was originally developed as an Src-kinase inhibitor but exhibited promising potency against BCR-ABL1 as well. Phase I and II trials demonstrated efficacy in patients failing imatinib, and thus dasatanib was approved in 2006 for the treatment of imatinib-resistant or -intolerant patients with chronic-phase CML harboring the BCR-ABL1 fusion protein. It has since shown promising efficacy and good overall tolerability in subsequent clinical trials, including the Phase III first-line DASISION trial that led to the extension of its approval for first-line treatment of chronic-phase CML. The following review summarizes the available data on the long-term efficacy and safety of dasatinib as a second-line therapy in chronic-phase CML. Keywords: BCR-ABL1, TKI, CML-CP, second-line treatment

  15. Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zech, N; Hansen, E; Bernardy, K; Häuser, W

    2017-02-01

    This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library, MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCTs) comparing GI/H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3-month follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI).Seven RCTs with 387 subjects were included into a comparison of GI/H versus controls. There was a clinically relevant benefit of GI/H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy. Acceptability at the end of treatment for GI/H was not significantly different to the control. Two RCTs with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow-up. No study reported on safety. GI/H hold promise in a multicomponent management of fibromyalgia. We provide a systematic review with meta-analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural therapy in reducing key symptoms of fibromyalgia. © 2016 European Pain Federation - EFIC®.

  16. Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema

    Directory of Open Access Journals (Sweden)

    Gandy JJ

    2011-09-01

    Full Text Available Justin J Gandy, Jacques R Snyman, Constance EJ van RensburgDepartment of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South AfricaBackground: The purpose of this study was to evaluate the efficacy and safety of carbohydrate-derived fulvic acid (CHD-FA in the treatment of eczema in patients two years and older.Methods: In this single-center, double-blind, placebo-controlled, parallel-group comparative study, 36 volunteers with predetermined eczema were randomly assigned to receive either the study drug or placebo twice daily for four weeks.Results: All safety parameters remained within normal limits, with no significant differences in either group. Significant differences were observed for both severity and erythema in the placebo and CHD-FA treated groups, and a significant difference was observed for scaling in the placebo-treated group. With regard to the investigator assessment of global response to treatment, a significant improvement was observed in the CHD-FA group when compared with the placebo group. A statistically significant decrease in visual analog scale score was observed in both groups, when comparing the baseline with the final results.Conclusion: CHD-FA was well tolerated, with no difference in reported side effects other than a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment with CHD-FA was significantly better than that with emollient therapy alone. The results of this small exploratory study suggest that CHD-FA warrants further investigation in the treatment of eczema.Keywords: fulvic acid, eczema, anti-inflammatory, efficacy, safety

  17. Efficacy and safety of micafungin for prophylaxis of invasive fungal infections in patients undergoing haplo-identical hematopoietic SCT.

    Science.gov (United States)

    El-Cheikh, J; Venton, G; Crocchiolo, R; Fürst, S; Faucher, C; Granata, A; Oudin, C; Coso, D; Bouabdallah, R; Vey, N; Duran, S; Fougereau, E; Berger, P; Chabannon, C; Blaise, D

    2013-11-01

    Invasive fungal infections (IFIs) such as candidiasis and mold infections have caused significant morbidity and mortality among immunocompromised patients in recent years. Micafungin, a new echinocandin, inhibits fungal cell wall β-glucan synthesis, with potent activity against most species of Candida and Aspergillus. The aim of this observational study was to investigate the efficacy and safety of micafungin in prophylaxis of IFIs in 26 high-risk adult patients with various hematological diseases receiving haplo-identical Allo-SCT. Only two patients had a history of possible aspergillosis before transplant treated by voriconazole. The patients received a median of four lines (2-7) of treatment before Allo-SCT. Thirteen patients (50%) received at least one prior Auto-SCT; and eight patients (31%) received a previous Allo-SCT. Patients received a median of 29 infusions (range, 15-85) of micafungin (50 mg/day i.v. as a 1-h infusion). The treatment was initiated at the beginning of the transplant conditioning regimen until the hospital discharge. None of our patients discontinued the treatment for drug-related adverse events. Micafungin was not associated with any hepatotoxicity. Only one patient (4%) discontinued the treatment because of early disease progression. In all patients no Candida and/or Aspergillus species was documented after 3 and 6 months from transplant. None of our patients presented a positive galactomannan antigenemia >0.5. Nine patients (35%) presented a CMV reactivation. Four patients presented an acute GVHD grade II and two patients presented a chronic GVHD. The median follow-up was 11 months (3-23). At the last follow-up, there were 20 patients (77%) who were alive; four patients (12%) died because of disease progression and two patients because of graft failure. Micafungin has a good safety and tolerability profile, with an efficacy in preventing IFI in this high-risk population. Our data provide support for an efficacy study in a

  18. 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

  19. 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.

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

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    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

  1. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

    Science.gov (United States)

    Russell, Jeffery; Lebbé, Céleste; Chmielowski, Bartosz; Gambichler, Thilo; Grob, Jean-Jacques; Kiecker, Felix; Rabinowits, Guilherme; Terheyden, Patrick; Zwiener, Isabella; Bajars, Marcis; Hennessy, Meliessa; Kaufman, Howard L.

    2018-01-01

    Importance Merkel cell carcinoma (MCC) is an aggressive skin cancer that is associated with poor survival outcomes in patients with distant metastatic disease. Results of part A of the JAVELIN Merkel 200 trial (avelumab in patients with Merkel cell carcinoma) showed that avelumab, an anti–programmed cell death ligand 1 (PD-L1) antibody, demonstrated efficacy in second-line or later treatment of patients with metastatic MCC (mMCC). Objective To evaluate the efficacy and safety of avelumab as first-line treatment for patients with distant mMCC. Design, Setting, and Participants JAVELIN Merkel 200 part B is an international, multicenter, single-arm, open-label clinical trial of first-line avelumab monotherapy. Eligible patients were adults with mMCC who had not received prior systemic treatment for metastatic disease. Patients were not selected for PD-L1 expression or Merkel cell polyomavirus status. Data were collected from April 15, 2016, to March 24, 2017, and enrollment is ongoing. Interventions Patients received avelumab, 10 mg/kg, by 1-hour intravenous infusion every 2 weeks until confirmed disease progression, unacceptable toxic effects, or withdrawal occurred. Main Outcomes and Measures Tumor status was assessed every 6 weeks and evaluated by independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1. The primary end point was durable response, defined as an objective response with a duration of at least 6 months. Secondary end points include best overall response, duration of response, progression-free survival, safety, and tolerability. Results As of March 24, 2017, 39 patients were enrolled (30 men and 9 women; median age, 75 years [range, 47-88 years]), with a median follow-up of 5.1 months (range, 0.3-11.3 months). In a preplanned analysis, efficacy was assessed in 29 patients with at least 3 months of follow-up; the confirmed objective response rate was 62.1% (95% CI, 42.3%-79.3%), with 14 of 18 responses (77.8%) ongoing

  2. 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.

  3. 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.

  4. Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.

    Science.gov (United States)

    Hall, W D; Reed, J W; Flack, J M; Yunis, C; Preisser, J

    1998-10-12

    Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.

  5. Efficacy and safety of topically applied Symphytum herb extract cream in the treatment of ankle distortion: results of a randomized controlled clinical double blind study.

    Science.gov (United States)

    Kucera, Miroslav; Barna, Milos; Horácek, Ondrej; Kováriková, Jaroslava; Kucera, Alexander

    2004-11-01

    In a controlled, double blind, randomized multicentre study, the efficacy and safety of the topical comfrey product Traumaplant (10% active ingredient of a 2.5:1 aqueous ethanolic pressed juice of freshly harvested, cultivated comfrey herb (Symphytum x uplandicum NYMAN), corresponding to 25 g of fresh herb per 100 g of cream; n = 104) was tested against a 1% product (corresponding to 2.5 g of fresh comfrey herb in 100 g of cream; n = 99) in 203 patients with acute ankle distortion. With the high concentration, decrease of the scores for pain on active motion, pain at rest and functional impairment was highly significant and clinically relevant on days T3-4 as well as T7 (p < 0.001). Amelioration of swellings as compared to reference was also significant on day 3-4 (p < 0.01). Efficacy was judged good to excellent in 85.6% of cases with verum and in 65.7% of cases with reference on day 3-4. Overall tolerability was excellent.

  6. Efficacy and Safety of Cerebrolysin for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Danfeng Zhang

    2017-01-01

    Full Text Available Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke (AIS in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials, which intervened within 72 hours after the stroke onset. We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving 1779 patients with AIS. The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis. Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.

  7. 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.

  8. 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

  9. Efficacy and Safety of a Mineral Oil-Based Head Lice Shampoo: A Randomized, Controlled, Investigator-Blinded, Comparative Study.

    Directory of Open Access Journals (Sweden)

    Luise Wolf

    Full Text Available Due to increased resistance and safety concerns with insecticide-based pediculicides, there is growing demand for head lice treatments with a physical mode of action. Certain mineral oils kill lice by blocking spiracles or by disrupting the epicuticular wax layer. The present study was performed to evaluate efficacy and safety of a mineral oil-based shampoo.This randomized, controlled, investigator-blinded, monocentric study (EudraCT registration no. 2014-002918-23 was performed from October 2014-June 2015 in Germany. A mineral oil shampoo (Mosquito® Med Läuse Shampoo 10 in Germany, Paranix or Silcap shampoo elsewhere, registered as medical device, was compared to a conventional, locally reimbursed, pyrethroid-based pediculicide (Goldgeist® Forte solution. In total, 107 patients (>1 year with confirmed head lice infestation were included (test arm: n = 53; control arm: n = 54. All subjects received two applications of either test or control product at day 0 and day 7, according to the instructions for use. Efficacy and safety was evaluated directly, 1h and 24h after first application, before and after second treatment, and at day 10. The main objective was demonstrating a cure rate for the test product, being superior to 70% at day 10.Cure rates at day 10 (corrected for re-infestation for the test product (96.1% and control (94% significantly exceeded the pre-defined target (70% (p < 0.001, 2-sided, 1-sample, chi-square test with confirmed non-inferiority for the test product. Over all visits, cure rates were consistently higher for the test product, whereas more initially-cured subjects remained lice-free until end of study (78%; control: 60%. Both products were safe and well tolerated, offering good esthetical effects.This study showed that substance-based medical devices (including the tested mineral oil shampoo can be safe and effective alternatives for insecticide-based pediculicides, with less risk for development of resistance because

  10. Exercise self-efficacy moderates the relation between anxiety sensitivity and body mass index and exercise tolerance in treatment-seeking smokers

    NARCIS (Netherlands)

    Farris, S.G.; Davis, M.L.; Rosenfield, D.; Kauffman, B.Y.; Baird, S.O.; Powers, M.B.; Otto, M.W.; Marcus, B.H.; Church, T.S.; Smits, J.A.J.; Zvolensky, M.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

  11. 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.

  12. A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia

    Directory of Open Access Journals (Sweden)

    Turkalj M

    2017-02-01

    Full Text Available Mirjana Turkalj,1,2 Ivana Banic,1 Srdjan Ante Anzic1 1Children’s Hospital Srebrnjak, Zagreb, 2Faculty of Medicine, JJ Strossmayer University of Osijek, Osijek, Croatia Abstract: Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic, and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems is one of the most important goals for AIT in the future, to further enhance treatment success. Keywords: allergic rhinitis, allergy, ragweed, allergen-specific immunotherapy, Ambrosia artemisiifolia

  13. 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

  14. Direct-acting antiviral agent efficacy and safety in renal transplant recipients with chronic hepatitis C virus infection

    OpenAIRE

    Chen, Keliang; Lu, Pei; Song, Rijin; Zhang, Jiexiu; Tao, Rongzhen; Wang, Zijie; Zhang, Wei; Gu, Min

    2017-01-01

    Abstract Background: The efficacy and safety of direct-acting antivirals (DAAs) for treating hepatitis C virus (HCV)-infected renal transplant recipients (RTRs) has not been determined. Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and assessed the quality of eligible studies using the Joanna Briggs Institute scale. DAA efficacy and safety were assessed using standard mean difference (SMD) with 95% confidence intervals (95%CIs). Results: Six studi...

  15. Efficacy and tolerability of rasagiline in daily clinical use--a post-marketing observational study in patients with Parkinson's disease.

    Science.gov (United States)

    Reichmann, H; Jost, W H

    2010-09-01

    The MAO-B inhibitor rasagiline is indicated for the treatment of idiopathic Parkinson's disease (PD), and its use is supported by evidence from large-scale, controlled clinical studies. The post-marketing observational study presented here investigated the efficacy and tolerability of rasagiline treatment (monotherapy or combination therapy) in daily clinical practice. The study included patients with idiopathic PD who received rasagiline (recommended dose 1 mg, once daily) as monotherapy or combination therapy. The treatment and observation period was approximately 4 months. Outcome measures included the change from baseline in the Columbia University Rating Scale (CURS), the Unified PD Rating Scale fluctuation subscale, daily OFF time (patient home diaries) and the PD Questionnaire-39. Adverse drug reactions/adverse events (ADRs/AEs) and the physician's global judgement of tolerability and efficacy were also examined. Overall, 754 patients received rasagiline during the study. Patients treated with rasagiline (monotherapy or combination therapy) showed significant improvements from baseline in symptom severity (including classical motor and non-classical motor/non-motor symptoms) and quality of life (QoL). Patients receiving combination therapy also experienced significant reductions in daily OFF time. Tolerability was rated as good/very good in over 90% of patients. In daily clinical practice, monotherapy or combination therapy with rasagiline is able to improve PD symptoms, reduce OFF time, and improve QoL, whilst demonstrating favourable tolerability. In addition, rasagiline has a simple dosing schedule of one tablet, once daily, with no titration. These results are consistent with the pivotal rasagiline clinical studies (TEMPO, LARGO and PRESTO).

