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Sample records for montelukast post-marketing comparative

  1. Developments in post-marketing comparative effectiveness research.

    Science.gov (United States)

    Schneeweiss, S

    2007-08-01

    Physicians and insurers need to weigh the effectiveness of new drugs against existing therapeutics in routine care to make decisions about treatment and formularies. Because Food and Drug Administration (FDA) approval of most new drugs requires demonstrating efficacy and safety against placebo, there is limited interest by manufacturers in conducting such head-to-head trials. Comparative effectiveness research seeks to provide head-to-head comparisons of treatment outcomes in routine care. Health-care utilization databases record drug use and selected health outcomes for large populations in a timely way and reflect routine care, and therefore may be the preferred data source for comparative effectiveness research. Confounding caused by selective prescribing based on indication, severity, and prognosis threatens the validity of non-randomized database studies that often have limited details on clinical information. Several recent developments may bring the field closer to acceptable validity, including approaches that exploit the concepts of proxy variables using high-dimensional propensity scores, within-patient variation of drug exposure using crossover designs, and between-provider variation in prescribing preference using instrumental variable (IV) analyses.

  2. Montelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults

    DEFF Research Database (Denmark)

    Bjermer, Leif; Bisgaard, Hans; Bousquet, Jean;

    2003-01-01

    patients whose symptoms remained uncontrolled by inhaled corticosteroids were randomised to add montelukast or salmeterol. PARTICIPANTS: Patients (15-72 years; n = 1490) had a clinical history of chronic asthma for > or = 1 year, a baseline forced expiratory volume in one second (FEV1) value 50......OBJECTIVES: To assess the effect of montelukast versus salmeterol added to inhaled fluticasone propionate on asthma exacerbation in patients whose symptoms are inadequately controlled with fluticasone alone. Design and setting A 52 week, two period, double blind, multicentre trial during which......-90% predicted, and a beta agonist improvement of > or = 12% in FEV1. MAIN OUTCOME MEASURES: The primary end point was the percentage of patients with at least one asthma exacerbation. RESULTS: 20.1% of the patients in the group receiving montelukast and fluticasone had an asthma exacerbation compared with 19...

  3. Closing the information gap: informing better medical decisionmaking through the use of post-market safety and comparative effectiveness information.

    Science.gov (United States)

    Fox, Bethany

    2012-01-01

    While FDA gathers vast amounts of data about prescription drugs prior to their marketing approval, important information about the relative effectiveness and long term safety of products is not required for approval, and often is never collected. Increased postmarket research on the safety and comparative effectiveness of products would improve medical decisionmaking and lead to better clinical outcomes. Fortunately, Congress has recognized the value of this information for healthcare professionals. In response to a congressional mandate in the FDA Amendments Act (FDAAA), FDA is developing the Sentinel Initiative, an active surveillance system for monitoring postmarket drug safety issues. FDAAA also authorized FDA to require a drug sponsor to conduct postmarket safety studies or clinical trials to address a specific safety concern. To increase the repository of comparative effectiveness information, Congress established the Patient-Centered Outcomes Research Institute (PCORI) in the Patient Protection and Affordable Care Act (PPACA), directing it to manage comparative effectiveness research (CER). This article discusses the need for better safety and comparative effectiveness information and outlines methods to efficiently conduct the research and communicate it effectively to healthcare professionals. Coordination between FDA and the PCORI in gathering and communicating postmarket information is recommended. Medical source data collected by the Sentinel Initiative should be used for CER in addition to postmarket safety surveillance, and FDA and the PCORI should adopt identical standards for the distribution and communication of CER. Coordination between the two entities is recommended to save costs, reduce duplication of efforts, and to generate and communicate more information on prescription drugs for medical decisionmakers.

  4. WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: results of an open label, non-comparative, multi-centric, post marketing observational study.

    Science.gov (United States)

    Kumbla, D K; Kumar, S; Reddy, Y V; Trailokya, A; Naik, M

    2014-01-01

    Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to olmesartan. All reported adverse events were recorded. A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  5. WIN OVER study: Efficacy and safety of olmesartan in Indian hypertensive patients: Results of an open label, non-comparative, multi-centric, post marketing observational study

    Science.gov (United States)

    Kumbla, D.K.; Kumar, S.; Reddy, Y.V.; Trailokya, A.; Naik, M.

    2014-01-01

    Background Hypertension is a global health problem. Multiple classes of drugs including angiotensin receptor blockers (ARBs) are available for the treatment of hypertension. Olmesartan is a relatively newer ARB used in hypertension management. Objective To assess the efficacy and safety of WIN-BP (Olmesartan 20 mg/40 mg) tablet in Indian patients with hypertension. Material and methods An open label, non-comparative, multi-centric, real world post marketing observational study included Indian adult hypertensive patients who were treated with olmesartan 20 mg/40 mg tablet once daily for six months. The primary outcome was reduction of systolic blood pressure (SBP) to <140 mmHg and diastolic BP (DBP) to <90 mmHg at 3 and 6 months after initiation of treatment with olmesartan. All reported adverse events were recorded. Results A total of 8940 patients were enrolled in this study. Baseline SBP of 164 mmHg was reduced to 153, 145, 134 and 130 mmHg at the end of 15 days, 1, 3 and 6 months respectively. Similarly, baseline DBP of 100 mmHg was reduced to 93, 89, 84 and 82 mmHg at the end of 15 days, 1, 3 and 6 months respectively. The reduction in both systolic and diastolic blood pressure from day 15 to month 6 was statistically significant (p < 0.0001) with olmesartan treatment. The percentage of responders for both systolic and diastolic blood pressure increased consistently from day 15 to month 6. Only 0.08% patients reported the adverse events. No serious adverse event was reported in the study. Conclusion Olmesartan 20 mg/40 mg is effective and well tolerated without any serious adverse events in patients with hypertension. PMID:24973841

  6. Hepatotoxicity caused by montelukast in a paediatric patient.

    Science.gov (United States)

    Lebensztejn, Dariusz M; Bobrus-Chociej, Anna; Kłusek, Monika; Uscinowicz, Miroslawa; Lotowska, Joanna; Sobaniec-Lotowska, Maria; Kaczmarski, Maciej

    2014-01-01

    Montelukast is a selective and competitive cysteinyl leukotriene receptor antagonist (CystLTRA) which is increasingly used for the treatment of allergic asthma. Recently, hepatotoxicity has been reported with this drug in adult patients, but only one letter to the editor has reported a case of probable montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year-old boy, receiving treatment with montelukast, who developed hepatocellular injury. The exclusion of other causes of increased activity of aminotransferases (viral, metabolic, autoimmune), improvement after dechallenge, the morphological findings and previous reports of comparable cases support the diagnosis of montelukast-induced liver injury in this boy. Physicians should strictly analyse indications for this drug and be aware of potential drug-induced liver disease caused by this agent. Therefore, the periodical assessment of aminotransferases should be recommended during treatment with this leukotriene modifier.

  7. Sleeptalking! Sleepwalking! Side effects of montelukast.

    Science.gov (United States)

    Alkhuja, Samer; Gazizov, Natalya; Alexander, Mary Ellen

    2013-01-01

    A 16-year-old Caucasian female presented to the pulmonary clinic for a followup on her asthma. Due to the worsening of allergy-related symptoms, therapy with montelukast 10 mg daily was started and resulted in good relief of the patient's symptoms. In the nights following initiating therapy with montelukast, the patient's mother reported daily parasomnias in the form of sleeptalking and sleepwalking. Montelukast was discontinued, and that resulted in absence of the parasomnias. In a second attempt montelukast was reinstituted to control the patient's symptoms. Parasomnias were immediately reported after resuming therapy. Montelukast was then discontinued indefinitely. Our patient has never had any history of parasomnias, and since the discontinuation of montelukast, parasomnias were never reported again. Parasomnias in the form of sleeptalking or sleepwalking were not previously reported as adverse effects of montelukast. Alternative modalities to treat allergy-related symptoms in patients, who develop parasomnias while receiving montelukast, should be explored.

  8. Comparative risk of major bleeding with new oral anticoagulants (NOACs) and phenprocoumon in patients with atrial fibrillation: a post-marketing surveillance study.

    Science.gov (United States)

    Hohnloser, Stefan H; Basic, Edin; Nabauer, Michael

    2017-08-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are at least as effective and safe as vitamin K antagonists (VKAs) for stroke prevention in atrial fibrillation (AF). All pivotal trials have compared NOACs to warfarin. However, other VKAs are commonly used, for instance phenprocoumon. A retrospective cohort study using a German claims database assessed the comparative risks of bleeding leading to hospitalization during therapy with NOACs and phenprocoumon in AF patients. Endpoints consisted of major bleeding, gastrointestinal bleeding, and any bleeding. Data were collected from January 1, 2013 to March 31, 2015. Patients newly initiated on dabigatran, apixaban, rivaroxaban, or phenprocoumon were included. Hazard Ratios for bleeding events were derived from Cox proportional hazard models, adjusting for differences in baseline characteristics. Propensity score matching was performed as a sensitivity analysis. A total of 35,013 patients were identified, including 3138 on dabigatran, 3633 on apixaban, 12,063 on rivaroxaban, and 16,179 on phenprocoumon. Patients prescribed apixaban or phenprocoumon were older compared to those on dabigatran or rivaroxaban and had a higher CHA2DS2-VASc score. After adjusting for baseline confounders, apixaban was associated with lower risks of major bleeding (HR 0.68, 95% CI 0.51-0.90, p = 0.008), gastrointestinal bleeding (HR 0.53, 95% CI 0.39-0.72, p < 0.001), and any bleeding (HR 0.80, 95% CI 0.70-0.92, p = 0.002) compared to phenprocoumon. There were no significant differences in bleeding risk between dabigatran and phenprocoumon. Rivaroxaban was associated with more gastrointestinal bleeding (HR 1.39, 95% CI 1.21-1.60, p < 0.001) and any bleeding (HR 1.19, 95% CI 1.10-1.28, p < 0.001). Sensitivity analysis using propensity score matching confirmed these observations. Apixaban therapy is associated with a significantly reduced risk of bleeding compared to phenprocoumon. Bleeding risk with dabigatran was

  9. Real-life treatment of acute exacerbations of chronic bronchitis with moxifloxacin or macrolides: a comparative post-marketing surveillance study in general practice.