  16. 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

  17. Epidemiological data, efficacy and safety of a paracetamol-tramadol fixed combination in the treatment of moderate-to-severe pain. SALZA: a post-marketing study in general practice.

    Science.gov (United States)

    Mejjad, O; Serrie, A; Ganry, H

    2011-05-01

    To evaluate the efficacy and safety of the paracetamol-tramadol combination (PTC) in treating moderate-to-severe pain, in patients aged 65 years and over within general practitioner (GP) practice centers. This was an observational, non-interventional, longitudinal, multicenter, open, non-comparative, prospective study. This intermediary analysis was of patients recruited before the French Health Authority confirmation (25th June, 2009) of the EMEA decision to withdraw all analgesics containing dextropropoxyphen. Trial registration information: This study has been submitted for approval to the CNIL and French Medical Council (CNOM) only. A total of 2663 patients aged 65 years or over were assessed 1 month after inclusion in the study. PTC was prescribed as first-line treatment in 30% of patients and, in the other cases, after failed or inadequate efficacy (69.8%), and/or as a result of safety problems (7.8%) with at least one other analgesic. During the month of the study period 14.7% of patients received an additional rescue analgesic. The study confirmed the efficacy of PTC with regard to pain intensity (-3.1 points reduction of pain scored 6.1 points on inclusion), pain relief (64.8% of patients experienced significant pain relief), patient satisfaction (90.5% of patients satisfied or completely satisfied) and clinical global impression evaluated by the patient (78.7% much or very much improved), regardless of the pain etiologies or duration of the underlying pathology. PTC was well-tolerated in this patient group, who had a mean age of 73.6 ± 6.6 years. A total of 119 patients (4.5%) reported at least one adverse event (AE). All were known and predictable AEs. This percentage is comparable to that found under similar conditions in patients of all ages (4.2%). PTC, due to the complementary action of its two analgesics, is effective in treating the different types of pain in a GP's practice setting and is well-tolerated, even in an elderly population. Study

  18. Efficacy and safety of an oral contraceptive containing ethinylestradiol 20 µg/drospirenone 3 mg (24/4 regimen) in three indications in the People's Republic of China: a comparison with international studies.

    Science.gov (United States)

    Marr, Joachim; Huang, Zirong; Wang, Baoxi; Zhang, Hongyan; Roth, Katrin

    2015-01-01

    While combined oral contraceptives are a popular choice in developed Western countries, they are used by only 1% of women who are married or in a relationship in the People's Republic of China. The purpose of this review is to describe the efficacy and safety of the combined oral contraceptive containing ethinylestradiol (EE) 20 µg/drospirenone 3 mg taken in a 24/4 regimen (YAZ ® ; Bayer HealthCare Pharmaceuticals, Berlin, Germany) by Chinese women and to compare these results with those in women assessed in the international studies. Studies of EE 20 µg/drospirenone 3 mg in three different indications (contraception, acne, and premenstrual dysphoric disorder [PMDD]) have been conducted in Chinese women. The results of these three studies indicate that the EE 20 µg/drospirenone 3 mg combined oral contraceptive is a good long-term contraceptive option in Chinese women, providing 99% contraceptive protection over the observed 1-year treatment period, and additionally had a favorable effect on moderate acne vulgaris and relieved the symptoms of PMDD. The contraceptive efficacy, improvement in acne, and relief from PMDD symptoms observed in these studies did not differ from the effects observed in other international studies of EE 20 µg/drospirenone 3 mg, indicating that EE 20 µg/drospirenone 3 mg is as effective in Chinese women as in other ethnicities. Further, EE 20 µg/drospirenone 3 mg demonstrated a similar safety and tolerability profile in women enrolled in the Chinese and international trials, with no unexpected adverse events reported in any of the three Chinese trials. Overall, the efficacy, tolerability, and degree of non-contraceptive benefits with EE 20 µg/drospirenone 3 mg appear similar in Chinese women when compared with those reported in larger studies done at other international centers.

  19. Safety evaluation of accident-tolerant FCM fueled core with SiC-coated zircalloy cladding for design-basis-accidents and beyond DBAs

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ji-Han, E-mail: chunjh@kaeri.re.kr; Lim, Sung-Won; Chung, Bub-Dong; Lee, Won-Jae

    2015-08-15

    Highlights: • Thermal conductivity model of the FCM fuel was developed and adopted in the MARS. • Scoping analysis for candidate FCM FAs was performed to select feasible FA. • Preliminary safety criteria for FCM fuel and SiC/Zr cladding were set up. • Enhanced safety margin and accident tolerance for FCM-SiC/Zr core were demonstrated. - Abstract: The FCM fueled cores proposed as an accident tolerant concept is assessed against the design-basis-accident (DBA) and the beyond-DBA (BDBA) scenarios using MARS code. A thermal conductivity model of FCM fuel is incorporated in the MARS code to take into account the effects of irradiation and temperature that was recently measured by ORNL. Preliminary analyses regarding the initial stored energy and accident tolerant performance were carried out for the scoping of various cladding material candidates. A 16 × 16 FA with SiC-coated Zircalloy cladding was selected as the feasible conceptual design through a preliminary scoping analysis. For a selected design, safety analyses for DBA and BDBA scenarios were performed to demonstrate the accident tolerance of the FCM fueled core. A loss of flow accident (LOFA) scenario was selected for a departure-from-nucleate-boiling (DNB) evaluation, and large-break loss of coolant accident (LBLOCA) scenario for peak cladding temperature (PCT) margin evaluation. A control element assembly (CEA) ejection accident scenario was selected for peak fuel enthalpy and temperature. Moreover, a station blackout (SBO) and LBLOCA without a safety injection (SI) scenario were selected as a BDBA. It was demonstrated that the DBA safety margin of the FCM core is satisfied and the time for operator actions for BDBA s is evaluated.

  20. 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

  1. Efficacy and safety of fidaxomicin compared with oral vancomycin for the treatment of adults with Clostridium difficile-associated diarrhea: data from the OPT-80-003 and OPT-80-004 studies.

    Science.gov (United States)

    Chen, Luke F; Anderson, Deverick J

    2012-06-01

    Clostridium difficile is emerging as one of the most important and devastating pathogens affecting hospitalized populations around the world. The incidence of C. difficile infection is increasing and disease severity is worsening. Thus, an effective alternative to metronidazole and oral vancomycin is urgently needed. Two Phase III trials, OPT-80-003 and OPT-80-004, showed that oral fidaxomicin for 10 days was noninferior compared with treatment with oral vancomycin among adult patients with toxin-positive C. difficile-associated diarrhea (CDAD). Furthermore, fidaxomicin was associated with a lower rate of recurrence of CDAD within 4 weeks of completion of therapy. The safety and tolerability of fidaxomicin was consistent with earlier studies and established that fidaxomicin is an efficacious and well-tolerated treatment option for CDAD. Despite these potential advantages, the cost-effectiveness of this expensive agent remains poorly understood.

  2. 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 ...

  3. 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

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

    Science.gov (United States)

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

    2013-12-01

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

  5. Lithium carbonate in amyotrophic lateral sclerosis: lack of efficacy in a dose-finding trial.

    Science.gov (United States)

    Chiò, A; Borghero, G; Calvo, A; Capasso, M; Caponnetto, C; Corbo, M; Giannini, F; Logroscino, G; Mandrioli, J; Marcello, N; Mazzini, L; Moglia, C; Monsurrò, M R; Mora, G; Patti, F; Perini, M; Pietrini, V; Pisano, F; Pupillo, E; Sabatelli, M; Salvi, F; Silani, V; Simone, I L; Sorarù, G; Tola, M R; Volanti, P; Beghi, E

    2010-08-17

    A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported. We performed a multicenter trial with lithium carbonate to assess its tolerability, safety, and efficacy in patients with ALS, comparing 2 different target blood levels (0.4-0.8 mEq/L, therapeutic group [TG], vs 0.2-0.4 mEq/L, subtherapeutic group [STG]). The study was a multicenter, single-blind, randomized, dose-finding trial, conducted from May 2008 to November 2009 in 21 Italian ALS centers. The trial was registered with the public database of the Italian Agency for Drugs (http://oss-sper-clin.agenziafarmaco.it/) (EudraCT number 2008-001094-15). As of October 2009, a total of 171 patients had been enrolled, 87 randomized to the TG and 84 to the STG. The interim data analysis, performed per protocol, showed that 117 patients (68.4%) discontinued the study because of death/tracheotomy/severe disability, adverse events (AEs)/serious AEs (SAEs), or lack of efficacy. The Data Monitoring Committee recommended stopping the trial on November 2, 2009. Lithium was not well-tolerated in this cohort of patients with ALS, even at subtherapeutic doses. The 2 doses were equivalent in terms of survival/severe disability and functional data. The relatively high frequency of AEs/SAEs and the reduced tolerability of lithium raised serious doubts about its safety in ALS. The study provides Class II evidence that therapeutic (0.4-0.8 mEq/L) vs subtherapeutic (0.2-0.4 mEq/L) lithium carbonate did not differ in the primary outcome of efficacy (survival/loss of autonomy) in ALS. Both target levels led to dropouts in more than 30% of participants due to patient-perceived lack of efficacy and AEs.

  6. Comparative efficacy and safety of mavacoxib and carprofen in the treatment of canine osteoarthritis.

    Science.gov (United States)

    Payne-Johnson, M; Becskei, C; Chaudhry, Y; Stegemann, M R

    2015-03-14

    A multi-site, masked, randomised parallel group study employing a double dummy treatment design was performed in canine veterinary patients to determine the comparative efficacy and safety of mavacoxib and carprofen in the treatment of pain and inflammation associated with osteoarthritis for a period of 134 days. Treatments were administered according to their respective summaries of product characteristics. Of 139 dogs screened, 124 were suitable for study participation: 62 of which were dosed with mavacoxib and 62 with carprofen. Both treatments resulted in a very similar pattern of considerable improvement as indicated in all parameters assessed by both owner and veterinarian. The primary efficacy endpoint 'overall improvement' was a composite score of owner assessments after approximately six weeks of treatment. Both drugs were remarkably effective, with 57/61 (93.4 per cent) of mavacoxib-treated dogs and 49/55 (89.1 per cent) of carprofen-treated dogs demonstrating overall improvement and with mavacoxib's efficacy being non-inferior to carprofen. The treatments had a similar safety profile as evidenced by documented adverse events and summaries of clinical pathology parameters. The positive clinical response to treatment along with the safety and dosing regimen of mavacoxib makes it an attractive therapy for canine osteoarthritis. British Veterinary Association.

  7. Automated discovery of safety and efficacy concerns for joint & muscle pain relief treatments from online reviews.

    Science.gov (United States)

    Adams, David Z; Gruss, Richard; Abrahams, Alan S

    2017-04-01

    Product issues can cost companies millions in lawsuits and have devastating effects on a firm's sales, image and goodwill, especially in the era of social media. The ability for a system to detect the presence of safety and efficacy (S&E) concerns early on could not only protect consumers from injuries due to safety hazards, but could also mitigate financial damage to the manufacturer. Prior studies in the field of automated defect discovery have found industry-specific techniques appropriate to the automotive, consumer electronics, home appliance, and toy industries, but have not investigated pain relief medicines and medical devices. In this study, we focus specifically on automated discovery of S&E concerns in over-the-counter (OTC) joint and muscle pain relief remedies and devices. We select a dataset of over 32,000 records for three categories of Joint & Muscle Pain Relief treatments from Amazon's online product reviews, and train "smoke word" dictionaries which we use to score holdout reviews, for the presence of safety and efficacy issues. We also score using conventional sentiment analysis techniques. Compared to traditional sentiment analysis techniques, we found that smoke term dictionaries were better suited to detect product concerns from online consumer reviews, and significantly outperformed the sentiment analysis techniques in uncovering both efficacy and safety concerns, across all product subcategories. Our research can be applied to the healthcare and pharmaceutical industry in order to detect safety and efficacy concerns, reducing risks that consumers face using these products. These findings can be highly beneficial to improving quality assurance and management in joint and muscle pain relief. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Kario, Kazuomi; Sun, Ningling; Chiang, Fu-Tien; Supasyndh, Ouppatham; Baek, Sang Hong; Inubushi-Molessa, Akiko; Zhang, Ying; Gotou, Hiromi; Lefkowitz, Martin; Zhang, Jack

    2014-04-01

    LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (Phypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.

  9. 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

  10. Open-label, randomized, multicenter, phase III study to evaluate the safety and efficacy of benzoyl peroxide gel in long-term use in patients with acne vulgaris: A secondary publication.

    Science.gov (United States)

    Kawashima, Makoto; Nagare, Toshitaka; Katsuramaki, Tsuneo

    2017-06-01

    An open-label, randomized, multicenter study was conducted to evaluate the safety and efficacy of long-term use of 2.5% and 5% benzoyl peroxide (BPO) gels administrated once daily for 52 weeks to Japanese patients with acne vulgaris. The efficacy of the study drugs was evaluated by counting inflammatory lesions and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. In total, 458 subjects were included in the efficacy and safety analyses. The total lesion count, the efficacy end-point, was similarly changed both in the 2.5% and 5% BPO groups over the course of the study. The median rates of reduction from baseline to week 12 were approximately 65%. Thereafter, the counts were maintained at a reduced level without increasing until week 52. The median rates at week 52 were approximately 80%. Similar trends were observed for inflammatory and non-inflammatory lesion counts. Bacteriological evaluation indicated similar distribution of the minimum inhibitory concentration of each of the antibacterial drugs against Propionibacterium acnes between the values at baseline and at week 52, suggesting that long-term use did not result in changes in the drug sensitivity. The incidence of adverse events was 84.0% in the 2.5% BPO group and 87.2% in the 5% BPO group. Many of the adverse events occurred within the first month and were mild or moderate in severity and transient. The results suggest that both 2.5% and 5% BPO gels are effective and safe for long-term treatment of patients with acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  11. Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in malian children: 24-month follow-up of a randomized, double-blinded phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Matthew B Laurens

    Full Text Available The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy.A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1 vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons.400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51 against first clinical malaria episodes and 9.9% (p = 0.19 against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98 against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up.Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during

  12. Efficacy and safety of dextromethorphan/quinidine at two dosage levels for diabetic neuropathic pain: a double-blind, placebo-controlled, multicenter study.