    Science.gov (United States)

    Schaberg, T; Möller, M; File, T; Stauch, K; Landen, H

    2006-01-01

    To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. This prospective, non-interventional, multicentre study included out-patients with AECB whose last exacerbation was treated with a macrolide. The current AECB was treated either with moxifloxacin or with one of the macrolides azithromycin, clarithromycin or roxithromycin. Data were obtained on the patient's characteristics, disease and treatment history, the course of the current AECB including time to improvement and cure, and the final assessments of efficacy and tolerability. All adverse events were recorded in patients treated with moxifloxacin; for patients receiving macrolides, only drug-related adverse events were reported. 464 physicians treated 904 patients with moxifloxacin and 846 patients with one of the macrolides. Age, sex and body mass index were well matched between the two treatment groups. However, more moxifloxacin than macrolide patients presented with a generally bad condition (62.8% vs 48.6%). About 42% of patients in both groups had had chronic bronchitis for 1-5 years, and about 27% for 5-10 years. The mean number of AECBs in the previous 12 months was 2.7 and 2.6, respectively. Moxifloxacin was administered to most patients for 5 (43.8%) or 7 days (42.4%). Patients in the macrolide group were treated in most cases with clarithromycin 500 mg for 4-7 days, roxithromycin 300 mg for 6-7 days or azithromycin 500 mg for 3 days. Physicians assessed overall efficacy and tolerability as 'very good' or 'good' in 96.1% and 98.1%, respectively, of moxifloxacin-treated patients and in 67.5% and 91.7%, respectively, of macrolide-treated patients. The mean duration until improvement and cure of AECB was 3.2 days (+/- SD 1.5) and 6.2 days (+/- 2.6) in moxifloxacin

  10. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Zielen, Stefen; Garcia-Garcia, María Luz

    2005-01-01

    The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel......-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms......, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2...

  11. Design and analysis of post-marketing research.

    Science.gov (United States)

    Zhou, Xiao-Hua Andrew; Yang, Wei

    2013-07-01

    A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.

  12. MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

    Science.gov (United States)

    Di Biase, Luigi; Tung, Roderick; Szili-Torok, Tamás; Burkhardt, J David; Weiss, Peter; Tavernier, Rene; Berman, Adam E; Wissner, Erik; Spear, William; Chen, Xu; Neužil, Petr; Skoda, Jan; Lakkireddy, Dhanunjaya; Schwagten, Bruno; Lock, Ken; Natale, Andrea

    2017-04-01

    Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia. The MAGNETIC VT trial will assess if VT ablation using the Niobe™ ES magnetic navigation system results in superior outcomes compared to a manual approach in subjects with ischemic scar VT and low ejection fraction. This is a randomized, single-blind, prospective, multicenter post-market study. A total of 386 subjects (193 per group) will be enrolled and randomized 1:1 between treatment with the Niobe ES system and treatment via a manual procedure at up to 20 sites. The study population will consist of patients with ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of ≤35% and implantable cardioverter defibrillator (ICD) who have sustained monomorphic VT. The primary study endpoint is freedom from any recurrence of VT through 12 months. The secondary endpoints are acute success; freedom from any VT at 1 year in a large-scar subpopulation; procedure-related major adverse events; and mortality rate through 12-month follow-up. Follow-up will consist of visits at 3, 6, 9, and 12 months, all of which will include ICD interrogation. The MAGNETIC VT trial will help determine whether substrate-based ablation of VT with RMN has clinical advantages over manual catheter manipulation. Clinicaltrials.gov identifier: NCT02637947.

  13. [Thought on several problems of clinical revaluation of post-marketing herb research].

    Science.gov (United States)

    He, Wei; Xie, Yanming; Wang, Yongyan

    2010-06-01

    The revaluation of post-marketing herb is a complex research work, which concerns widely content and difficult to put it into practice. The starting of our country's revaluation post-marketing herb was comparatively late. It should profect it both in laws and regulations mechanism as well as technological specification. This article is try to focus on some attention problems in revaluation of postmarketing herb process. Such as the laws and regulations demand, the basement and the subject of revaluation of post-marketing herb.

  14. Sleeptalking! Sleepwalking! Side Effects of Montelukast

    Directory of Open Access Journals (Sweden)

    Samer Alkhuja

    2013-01-01

    Full Text Available A 16-year-old Caucasian female presented to the pulmonary clinic for a followup on her asthma. Due to the worsening of allergy-related symptoms, therapy with montelukast 10 mg daily was started and resulted in good relief of the patient’s symptoms. In the nights following initiating therapy with montelukast, the patient’s mother reported daily parasomnias in the form of sleeptalking and sleepwalking. Montelukast was discontinued, and that resulted in absence of the parasomnias. In a second attempt montelukast was reinstituted to control the patient’s symptoms. Parasomnias were immediately reported after resuming therapy. Montelukast was then discontinued indefinitely. Our patient has never had any history of parasomnias, and since the discontinuation of montelukast, parasomnias were never reported again. Parasomnias in the form of sleeptalking or sleepwalking were not previously reported as adverse effects of montelukast. Alternative modalities to treat allergy-related symptoms in patients, who develop parasomnias while receiving montelukast, should be explored.

  15. Safety of lornoxicam in the treatment of postoperative pain: a post-marketing study of analgesic regimens containing lornoxicam compared with standard analgesic treatment in 3752 day-case surgery patients.

    Science.gov (United States)

    Rawal, Narinder; Krøner, Karsten; Simin-Geertsen, Marija; Hejl, Charlotte; Likar, Rudolf

    2010-01-01

    Post-marketing surveillance studies can provide supplemental data on the safety of medications in the general population. This study aimed to evaluate the safety of analgesic regimens including the NSAID lornoxicam in the short-term treatment of postoperative pain in a clinically relevant population. Randomized, open-label, multicentre, multinational, observational cohort study of 4 days' duration. In-hospital postoperative setting, with discharge to home treatment within 24 hours of surgery. Adults aged > or =18 years expected to be in need of analgesic treatment after day-case surgery. Analgesic regimens containing lornoxicam were compared with a standard analgesic treatment, which was defined as the treatment that the patient would normally receive at the centre. Following day-case surgery, patients were provided with appropriate analgesic medication, and adverse events (AEs; defined as all recorded events with symptoms) were recorded by the investigator during the in-hospital stay and by the patient for the next 3 days using entries recorded morning and evening in a patient diary. Statistical analyses tested for between-treatment differences in AEs, adverse drug reactions (ADRs; defined as events probably, possibly or unlikely to be related to treatment) and gastrointestinal AEs (GI-AEs). A total of 4152 patients were randomized to treatment. Since 400 patients did not take any analgesic, the safety population consisted of 1838 patients for lornoxicam and 1914 patients for standard analgesic treatment. Demographic and disease characteristics were similar between the two treatment groups, as were the type of surgery and the anaesthesia used in surgery. In the safety population, 16.9% of patients received no analgesic in hospital, and when analgesics were provided they were often administered in combination. Similarly, approximately 17% of patients did not take any analgesics at home. AEs were reported in 27.1% and 29.4% of patients in the lornoxicam and standard

  16. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...... subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut...... = 0.015). Daytime cough was significantly reduced on active treatment (p = 0.04). Exacerbations were significantly delayed from montelukast compared with placebo (p bronchiolitis....

  17. Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.

    Science.gov (United States)

    Kim, Dong Wuk; Kim, Young Hun; Yousaf, Abid Mehmood; Kim, Dong Shik; Kwon, Taek Kwan; Park, Jung Hee; Kim, Yong Il; Park, Jae-Hyun; Jin, Sung Giu; Kim, Kyung Soo; Cho, Kwan Hyung; Li, Dong Xun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2016-04-01

    To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.

  18. Social Media Listening for Routine Post-Marketing Safety Surveillance.

    Science.gov (United States)

    Powell, Gregory E; Seifert, Harry A; Reblin, Tjark; Burstein, Phil J; Blowers, James; Menius, J Alan; Painter, Jeffery L; Thomas, Michele; Pierce, Carrie E; Rodriguez, Harold W; Brownstein, John S; Freifeld, Clark C; Bell, Heidi G; Dasgupta, Nabarun

    2016-05-01

    Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

  19. Comparative study of inhaled corticosteroid combined with theophylline or with montelukast in treatment of asthma%吸入糖皮质激素联合茶碱或孟鲁司特治疗哮喘的对照研究

    Institute of Scientific and Technical Information of China (English)

    李英; 丁娟娟

    2012-01-01

    目的 比较吸入糖皮质激素(ICS)联合荼碱与ICS联合孟鲁司特治疗哮喘的疗效.方法 80例中重度哮喘患者随机分为布地奈德联合缓释茶碱组(S组)及布地奈德联合孟鲁司特组(L组),比较两组患者治疗前后呼气峰流速(PEF)以及应用沙丁胺醇的次数.结果 两组患者达到良好控制者比较差异无统计学意义(P>0.05),治疗后两组PEF较治疗前显著降低(P<0.05),但上述两指标改善率两组间比较差异无统计学意义(P>0.05).结论 与ICS联合孟鲁司特比较,ICS联合茶碱治疗哮喘疗效相同且费用低廉.%Objective To compare the efficacy of inhaled corticosteroid (ICS) combined with theophylline or with montelukast on asthma.Methods Eighty patients with asthma were randomly divided into ICS combined with theophylline group(group S) and ICS combined with montelukast group(group L).The peak expiratory flow rate(PEF) and the times of used salbutamol were measured between the two groups.Results Between the two groups,the PEF and the clinical reaction has no significant difference (P < 0.05).Conclusions ICS combined with theophylline or with montelukast in the treatment of asthma have the same effects,but the cost of ICS combined with theophylline is lower than that of ICS combined with montelukast.