    Science.gov (United States)

    Shaibani, Aziz I; Pope, Laura E; Thisted, Ronald; Hepner, Adrian

    2012-02-01

    To evaluate dextromethorphan coadministered with quinidine as treatment of diabetic peripheral neuropathic pain. In a 13-week, phase 3, randomized controlled trial, 379 adults with daily symmetric diabetic peripheral neuropathy (DPN) leg pain for ≥3 months received double-blind placebo, dextromethorphan/quinidine (DMQ) 45/30 mg, or DMQ 30/30 mg, administered once daily for 7 days and twice daily thereafter. Efficacy measures included four pain rating scales applied daily using patient diaries, and another two applied at five clinic visits. On all six scales, DMQ 45/30 mg was significantly superior to placebo, including the primary efficacy analysis, which utilized mixed-effects modeling to test all scores on an 11-point numerical Pain Rating Scale (P < 0.0001). Sensitivity analyses gave consistent results. Efficacy vs placebo was also seen for diary ratings of present pain intensity, and pain interference with sleep and with activities (all P < 0.0001). Among clinic visit assessments, DMQ 45/30 mg demonstrated greater leg pain relief (P = 0.0002) and greater reduction of leg pain intensity (P = 0.0286) vs placebo. The efficacy of DMQ 30/30 mg was numerically less than for 45/30 mg but for most outcomes remained significantly greater vs placebo. Adverse events were mostly mild or moderate and of expected types. Discontinuation for adverse events in the DMQ groups was at least twice as common as placebo. Throughout a 13-week trial, DMQ was effective, with an acceptable safety profile, for treatment of DPN pain. Other fixed-dose combinations of DMQ should be studied to improve overall tolerability while maintaining significant efficacy. Wiley Periodicals, Inc.

  13. Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancers.

    Science.gov (United States)

    Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A; Gettinger, Scott N

    2015-11-01

    Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity. In this phase I trial we evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Nine patients enrolled before premature termination of the study. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Regorafenib had acceptable tolerability and minor pharmacokinetic interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. The combination of bevacizumab, an antiangiogenesis agent, with cytotoxic chemotherapy improves survival in patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. In this phase I trial we evaluated the safety, pharmacokinetics (PK), and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Chemotherapy-naive patients with advanced nsNSCLCs were treated with regorafenib 60 mg/d continuously and cisplatin 75 mg/m(2) with pemetrexed 500 mg/m(2) once every 21 days for up to 6 cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Nine patients enrolled before premature termination of the study because of slow recruitment and a change in the development strategy of regorafenib by the study sponsor. Five patients experienced at least 1 treatment-related Grade 3 adverse event. No Grade 4 or 5 toxicity occurred. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Minor PK interactions between regorafenib and chemotherapy were observed. Regorafenib had acceptable

  14. Tincture of opium for treating opioid dependence: a systematic review of safety and efficacy.

    Science.gov (United States)

    Nikoo, Mohammadali; Nikoo, Nooshin; Anbardan, Sanam Javid; Amiri, Afshar; Vogel, Marc; Choi, Fiona; Sepehry, Amir Ali; Bagheri Valoojerdi, Amir Hooshang; Jang, Kerry; Schütz, Christian; Akhondzadeh, Shahin; Krausz, Michael

    2017-03-01

    Recently, there has been a growing interest in using opium tincture (OT) for treating opioid dependence in certain regions. We aimed to assess the evidence on its safety and efficacy for this indication. We searched several databases (CENTRAL, Medline, EMBASE, Web of Science, PsychINFO, ProQuest Dissertation and Theses Database, Iran Medex, clinicaltrials.gov and who.int/trialsearch) with no language or publication date limitations. Two reviewers selected randomized controlled trials (RCT), cohort/case-control/cross-sectional studies and case-series on safety or efficacy of OT for treating opioid dependence and then extracted reported measures of mentioned outcomes from selected studies. We used the Effective Public Health Practice Project (EPHPP) Quality Assessment tool for appraisal. From nine selected studies; in three RCTs and one cohort analytical analysis on detoxification, 110 patients were treated with 15-140 morphine equivalents/day (mEq/d) of OT; in four prospective and one retrospective uncontrolled case-series on long-term/maintenance treatment, 570 patients were treated with 100-400 mEq/d of OT. Only two studies on detoxification included a comparison: one concluded equal efficacy of OT and methadone in suppressing withdrawal symptoms (P = 0.32) and the other concluded OT to be less efficacious than buprenorphine/naloxone in suppressing withdrawal [OT = 12.20, 95% confidence interval (CI) = 11.00, 13.40]; control: 5.20 (95% CI = 4.69, 5.71) and craving (OT = 303.0, 95% CI = -144.664, 750.664; control: 0.0) but not significantly different (P = 0.26) in retaining participants in treatment. No major adverse events were reported. Conclusive recommendations about the safety and efficacy of opium tincture for treating opioid dependence are not possible at this time. © 2016 Society for the Study of Addiction.

  15. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

    Directory of Open Access Journals (Sweden)

    Ping Fang

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

  16. Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast in childhood asthma: A prospective, randomized, double-blind, double-dummy, parallel-group study

    DEFF Research Database (Denmark)

    Maspero, Jorge; Guerra, Frances; Cuevas, Francisco

    2008-01-01

    BACKGROUND: Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma. OBJECTIVE: This study, the PEdiatric Asthma Control Evaluation (PEACE......), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children. METHODS: Children with asthma (forced expiratory volume in 1 second [FEV(1)] 55%-80% predicted; reversibility >or=12%) aged 6 to 14 years who were receiving only short-acting beta(2)-agonists...... in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations. RESULTS: Of 607 patients screened, 548...

  17. Quetiapine versus aripiprazole in children and adolescents with psychosis - protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers

    2014-01-01

    BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus...... aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients...... about head-to-head differences in efficacy and tolerability of antipsychotics are scarce in children and adolescents. The TEA trial aims at expanding the evidence base for the use of antipsychotics in early onset psychosis in order to inform more rational treatment decisions in this vulnerable...

  18. Increasing the safety and efficacy of chimeric antigen receptor T cell therapy

    Directory of Open Access Journals (Sweden)

    Hua Li

    2017-04-01

    Full Text Available Abstract Chimeric antigen receptor (CAR T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or “on-target/off-tumor” toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells. All these efforts promote the development and evolution of CAR T cell therapy and move toward our ultimate goal—curing cancer with high safety, high efficacy, and low cost.

  19. 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.

  20. Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua New Guinea.

    Science.gov (United States)

    Karunajeewa, Harin A; Kemiki, Adedayo; Alpers, Michael P; Lorry, Kerry; Batty, Kevin T; Ilett, Kenneth F; Davis, Timothy M

    2003-03-01

    Although suppositories of artemisinin derivatives may be a valuable option for treatment of malaria in children when circumstances prevent oral and parenteral therapy, few confirmatory data have been published. We assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to 10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New Guinea. Thirty were symptomatic and had Plasmodium falciparum parasitemia >2000/microl (Group 1), 12 had and either a parasitemia suppositories were well-tolerated. After 24 h only one child (from Group 1) had persistent parasitemia, and only one (from Group 3) had not defervesced. These two children received intramuscular quinine and recovered uneventfully. Three Group 2 children redeveloped fever and tachycardia at 24 h, but each responded to simple supportive measures and remained aparasitemic. Intrarectal artesunate is safe, effective initial treatment for uncomplicated malaria in children. A transient fever spike can sometimes occur after parasite clearance. We recommend that children with uncomplicated malaria receive two doses of > or =10 mg/kg rectal artesunate within the first 24 h.

  1. Multicenter, double-blind, parallel group study investigating the non-inferiority of efficacy and safety of a 2% miconazole nitrate shampoo in comparison with a 2% ketoconazole shampoo in the treatment of seborrhoeic dermatitis of the scalp.

    Science.gov (United States)

    Buechner, Stanislaw A

    2014-06-01

    This study investigated the non-inferiority of efficacy and tolerance of 2% miconazole nitrate shampoo in comparison with 2% ketoconazole shampoo in the treatment of scalp seborrheic dermatitis. A randomized, double-blind, comparative, parallel group, multicenter study was done. A total of 274 patients (145 miconazole, 129 ketoconazole) were enrolled. Treatment was twice-weekly for 4 weeks. Safety and efficacy assessments were made at baseline and at weeks 2 and 4. Assessments included symptoms of erythema, itching, scaling ['Symptom Scale of Seborrhoeic Dermatitis' (SSSD)], disease severity and global change [Clinical Global Impressions (CGIs) and Patient Global Impressions (PGIs)]. Miconazole shampoo is at least as effective and safe as ketoconazole shampoo in treating scalp seborrheic dermatitis scalp.

  2. Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis.

    Science.gov (United States)

    LeWitt, Peter A; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

    Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.

  3. Effects of first-dose volume and exercise on the efficacy and tolerability of bowel preparations for colonoscopy in Chinese people

    Directory of Open Access Journals (Sweden)

    Qin Y

    2016-04-01

    Full Text Available Ying Qin, Wei Liu, Songbai Lin, Xiangfeng Li International Medical Services, Peking Union Medical College Hospital, Beijing, People’s Republic of China Aim: This study was designed to compare the efficacy and tolerability of bowel preparations with and without the higher first-dose volume of polyethylene glycol (PEG solution or exercise after drinking PEG solution in Chinese people. Methods: A total of 330 participants who had a colonoscopy done in Peking Union Medical College Hospital were randomly and evenly assigned to three groups. Participants in Group A ingested 1 L PEG solution and then ingested 2 L PEG solution at a rate of 250 mL every 15 minutes. Participants in Group B ingested 3 L PEG solution at a rate of 250 mL every 15 minutes and then exercised more than 10 minutes after ingesting each liter of PEG solution. Participants in Group C ingested 3 L PEG solution at a rate of 250 mL every 15 minutes. Experienced gastrointestinal endoscopists rated the efficacy of bowel preparations based on the Boston Bowel Preparation Scale score. A questionnaire regarding participants’ symptoms associated with bowel preparations was administered to evaluate participants’ tolerability. Results: The three groups had insignificant difference in the percentages of participants’ symptoms including dizziness, nausea, stomach ache, bloating, and asthenia. However, the percentages of participants having hunger sensation, sleep disturbance, and anal discomfort were significantly higher in groups with the higher first-dose volume of PEG solution or exercise after drinking PEG solution than without them. The three groups had insignificant difference in the Boston Bowel Preparation Scale score. Conclusion: Whether to add the higher first-dose volume of PEG solution and exercise after drinking PEG solution or not, all participants achieved a similar quality of bowel preparations. Bowel preparations without the additional first-dose volume of PEG

  4. Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Yang YM

    2015-09-01

    Full Text Available Young-Mo Yang, Eun Joo Choi College of Pharmacy, Chosun University, Gwangju, South Korea Background: Polycystic ovary syndrome (PCOS is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles.Methods: A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS.  Results: Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported.  Conclusion: The clinical trials suggest that metformin or oral

  5. 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.

  6. 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.

  7. 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...

  8. Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies.

    Science.gov (United States)

    Elger, Christian; Koepp, Mathias; Trinka, Eugen; Villanueva, Vicente; Chaves, João; Ben-Menachen, Elinor; Kowacs, Pedro A; Gil-Nagel, António; Moreira, Joana; Gama, Helena; Rocha, José-Francisco; Soares-da-Silva, Patrício

    2017-12-01

    Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures. Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period). Pooled efficacy variable was standardized (/4 weeks) seizure frequency (SSF) analyzed over the maintenance period as reduction in absolute and relative SSF and proportion of responders (≥50% reduction in SSF). Pooled safety was analyzed by means of adverse events and clinical laboratory assessments. SSF was significantly reduced with ESL 800 mg (P ESL 800 mg and 37.8% for 1200 mg (placebo: 17.6%), and responder rate was 33.8% and 43.1% (placebo: 22.2%). ESL was more efficacious than placebo regardless of gender, geographical region, epilepsy duration, age at time of diagnosis, seizure type, and type of concomitant antiepileptic drugs (AED). Incidence of adverse events (AEs) and AEs leading to discontinuation was dose dependent. Most common AEs (>10% patients) were dizziness, somnolence, and nausea. The incidence of treatment-emergent AEs (dizziness, somnolence, ataxia, vomiting, and nausea) was lower in patients who began taking ESL 400 mg (followed by 400 mg increments to 800 or 1200 mg) than in those who began taking ESL 600 mg or 800 mg. Once-daily ESL 800 mg and 1200 mg showed consistent results across all efficacy and safety endpoints, independent of study population characteristics and type of concomitant AEDs. Treatment initiated with ESL 400 mg followed by 400 mg increments to 800 or 1200 mg provides optimal balance of efficacy and tolerability. © 2017 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

  9. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin

    DEFF Research Database (Denmark)

    Barnett, AH; Dreyer, M; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an open-label, parallel, 24-week multicenter trial. Patients...... associated clinical manifestations. CONCLUSIONS: In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated...

  10. 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.

  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. Safety and efficacy of subretinal visual implants in humans: methodological aspects.