  20. Registries in European post-marketing surveillance

    DEFF Research Database (Denmark)

    Bouvy, Jacoline C; Blake, Kevin; Slattery, Jim

    2017-01-01

    PURPOSE: Regulatory agencies and other stakeholders increasingly rely on data collected through registries to support their decision-making. Data from registries are a cornerstone of post-marketing surveillance for monitoring the use of medicines in clinical practice. This study was aimed...... for a registry was made as a condition of the marketing authorisation. All centrally authorised products that received a positive opinion of the EMA Committee for Medicinal Products for Human Use between 1 January 2005 and 31 December 2013 were included. Data regarding registry design and experiences were...... registries and 71% of the registries had a primary safety objective. Most commonly reported issues with registries were delayed time to start and low patient accrual rates. CONCLUSIONS: The delays found in getting new registries up and running support the need to improve the timeliness of data collection...

  1. [Exploration of how to formulate guidelines on post-marketing traditional Chinese medicine surveillance].

    Science.gov (United States)

    Zhang, Wen; Xie, Yan-Ming; Yu, Wen-Ya

    2013-09-01

    Combining the world health organization's (WHO), the United States and the European union's relevant laws and guidelines on post-marketing drug surveillance to judge the status of post-marketing surveillance of traditional Chinese medicine(TCM) in China. We found that due to the late start of post-marketing surveillance of traditional Chinese medicine, the appropriate guidelines are yet to be developed. Hence, hospitals, enterprises and research institutions do not have a shared foundation from which to compare their research results. Therefore there is an urgent need to formulate such post-marketing surveillance guidelines. This paper has used as guidance various technical documents such as, "procedures to formulate national standards" and "testing methods of management in formulating traditional Chinese medicine standards" and has combined these to produce a version of post-marketing surveillance particular to Chinese medicine in China. How to formulate these guidelines is discussed and procedures and methods to formulate technical specifications are introduced. These provide a reference for future technical specifications and will assist in the development of TCM.

  2. Potentiation of indomethacin-induced anti-inflammatory response by montelukast in formalin-induced inflammation in rats.

    Directory of Open Access Journals (Sweden)

    Ali Asghar Hemmati

    2013-10-01

    Full Text Available The leukotrienes and prostaglandins are biologically active metabolites derived from arachidonic acid. The leukotrienes have a role in inflammatory diseases such as allergic rhinitis, inflammatory bowel disease and asthma. Montelukast, a cysteinyl leukotriene receptor antagonist, is claimed to be effective in asthma. The present study aimed to assess the role of cysteinyl leukotriene receptor antagonist on peripheral inflammation and whether montelukast treatment enhances the anti-inflammatory effect of indomethacin. Anti-inflammatory response was measured using a plethysmometer. Histopathologic examination for leukocyte accumulation was done. Montelukast (0.5-2mg/kg, i.p. produced a significant anti-inflammatory effect in dose dependent manner against formalin-induced rat paw oedema at 1h but not in 3 and 5 h. When indomethacin (5 mg/kg, i.p was co-administered with montelukast (1 mg/kg, i.p, the anti-inflammatory effects of indomethacin were significantly increased as compared to the per se effect at 3 and 5 hour after formalin challenge. In histopathology it has been found that combination therapy significantly decreased migration of leucocytes into the site of inflammation. These results show that montelukast has anti-inflammatory properties in peripheral tissue and markedly potentiates the anti-inflammatory activity of indomethacin at 3 and 5 h. It is expected that combination of montelukast with cyclooxygenase inhibitor would prove to be a novel approach to manage complex inflammatory conditions.

  3. Montelukast

    Science.gov (United States)

    ... is in a class of medications called leukotriene receptor antagonists (LTRAs). It works by blocking the action ... taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring ...

  4. Montelukast or salmeterol combined with an inhaled steroid in adult asthma

    DEFF Research Database (Denmark)

    Bjermer, L; Bisgaard, H; Bousquet, J

    2000-01-01

    , Latin America, Middle East, Africa and the Asia-Pacific region in early 2000. The study will compare the oral LTRA montelukast with the inhaled LABA salmeterol, each administered on a background of inhaled fluticasone, on asthma attacks, quality of life, lung function, eosinophil levels, healthcare...

  5. Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults.

    Science.gov (United States)

    Fey, Constanze; Thyroff-Friesinger, Ursula; Jones, Spencer

    2014-01-01

    Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair(®) mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18-55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration-time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00%: 92.2% (90% CI: 87.42-97.30%) for Cmax, 98.1% (90% CI: 94.49-101.81%) for AUC0-t and 97.6% (90% CI: 94.14-101.27%) for AUC0-∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair(®) 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice.

  6. Post-Marketing Survey of Adverse Events Following Ocriplasmin.

    Science.gov (United States)

    Shah, Sumit P; Jeng-Miller, Karen W; Fine, Howard F; Wheatley, H Matthew; Roth, Daniel B; Prenner, Jonathan L

    2016-02-01

    To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin. Copyright 2016, SLACK Incorporated.

  7. Montelukast use-a 19-year nationwide drug utilisation study

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Davidsen, Jesper Rømhild; Laursen, Christian B

    2017-01-01

    PURPOSE: Montelukast is a leukotriene receptor antagonist used in asthma and rhinitis treatment. Despite being marketed nearly two decades ago, little is known about its utilisation pattern. METHODS: Using the Danish National Prescription Registry, we identified subjects filling a montelukast pre...

  8. Fluticasone propionate-salmeterol versus inhaled corticosteroids plus montelukast: outcomes study in pediatric patients with asthma

    Directory of Open Access Journals (Sweden)

    Stanford RH

    2012-12-01

    Full Text Available Richard H Stanford,1 Manan Shah,2 Anna O D'Souza21GlaxoSmithKline, Research Triangle Park, Durham, NC, 2Xcenda, Palm Harbor, FL, USABackground: The purpose of this study (GSK ADA111194 was to compare asthma-related health care utilization and costs associated with fluticasone propionate (an inhaled corticosteroid [ICS] and salmeterol (a long-acting beta-agonist in a single inhalation device (fluticasone propionate-salmeterol versus the combination of ICS + montelukast in the treatment of pediatric patients with asthma.Methods: This was a retrospective, observational cohort study using a large health insurance claims database spanning January 1, 2000 to January 31, 2008. The target population was patients aged 4–11 years with at least one pharmacy claim for fluticasone propionate-salmeterol, any ICS, or montelukast during the study period. The date of first claim for the medication of interest was deemed the index date. Patients were required to be continuously eligible to receive health care services one year prior to and 30 days after the index date, and have at least one claim with an ICD-9-CM code for asthma (493.xx in the one-year pre-index period. Patients with prescriptions for fluticasone propionate-salmeterol, ICS + montelukast, or long-acting beta-agonists during the pre-index period were excluded. Patients were matched on a 1:1 basis according to three variables, ie, pre-index use of oral corticosteroids, ICS, and presence of pre-index respiratory-related hospitalizations/emergency department visits. The risk of asthma-related hospitalization, combined hospitalization/emergency department visit, and monthly asthma-related costs were assessed using multivariate methods.Results: Of the 3001 patients identified, 2231 patients were on fluticasone propionate-salmeterol and 770 were on ICS + montelukast. After matching, there were 747 pairs of fluticasone propionate-salmeterol and ICS + montelukast patients, which were well matched for

  9. Patients' motives for participating in active post-marketing surveillance

    NARCIS (Netherlands)

    Harmark, Linda; Lie-Kwie, Miguel; Berm, Lisette; de Gier, Han; van Grootheest, Kees

    2013-01-01

    Purpose Web-based intensive monitoring is a method to actively collect information about adverse drug reactions (ADRs) using patients as a source of information. To date, little is known about patients' motivation to participate in this kind of active post-marketing surveillance (PMS). Increased ins

  10. Montelukast in Adenoid Hypertrophy: Its Effect on Size and Symptoms

    Directory of Open Access Journals (Sweden)

    Farshid Shokouhi

    2015-11-01

    Conclusion:  Montelukast chewable tablets achieved a significant reduction in adenoid size and improved the related clinical symptoms of AH and can therefore be considered an effective alternative to surgical treatment in children with adenoid hypertrophy.

  11. Plasma total thiol pool in children with asthma: Modulation during montelukast monotherapy.

    Science.gov (United States)

    Dilek, Fatih; Ozkaya, Emin; Kocyigit, Abdurrahim; Yazici, Mebrure; Guler, Eray Metin; Dundaroz, Mehmet Rusen

    2016-03-01

    Inflammation, which is a hallmark of asthma, is one of the main sources of oxidative stress in the human body. Thiols are powerful antioxidants that protect cells against the consequences of oxidative stress. We aimed to investigate whether asthma and montelukast monotherapy affect the total plasma thiol pool in children. A total of 60 children with asthma and 35 healthy controls participated in the study. Group I consisted of newly diagnosed asthmatics who did not have regular anti-asthmatic therapy previously. Group II consisted of patients who had been undertaking montelukast monotherapy regularly for at least 4 months. Plasma total antioxidant status (TAS) and plasma total thiol (PTT) were measured using spectrophotometric methods. Bronchial asthma patients in both groups I and II had decreased median TAS levels compared with the control group (1.59 [interquartile range, 1.04-1.70] and 1.67 [1.50-1.75] vs. 2.98 [2.76-3.16] Trolox equiv./L, respectively; P0.05). In addition, the median TAS and PTT levels for groups I and II were not statistically different (P>0.05). There was a positive correlation between TAS and PTT levels (rho=0.38, Pchildren with asthma. Montelukast monotherapy can limit oxidative stress and thus restore PTT levels but not TAS levels in asthmatic children. © The Author(s) 2015.

  12. The involvement of extracellular matrix remodeling and up-regulated TNF-α in asthma rat and the interventions of montelukast sodium

    Institute of Scientific and Technical Information of China (English)

    Wei-Qiang Cao; Zu-Yong Li; Jin-Zhong Su

    2015-01-01

    Objective: The present research aimed to explore the involvement of extracellular matrix remodeling and up-regulated TNF-α in asthma rat and the interventions of montelukast sodium. Methods: Clean SD rats were divided into 3 groups: control, model and drug intervention group. The expression of TNF-α, MMP2, MMP9 and its inhibitor TIMP1 was detected by Western Blotting. Results: The expression of TNF-α, MMP2, MMP9 and its inhibitor TIMP1 was increased in asthma lung when compared with control. These abnormalities were normalized by the medication of montelukast sodium with a statistical difference when compared with model group. Conclusions: Extracellular matrix remodeling and up-regulated TNF-α were participated in the pathogenesis of asthma lung injury and montelukast sodium alleviates the injury by normalizing those abnormal proteins expression.