    Science.gov (United States)

    Stingl, Katarina; Bach, Michael; Bartz-Schmidt, Karl-Ulrich; Braun, Angelika; Bruckmann, Anna; Gekeler, Florian; Greppmaier, Udo; Hörtdörfer, Gernot; Kusnyerik, Akos; Peters, Tobias; Wilhelm, Barbara; Wilke, Robert; Zrenner, Eberhart

    2013-01-01

    Replacing the function of visual pathway neurons by electronic implants is a novel approach presently explored by various groups in basic research and clinical trials. The novelty raises unexplored methodological aspects of clinical trial design that may require adaptation and validation. We present procedures of efficacy and safety testing for subretinal visual implants in humans, as developed during our pilot trial 2005 to 2009 and multi-centre clinical trial since 2010. Planning such a trial requires appropriate inclusion and exclusion criteria. For subretinal electronic visual implants, patients with photoreceptor degeneration are the target patient group, whereas presence of additional diseases affecting clear optic media or the visual pathway must be excluded. Because sham surgery is not possible, a masked study design with implant power ON versus OFF is necessary. Prior to the efficacy testing by psychophysical tests, the implant's technical characteristics have to be controlled via electroretinography (ERG). Moreover the testing methods require adaptation to the particular technology. We recommend standardised tasks first to determine the light perception thresholds, light localisation and movement detection, followed by grating acuity and vision acuity test via Landolt C rings. A laboratory setup for assessing essential activities of daily living is presented. Subjective visual experiences with the implant in a natural environment, as well as questionnaires and psychological counselling are further important aspects. A clinical trial protocol for artificial vision in humans, which leads a patient from blindness to the state of very low vision is a challenge and cannot be defined completely prior to the study. Available tests of visual function may not be sufficiently suited for efficacy testing of artificial vision devices. A protocol based on experience with subretinal visual implants in 22 patients is presented that has been found adequate to monitor

  13. Relationship between knowledge, attitude, behavior, and self-efficacy on the radiation safety on dental hygienist

    International Nuclear Information System (INIS)

    Han, Eun Ok; Jun, Sung Hee

    2008-01-01

    The objective of this study is to draw an educational plant for reducing the probability of troubles caused by radiation for dental hygienists who are the major applicants of radiation equipments used in dental offices. This study investigated the knowledge and self-efficacy, which is the major variable that affects the attitude and behavior, on the radiation safety that is an educational approach. Also, this study obtained following results from a survey for 25 days from June 15, 2008 that was applied for 225 dental hygienists worked at dental offices and clinics in the area of Youngnam in order to verify the relationship between such variables. The average scores for the knowledge, attitude, and behavior were 54.28±16.33, 87.93±9.75, and 59.85±14.76, respectively. Also, the average score of the self-efficacy was 72.88±8.60. In the knowledge level for the radiation safety, ‘a case that prepares personal dosimeters’, ‘a case that establishes protection facilities’, ‘a case that presents 6⁓10 dental hygienists’, ‘a case that presents radiological technologists’, and ‘a case that is a general hospital’ represented high values. In the attitude level for the radiation safety, ‘a case who is a married person’, ‘a case that prepares personal dosimeters’, and ‘a case that is a general hospital’ showed high values. In the behavior level for the radiation safety, ‘a case that shows a career in dental hygienist or radiographic for 6⁓10 years’, ‘a case that attends radiation safety education’, ‘a case that establishes protection facilities’ showed high values. Also, in the self-efficacy level, ‘a case that who has a high education level more than graduate school education’ and ‘a case that establishes protection facilities’ represented high values. In the relationship between the knowledge, attitude, behavior, and self-efficacy for the radiation safety, it showed statistically significant differences in this

  14. Relationship between knowledge, attitude, behavior, and self-efficacy on the radiation safety on dental hygienist

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Ok; Jun, Sung Hee [Daegu Health College, Daegu (Korea, Republic of)

    2008-11-15

    The objective of this study is to draw an educational plant for reducing the probability of troubles caused by radiation for dental hygienists who are the major applicants of radiation equipments used in dental offices. This study investigated the knowledge and self-efficacy, which is the major variable that affects the attitude and behavior, on the radiation safety that is an educational approach. Also, this study obtained following results from a survey for 25 days from June 15, 2008 that was applied for 225 dental hygienists worked at dental offices and clinics in the area of Youngnam in order to verify the relationship between such variables. The average scores for the knowledge, attitude, and behavior were 54.28±16.33, 87.93±9.75, and 59.85±14.76, respectively. Also, the average score of the self-efficacy was 72.88±8.60. In the knowledge level for the radiation safety, ‘a case that prepares personal dosimeters’, ‘a case that establishes protection facilities’, ‘a case that presents 6⁓10 dental hygienists’, ‘a case that presents radiological technologists’, and ‘a case that is a general hospital’ represented high values. In the attitude level for the radiation safety, ‘a case who is a married person’, ‘a case that prepares personal dosimeters’, and ‘a case that is a general hospital’ showed high values. In the behavior level for the radiation safety, ‘a case that shows a career in dental hygienist or radiographic for 6⁓10 years’, ‘a case that attends radiation safety education’, ‘a case that establishes protection facilities’ showed high values. Also, in the self-efficacy level, ‘a case that who has a high education level more than graduate school education’ and ‘a case that establishes protection facilities’ represented high values. In the relationship between the knowledge, attitude, behavior, and self-efficacy for the radiation safety, it showed statistically significant differences in this

  15. 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...

  16. Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.

    Science.gov (United States)

    Palmeirim, Marta S; Hürlimann, Eveline; Knopp, Stefanie; Speich, Benjamin; Belizario, Vicente; Joseph, Serene A; Vaillant, Michel; Olliaro, Piero; Keiser, Jennifer

    2018-04-01

    The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31-0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87-1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin

  17. Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis

    Science.gov (United States)

    Palmeirim, Marta S.; Hürlimann, Eveline; Knopp, Stefanie; Belizario, Vicente; Joseph, Serene A.; Olliaro, Piero

    2018-01-01

    Background The soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood. Methods and findings We conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis

  18. Randomized study comparing the efficacy and tolerance of a lipohydroxy acid shampoo to a ciclopiroxolamine shampoo in the treatment of scalp seborrheic dermatitis.

    Science.gov (United States)

    Seite, Sophie; Rougier, André; Talarico, Sergio

    2009-12-01

    The success of a dandruff treatment depends not only on the ability of a shampoo to control dandruff, but also on patient compliance, which is closely linked to the cosmetic attributes of the product. The aim of this study was to compare efficacy, tolerance, and cosmetic properties of a LHA Shampoo [containing 0.1% lipohydroxy acid (LHA) and 1.3% salicylic acid] to a CPO shampoo [containing 1.5% ciclopiroxolamine (CPO), 3% salicylic acid, and 0.5% menthol] in subjects with seborrheic dermatitis (SD) of the scalp. One hundred subjects with mild to moderate scalp SD were randomized to receive either the LHA shampoo or the CPO shampoo every 2 days for 4 weeks. Efficacy and tolerance were evaluated at days 0, 14, and 28. The LHA and the CPO shampoo both decreased symptoms of scale, erythema, itching, cutaneous discomfort, and dryness from baseline to day 28. A higher percentage of patients showed improvement in the group treated with the LHA formulation than in the group treated with the CPO formulation, but the difference did not reach statistical significance. At day 28, the tolerance and the global efficacy of the LHA shampoo were significantly better (P = 0.03 and P = 0.01, respectively) than those of the CPO shampoo. Furthermore, the cosmetic acceptability was better or significantly better for all the endpoints evaluated for the LHA shampoo (P = 0.02 for cleaning, P = 0.04 for lathering). In conclusion, these results demonstrated that the lipohydroxy acid shampoo evaluated in this study is a more convenient, efficient, safe, and well-tolerated cosmetic treatment for mild-to-moderate seborrheic dermatitis of the scalp than a ciclopiroxolamine shampoo.

  19. Review of the efficacy and tolerability of the diclofenac epolamine topical patch 1.3% in patients with acute pain due to soft tissue injuries.

    Science.gov (United States)

    Kuehl, Kerry S

    2010-06-01

    The diclofenac epolamine topical patch 1.3% (DETP) was approved by the US Food and Drug Administration in January 2007 for the treatment of soft tissue injuries such as strains, sprains, and contusions, although it has been available for many years in >40 countries worldwide. The aim of this study was to review the efficacy and tolerability of the DETP in relieving acute pain caused by soft tissue injuries. The MEDLINE, Derwent Drug File, BIOSIS, and EMBASE databases were searched for literature published between 1984 and October 30, 2009, in any language, using the terms diclofenac epolamine patch, diclofenac hydroxyethylpyrrolidine patch, and FLECTOR Patch. Clinical studies of the efficacy and/or tolerability of the DETP in patients with acute pain due to soft tissue injuries or localized periarticular disorders were included. Efficacy studies that enrolled patients with other medical conditions were excluded, except for reports that focused on tolerability, which were included to supplement tolerability data. The bibliographies of included studies were reviewed manually for relevant articles based on inclusion and exclusion criteria, and the manufacturer was contacted for additional relevant postmarketing surveillance information and presentations from scientific meetings. The search identified 6 placebo-controlled clinical studies, 1 active-comparator-controlled clinical study, and 1 open-label comparator clinical study of the efficacy and tolerability of the DETP in patients with soft tissue injuries. Three studies reported on tolerability. Primary analyses among the 8 studies reported DETP-associated reductions in spontaneous pain from baseline, assessed using a visual analog scale, ranging from 26% to 88% on day 7 and 56% to 61% on day 14. The use of the DETP was associated with significantly greater reductions in pain scores compared with a placebo patch (2 studies) on day 7 (88% vs 74%; P = 0.001) and day 14 (56.5% vs 46.8%; P = 0.001) and compared with

  20. 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

  1. 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....

  2. 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

  3. 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

  4. A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Iclaprim Vs Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed to be Due to Gram-Positive Pathogens: REVIVE-1.

    Science.gov (United States)

    Huang, David B; O'Riordan, William; Overcash, J Scott; Heller, Barry; Amin, Faisal; File, Thomas M; Wilcox, Mark H; Torres, Antoni; Dryden, Matthew; Holland, Thomas L; McLeroth, Patrick; Shukla, Rajesh; Corey, G Ralph

    2018-04-03

    Our objective in this study was to demonstrate the safety and efficacy of iclaprim compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs). REVIVE-1 was a phase 3, 600-patient, double-blinded, randomized (1:1), active-controlled trial among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg, both administered intravenously every 12 hours for 5-14 days. The primary endpoint of this study was a ≥20% reduction in lesion size (early clinical response [ECR]) compared with baseline among patients randomized to iclaprim or vancomycin at the early time point (ETP), 48 to 72 hours after the start of administration of study drug in the intent-to-treat population. ECR among patients who received iclaprim and vancomycin at the ETP was 80.9% (241 of 298) of patients receiving iclaprim compared with 81.0% (243 of 300) of those receiving vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42%-6.17%). Iclaprim was well tolerated in the study, with most adverse events categorized as mild. Iclaprim achieved noninferiority (10% margin) at ETP compared with vancomycin and was well tolerated in this phase 3 clinical trial for the treatment of ABSSSI. Based on these results, iclaprim appears to be an efficacious and safe treatment for ABSSSI suspected or confirmed to be due to gram-positive pathogens. NCT02600611.

  5. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  6. 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.)

  7. 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.

  8. 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.)

  9. 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

  10. Safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% for the treatment of inflammation and pain following cataract surgery.

    Science.gov (United States)

    Comstock, Timothy L; Paterno, Michael R; Singh, Angele; Erb, Tara; Davis, Elizabeth

    2011-01-01

    To compare the safety and efficacy of loteprednol etabonate ophthalmic ointment 0.5% (LE ointment), a new topical ointment formulation, with vehicle for the treatment of inflammation and pain following cataract surgery. Two randomized, multicenter, double-masked, parallel-group, vehicle-controlled studies were conducted. Patients aged ≥18 years with a combined postoperative anterior chamber cells and flare (ACI) ≥ Grade 3 following uncomplicated cataract surgery participated in seven study visits. Patients self-administered either topical LE ointment or vehicle four times daily for 14 days. Efficacy outcomes included the proportion of patients with complete resolution of ACI and the proportion of patients with no (Grade 0) pain at postoperative day 8. Safety outcomes included the incidence of adverse events, ocular symptoms, changes in intraocular pressure and visual acuity, and biomicroscopy and funduscopy findings. Data from the two studies were combined. The integrated intent-to-treat population consisted of 805 patients (mean [standard deviation] age 69.0 [9.2] years; 58.0% female and 89.7% white). Significantly more LE ointment-treated patients than vehicle-treated patients had complete resolution of ACI (27.7% versus 12.5%) and no pain (75.5% versus 43.1%) at day 8 (P < 0.0001 for both). Fewer LE ointment-treated patients required rescue medication (27.7% versus 63.8%), and fewer had an ocular adverse event (47.2% versus 78.0%, P < 0.0001) while on study treatment. The most common ocular adverse events with LE ointment were anterior chamber inflammation, photophobia, corneal edema, conjunctival hyperemia, eye pain, and iritis. Mean intraocular pressure decreased in both treatment groups. Four patients had increased intraocular pressure ≥10 mmHg (three LE ointment and one vehicle) prior to rescue medication. Visual acuity and dilated funduscopy results were similar between the treatment groups, with the exception of visual acuity at visits 5 and 6, which

  11. 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

  12. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial

    Science.gov (United States)