  13. Post-market surveillance to detect adverse events associated with Melody® valve implantation.

    Science.gov (United States)

    Hill, Kevin D; Goldstein, Bryan H; Angtuaco, Michael J; Chu, Patricia Y; Fleming, Gregory A

    2017-08-01

    The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation. In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events. We reviewed the United States Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials. We identified 631 adverse events associated with "on-label" Melody® valve implants and 84 adverse events associated with "off-label" implants. The most frequent "on-label" adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5). Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with "on-label" Melody® valve implantation. Further study is needed to evaluate safety of "off-label" uses.

  14. Montelukast: More than a Cysteinyl Leukotriene Receptor Antagonist?

    Directory of Open Access Journals (Sweden)

    Gregory R. Tintinger

    2010-01-01

    Full Text Available The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the therapy of exercise- and aspirin-induced asthma. It is also used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma, chronic obstructive pulmonary disease, cystic fibrosis, and viral bronchiolitis, which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this mini-review is to present evidence for the cysteinyl leukotrien–independent mechanisms of action of montelukast and their potential clinical relevance.

  15. Continuous versus group sequential analysis for post-market drug and vaccine safety surveillance.

    Science.gov (United States)

    Silva, I R; Kulldorff, M

    2015-09-01

    The use of sequential statistical analysis for post-market drug safety surveillance is quickly emerging. Both continuous and group sequential analysis have been used, but consensus is lacking as to when to use which approach. We compare the statistical performance of continuous and group sequential analysis in terms of type I error probability; statistical power; expected time to signal when the null hypothesis is rejected; and the sample size required to end surveillance without rejecting the null. We present a mathematical proposition to show that for any group sequential design there always exists a continuous sequential design that is uniformly better. As a consequence, it is shown that more frequent testing is always better. Additionally, for a Poisson based probability model and a flat rejection boundary in terms of the log likelihood ratio, we compare the performance of various continuous and group sequential designs. Using exact calculations, we found that, for the parameter settings used, there is always a continuous design with shorter expected time to signal than the best group design. The two key conclusions from this article are (i) that any post-market safety surveillance system should attempt to obtain data as frequently as possible, and (ii) that sequential testing should always be performed when new data arrives without deliberately waiting for additional data. © 2015, The International Biometric Society.

  16. [Study of post marketing safety reevaluation of shenqi fuzheng injection].

    Science.gov (United States)

    Ai, Qing-Hua; Li, Yuan-Yuan; Xie, Yan-Ming

    2014-09-01

    In order to promote the Shenqifuzheng injection (SQFZ) clinical medication safety, this study reevaluate on SQFZ post marketing safety study systematically. Including multi center large sample registration type safety monitoring research, the analysis based on national spontaneous reporting system data, the analysis based on the 20 national hospital information system data and literature research. Above the analysis, it suggests that SQFZ has good security. The more adverse drug reaction (ADR) as allergic reactions, mainly involved in the damage of skin, appendages and its systemic damage, serious person can appear allergic shock. ADR/E is more common in the elderly, may be related to medication (tumor) populations. Early warning analysis based on SRS data and literature research are of the view that "phlebitis" has a strong association with SQFZ used.

  17. Effect of montelukast on time-course of exhaled nitric oxide in asthma: influence of LTC4 synthase A(-444)C polymorphism.

    Science.gov (United States)

    Whelan, Glenn J; Blake, Kathryn; Kissoon, Niranjan; Duckworth, Laurie J; Wang, Jainwei; Sylvester, James E; Lima, John J

    2003-11-01

    Leukotrienes (LT) mediate inflammation in asthma. The fraction of exhaled nitric oxide (FE(NO)) is thought to be a sensitive and reproducible method for assessing airway inflammation in asthmatics and the anti-inflammatory effects of drugs. A number of factors are known to contribute to intrapatient variation in FE(NO) which can confound interpretation. The aims of this study were to characterize the time-course of FE(NO), determine the effect of montelukast on the time-course of FE(NO), and evaluate the influence of the LTC(4) synthase A(-444)C polymorphism on montelukast-evoked changes in FE(NO). Following a 2-week run-in, 7 males and 5 females with asthma, 10-16 years old, received 5 or 10 mg of montelukast or an identical placebo at bedtime for 7 days in double-blind, crossover fashion, followed by a 7-day washout. FE(NO)was quantified every 30 min for 3 or 6 hr at baseline and on days 1, 2, 3, and 7 of treatment. A time-averaged value for FE(NO) was calculated (FE(NO)*), and % changes in FE(NO)* relative to baseline vs. time following placebo and montelukast were compared. The genotype of the A(-444)C polymorphism was determined by PCR and RFLP. FE(NO) varied markedly as a function of time in each patient. Time-averaged values of FE(NO) (FE(NO)*) during placebo and montelukast treatment were similar. Montelukast significantly reduced the slope of the % change in FE(NO)* vs. time curve in heterozygotes (n = 4), but not in A/A homozygotes (n = 8). These data suggest that heterozygotes respond better to montelukast compared to A/A homozygotes, at least with respect to changes in FE(NO). We conclude that assessment of inflammation or the anti-inflammatory effects of drugs in asthma based on single determinations of FE(NO) can be misleading. We further conclude that the A(-444)C polymorphism in the LTC(4) synthase gene probably contributes to interpatient variability in montelukast-evoked changes in FE(NO)* and warrants further study.

  18. Japanese Physicians' Views on Drug Post-Marketing Surveillance.

    Science.gov (United States)

    Maeda, Kazuki; Katashima, Rumi; Ishizawa, Keisuke; Yanagawa, Hiroaki

    2015-12-01

    Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians' views on PMS with the aim of conducting PMS more effectively. We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians' attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure.

  19. [Discussion on the building of post market risk analysis method in hemodialysis device].

    Science.gov (United States)

    Xu, Honglei; Peng, Xiaolong; Tian, Xiaojun; Wang, Peilian

    2014-09-01

    This paper discussed the building of post market risk analysis method in hemodialysis device from the point of government supervision. By proposing practical research methods for post market risk identification and estimation on hemodialysis device, providing technical guidance for government to put risk management of hemodialysis device into effect, and offering reference for enterprises to carry out post market risk evaluation on their products as well.

  20. [Application of nested case-control study on safe evaluation of post-marketing traditional Chinese medicine injection].

    Science.gov (United States)

    Xiao, Ying; Zhao, Yubin; Xie, Yanming

    2011-10-01

    The nested case-control study design (or the case-control in a cohort study) is described here as a new study design used in safe evaluation of post-marketing traditional Chinese medicine injection. In the nested case-control study, cases of a disease that occur in a defined cohort are identified and, for each, a specified number of matched controls is selected from among those in the cohort who have not developed the disease by the time of disease occurrence in the case. For many research questions, the nested case-control design potentially offers impressive reductions in costs and efforts of data collection and analysis compared with the full cohort approach, with relatively minor loss in statistical efficiency. The nested case-control design is particularly advantageous for studies in safe evaluation of post-marketing traditional Chinese medicine injection. Some examples of the application of nested case-control study were given.

  1. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey.

    Science.gov (United States)

    Ross, Joseph S; Blount, Katrina L; Ritchie, Jessica D; Hodshon, Beth; Krumholz, Harlan M

    2015-01-01

    In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA) pathway. We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%), nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives.

  2. 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.

  3. Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

    Science.gov (United States)

    Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

    2017-07-20

    This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79-653). The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

  4. 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.)

  5. Estudio de bioequivalencia de montelukast en tabletas masticables de 5 mg

    Directory of Open Access Journals (Sweden)

    Ángela Piedad Medina

    2012-04-01

    Full Text Available Introducción. La importancia de los medicamentos genéricos radica en la posibilidad de la disminuciónde los costos en el sistema nacional de salud, sin sacrificar la calidad del servicio ni la eficacia y laseguridad de los tratamientos.Es importante resaltar que los estudios de bioequivalencia pretenden demostrar que los perfilesfarmacocinéticos del producto de prueba y del producto de referencia son similares e intercambiables.El montelukast sódico está indicado para la profilaxis y el tratamiento crónico del asma, en adultosy pacientes pediátricos de 12 meses de edad o más. En general, es bien tolerado y las reaccionesadversas son un poco más frecuentes en los pacientes tratados con el fármaco que en los tratadoscon placebo. Objetivos. Comparar la biodisponibilidad de Amisped®, montelukast en tabletas masticables de 5mg fabricadas por Sanofi-Aventis con la de Singulair®, montelukast en tabletas masticables de 5 mgelaboradas por Merck Sharp & Dohme. Materiales y métodos. Se comparó la magnitud y la velocidad de la absorción de montelukast en 18voluntarios sanos, empleando un diseño cruzado completo al azar. El bioanálisis de las muestras sehizo por cromatografía líquida de alta resolución. Resultados. Los resultados para el genérico y el innovador, respectivamente, fueron: Tmax (horas2,17±0,73 y 2,28±0,88; Cmax (ng/ml 607,42±122,92 y 627,69±134,17; AUC0-t (ng*h/ml 3.316,39±861,57y 3.545,40±1.070,07; AUC0-∞ (ng*h/ml 3.450,92±904,89 y 3.722,03±1120,60; Ke (1/h 0,25±0,05 y0,23±0,04 en el intervalo de confianza de 0,99-1,00 para lnCmax y 0,94-1,06 para lnAUC0-∞. Conclusiones. La formulación ensayada de Amisped® de Sanofi-Aventis es bioequivalente a laformulación de referencia Singulair® de Merck Sharp & Dohme.   doi: http://dx.doi.org/10.7705/biomedica.v32i3.708

  6. Effect of montelukast combined with procaterol treatment on airway remodeling and inflammatory response in children with mycoplasma pneumonia

    Institute of Scientific and Technical Information of China (English)

    Jian-Mei Zhang; Fen-Xia Zhang; Yan Jia; Min Wang; Jue Bai

    2016-01-01

    Objective:To study the effect of montelukast combined with procaterol treatment on airway remodeling and inflammatory response in children with mycoplasma pneumonia.Methods:A total of 60 mycoplasma pneumonia children with acute asthma attack treated in our hospital were selected and randomly divided into two groups, observation group received conventional anti-infection, cough-relieving and sputum-reducing combined with montelukast and procaterol spasmolysis and asthma-relieving treatment, control group received conventional anti-infection, cough-relieving and sputum-reducing combined with procaterol spasmolysis and asthma-relieving treatment, and then the degree of airway remodeling and inflammatory response was compared between two groups.Results:Serum MCP-4, MDC and CysLTs levels of both groups 1 week after treatment were significantly lower than those before treatment and serum MCP-4, MDC and CysLTs levels of observation group after treatment were lower than those of control group; 1 week after treatment, LD and the proportion of Treg in induced sputum of observation group were significantly higher than those of control group, WT, WA%, PEF25, PEF50 and PEF75 as well as FN1 and Col-1 levels and the proportion of Th17 in induced sputum were significantly lower than those of control group, and FVC, PEF and FEV1 were not different from those of control group.Conclusions:Montelukast combined with procaterol treatment can significantly improve the airway remodeling and inflammatory response in mycoplasma pneumonia children with acute asthma attack.

  7. Effect of azithromycin, montelukast combined with pulmicort respulas therapy on the degree of inflammation and lung function in children with mycoplasma pneumonia

    Institute of Scientific and Technical Information of China (English)

    Jian-mei Zhang; Jin-fang Zhou; Min Wang; Jue Bai; Yan Jia

    2016-01-01

    Objective:To analyze the effect of azithromycin, montelukast combined with pulmicort respulas therapy on the degree of inflammation and lung function in children with mycoplasma pneumonia.Methods:A total of 318 cases of children with mycoplasma pneumonia treated in our hospital from February 2013 to February 2016 were randomly divided into observation group and control group (n=159). Control group received azithromycin and montelukast therapy, observation group received azithromycin, montelukast combined with pulmicort respulas therapy, and then the degree of inflammation, lung function, etc. were compared between two groups.Results:V-T, t-PTEF/t-E, TEF25/PTEF, FEV1, FVC, FEV1/FVC and MVV values of observation group after treatment were higher than those of control groupand differences in MTIF/MTEF values were not statistically significant between groups; serum CCSP value was higher than that of control group, and IL-17, MCP-4, MDC and CysLTs values were lower than those of control group.Conclusion:Azithromycin, montelukast combined with pulmicort respulas therapy can reduce the systemic inflammatory state and optimize lung function in children with mycoplasma pneumonia, and it has positive clinical significance.

  8. Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

    Science.gov (United States)

    Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

    2017-08-16

    Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

  9. Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems.

    Science.gov (United States)

    Aronson, Jeffrey K

    2017-03-30

    Modern pharmacovigilance began in the 1960s, since when the subject has grown markedly, interest having particularly increased since 2010. One index of its success is the increasing speed with which serious adverse drug reactions are discovered after marketing of a medicinal product. However, the speed with which products have subsequently been withdrawn as a result of the discovery of serious adverse reactions has not consistently changed. This highlights problems that regulators and manufacturers face when serious reactions are discovered, with difficulties in deciding which of several consequent actions to take: to add specific warnings (cautions) or contraindications to the product label; to issue a Direct Healthcare Professional Communication; to allow informed patients to decide whether they will take the drug; or, in the most serious cases, to withdraw the product or revoke the licence. Conflicts of interest may inhibit decision-making. Recommendations that arise from these observations are that: health professionals and patients should be more vigorously encouraged to report suspected adverse drug reactions; regulatory authorities and drug manufacturers should take quicker confirmatory action when serious suspected adverse drug reactions are reported, even anecdotally, with formal studies to test for causality conducted sooner rather than later, applying lower than usual thresholds for suspicion; temporary suspensions or restrictions could be considered during such assessments; universal guidelines are needed for determining when a drug should be withdrawn if serious adverse drug reactions are suspected; there should be more rigorous monitoring and verification of deaths and reporting of reasons for drop-outs during clinical trials, with more transparency in reporting adverse events and ready access to premarketing clinical study reports; post-marketing drug monitoring systems and medicines regulation in low-to-middle income economies, especially in Africa

  10. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Ross JS

    2015-05-01

    Full Text Available Joseph S Ross, Katrina L Blount, Jessica D Ritchie, Beth Hodshon, Harlan M Krumholz Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA Background: In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate post-market clinical studies or augment FDA post-market surveillance requirements for higher-risk devices that are most often approved via the FDA's pre-market approval (PMA pathway. Methods and results: We conducted a cross-sectional survey of 47 manufacturers with operations in California, Minnesota, and Massachusetts who market devices approved via the PMA pathway. Among 22 respondents (response rate =47%, nearly all self-reported conducting post-market clinical research studies, commonly between 1 and 5; only 1 respondent reported never conducting post-market clinical research studies. While manufacturers most often engaged in these studies to satisfy FDA requirements, other reasons were reported, including performance monitoring and surveillance and market acceptance initiatives. Risks of conducting and not conducting post-market clinical research studies were described through open-ended response to questions. Conclusion: Medical device manufacturers commonly initiate post-market clinical studies at the request of the FDA. Clinical data from these studies should be integrated into national post-market surveillance initiatives. Keywords: FDA, PMA pathway, post-market surveillance

  11. Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

    Science.gov (United States)

    Schick, Andreas; Miller, Kathleen L; Lanthier, Michael; Dal Pan, Gerald; Nardinelli, Clark

    2017-06-01

    An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied. In this paper, we examine whether any pre-marketing drug characteristics are associated with serious post-marketing safety actions. We study this question using an internal FDA database containing every new small molecule drug submitted to the FDA's Center for Drug Evaluation and Research (CDER) on or after November 21, 1997, and approved and commercially launched before December 31, 2009. Serious post-marketing safety actions include whether these drugs ever experienced either a post-marketing boxed warning or a withdrawal from the market due to safety concerns. A random effects logistic regression model was used to test whether any pre-marketing characteristics were associated with either post-marketing safety action. A total of 219 new molecular entities were analyzed. Among these drugs, 11 experienced a safety withdrawal and 30 received boxed warnings by July 31, 2016. Contrary to prevailing hypotheses, we find that neither clinical trial sample sizes nor review time windows are associated with the addition of a post-marketing boxed warning or safety withdrawal. However, we do find that new drugs approved with either a boxed warning or priority review are more likely to experience post-marketing boxed warnings. Furthermore, drugs approved with boxed warnings tend to receive post-marketing boxed warnings resulting from new safety information that are unrelated to the original warning. Drugs approved with a boxed warning are 3.88 times more likely to receive a post-marketing boxed warning, while drugs approved with a priority review are 3.51 times more likely to receive a post-marketing

  12. [Technical specifications for post-marketing pharmacoeconomic evaluation of Chinese medicine (draft version for comments)].

    Science.gov (United States)

    Xie, Yan-Ming; Wang, Xin; Wang, Nuo; Chang, Yan-Peng

    2013-09-01

    Pharmacoeconomics is an important part of the post-marketing evaluation of Chinese medicine, post-marketing pharmacoeconomic evaluation can better reflect the clinical and market value of Chinese medicine, the purpose of establishing the technical specifications for pharmacoeconomic evaluation is to make the evaluation process and results regarding Chinese patent medicines more scientific and fair. Every country's technical specifications for pharmacoeconomic evaluation act as reference guidelines, we have already drawn up the technical specifications which take into account the special characteristics of Chinese medicine; these are in preparation for post-marketing pharmacoeconomic evaluation Chinese medicine.

  13. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro-in vivo aerosol performance.

    Science.gov (United States)

    Patil-Gadhe, Arpana; Kyadarkunte, Abhay; Patole, Milind; Pokharkar, Varsha

    2014-09-01

    The aim of the present study was to establish the potential of montelukast loaded nanostructured lipid carrier (MNLC) for pulmonary application. The formulated nanoparticles were evaluated in vitro for aerodynamic characterization and in vivo for pulmokinetics in Wistar rats. The in vitro cytotoxicity was performed on A549 cell line and compared with montelukast-aqueous solution. MNLC was prepared with montelukast (0.2%), Precirol ATO5 (solid lipid), and Capryol-90 (liquid lipid) in the ratio of 7:3 using melt-emulsification-homogenization method. dl-Pyrrolidonecarboxylic acid salt of l-cocyl arginine ethyl ester (CAE), a biodegradable surfactant in the concentration of 1% was used to stabilize the nanoparticles. The particle size and encapsulation efficiency (EE) were 184.6 ± 2.7 nm and >95%, respectively. MNLC-Dry powder for inhalation (DPI) was prepared by lyophilization using 3% mannitol as cryoprotectant and carrier. MNLC-DPI was evaluated for flow, crystallographic and thermal properties. Mass median diameters (MMD) and density for MNLC-DPI were found to be 15.1 ± 1.4 μm and 0.051 ± 0.002 g/cc, respectively. In vitro aerosol performance study indicated more than 95% of the emitted dose (ED) at both the flow rates studied. Mass median aerodynamic diameters (MMAD) of 3.24 ± 0.67 μm with 69.98 ± 1.9% fine particle fraction (FPF) were obtained at 30 L/min flow rate, whereas at 60 L/min MMAD and FPF were found to be 2.83 ± 0.46 μm and 90.22 ± 2.6%, respectively. In vitro cytotoxicity study on A549 cells revealed higher safety of MNLC than pure drug. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 11.76 for MNLC as compared to montelukast-aqueous solution. Thus, the results of the study demonstrated the potential of montelukast lipidic nanoparticulate formulation to improve the efficacy with reduced toxicity leading to better performance of drug as MNLC-DPI for

  14. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, H.; Flores-Nunez, A.; Goh, A.;

    2008-01-01

    RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial viru...

  15. [Treatment with montelukast in children with asthma. Test trial].

    Science.gov (United States)

    Pérez, O

    2000-01-01

    To study of antileukotrienes with participation in the genesis of the asthma appeared in the last years. 17 children with a mean age of 10.29 years, male seven and ten girls. They were tried with montelukast 5 mg/day the 12-year-old smellers and with 10 mg/day the such age greats, during a period middle to 5.7 months. Ten of they had a concomitant treatment fluticasona, budesonide, salmeterol or formoterol. Was valued the clinic improvement, the saving in medication and the sound effects. a) Clinic improvement in 82.3%; b) elimination of medication associated in 90% and c) sound effects: in a case drowsiness and in other abdominal pain. Montelukast seems be a very useful product in the treatment of the bronchial asthma in children since generates a saving of corticoids and longtime beta 2 in the mild or moderate asthma, associate or not with the inmunoterapia.