    French, JA; Baroldi, P; Brittain, ST; Johnson, JK

    2014-01-01

    Objective To evaluate the efficacy, tolerability, and safety of once-daily 1200 mg and 2400 mg SPN-804 (Oxtellar XR™, Supernus Pharmaceuticals), an extended-release tablet formulation of oxcarbazepine (OXC), added to 1-3 concomitant antiepileptic drugs (AEDs) in adults with refractory partial-onset seizures, with or without secondary generalization. Methods The Prospective, Randomized Study of OXC XR in Subjects with Partial Epilepsy Refractory (PROSPER) study was a multinational, randomized, double-blind, parallel-group Phase 3 study. The primary efficacy endpoint was median percent reduction from baseline in monthly (28-day) seizure frequency for the 16-week double-blind treatment period in the intent-to-treat (ITT) population with analyzable seizure data. Other efficacy analyses included proportion of patients with ≥ 50% seizure reduction, proportion of patients seizure free, and the relationship between clinical response and plasma concentration. Results Median percent reduction was -28.7% for placebo, −38.2% (P = 0.08 vs placebo) for once-daily SPN-804 1200 mg, and −42.9% (P = 0.003) for SPN-804 2400 mg. Responder rates were 28.1%, 36.1% (P = 0.08), and 40.7% (P = 0.02); 16-week seizure-free rates in a pragmatic ITT analysis were 3.3%, 4.9% (P = 0.59), and 11.4% (P = 0.008), respectively. When data were analyzed separately for study site clusters, a post hoc analysis demonstrated that both SPN-804 dosages were significantly superior to placebo in median percent seizure reduction (placebo: −13.3%; 1200 mg: −34.5%, P = 0.02; 2400 mg: −52.7%, P = 0.006) in the North American study site cluster. A concentration–response analysis also supported a clinically meaningful effect for 1200 mg. Adverse event types reflected the drug's established profile. Adverse event frequency was consistent with a pharmacokinetic profile in which SPN-804 produces lower peak plasma concentrations vs immediate-release OXC. Once-daily dosing was not

  13. Efficacy and safety of a new microneedle patch for skin brightening: A Randomized, split-face, single-blind study.

    Science.gov (United States)

    Park, Kui Young; Kwon, Hyun Jung; Lee, Changjin; Kim, Daegun; Yoon, Jun Jin; Kim, Myeong Nam; Kim, Beom Joon

    2017-09-01

    Although microneedles are one of the best transdermal drug delivery systems for active compounds, few clinical trials have examined the safety and efficacy of brightening microneedle patches. To determine the efficacy and safety of a newly developed whitening microneedle patch. A split-face study was designed for efficacy assessment with 34 Korean women applying the tested product (a whitening microneedle patch) on one cheek and a control whitening essence on the other. We objectively measured changes in melanin index values and skin brightness by mexameter and chromameter. Each participant also used global assessment to determine skin whitening. In addition, 55 participants were selected for primary skin irritation tests and repeated insult patch tests for safety assessments. Mean skin brightness and melanin indexes improved (Pmicroneedle patch was effective and safe for skin brightening and would be a promising functional cosmetic product. © 2017 Wiley Periodicals, Inc.

  14. 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.

  15. [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.

  16. 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.

  17. Rapeseed with tolerance to the non selective herbicide glufosinate ammonium

    Energy Technology Data Exchange (ETDEWEB)

    Rasche, E. [Hoechst Schering AgrEvo GmbH, Frankfurt am Main (Germany)

    1998-12-31

    Weed control with herbicides is essential to grow rapeseed. Glufosinate Ammonium is used as a non selective herbicide successfully in many countries for over 10 years. It conforms well with ever increasing safety standards for human beings, animals and the environment. The tolerance of rapeseed and other crop plants was achieved by genetic modification. A resistance gene (PAT or BAR) was transfered into previously susceptible rapeseed plants. This new approach allowed the development of Glufosinate Ammonium as an almost ideal selective herbicide. In cooperation with major seed companies and by own breeding programmes new Glufosinate tolerant rapeseed varieties and hybrids are developed. Data on metabolism, toxicity, residues, efficacy etc. were generated to get registration for the selective herbicide use. In addition various studies were done for safety assessments of the PAT gene and the modified rapeseed. In spring 1995 Canadian authorities granted worldwide the first approvals for the selective use of Glufosinate Ammonium (trademark Liberty) and Glufosinate tolerant (trademark and logo Liberty Link) spring rapeseed (Canola). After a successful launch in 1995 about 150.000 ha of Liberty Link Canola were grown and treated with Liberty in 1996. The Liberty Link Canola growers were very well satisfied. In a grower survey 84% stated that they will definitely use the Liberty Link System again. In Europe registrations for Glufosinate Ammonium as a selective herbicide and for the first Glufosinate tolerant rapeseed varieties are expected in the course of 1997. The Liberty Link System will be launched in rapeseed most probably in 1998. (orig.)

  18. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  19. An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

    DEFF Research Database (Denmark)

    Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter

    2006-01-01

    OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1......: In patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated....

  20. Efficacy and safety of deep transcranial magnetic stimulation for major depression: a prospective multicenter randomized controlled trial.

    Science.gov (United States)

    Levkovitz, Yechiel; Isserles, Moshe; Padberg, Frank; Lisanby, Sarah H; Bystritsky, Alexander; Xia, Guohua; Tendler, Aron; Daskalakis, Zafiris J; Winston, Jaron L; Dannon, Pinhas; Hafez, Hisham M; Reti, Irving M; Morales, Oscar G; Schlaepfer, Thomas E; Hollander, Eric; Berman, Joshua A; Husain, Mustafa M; Sofer, Uzi; Stein, Ahava; Adler, Shmulik; Deutsch, Lisa; Deutsch, Frederic; Roth, Yiftach; George, Mark S; Zangen, Abraham

    2015-02-01

    Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the efficacy and safety of dTMS in MDD. We recruited 212 MDD outpatients, aged 22-68 years, who had either failed one to four antidepressant trials or not tolerated at least two antidepressant treatments during the current episode. They were randomly assigned to monotherapy with active or sham dTMS. Twenty sessions of dTMS (18 Hz over the prefrontal cortex) were applied during 4 weeks acutely, and then biweekly for 12 weeks. Primary and secondary efficacy endpoints were the change in the Hamilton Depression Rating Scale (HDRS-21) score and response/remission rates at week 5, respectively. dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p=0.008), resulting in a 0.76 effect size. Response and remission rates were higher in the dTMS than in the sham group (response: 38.4 vs. 21.4%, p=0.013; remission: 32.6 vs. 14.6%, p=0.005). These differences between active and sham treatment were stable during the 12-week maintenance phase. dTMS was associated with few and minor side effects apart from one seizure in a patient where a protocol violation occurred. These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, and whose effect remains stable over 3 months of maintenance treatment. © 2015 World Psychiatric Association.

  1. Comparison of efficacy and safety of topiramate with gabapentin in migraine prophylaxis: randomized open label control trial

    International Nuclear Information System (INIS)

    Zain, S.; Khan, M.; Alam, R.; Zafar, I.; Ahmed, S.

    2013-01-01

    Objective: To compare the efficacy and safety of topiramate with gabapentin in the prophylaxis of migraine patients. Methods: A 12-week randomised open label control trial was conducted at the Department of Pharmacology and Therapeutics, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre (JPMC), Karachi from January to March 2011 involving 80 outpatients who had a history of migraine. The sample was divided into two equal groups. Primary efficacy measure was changed into mean monthly migraine frequency. Secondary efficacy measure included reduction in severity and average duration of an attack. Chi square test and paired t-test were used to analyse the data through SPSS 15. Result: Reduction in mean monthly migraine frequency (10.67+-4.25 to 1.82+-2.02) in the topiramate group was significantly greater compared with (11.97+-4.452 to 2.73+-2.59) that in the gabapentin group (p<0.001). Reduction in severity from 6.60+-2.122 to 1.03+-0.92 in the topiramate group was also significantly greater compared with 6.93+-1.90 to 1.18+-1.01 in the gabapentin group (p<0.001). Reduction in the average duration of attacks from 25.77+-22.32 hours to 1.0 1.06 hours in the topiramate group was significantly greater compared with 22.20+-20.72 to 1.08+-1.40 hours in the gabapentin group (p<0.001). Weight loss and numbness were common adverse effects in the topiramate group. Dizziness, weight gain and somnolence were reported in the gabapentin group. Conclusion: Gabapentin appeared well tolerated in 30(75%) patients compared to topiramate in 23(57.5%) patients. Both drugs were equally effective in migraine prophylaxis. (author)

  2. An open-label, long-term study examining the safety and tolerability of pregabalin in Japanese patients with central neuropathic pain

    Directory of Open Access Journals (Sweden)

    Onouchi K

    2014-07-01

    Full Text Available Kenji Onouchi,1 Hiroaki Koga,2 Kazumasa Yokoyama,3 Tamotsu Yoshiyama4 1Aida Memorial Rehabilitation Hospital, Moriya, Japan; 2Kumamoto Rehabilitation Hospital, Kikuchi-Gun, Japan; 3Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan; 4Pfizer Japan Inc., Tokyo, Japan Purpose: Studies of pregabalin for the treatment of central neuropathic pain have been limited to double-blind trials of 4–17 weeks in duration. The purpose of this study was to assess the long-term safety and tolerability of pregabalin in Japanese patients with central neuropathic pain. The efficacy of pregabalin was also assessed as a secondary measure. Patients and methods: This was a 53-week, multicenter, open-label trial of pregabalin (150–600 mg/day in Japanese patients with central neuropathic pain due to spinal cord injury, multiple sclerosis, or cerebral stroke. Results: A total of 103 patients received pregabalin (post-stroke =60; spinal cord injury =38; and multiple sclerosis =5. A majority of patients (87.4% experienced one or more treatment-related adverse events, most commonly somnolence, weight gain, dizziness, or peripheral edema. The adverse event profile was similar to that seen in other indications of pregabalin. Most treatment-related adverse events were mild (89.1% or moderate (9.2% in intensity. Pregabalin treatment improved total score, sensory pain, affective pain, visual analog scale (VAS, and present pain intensity scores on the Short-Form McGill Pain Questionnaire (SF-MPQ and ten-item modified Brief Pain Inventory (mBPI-10 total score at endpoint compared with baseline. Improvements in SF-MPQ VAS and mBPI-10 total scores were evident in all patient subpopulations. Mean changes from baseline in SF-MPQ VAS and mBPI-10 scores at endpoint were –20.1 and –1.4, respectively. Conclusion: These findings demonstrate that pregabalin is generally well tolerated and provides sustained efficacy over a 53-week treatment period in

  3. 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

  4. 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

  5. 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

  6. Efficacy and Safety Evaluation of Myostaal Forte, a Polyherbal Formulation, in Treatment of Knee Osteoarthritis: A Randomised Controlled Pilot Study

    Directory of Open Access Journals (Sweden)

    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.

  7. Safety and efficacy of teduglutide after 52 weeks of treatment in patients with short bowel intestinal failure

    DEFF Research Database (Denmark)

    O'Keefe, Stephen J D; Jeppesen, Palle B; Gilroy, Richard

    2013-01-01

    Although home parenteral nutrition (PN) can save the lives of patients with massive bowel loss that results in short-bowel syndrome and intestinal failure, quality of life is impaired by PN and its complications. We examined the 12-month tolerability and efficacy of teduglutide to reduce PN depen...

  8. Combined autophagy and HDAC inhibition: a phase I safety, tolerability, pharmacokinetic, and pharmacodynamic analysis of hydroxychloroquine in combination with the HDAC inhibitor vorinostat in patients with advanced solid tumors.

    Science.gov (United States)

    Mahalingam, Devalingam; Mita, Monica; Sarantopoulos, John; Wood, Leslie; Amaravadi, Ravi K; Davis, Lisa E; Mita, Alain C; Curiel, Tyler J; Espitia, Claudia M; Nawrocki, Steffan T; Giles, Francis J; Carew, Jennifer S

    2014-08-01

    We previously reported that inhibition of autophagy significantly augmented the anticancer activity of the histone deacetylase (HDAC) inhibitor vorinostat (VOR) through a cathepsin D-mediated mechanism. We thus conducted a first-in-human study to investigate the safety, preliminary efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the combination of the autophagy inhibitor hydroxychloroquine (HCQ) and VOR in patients with advanced solid tumors. Of 27 patients treated in the study, 24 were considered fully evaluable for study assessments and toxicity. Patients were treated orally with escalating doses of HCQ daily (QD) (d 2 to 21 of a 21-d cycle) in combination with 400 mg VOR QD (d one to 21). Treatment-related adverse events (AE) included grade 1 to 2 nausea, diarrhea, fatigue, weight loss, anemia, and elevated creatinine. Grade 3 fatigue and/or myelosuppression were observed in a minority of patients. Fatigue and gastrointestinal AE were dose-limiting toxicities. Six-hundred milligrams HCQ and 400 mg VOR was established as the maximum tolerated dose and recommended phase II regimen. One patient with renal cell carcinoma had a confirmed durable partial response and 2 patients with colorectal cancer had prolonged stable disease. The addition of HCQ did not significantly impact the PK profile of VOR. Treatment-related increases in the expression of CDKN1A and CTSD were more pronounced in tumor biopsies than peripheral blood mononuclear cells. Based on the safety and preliminary efficacy of this combination, additional clinical studies are currently being planned to further investigate autophagy inhibition as a new approach to increase the efficacy of HDAC inhibitors.

  9. Safety and Efficacy of MLC601 in Iranian Patients after Stroke: A Double-Blind, Placebo-Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    A. A. Harandi

    2011-01-01

    Full Text Available Objective. To investigate the safety and efficacy of MLC601 (NeuroAid as a traditional Chinese medicine on motor recovery after ischemic stroke. Methods. This study was a double-blind, placebo-controlled clinical trial on 150 patients with a recent (less than 1 month ischemic stroke. All patients were given either MLC601 (100 patients or placebo (50 patients, 4 capsules 3 times a day, as an add-on to standard stroke treatment for 3 months. Results. Sex, age, elapsed time from stroke onset, and risk factors in the treatment group were not significantly different from placebo group at baseline (P>.05. Repeated measures analysis showed that Fugl-Meyer assessment was significantly higher in the treatment group during 12 weeks after stroke (P<.001. Good tolerability to treatment was shown, and adverse events were mild and transient. Conclusion. MLC601 showed better motor recovery than placebo and was safe on top of standard ischemic stroke medications especially in the severe and moderate cases.