  16. A pre-marketing ALT signal predicts post-marketing liver safety.

    Science.gov (United States)

    Moylan, Cynthia A; Suzuki, Ayako; Papay, Julie I; Yuen, Nancy A; Ames, Michael; Hunt, Christine M

    2012-08-01

    Drug induced liver injury during drug development is evidenced by a higher incidence of serum alanine aminotransferase (ALT) elevations in treated versus placebo populations and termed an "ALT signal". We sought to quantify whether an ALT signal in pre-marketing clinical trials predicted post-marketing hepatotoxicity. Incidence of ALT elevations (ALT ≥ 3 times upper limits normal [× ULN]) for drug and placebo of new chemical entities and approved drugs associated with hepatotoxicity was calculated using the Food and Drug Administration (FDA) website. Post-marketing liver safety events were identified using the FDA Adverse Event Reporting System (AERS). The association of FDA AERS signal score (EB05 ≥ 2) and excess risk of pre-marketing ALT elevation (difference in incidence of ALT ≥ 3× ULN in treated versus placebo) was examined. An ALT signal of ≥ 1.2% was significantly associated with a post-marketing liver safety signal (p ≤ 0.013) and a 71.4% positive predictive value. An absent ALT signal was associated with a high likelihood of post-marketing liver safety; negative predictive value of 89.7%. Daily drug dose information improved the prediction of post-marketing liver safety. A cut-off of 1.2% increase in ALT ≥ 3× ULN in treated versus placebo groups provides an easily calculated method for predicting post-marketing liver safety.

  17. ROLE OF ORAL MONTELUKAST IN ACUTE ASTHMA EXACERBATIONS : A RANDOMIZED PLACEBO CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    Gaude

    2015-08-01

    Full Text Available BACKGROUND: Leukotriene receptor antagonists (LTRAs are well established in the management of outpatient asthma. However, there is very little information as to their role in acute asthma exacerbations. The present study was done to evaluate the clinical efficacy of oral Montelukast as an add on therapy to the usual standard therapy of acute attack of bronchial asthma. MATERIALS AND METHODS: A randomized single blinded controlled study was conducted in a tertiary car e teaching hospital. A total of 320 patients with age >18 years of acute exacerbations due to bronchial asthma were included in the study. The patients were randomized into two study and control groups. The study group patients received oral Montelukast (1 0mg once daily for 2 weeks, while the control group received a placebo. All the patients received standard therapy according to GINA guidelines. Improvements in lung function tests, clinical symptoms and relapse rates were monitored at baseline, at discha rge and at 2 weeks. Side effects profile was also monitored. RESULTS: A total of 255 patients were finally assessed. One hundred thirty patients belonged to study group and 125 in the control group. Baseline characteristics were similar and well matched in both the groups. Mean age was 39.9±15.8 years in study group and 42.8±12.8 in the control group and majority were female patients in both the groups. At the end of 2 weeks, it was observed that there were no significant improvements in FEV 1 and FVC as com pared to the control group. However, there was significant improvement in PEFR at 2 weeks (0.4 L/sec, 12% as compared to the control group (p <0.0376. Length of hospital stay was similar in both the groups. No serious adverse effects were noted during th e course of the study. CONCLUSIONS: In acute asthma exacerbations, the present study showed that additional administration of oral Montelukast resulted in significantly higher PEFR at 2 weeks as compared to the standard

  18. Montelukast versus inhaled corticosteroids in the management of pediatric mild persistent asthma.

    Science.gov (United States)

    Scaparrotta, Alessandra; Di Pillo, Sabrina; Attanasi, Marina; Rapino, Daniele; Cingolani, Anna; Consilvio, Nicola Pietro; Verini, Marcello; Chiarelli, Francesco

    2012-07-05

    International guidelines recommend the use of inhaled corticosteroids (ICSs) as the preferred therapy, with leukotriene receptor antagonists (LTRAs) as an alternative, for the management of persistent asthma in children. Montelukast (MLK) is the first LTRA approved by the Food and Drug Administration for the use in young asthmatic children.Therefore, we performed an analysis of studies that compared the efficacy of MLK versus ICSs. We considered eligible for the inclusion randomized, controlled trials on pediatric populations with Jadad score > 3, with at least 4 weeks of treatment with MLK compared with ICS.Although it is important to recognize that ICSs use is currently the recommended first-line treatment for asthmatic children, MLK can have consistent benefits in controlling asthmatic symptoms and may be an alternative in children unable to use ICSs or suffering from poor growth. On the contrary, low pulmonary function and/or high allergic inflammatory markers require the corticosteroid use.

  19. Montelukast versus inhaled corticosteroids in the management of pediatric mild persistent asthma

    Directory of Open Access Journals (Sweden)

    Scaparrotta Alessandra

    2012-07-01

    Full Text Available Abstract International guidelines recommend the use of inhaled corticosteroids (ICSs as the preferred therapy, with leukotriene receptor antagonists (LTRAs as an alternative, for the management of persistent asthma in children. Montelukast (MLK is the first LTRA approved by the Food and Drug Administration for the use in young asthmatic children. Therefore, we performed an analysis of studies that compared the efficacy of MLK versus ICSs. We considered eligible for the inclusion randomized, controlled trials on pediatric populations with Jadad score > 3, with at least 4 weeks of treatment with MLK compared with ICS. Although it is important to recognize that ICSs use is currently the recommended first-line treatment for asthmatic children, MLK can have consistent benefits in controlling asthmatic symptoms and may be an alternative in children unable to use ICSs or suffering from poor growth. On the contrary, low pulmonary function and/or high allergic inflammatory markers require the corticosteroid use.

  20. Post market surveillance in the german medical device sector - current state and future perspectives.

    Science.gov (United States)

    Zippel, Claus; Bohnet-Joschko, Sabine

    2017-08-01

    Medical devices play a central role in the diagnosis and treatment of diseases but also bring the potential for adverse events, hazards or malfunction with serious consequences for patients and users. Medical device manufacturers are therefore required by law to monitor the performance of medical devices that have been approved by the competent authorities (post market surveillance). Conducting a nationwide online-survey in the German medical device sector in Q2/2014 in order to explore the current status of the use of post market instruments we obtained a total of 118 complete data sets, for a return rate of 36%. The survey included manufacturers of different sizes, producing medical devices of all risk classes. The post market instruments most frequently reported covered the fields of production monitoring and quality management as well as literature observation, regulatory vigilance systems, customer knowledge management and market observation while Post Market Clinical Follow-up and health services research were being used less for product monitoring. We found significant differences between the different risk classes of medical devices produced and the intensity of use of post market instruments. Differences between company size and the intensity of instruments used were hardly detected. Results may well contribute to the development of device monitoring which is a crucial element of the policy and regulatory system to identify device-related safety issues. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effect of montelukast on platelet activating factor- and tachykinin induced mucus secretion in the rat

    Directory of Open Access Journals (Sweden)

    Groneberg David A

    2008-02-01

    Full Text Available Abstract Background Platelet activating factor and tachykinins (substance P, neurokinin A, neurokinin B are important mediators contributing to increased airway secretion in the context of different types of respiratory diseases including acute and chronic asthma. Leukotriene receptor antagonists are recommended as add-on therapy for this disease. The cys-leukotriene-1 receptor antagonist montelukast has been used in clinical asthma therapy during the last years. Besides its inhibitory action on bronchoconstriction, only little is known about its effects on airway secretions. Therefore, the aim of this study was to evaluate the effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity. Methods The effects of montelukast on platelet activating factor- and tachykinin induced tracheal secretory activity in the rat were assessed by quantification of secreted 35SO4 labelled mucus macromolecules using the modified Ussing chamber technique. Results Platelet activating factor potently stimulated airway secretion, which was completely inhibited by the platelet activating factor receptor antagonist WEB 2086 and montelukast. In contrast, montelukast had no effect on tachykinin induced tracheal secretory activity. Conclusion Cys-leukotriene-1 receptor antagonism by montelukast reverses the secretagogue properties of platelet activating factor to the same degree as the specific platelet activating factor antagonist WEB 2086 but has no influence on treacheal secretion elicited by tachykinins. These results suggest a role of montelukast in the signal transduction pathway of platelet activating factor induced secretory activity of the airways and may further explain the beneficial properties of cys-leukotriene-1 receptor antagonists.

  2. Use of Carabids for the Post-Market Environmental Monitoring of Genetically Modified Crops

    Directory of Open Access Journals (Sweden)

    Oxana Skoková Habuštová

    2017-03-01

    Full Text Available Post-market environmental monitoring (PMEM of genetically modified (GM crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles as surrogates for the detection of unintended effects of GM crops in general PMEM surveillance. Our study combines data on carabid communities from five maize field trials in Central Europe. Altogether, 86 species and 58,304 individuals were collected. Modeling based on the gradual elimination of the least abundant species, or of the fewest categories of functional traits, showed that a trait-based analysis of the most common species may be suitable for PMEM. Species represented by fewer than 230 individuals (all localities combined should be excluded and species with an abundance higher than 600 should be preserved for statistical analyses. Sixteen species, representing 15 categories of functional traits fulfill these criteria, are typical dominant inhabitants of agroecocoenoses in Central Europe, are easy to determine, and their functional classification is well known. The effect of sampling year is negligible when at least four samples are collected during maize development beginning from 1 April. The recommended methodology fulfills PMEM requirements, including applicability to large-scale use. However, suggested thresholds of carabid comparability should be verified before definitive conclusions are drawn.

  3. Use of Carabids for the Post-Market Environmental Monitoring of Genetically Modified Crops

    Directory of Open Access Journals (Sweden)

    Oxana Skoková Habuštová

    2017-03-01

    Full Text Available Post-market environmental monitoring (PMEM of genetically modified (GM crops is required by EU legislation and has been a subject of debate for many years; however, no consensus on the methodology to be used has been reached. We explored the suitability of carabid beetles as surrogates for the detection of unintended effects of GM crops in general PMEM surveillance. Our study combines data on carabid communities from five maize field trials in Central Europe. Altogether, 86 species and 58,304 individuals were collected. Modeling based on the gradual elimination of the least abundant species, or of the fewest categories of functional traits, showed that a trait-based analysis of the most common species may be suitable for PMEM. Species represented by fewer than 230 individuals (all localities combined should be excluded and species with an abundance higher than 600 should be preserved for statistical analyses. Sixteen species, representing 15 categories of functional traits fulfill these criteria, are typical dominant inhabitants of agroecocoenoses in Central Europe, are easy to determine, and their functional classification is well known. The effect of sampling year is negligible when at least four samples are collected during maize development beginning from 1 April. The recommended methodology fulfills PMEM requirements, including applicability to large-scale use. However, suggested thresholds of carabid comparability should be verified before definitive conclusions are drawn.

  4. [Planning, realization and evaluation of post-marketing surveillance studies. Recommendations of the Society for Phytotherapy].

    Science.gov (United States)

    Kraft, K; Loew, D; Schneider, B; Kemper, F H

    1997-08-01

    Post-marketing-surveillance studies with herbal drugs usually are prospective prescription-epidemiological studies, which should allow statements on quality, efficacy and safety. Until now neither laws nor concrete normative guidelines for the methodology and the evaluation of post-marketing-surveillance studies are existing which could be used for pharmacovigilance. In the present paper guidelines for planning, realisation and evaluation are presented which should allow studies of high quality. The essential components required for the investigational plan are focussed. Also recommendations on the obligatory, optional and special components of the study protocols are made. Additionally statistical methods which allow the evaluation of the therapeutic efficacy are presented.

  5. Comparison of oral montelukast with oral zileuton in acute asthma: A randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Rahul Magazine

    2016-01-01

    Full Text Available Background: Leukotriene modifiers have an established role in the management of chronic asthma but their role in acute asthma is still under evaluation. Objective: To study and compare the effects of oral montelukast with oral zileuton in acute asthma. Materials and Methods: This study included 120 asthmatics and was conducted from September 2012 to March 2014. Patients were randomized into three different groups to receive montelukast or zileuton or placebo in addition to standard treatment for asthma exacerbation. Peak expiratory flow rate (PEFR values, details of rescue medication and vital signs were recorded at 6 h, 12 h, 24 h, and 48 h of drug or placebo administration and at discharge. Additional recording was done in the morning (8-10 am following admission. The primary endpoint was the mean PEFR of each group at these time points; the secondary end point being the need for rescue medications. Results: The mean PEFR recordings of the three study groups - placebo, montelukast, and zileuton - respectively, at various time points were as follows: at 6 h (223.25 ± 90.40, 199.00 ± 82.52, 233.75 ± 84.05; P = 0.240; at 12 h (271.00 ± 109.38, 251.50 ± 101.44, 309.50 ± 129.63; P = 0.048; at 24 h (288.25 ± 114.26, 269.00 ± 107.51, 324.50 ± 127.88; P = 0.080; and at 48 h (295.00 ± 114.80, 293.50 ± 113.24, 344.75 ± 119.91; P = 0.015; discharge (305.00 ± 118.56, 305.25 ± 119.51, 361.25 ± 119.70; P = 0.010. The mean PEFR for the three study groups at 8-10 am on the morning following admission was 268.75 ± 111.43, 252.50 ± 99.99, 306.75 ± 114.44; P = 0.047. Total rescue doses needed were 10, 1, and 0, respectively (P = 0.049. Conclusion: Zileuton is better than montelukast as an additional drug in acute asthma and results in significant improvement in lung function, and reduction in the need for rescue medications.

  6. Comparison of oral montelukast with oral zileuton in acute asthma: A randomized, double-blind, placebo-controlled study

    Science.gov (United States)

    Magazine, Rahul; Shahul, Hameed Aboobackar; Chogtu, Bharti; Kamath, Asha

    2016-01-01

    Background: Leukotriene modifiers have an established role in the management of chronic asthma but their role in acute asthma is still under evaluation. Objective: To study and compare the effects of oral montelukast with oral zileuton in acute asthma. Materials and Methods: This study included 120 asthmatics and was conducted from September 2012 to March 2014. Patients were randomized into three different groups to receive montelukast or zileuton or placebo in addition to standard treatment for asthma exacerbation. Peak expiratory flow rate (PEFR) values, details of rescue medication and vital signs were recorded at 6 h, 12 h, 24 h, and 48 h of drug or placebo administration and at discharge. Additional recording was done in the morning (8–10 am) following admission. The primary endpoint was the mean PEFR of each group at these time points; the secondary end point being the need for rescue medications. Results: The mean PEFR recordings of the three study groups – placebo, montelukast, and zileuton – respectively, at various time points were as follows: at 6 h (223.25 ± 90.40, 199.00 ± 82.52, 233.75 ± 84.05; P = 0.240); at 12 h (271.00 ± 109.38, 251.50 ± 101.44, 309.50 ± 129.63; P = 0.048); at 24 h (288.25 ± 114.26, 269.00 ± 107.51, 324.50 ± 127.88; P = 0.080); and at 48 h (295.00 ± 114.80, 293.50 ± 113.24, 344.75 ± 119.91; P = 0.015); discharge (305.00 ± 118.56, 305.25 ± 119.51, 361.25 ± 119.70; P = 0.010). The mean PEFR for the three study groups at 8–10 am on the morning following admission was 268.75 ± 111.43, 252.50 ± 99.99, 306.75 ± 114.44; P = 0.047. Total rescue doses needed were 10, 1, and 0, respectively (P = 0.049). Conclusion: Zileuton is better than montelukast as an additional drug in acute asthma and results in significant improvement in lung function, and reduction in the need for rescue medications. PMID:27185992

  7. Montelukast improves air trapping, not airway remodeling, in patients with moderate-to-severe asthma: a pilot study

    Institute of Scientific and Technical Information of China (English)

    GAO Jin-ming; CAI Feng; PENG Min; MA Yi; WANG Bin

    2013-01-01

    Background Evidence has demonstrated that the distal lung,which includes airways of <2 mm in diameter and lung parenchyma,constitutes an important component of asthma pathology.Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators and bronchoconstrictors involved in the asthmatic process.Guidelines recommend the leukotriene-modifying agents for asthma treatment.We hypothesized that a leukotriene receptor antagonist with an inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combination would improve small airways function in moderate-tosevere asthmatics evaluated by physiological tests and high-resolution computed tomography (HRCT) analysis.This study was performed at a tertiary university hospital in Beijing.Methods This was a randomized,double-blind,parallel study performed in 38 patients with moderate-to-severe asthma treated with salmeterol/fluticasone (SFC) plus montelukast (SFC+M) or SFC plus placebo over 24 weeks.Small airway function was assessed by physiological studies and HRCT image analysis.Results Montelukast significantly improved air trapping as expressed by the residual volume (RV)/total lung capacity (TLC).Over 24 weeks of treatment,RV/TLC was improved by (15.41±6.67)% in patients receiving SFC+M while RV/TLC was decreased by (8.57±10.26)% in patients receiving SFC alone,the difference between the two groups was significant (P=0.02).There was a trend towards a significant difference in forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) in the SFC+M group compared to that in the SFC group ((17.87±8.17)% vs.(12.28±9.20)%,P=0.056).There was no significant change in percentage wall area (WA%) after 24 weeks of add-on treatment with montelukast.Patients receiving SFC+M showed significant improvement in the ratio of CT-determined values at full expiration to those at full inspiration (E/I ratio) (0.894±0.005 vs.0.871±0.003,P=0.002).Conclusion We have shown,using lung function tests

  8. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    Science.gov (United States)

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. [Post-marketing drug safety-risk management plan(RMP)].

    Science.gov (United States)

    Ezaki, Asami; Hori, Akiko

    2013-03-01

    The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

  10. The ability of animal studies to detect serious post marketing adverse events is limited

    NARCIS (Netherlands)

    van Meer, P.J.K.|info:eu-repo/dai/nl/34153790X; Kooijman, M.|info:eu-repo/dai/nl/322905788; Gispen-de Wied, C.C.; Moors, E.H.M.|info:eu-repo/dai/nl/20241664X; Schellekens, H.|info:eu-repo/dai/nl/068406762

    2012-01-01

    The value of animalstudies to the assessment of drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing seriousadverse reactions to small molecule drugs could have been detected on the basis of animalstudy data included in

  11. Effect of Montelukast on bradykinin-induced contraction of isolated tracheal smooth muscle of guinea pig

    Directory of Open Access Journals (Sweden)

    A Noor

    2011-01-01

    Conclusion: It is concluded that montelukast significantly inhibits, in a dose-dependent manner, the bradykinin-induced contraction of the guinea pig tracheal smooth muscle, and alludes to an interaction between the bradykinin and leukotriene mediators.

  12. Effect of azithromycin, terbutaline combined with montelukast on airway function and gradient of infection in cough variant asthma children with infection

    Institute of Scientific and Technical Information of China (English)

    Xin-Xin Pei

    2016-01-01

    Objective:To analyze the effect of azithromycin, terbutaline combined with montelukast on airway function and gradient of infection in cough variant asthma children with infection. Methods: A total of 116 cases of cough variant asthma children with infection were included in the study and randomly divided into observation group and control group (n=58), control group received azithromycin treatment, observation group received azithromycin, terbutaline combined with montelukast treatment, and then differences in basic lung function and small airway function, asthma attack and airway remodeling-related indicators, infection-related indicators, etc. were compared between two groups after treatment.Results: Basic lung function indexes FEV1 and FVC of observation group after treatment were significantly higher than those of control group, and small airway function indexes MMEF, FEF50% and FEF75% were significantly lower than those of control group; serum ECP, IgE, IL-5, MMP-2, MMP-9, TIMP-1, PET, CRP and IL-4 levels of observation group after treatment were lower than those of control group while IFN-γ and hBD-1 levels were higher than those of control group.Conclusion:Azithromycin, terbutaline combined with montelukast can improve airway function and infection status and promote disease rehabilitation in cough variant asthma children with infection.