  10. Efficacy and safety of CPAP in low- and middle-income countries.

    Science.gov (United States)

    Thukral, A; Sankar, M J; Chandrasekaran, A; Agarwal, R; Paul, V K

    2016-05-01

    We conducted a systematic review to evaluate the (1) feasibility and efficacy and (2) safety and cost effectiveness of continuous positive airway pressure (CPAP) therapy in low- and middle-income countries (LMIC). We searched the following electronic bibliographic databases-MEDLINE, Cochrane CENTRAL, CINAHL, EMBASE and WHOLIS-up to December 2014 and included all studies that enrolled neonates requiring CPAP therapy for any indication. We did not find any randomized trials from LMICs that have evaluated the efficacy of CPAP therapy. Pooled analysis of four observational studies showed 66% reduction in in-hospital mortality following CPAP in preterm neonates (odds ratio 0.34, 95% confidence interval (CI) 0.14 to 0.82). One study reported 50% reduction in the need for mechanical ventilation following the introduction of bubble CPAP (relative risk 0.5, 95% CI 0.37 to 0.66). The proportion of neonates who failed CPAP and required mechanical ventilation varied from 20 to 40% (eight studies). The incidence of air leaks varied from 0 to 7.2% (nine studies). One study reported a significant reduction in the cost of surfactant usage with the introduction of CPAP. Available evidence suggests that CPAP is a safe and effective mode of therapy in preterm neonates with respiratory distress in LMICs. It reduces the in-hospital mortality and the need for ventilation thereby minimizing the need for up-transfer to a referral hospital. But given the overall paucity of studies and the low quality evidence underscores the need for large high-quality studies on the safety, efficacy and cost effectiveness of CPAP therapy in these settings.

  11. Safety, Efficacy, and Cost-effectiveness of Tranexamic Acid in Orthopedic Surgery.

    Science.gov (United States)

    Lin, Zilan X; Woolf, Shane K

    2016-01-01

    Perioperative bleeding and postsurgical hemorrhage are common in invasive surgical procedures, including orthopedic surgery. Tranexamic acid (TXA) is a pharmacologic agent that acts through an antifibrinolytic mechanism to stabilize formed clots and reduce active bleeding. It has been used successfully in orthopedics to reduce perioperative blood loss, particularly in total hip and knee arthroplasty and spine surgery. Numerous research studies have reported favorable safety and efficacy in orthopedic cases, although there is no universal standard on its administration and its use has not yet become the standard of practice. Reported administration methods often depend on the surgeon's preference, with both topical and intravenous routes showing efficacy. The type and anatomic site of the surgery seem to influence the decision making but also result in conflicting opinions. Reported complication rates with TXA use are low. The incidence of both arterial and venous thromboembolic events, particularly deep venous thrombosis and pulmonary embolism, has not been found to be significantly different with TXA use for healthy patients. The route of administration and dosage do not appear to affect complication rates either. However, data on patients with higher-risk conditions are deficient. In addition, TXA has shown potential to reduce blood loss, transfusion rates and volumes, perioperative hemoglobin change, and hospital-related costs at various degrees among the published studies. Conservation of blood products, reduced laboratory costs, and shorter hospital stays are likely the major factors driving the cost savings associated with TXA use. This article reviews current data supporting the safety, efficacy, and cost-effectiveness of TXA in orthopedic surgery. Copyright 2016, SLACK Incorporated.

  12. Safety and Efficacy of Lacrimal Drainage System Plugs for Dry Eye Syndrome: A Report by the American Academy of Ophthalmology.

    Science.gov (United States)

    Marcet, Marcus M; Shtein, Roni M; Bradley, Elizabeth A; Deng, Sophie X; Meyer, Dale R; Bilyk, Jurij R; Yen, Michael T; Lee, W Barry; Mawn, Louise A

    2015-08-01

    level II and III evidence in these studies, plugs improve the signs and symptoms of moderate dry eye that are not improved with topical lubrication, and they are well tolerated. There are no level I studies that describe the efficacy or safety of lacrimal drainage system plugs. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

    Science.gov (United States)

    Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

    2016-04-01

    Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis

    NARCIS (Netherlands)

    Bergmann, Karl-Christian; Demoly, Pascal; Worm, Margitta; Fokkens, Wytske J.; Carrillo, Teresa; Tabar, Ana I.; Nguyen, Hélène; Montagut, Armelle; Zeldin, Robert K.

    2014-01-01

    Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. Adults with

  15. Efficacy and safety of the long-acting β2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Ichinose M

    2015-08-01

    and FVC AUC0–3 supported FEV1 outcomes. All doses of olodaterol were well tolerated, and no safety concerns were identified.Conclusion: QD olodaterol demonstrated 24-hour bronchodilator efficacy and was well tolerated in Japanese patients with COPD.Trial registration: ClinicalTrials.gov: NCT00824382.Keywords: trough FEV1, trough FVC, plasma concentration, pulmonary function, once-daily, dose-finding

  16. Safety and efficacy of AMG 334 for prevention of episodic migraine

    DEFF Research Database (Denmark)

    Sun, Hong Yan; Dodick, David W; Silberstein, Stephen D

    2016-01-01

    BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. METHODS: In this multicentre...... in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical...... laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. FINDINGS: From Aug 6, 2013, to June 30, 2014, 483 patients were...

  17. Long-term efficacy of rasagiline in early Parkinson's disease.

    Science.gov (United States)

    Lew, Mark F; Hauser, Robert A; Hurtig, Howard I; Ondo, William G; Wojcieszek, Joanne; Goren, Tamar; Fitzer-Attas, Cheryl J

    2010-06-01

    This study was designed to follow the long-term efficacy, safety, and tolerability of rasagiline for Parkinson's disease (PD) with data collected from all patients who had ever taken rasagiline during the 12-month TEMPO monotherapy trial (N = 398) and subsequent open-label extension. Patients were followed for up to 6.5 years with a mean of 3.5 +/- 2.1 years. After 12 months, additional PD medications were added as required. Of patients remaining in the trial at 2 years, 46% were maintained on rasagiline monotherapy. The majority of patients received a dopamine agonist prior to levodopa as the first additional dopaminergic agent. Analysis using a Kaplan-Meier method indicated that by 5.4 years only 25% of patients progressed to Hoehn & Yahr stage III. Rasagiline was well tolerated, with 11.3% of patients (45/398) withdrawing because of an adverse event. Rasagiline therapy for PD was effective, well tolerated, and safe in this long-term trial.

  18. Retrospective study of tolerability and efficacy of linezolid in patients with multidrug-resistant tuberculosis (1998-2014).

    Science.gov (United States)

    Ramírez-Lapausa, Marta; Pascual Pareja, José Francisco; Carrillo Gómez, Raquel; Martínez-Prieto, Mónica; González-Ruano Pérez, Patricia; Noguerado Asensio, Arturo

    2016-02-01

    Although linezolid is known to be effective when used as an adjunct therapy in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB), the clinical experience is limited. In this study the efficacy and adverse effects of linezolid treatment were evaluated. A retrospective study of tolerability and efficacy of linezolid in MDR-TB patients was performed in Madrid, Spain. Demographic characteristics, microbiological and clinical features and data on treatment tolerability were collected. Regimens were constructed with a target of prescribing, at least, five anti-tuberculosis agents likely to be effective. Linezolid, at a dosage of 1200 or 600 mg daily, was included to complete the treatment if no other sensitive drugs were available. Vitamin B6 was used to reduce toxicity. Treatment outcome and clinical status at last contact were compared between patients with linezolid-containing regimens and with those without linezolid-containing regimens. During the period 1998-2014, 55 patients with MDR-TB received treatment. In 21 of these patients, linezolid was added. The median of linezolid administration was 23.9 months (IQT 13.1-24.7). Patients using linezolid showed a greater resistance to drugs, with a median of 6 (IQR 5-7) compared with those who did not use it, with a median of 4 drugs (IQR 3-5) (plinezolid group (73.5 days) did not differ significantly from those in the non-linezolid group (61 days) (p=0.29). There were no significant differences in the outcomes of the two patient groups. There were no reported adverse events in 81% of patients assigned to linezolid therapy. Only four patients developed toxicity attributed to linezolid. The most serious adverse event in these patients was anemia observed in the two patients treated with 1200 mg per day. One of them also developed moderate paresthesia. In both cases the dosage was reduced to 600 mg per day, with improvement of the anemia and paresthesias. No patients stopped linezolid therapy. A daily

  19. Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

    Science.gov (United States)

    Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

    2017-03-01

    Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

  20. Possible new roles for tolerable risk mediators

    International Nuclear Information System (INIS)

    O'Riordan, T.

    1989-01-01

    In his report on the Sizewell B Inquiry, the Inspector, Sir Frank Layfield, Q.C. introduced the term ''tolerable risk''. He regarded this as a better concept than the much abused and mis-interpreted phrase ''acceptable risk''. The application of tolerable risk implies that, even after regulation and incorporation of appropriate design safety criteria, there will always be a residual risk over which elements of the public will remain uneasy. They may tolerate, but they do not accept. They only tolerate because they have come to trust the process by which safety is assessed and delivered. This interpretation also implies that no safety target, the central theme of this meeting, should ever be regarded as stable or final. Such targets should continually be argued about and subject to regular searching review. Above all, such targets need to be re-justified to a doubting public so that they can be assured that the safety delivery process, namely the principles and management methods to ensure safety levels are actually met, is accountable and open for them to inspect. Thus the ''tolerable zone'' of nuclear plant safety is the product of procedures not simply assessments. These procedures need to be robust and adaptable. They need to be able to incorporate diversity of viewpoints and have a capacity to enable all who are involved to learn from each other's viewpoints and experience. In short the safety determination process needs to be more participatory and creative. (author)

  1. Efficacy and safety of sustained-delivery fluocinolone acetonide intravitreal implant in patients with chronic diabetic macular edema insufficiently responsive to available therapies: a real-life study

    Directory of Open Access Journals (Sweden)

    Massin P

    2016-07-01

    Full Text Available Pascale Massin, Ali Erginay, Bénédicte Dupas, Aude Couturier, Ramin Tadayoni Ophthalmology Department, Lariboisière Hospital, Paris, France Purpose: To evaluate the efficacy and safety of sustained-delivery fluocinolone acetonide (FAc intravitreal implant for diabetic macular edema (DME. Patients and methods: Prospective study in patients with DME insufficiently responsive to laser and anti-vascular endothelial growth factor (anti-VEGF. Patients with history of rise of intraocular pressure after intravitreal corticosteroids were excluded. Results: The macular edema rapidly decreased both in group 1 (prior laser only; n=7 eyes and group 2 (prior laser and ≥3 monthly anti-VEGF therapy; n=10 eyes and central subfield thickness was reduced by -299 µm (P=0.008 and -251 µm (P=0.016 at 12 months, respectively. Mean area under the curve from baseline to last value for pseudophakic eyes was +4.2 letters in group 1 and +9.5 letters in group 2. Overall, the FAc implant was well tolerated. Conclusion: This prospective study confirms the efficacy of the FAc implant in DME patients insufficiently responsive to laser and anti-VEGF. Moreover, with a careful patient selection, our safety results would support an earlier use of FAc in the DME treatment pathway. Keywords: diabetic macular edema, intravitreal corticosteroid, corticosteroid intravitreal implant, fluocinolone acetonide

  2. 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...

  3. [Intraoperative intraperitoneal chemoperfusion treatment with cisplatin and dioxadet on a model of peritoneal carcinomatosis in ovarian cancer: safety and efficacy evaluation].

    Science.gov (United States)

    Bespalov, V G; Kireeva, G S; Belyaeva, O A; Senchik, K Yu; Stukov, A N; Gafton, G I; Soloviev, L A; Vasilchenko, M V; Guseinov, K D; Alexeev, V V; Belyaev, A M

    2015-01-01

    A comparative study of safety and efficacy of normothermic and hyperthermic intraperitoneal chemoperfusion (IPEC and HIPEC) with cisplatin and dioxadet was carried out in 143 female Wistar rats. Ovarian cancer was inoculated intraperitoneally (i.p.). In 48 hours after ovarian cancer inoculation the drugs were administered i.p. or IPEC and HIPEC with the drugs were performed using maximum tolerated doses (MTD). Content of cisplatin was determined in the perfusate and blood plasma during HIPEC with the drug. The leukocyte count was measured using veterinary hematologic analyzer in peripheral blood of rats at different time points after HIPEC with dioxadet. Efficacy of the treatment was estimated in increase in median survival time (MST). During HIPEC cisplatin was accumulated in the abdominal cavity in a considerable amount with minimal systemic absorption. HIPEC with dioxadet didn't significantly affect the leukocyte count in peripheral blood while i.p. administration of dioxadet suppressed leukopoiesis. MST of rats after IPEC with cisplatin was 37.5 days which was significantly higher compared to MST after i.p. administration of cisplatin (19.5 days, p = 0.037). HIPEC with dioxadet was the most effective regimen of treatment with MST of rats reaching 49 days which was significantly higher compared to MST after HIPEC with cisplatin (25.5 days, p = 0.002).

  4. 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.

  5. Tolerance through Education: How Tolerogenic Dendritic Cells Shape Immunity

    Directory of Open Access Journals (Sweden)

    Matthias P. Domogalla

    2017-12-01

    Full Text Available Dendritic cells (DCs are central players in the initiation and control of responses, regulating the balance between tolerance and immunity. Tolerogenic DCs are essential in the maintenance of central and peripheral tolerance by induction of clonal T cell deletion and T cell anergy, inhibition of memory and effector T cell responses, and generation and activation of regulatory T cells. Therefore, tolerogenic DCs are promising candidates for specific cellular therapy of allergic and autoimmune diseases and for treatment of transplant rejection. Studies performed in rodents have demonstrated the efficacy and feasibility of tolerogenic DCs for tolerance induction in various inflammatory diseases. In the last years, numerous protocols for the generation of human monocyte-derived tolerogenic DCs have been established and some first phase I trials have been conducted in patients suffering from autoimmune disorders, demonstrating the safety and efficiency of this cell-based immunotherapy. This review gives an overview about methods and protocols for the generation of human tolerogenic DCs and their mechanisms of tolerance induction with the focus on interleukin-10-modulated DCs. In addition, we will discuss the prerequisites for optimal clinical grade tolerogenic DC subsets and results of clinical trials with tolerogenic DCs in autoimmune diseases.

  6. Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

    Science.gov (United States)

    Scarfe, Lauren; Brillant, Nathalie; Kumar, J. Dinesh; Ali, Noura; Alrumayh, Ahmed; Amali, Mohammed; Barbellion, Stephane; Jones, Vendula; Niemeijer, Marije; Potdevin, Sophie; Roussignol, Gautier; Vaganov, Anatoly; Barbaric, Ivana; Barrow, Michael; Burton, Neal C.; Connell, John; Dazzi, Francesco; Edsbagge, Josefina; French, Neil S.; Holder, Julie; Hutchinson, Claire; Jones, David R.; Kalber, Tammy; Lovatt, Cerys; Lythgoe, Mark F.; Patel, Sara; Patrick, P. Stephen; Piner, Jacqueline; Reinhardt, Jens; Ricci, Emanuelle; Sidaway, James; Stacey, Glyn N.; Starkey Lewis, Philip J.; Sullivan, Gareth; Taylor, Arthur; Wilm, Bettina; Poptani, Harish; Murray, Patricia; Goldring, Chris E. P.; Park, B. Kevin

    2017-10-01

    Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

  7. 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.

  8. Efficacy and tolerability of vilazodone for major depressive disorder: evidence from phase III/IV randomized controlled trials

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  10. 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.

  11. Long-term (52-week) safety and efficacy of Sacubitril/valsartan in Asian patients with hypertension.

    Science.gov (United States)

    Supasyndh, Ouppatham; Sun, Ningling; Kario, Kazuomi; Hafeez, Kudsia; Zhang, Jack

    2017-05-01

    Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD. The sacubitril/valsartan dose was uptitrated to 400 mg QD if BP was uncontrolled (>140/90 mm Hg) after 4 weeks. Subsequently, in patients with uncontrolled BP, treatment was intensified every 4 weeks with amlodipine 5-10 mg followed by hydrochlorothiazide 6.25-25 mg. Of the 341 patients enrolled, 7 (2.1%) discontinued the study drug due to adverse events (AEs). The incidence of AEs and serious AEs were 63.9 and 3.8%, respectively, and no deaths were reported in this study. The most frequent AEs were nasopharyngitis (18.2%) and dizziness (8.8%). Events that were potentially indicative of low BP were infrequent. One patient reported mild transient angioedema (lasting 2.5 h) that resolved without treatment but led to study drug discontinuation. The sacubitril/valsartan-based regimen provided clinically significant mean sitting systolic BP (msSBP) and mean sitting diastolic BP (msDBP) reductions from baseline (-24.7/-16.2 mm Hg). The overall BP control, msSBP and msDBP response rates were 75.3, 90.6 and 87.6%, respectively. Long-term use of sacubitril/valsartan was generally safe and well-tolerated in patients with hypertension and provided significant BP reductions from baseline.

  12. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study.

    NARCIS (Netherlands)

    Leonardi, C.; Strober, B.; Gottlieb, A.B.; Elewski, B.E.; Ortonne, J.P.; Kerkhof, P.C.M. van de; Chiou, C.F.; Dunn, M.; Jahreis, A.

    2010-01-01

    BACKGROUND: In two previous phase 3 studies, up to 60 weeks of etanercept therapy significantly improved the symptoms of psoriasis and was well tolerated. OBJECTIVE: To evaluate the long-term safety of etanercept in an open-label extension study for up to 72 weeks in patients with moderate-to-severe

  13. 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.

  14. Surveillance on The Safety and Efficacy of Ambrisentan (Volibris Tablet 2.5 mg) in Patients with Pulmonary Arterial Hypertension in Real Clinical Practice: Post-marketing Surveillance (Interim Analysis Report).

    Science.gov (United States)

    Takahashi, Tomohiko; Hayata, Satoru; Kobayashi, Akihiro; Onaka, Yuna; Ebihara, Takeshi; Hara, Terufumi

    2018-03-01

    Pulmonary arterial hypertension (PAH) is an intractable and rare disease and the accumulation of clinical evidence under real-world setting is needed. A post-marketing surveillance for the endothelin receptor antagonist ambrisentan (Volibris tablet) has been conducted by all-case investigation since September 2010. This paper is an interim report on the safety and efficacy of ambrisentan in 702 patients with PAH. PAH patients aged 15 years or older were subjected to the analysis. The safety analysis by overall cases or stratification of patient backgrounds and the efficacy analysis were investigated. Regarding patient characteristics, the 702 patients subjected to safety analysis included 543 (77.4%) women and 546 (77.8%) patients at WHO functional class II/III. The mean observational time was 392.7 days. A total of 324 adverse drug reaction (ADR) occurred in 204 (29.1%) patients. Common ADRs (≥ 2%) included anemia (4.6%), peripheral edema (4.1%), headache (3.6%), edema and face edema (2.6% each), abnormal hepatic function (2.3%), and epistaxis (2.1%). There were 82 serious ADRs occurring in 44 (6.3%) patients (385 serious adverse events in 184 (26.2%) patients). Although 11 (1.6%) interstitial lung disease (ILD) cases were reported, all were observed in patients with disease that may contribute to ILD and therefore it is difficult to assess if ambrisentan was associated with these events. There was no difference in safety in relation to the presence/absence of connective tissue disease-related PAH (CTD-PAH) or combination therapy. Among 677 patients subjected to efficacy analysis, those in whom hemodynamic status was determined before and after treatment showed improvement in the mean pulmonary arterial pressure and pulmonary vascular resistance after treatment. The interim results showed safety consistent with the known profile of ambrisentan in terms of the types and frequencies of ADRs in patients with PAH in real clinical practice, in comparison with

  15. 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…

  16. 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.

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

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    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

  18. Tolerance and safety of superficial chemical peeling with salicylic acid in various facial dermatoses

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    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.

  19. Efficacy and safety of amphotericin B emulsion versus liposomal formulation in Indian patients with visceral leishmaniasis: a randomized, open-label study.

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    Shyam Sundar

    2014-09-01

    Full Text Available India is home to 60% of the total global visceral leishmaniasis (VL population. Use of long-term oral (e.g. miltefosine and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB lipid emulsion (ABLE in comparison with that of liposomal formulation (LAmB.In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3:1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376 or LAmB (N = 124. Initial cure (Day 30/45, clinical improvement (Day 30 and long term definitive cure (Day 180 were assessed.A total of 326 (86.7% patients in the ABLE group and 122 (98.4% patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: -0.0663, -0.0150. Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%. Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3% and chills (18.4% vs. 18.5% were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3% compared to LAmB (1.6%. Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.www.clinicaltrials.gov NCT00876824.

  20. Comparison of the efficacy and safety of rosuvastatin 10 mg and atorvastatin 20 mg in high-risk patients with hypercholesterolemia – Prospective study to evaluate the Use of Low doses of the Statins Atorvastatin and Rosuvastatin (PULSAR

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    García Hugo

    2006-12-01

    Full Text Available Abstract Background Many patients at high risk of cardiovascular disease do not achieve recommended low-density lipoprotein cholesterol (LDL-C goals. This study compared the efficacy and safety of low doses of rosuvastatin (10 mg and atorvastatin (20 mg in high-risk patients with hypercholesterolemia. Methods A total of 996 patients with hypercholesterolemia (LDL-C ≥ 3.4 and Results Rosuvastatin 10 mg reduced LDL-C levels significantly more than atorvastatin 20 mg at week 6 (44.6% vs. 42.7%, p Conclusion In high-risk patients with hypercholesterolemia, rosuvastatin 10 mg was more efficacious than atorvastatin 20 mg at reducing LDL-C, enabling LDL-C goal achievement and improving other lipid parameters. Both treatments were well tolerated.

  1. 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.

  2. Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

    Science.gov (United States)

    Mizokami, Yuji

    2009-10-28

    To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

  3. Safety, pharmacokinetics and efficacy findings in an open-label, single-arm study of weekly paclitaxel plus lapatinib as first-line therapy for Japanese women with HER2-positive metastatic breast cancer.

    Science.gov (United States)

    Inoue, Kenichi; Kuroi, Katsumasa; Shimizu, Satoru; Rai, Yoshiaki; Aogi, Kenjiro; Masuda, Norikazu; Nakayama, Takahiro; Iwata, Hiroji; Nishimura, Yuichiro; Armour, Alison; Sasaki, Yasutsuna

    2015-12-01

    Lapatinib is the human epidermal growth factor receptor 2 (HER2) targeting agent approved globally for HER2-positive metastatic breast cancer (MBC). The efficacy, safety and pharmacokinetics (PK) of lapatinib combined with paclitaxel (L+P) were investigated in this study, to establish clear evidence regarding the combination in Japanese patients. In this two-part, single-arm, open-label study, the tolerability of L+P as first-line treatment in Japanese patients with HER2-positive MBC was evaluated in six patients in the first part, and the safety, efficacy and PK were evaluated in a further six patients (making a total of twelve patients) in the second part. Eligible women were enrolled and received lapatinib 1500 mg once daily and paclitaxel 80 mg/m(2) weekly for at least 6 cycles. The only dose-limiting toxicity reported was Grade 3 diarrhea in one patient. The systemic exposure to maximum plasma concentration and area under the plasma concentration curve (AUC) for lapatinib, as well as the AUC of paclitaxel, were increased when combined. The most common adverse events (AEs) related to the study treatment were alopecia, diarrhea and decreased hemoglobin. The majority of drug-related AEs were Grade 1 or 2. The median overall survival was 35.6 months (95 % confidence interval 23.9, not reached). The response rate and clinical benefit rate were both 83 % (95 % confidence interval 51.6, 97.9). The L+P treatment was well tolerated in Japanese patients with HER2-positive MBC. Although the PK profiles of lapatinib and paclitaxel influenced each other, the magnitudes were not greatly different from those in non-Japanese patients.

  4. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)).

    Science.gov (United States)

    Emery, P; Deodhar, A; Rigby, W F; Isaacs, J D; Combe, B; Racewicz, A J; Latinis, K; Abud-Mendoza, C; Szczepanski, L J; Roschmann, R A; Chen, A; Armstrong, G K; Douglass, W; Tyrrell, H

    2010-09-01

    This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment. Patients with active disease on stable MTX (10-25 mg/week) were randomised to rituximab 2 x 500 mg (n=168), rituximab 2 x 1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) > or =2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2 x 500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48. At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2 x 500 mg) + MTX, rituximab (2 x 1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48. Rituximab (at 2 x 500 mg and 2 x 1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.

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

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    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.

  6. Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B : A European multicenter study

    NARCIS (Netherlands)

    Si-Ahmed, Si-Nafa; Pradat, Pierre; Zoutendijk, Roeland; Buti, Maria; Mallet, Vincent; Cruiziat, Claire; Deterding, Katja; Dumortier, Jerome; Bailly, Francois; Esteban, Rafael; Wedemeyer, Heiner; Janssen, Harry L.; Zoulim, Fabien

    2011-01-01

    Background and aims: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in

  7. 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.

  8. Nebulized formoterol: a review of clinical efficacy and safety in COPD

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    Nicholas J Gross

    2010-06-01

    Full Text Available Nicholas J Gross1, James F Donohue21Hines VA Hospital, Stritch Loyola School of Medicine, Hines, IL, USA; 2University of North Carolina School of Medicine, Chapel Hill, NC, USAAbstract: A nebulized formulation of formoterol, Perforomist®, 20 μg/2 ml, has been available since 2007 for the maintenance treatment of chronic obstructive pulmonary disease (COPD. We review the safety and efficacy data obtained during its development. In a dose-finding study, formoterol inhalation solution (FFIS was similar to the formoterol originator, Foradil® 12 μg DPI (FA in patients with COPD. In a 12-week efficacy study, FFIS manifested a rapid onset of action and FEV1 peak, AUC0–12, and trough levels similar to FA. No loss of efficacy, tachyphylaxis, was observed over 12 weeks of regular administration. In placebo-controlled studies in COPD patients receiving maintenance tiotropium, the addition of FFIS significantly augmented bronchodilation over the 6-week treatment duration, signifying that nebulized formoterol can further improve lung function in patients who are receiving tiotropium without an observed increase in adverse reactions. The safety profile of FFIS during 12-week and 1-year studies revealed adverse events that were similar to those of placebo and FA. Cardiac rhythm studies, including frequent ECGs and Holter monitoring, did not indicate any increase in rate or rhythm disturbances greater than placebo or FA. We conclude that maintenance use of Perforomist® is appropriate for patients with COPD who require or prefer a nebulizer for management of their disease.Keywords: long-acting bronchodilator, β-agonist, chronic bronchitis, pulmonary emphysema, Perforomist®, chronic obstructive pulmonary disease

  9. Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma

    OpenAIRE

    Lee, Geun Young; Lee, Chong Eun; Lee, Kyoo Won; Seo, Sam

    2017-01-01

    AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS...

  10. EFFICACY AND SAFETY OF A NEW TOPICAL TESTOSTERONE REPLACEMENT GEL THERAPY FOR THE TREATMENT OF MALE HYPOGONADISM.

    Science.gov (United States)

    Cunningham, Glenn; Belkoff, Laurence; Brock, Gerald; Efros, Mitchell; Gittelman, Marc; Carrara, Dario; Neijber, Anders; Ando, Masakazu; Mitchel, Jules

    2017-05-01

    Testosterone replacement therapy is indicated for male hypogonadism. This study aimed to evaluate the efficacy and safety of testosterone gel 2% (Tgel) over 90 days. This phase 3, open-label, noncomparator study was conducted in adult hypogonadal men (2 consecutive fasting serum testosterone values 86% subjects with symptoms consistent with testosterone deficiency). Subjects applied Tgel 23 mg/day (single pump-actuation using a hands-free cap applicator). The dose was uptitrated to 46 mg/day after 2 weeks if the 4-hour serum total testosterone level was <500 ng/dL. The dose could be further up- or downtitrated to 23, 46, and 69 mg on Days 21, 42, and 63. The primary endpoint included the percentage of subjects with average testosterone concentration (C ave (0-24) ) between 300 and 1,050 ng/dL on Day 90. Safety endpoints were adverse events (AEs), laboratory parameters, and vital signs. Of the 159 who enrolled, 139 men completed the study. Approximately three-quarters (76.1%) of subjects met C ave criteria on Day 90. Most AEs were mild to moderate. There were 5 serious AEs, and 1 (myocardial infarction) was judged as possibly related to Tgel. Confirmed excessive increases in prostate-specific antigen or hematocrit levels were rare. Tgel had a favorable local skin tolerability profile. Overall, 76% of subjects achieved C ave between 300 and 1,050 ng/dL with Tgel. Symptoms of testosterone deficiency improved with few safety concerns. AE = adverse event C ave(0-24) = average testosterone concentration CI = confidence interval C max = maximum concentration IIEF = International Index of Erectile Function MAF = Multidimensional Assessment of Fatigue PK = pharmacokinetic PSA = prostate-specific antigen SAE = serious adverse event SF-12 = Short Form 12 Health Survey Tgel = testosterone gel 2% T max = time to achieve maximum concentration TRT = testosterone replacement therapy.

  11. 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.

  12. 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.

  13. Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label, Multicenter Study of a New Water-Dispersible Pediatric Formulation of Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in African Infants.

    Science.gov (United States)

    Gargano, Nicola; Madrid, Lola; Valentini, Giovanni; D'Alessandro, Umberto; Halidou, Tinto; Sirima, Sodiomon; Tshefu, Antoinette; Mtoro, Ali; Gesase, Samwel; Bassat, Quique

    2018-01-01

    Artemisinin combination therapies are considered the mainstay of malaria treatment, but pediatric-friendly formulations for the treatment of infants are scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison to the marketed tablet (Eurartesim) in the treatment of infants with uncomplicated Plasmodium falciparum malaria. Reported here are the results of a large phase II, randomized, open-label, multicenter trial conducted in African infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28. Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP) populations. A total of 201 patients received the dispersible-tablet formulation, and 99 received the conventional one administered as crushed tablets. At day 28, the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8% (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival curves for time to new infections showed no statistically significant differences ( P = 0.409). The safety and tolerability profile for the two groups was similar in terms of type and frequency of adverse events and was consistent with that expected in African infants with malaria. A standard 3-day treatment with the new dispersible DHA/PQP formulation is as efficacious as the currently used tablet in African infants and has a comparable safety profile. (This trial was registered at ClinicalTrials.gov under registration no. NCT01992900.). Copyright © 2017 Gargano et al.

  14. Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

    Directory of Open Access Journals (Sweden)

    Osvaldo Kohlmann Jr

    1999-05-01

    Full Text Available OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

  15. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic.

    Science.gov (United States)

    Citrome, L

    2011-02-01

    To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were

  16. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    International Nuclear Information System (INIS)

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-01-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  17. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    Energy Technology Data Exchange (ETDEWEB)

    Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Nolte, Marc W. [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Solomon, Cristina [CSL Behring GmbH, Medical Affairs, Marburg (Germany); Department of Anaesthesiology, Perioperative Medicine and General Intensive Care, Paracelsus Medical University, Salzburg (Austria); Herzog, Eva; Dickneite, Gerhard [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany)

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  18. 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.

  19. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.

    Science.gov (United States)

    Botta, Cirino; Ciliberto, Domenico; Rossi, Marco; Staropoli, Nicoletta; Cucè, Maria; Galeano, Teresa; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2017-02-28

    Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM.

  20. Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial

    DEFF Research Database (Denmark)

    Dahl, Ronald; Calverley, Peter M A; Anzueto, Antonio

    2015-01-01

    OBJECTIVES: This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patie...

  1. 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.

  2. EFFICACY OF DEPURATION ON SAFETY OF MEDITERRANEAN MUSSELS (Mytilus galloprovincialis REARED IN THE OLBIA GULF

    Directory of Open Access Journals (Sweden)

    R. Mazzette

    2013-02-01

    Full Text Available The aim of the present study was to investigate the effect of depuration on the safety of Mediterranean mussels harvested in the Olbia gulf and to evaluate the efficacy of E.coli and Salmonella spp. as indicators of the presence of naturally occurring Vibrios and other pathogens (viruses causing hepatitis, L.monocytogenes and S.aureus. Samples of mussels belonging to 5 batches of products, from 2 Depuration Centers, were collected before depuration (T0, after 4h (T4 and at the end of depuration (T8. Results showed an overall efficacy of the depuration in respect to E.coli moderate counts. A depuration for ~8 hours led to a rapid decline in the concentration, complying to the Food Safety Criteria of the Reg. (EC 2073/2005. The decline in numbers of E.coli, does not correlate with the presence of naturally occurring Vibrios, which decline at an even slower rate. The adoption of shorter treatments times for mussels with high initial counts of Vibrios could lead to a reduction unfitted to guarantee the safety of consumers.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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. Clinical efficacy and safety of imepitoin in comparison with phenobarbital for the control of idiopathic epilepsy in dogs.

    Science.gov (United States)

    Tipold, A; Keefe, T J; Löscher, W; Rundfeldt, C; de Vries, F

    2015-04-01

    The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  7. 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.

  8. 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.

  9. 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...

  10. Safety and efficacy of pharmacologic thromboprophylaxis following blunt head injury: a systematic review.

    Science.gov (United States)

    Reeves, Fairleigh; Batty, Lachlan; Pitt, Veronica; Chau, Marisa; Pattuwage, Loyal; Gruen, Russell L

    2013-10-01

    Patients with blunt head injury are at high risk of venous thromboembolism. However, pharmacologic thromboprophylaxis (PTP) may cause progression of intracranial hemorrhage, and clinicians must often weigh up the risks and benefits. This review aimed to determine whether adding PTP to mechanical prophylaxis confers net benefit or harm and the optimal timing, dose, and agent for PTP in patients with blunt head injury. We searched MEDLINE, EMBASE, The Cochrane Library Central Register of Controlled Trials (CENTRAL), and www.clinicaltrials.gov on April 24, 2013, to identify controlled studies and ongoing trials that assessed the efficacy or safety of thromboprophylaxis interventions in the early management of head-injured patients. Studies were classified based on types of interventions and comparisons, and the quality of included studies was assessed using Cochrane risk-of-bias tool and the Newcastle-Ottawa Quality Assessment Scale. We intended to undertake a meta-analysis if studies were sufficiently similar. Sixteen studies met the inclusion criteria, including four randomized controlled trials. At least two randomized controlled trials were at high risk of bias owing to inadequate randomization and concealment of allocation, and observational studies were potentially confounded by substantial differences between comparison groups. Heterogeneity of included studies precluded meta-analysis. Results were mixed, with some studies supporting and others refuting addition of PTP to mechanical interventions. Little evidence was available about dose or choice of agent. The safety and efficacy of early PTP in patients without early progression of hemorrhage is unclear. There is currently insufficient evidence to guide thromboprophylaxis in patients with blunt head injury. Standardized definitions and outcome measurements would facilitate comparison of outcomes across future studies. Studies in mixed populations should report head-injured specific subgroup data. Future

  11. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents

    Directory of Open Access Journals (Sweden)

    J.B. Calixto

    2000-02-01

    Full Text Available This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs. Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

  12. Safety and efficacy of herbal tea for patients with diabetes mellitus

    OpenAIRE

    Siti Syarihan Abdullah; Ali Saleh Alkhoshaiban; Vasudevan Mani; Muhammad Eid Akkawi; Long Chiau Ming

    2016-01-01

    Purpose: The aim of this report is to review (i) safety and efficacy and (ii) medical marketing and regulation of Glucos Cut (GC) Tea. Methodology: The electronic databases such as PubMed, ScienceDirect, Google Scholar, and MEDLINE via EBSCOhost were searched with no limit to year of publication. Additional information was obtained from the Micromedex, “Medicines (Advertisement and Sales) Act 1956” and the “Guideline on Advertising of Medicines and Medicinal Products to General Public 2006...

  13. Safety and efficacy of generic drugs with respect to brand formulation

    OpenAIRE

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-01-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

  14. [Legislation and inspection for the health and safety of workers. Efficacy and limits].

    Science.gov (United States)

    Tozzi, G A

    2009-01-01

    To provide information regarding Occupational Health and Safety (OHS) Inspections in Europe. The dynamics that are transforming regulatory subsystems and complementary inspection services are described. Simplification initiatives, the limits and difficulties of applying the different models of Health and Safety Management Systems are discussed. Examples are given on how to evaluate legislation and technical standards during planning and enforcement. Different approaches for studying characteristics, methodologies and efficacy in practice of OHS Inspection are provided. Targeted inspections need to respond to the needs of enterprises and workers. Impartiality must be guaranteed and workers' participation should be facilitated.

  15. 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

  16. Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute Iliofemoral Deep Vein Thrombosis: A Systematic Review.

    Science.gov (United States)

    Elbasty, Ahmed; Metcalf, James

    2017-12-01

    Catheter direct thrombolysis (CDT) has been shown to be an effective treatment for deep venous thrombosis. The objective of the review is to improve safety and efficacy of the CDT by using ward based protocol, better able to predict complications and treatment outcome through monitoring of haemostatic parameters and clinical observation during thrombolysis procedure. MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all articles on deep venous thrombosis, thrombolysis and correlations of clinical events (bleeding, successful thrombolysis) during thrombolysis with hemostatic parameters to March 2016. The risk of bias in included studies was assessed by Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions. Twenty-four studies were included in the review and we found that improving safety and efficacy of CDT by using ward based protocol depending on eight factors; strict patient selection criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection, biochemical markers monitoring (fibrinogen, D-dimer, activated partial thromboplastin time, plasminogen activator inhibitor-1), timing of intervention, usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging assessment (intravascular ultrasound). These factors may help to improve safety and efficacy by reducing total thrombolytic drug dosage and at the same time ensure successful lysis. There is a marked lack of randomized controlled trials discussing the safety and efficacy of catheter direct thrombolysis. CDT can be performed safely and efficiently in clinical ward, providing that careful nursing, biochemical monitoring, proper selection and mode of infusion of fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate thrombolysis imaging assessment are ensured.

  17. 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.

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

    OpenAIRE

    Ángela María Ruiz-Sternberg; Edson D. Moreira, Jr; Jaime A. Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi

    2018-01-01

    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...

  19. Efficacy and safety testing of mycotoxin-detoxifying agents in broilers following the European Food Safety Authority guidelines.

    Science.gov (United States)

    Osselaere, A; Devreese, M; Watteyn, A; Vandenbroucke, V; Goossens, J; Hautekiet, V; Eeckhout, M; De Saeger, S; De Baere, S; De Backer, P; Croubels, S

    2012-08-01

    Contamination of feeds with mycotoxins is a worldwide problem and mycotoxin-detoxifying agents are used to decrease their negative effect. The European Food Safety Authority recently stated guidelines and end-points for the efficacy testing of detoxifiers. Our study revealed that plasma concentrations of deoxynivalenol and deepoxy-deoxynivalenol were too low to assess efficacy of 2 commercially available mycotoxin-detoxifying agents against deoxynivalenol after 3 wk of continuous feeding of this mycotoxin at concentrations of 2.44±0.70 mg/kg of feed and 7.54±2.20 mg/kg of feed in broilers. This correlates with the poor absorption of deoxynivalenol in poultry. A safety study with 2 commercially available detoxifying agents and veterinary drugs showed innovative results with regard to the pharmacokinetics of 2 antibiotics after oral dosing in the drinking water. The plasma and kidney tissue concentrations of oxytetracycline were significantly higher in broilers receiving a biotransforming agent in the feed compared with control birds. For amoxicillin, the plasma concentrations were significantly higher for broilers receiving an adsorbing agent in comparison to birds receiving the biotransforming agent, but not to the control group. Mycotoxin-detoxifying agents can thus interact with the oral bioavailability of antibiotics depending on the antibiotic and detoxifying agent, with possible adverse effects on the health of animals and humans.

  20. Efficacy and safety of acupuncture therapy for nerve deafness: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Jiang, Yuebo; Shi, Xian; Tang, Yan

    2015-01-01

    Acupuncture is one of the important parts of therapeutic methods in traditional Chinese medicine, and has been widely used for the treatment of nerve deafness in recent years. The current study was to evaluate the efficacy and safety of acupuncture therapy for nerve deafness compared with conventional medicine therapy. PubMed, the Chinese National Knowledge Infrastructure Database, the Chinese Science and Technology Periodical Database, the Chinese Biomedical Database, the Wanfang Database were searched for articles published to identify randomized controlled trials evaluating efficacy and side effects between acupuncture and conventional medicine therapies up to 2013/06. A total of 12 studies, including 527 patients assessed the efficacy and safety of acupuncture therapy for nerve deafness. Overall, the efficacy of acupuncture was significantly better than that of the conventional western medication (RR: 1.54, 95% CI: 1.36-1.74) or traditional Chinese medicines (RR: 1.51, 95% CI: 1.24-1.84), and the efficacy of acupuncture in combination with conventional western medication or traditional Chinese medicine was better than that of the conventional western medication alone (RR: 1.51, 95% CI: 1.29-1.77) or traditional Chinese medicine alone (RR: 1.59, 95% CI: 1.30-1.95). Based on the comparison of number of deafness patients who were completely cured, the efficacy of acupuncture in combination with traditional Chinese medicines was better than that of traditional Chinese medicine alone (RR: 4.62, 95% CI: 1.38-15.47). Acupuncture therapy can significantly improve the hearing of patients with nerve deafness, and the efficacy of acupuncture in combination with medication is superior to medication alone.