  13. DESIGN DEVELOPMENT AND EVALUATION OF MODIFIED RELEASE TABLET OF MONTELUKAST SODIUM USING ETHYL CELLULOSE AND TRAGACANTH

    OpenAIRE

    Patel Krunal M

    2011-01-01

    The purpose of this research was to prepare a modified release tablet of montelukast sodium. Montelukast sodium is Leukotriene antagonist which is rapidly absorbed after the oral administration. The drug was mixed with Ethyl Cellulose and Tragacanth as a dry binder and ethanol was used as solvent to perform the granulation in FBD by the bottom spray method. The granules obtain were mixed with the other ingredients and were compressed using 10 station tablet rotary press. The dissolution was c...

  14. Effect of montelukast on clinical score and cytokine levels of infants for clinically diagnosed acute bronchiolitis.

    Science.gov (United States)

    Tahan, Fulya; Celik, Serkan; Eke Gungor, Hatice

    2015-01-01

    Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. No significant differences was found in clinical severity score with five-day montelukast treatment (p>0.05, Mann-Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p>0.05 Mann-Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p=0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p>0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p=0.009, Wilcoxon). Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  15. Montelukast potentiates the anticonvulsant effect of phenobarbital in mice: an isobolographic analysis.

    Science.gov (United States)

    Fleck, Juliana; Marafiga, Joseane Righes; Jesse, Ana Cláudia; Ribeiro, Leandro Rodrigo; Rambo, Leonardo Magno; Mello, Carlos Fernando

    2015-04-01

    Although leukotrienes have been implicated in seizures, no study has systematically investigated whether the blockade of CysLT1 receptors synergistically increases the anticonvulsant action of classic antiepileptics. In this study, behavioral and electroencephalographic methods, as well as isobolographic analysis, are used to show that the CysLT1 inverse agonist montelukast synergistically increases the anticonvulsant action of phenobarbital against pentylenetetrazole-induced seizures. Moreover, it is shown that LTD4 reverses the effect of montelukast. The experimentally derived ED50mix value for a fixed-ratio combination (1:1 proportion) of montelukast plus phenobarbital was 0.06±0.02 μmol, whereas the additively calculated ED50add value was 0.49±0.03 μmol. The calculated interaction index was 0.12, indicating a synergistic interaction. The association of montelukast significantly decreased the antiseizure ED50 for phenobarbital (0.74 and 0.04 μmol in the absence and presence of montelukast, respectively) and, consequently, phenobarbital-induced sedation at equieffective doses. The demonstration of a strong synergism between montelukast and phenobarbital is particularly relevant because both drugs are already used in the clinics, foreseeing an immediate translational application for epileptic patients who have drug-resistant seizures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Stability-indicating HPLC method for simultaneous determination of montelukast and fexofenadine hydrochloride

    Directory of Open Access Journals (Sweden)

    Mona Pankhaniya

    2013-01-01

    Full Text Available A simple, specific, accurate, and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of montelukast and fexofenadine hydrochloride, using a Lichrospher ® 100, RP-18e column and a mobile phase composed of methanol:0.1% o-phosphoric acid (90:10 v/v, pH 6.8. The retention times of montelukast and fexofenadine hydrochloride were found to be 10.16 and 12.03 min, respectively. Linearity was established for montelukast and fexofenadine hydrochloride in the range of 2-10 μg/ml and 24-120 μg/ml, respectively. The percentage recoveries of montelukast and fexofenadine hydrochloride were found to be in the range of 99.09 and 99.81%, respectively. Both the drugs were subjected to acid and base hydrolysis, oxidation, photolytic, and thermal degradation conditions. The degradation products of montelukast and fexofenadine hydrochloride were well resolved from the pure drug with significant differences in their retention time values. This method can be successfully employed for simultaneous quantitative analysis of montelukast and fexofenadine hydrochloride in bulk drugs and formulations.

  17. Post-marketing surveillance study with iodixanol in 20 185 Chinese patients from routine clinical practices.

    Science.gov (United States)

    Zhang, B-C; Hou, L; Lv, B; Xu, Y-W

    2014-02-01

    To determine the incidence of immediate and delayed adverse drug reactions (ADRs), and to assess patient discomfort following administration of iodixanol during imaging examinations in routine clinical practice. A total of 20 185 patients across 95 clinical centres were enrolled in a prospective post-marketing surveillance registry with iodixanol. Patients were monitored for occurrence of ADRs immediately following iodixanol administration and for up to 7 days after administration. The overall rate of ADRs was 1.52%, of which 0.58% was immediate and 0.97% was delayed onset. Two patients had non-fatal serious ADRs (0.01%). The ADRs were significantly more common in patients who underwent contrast-enhanced CT/coronary CT angiography vs others (p Multivariate analysis showed that female gender, intravenous route of contrast injection, body weight ≥ 80 kg, age less than 65 years, contrast flow rate ≥ 4 ml s⁻¹ and prior reaction to iodinated contrast medium were all significant and independent contributors to ADRs. Pre-treatment contrast volume and history of cardiac disease, gout, hypertension, diabetes mellitus or asthma did not affect the rate of ADRs. Discomfort was generally mild, with 94.8% of patients reporting a composite score of 0-3. The safety of iodixanol in routine clinical practice was shown to be similar to the published safety profiles of other non-ionic iodinated contrast agents. Patient discomfort during administration was mild or absent in most patients. The major strength of this study is that it included 20 185 patients enrolled in various types of imaging examinations. The safety profile of iodixanol was comparable to previously published work.

  18. Systematic review of reporting rates of adverse events following immunization: an international comparison of post-marketing surveillance programs with reference to China.

    Science.gov (United States)

    Guo, Biao; Page, Andrew; Wang, Huaqing; Taylor, Richard; McIntyre, Peter

    2013-01-11

    China is the most populous country in the world, with an annual birth cohort of approximately 16 million, requiring an average of 500 million vaccine doses administered annually. In China, over 30 domestic and less than 10 overseas vaccine manufacturers supply over 60 licensed vaccine products, representing a growing vaccine market mainly due to recent additions to the national immunization schedule, but data on post-marketing surveillance for adverse events following immunization (AEFI) are sparse. To compare reporting rates for various categories of AEFI from China with other routine post-marketing surveillance programs internationally. Systematic review of published studies reporting rates of AEFI by vaccine, category of reaction and age from post-marketing surveillance systems in English and Chinese languages. Overall AEFI reporting rates (all vaccines, all ages) in Chinese studies were consistent with those from similar international studies elsewhere, but there was substantial heterogeneity in regional reporting rates in China (range 2.3-37.8/100,000 doses). The highest AEFI reporting rates were for diphtheria-tetanus-pertussis whole-cell (DTwP) and acellular (DTaP) vaccines (range 3.3-181.1/100,000 doses for DTwP; range 3.5-92.6/100,000 doses for DTaP), with higher median rates for DTwP than DTaP, and higher than expected rates for DTaP vaccine. Similar higher rates for DTwP and DTaP containing vaccines, and relatively lower rates for vaccines against hepatitis B virus, poliovirus, and Japanese encephalitis virus were found in China and elsewhere in the world. Overall AEFI reporting rates in China were consistent with similar post-marketing surveillance systems in other countries. Sources of regional heterogeneity in AEFI reporting rates, and their relationships to differing vaccine manufacturers versus differing surveillance practices, require further exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. [Process and key points of clinical literature evaluation of post-marketing traditional Chinese medicine].

    Science.gov (United States)

    Liu, Huan; Xie, Yanming

    2011-10-01

    The clinical literature evaluation of the post-marketing traditional Chinese medicine is a comprehensive evaluation by the comprehensive gain, analysis of the drug, literature of drug efficacy, safety, economy, based on the literature evidence and is part of the evaluation of evidence-based medicine. The literature evaluation in the post-marketing Chinese medicine clinical evaluation is in the foundation and the key position. Through the literature evaluation, it can fully grasp the information, grasp listed drug variety of traditional Chinese medicines second development orientation, make clear further clinical indications, perfect the medicines, etc. This paper discusses the main steps and emphasis of the clinical literature evaluation. Emphasizing security literature evaluation should attach importance to the security of a comprehensive collection drug information. Safety assessment should notice traditional Chinese medicine validity evaluation in improving syndrome, improveing the living quality of patients with special advantage. The economics literature evaluation should pay attention to reliability, sensitivity and practicability of the conclusion.

  20. [Opportunity and challenge of post-marketing evaluation of traditional Chinese medicine].

    Science.gov (United States)

    Du, Xiao-Xi; Song, Hai-Bo; Ren, Jing-Tian; Yang, Le; Guo, Xiao-Xin; Pang, Yu

    2014-09-01

    Post-marketing evaluation is a process which evaluate the risks and benefits of drug clinical application comprehensively and systematically, scientific and systematic results of post-marketing evaluation not only can provide data support for clinical application of traditional Chinese medicine, but also can be a reliable basis for the supervision department to develop risk control measures. With the increasing demands for treatment and prevention of disease, traditional Chinese medicine has been widely used, and security issues are also exposed. How to find risk signal of traditional Chinese medicine in the early stages, carry out targeted evaluation work and control risk timely have become challenges in the development of traditional Chinese medicine industry.

  1. Post-market clinical research conducted by medical device manufacturers: a cross-sectional survey

    OpenAIRE

    Ross JS; Blount KL; Ritchie JD; Hodshon B; Krumholz HM

    2015-01-01

    Joseph S Ross, Katrina L Blount, Jessica D Ritchie, Beth Hodshon, Harlan M Krumholz Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT, USA Background: In the US, once a medical device is made available for use, several requirements have been established by the US Food and Drug Administration (FDA) to ensure ongoing post-market surveillance of device safety and effectiveness. Our objective was to determine how commonly medical device manufacturers initiate po...

  2. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Flores-Nunez, Alejandro; Goh, Anne

    2008-01-01

    (RSV) bronchiolitic respiratory symptoms. OBJECTIVES: To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. METHODS: This was a double-blind study of 3- to 24-month-old children who...... had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom.......7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. CONCLUSIONS: In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children....

  3. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Wu, Shenbao; Zhu, Xuxing; Jin, Zhonghai; Tong, Xiuping; Zhu, Liqin; Hong, Xiaofei; Zhu, Xianfei; Liu, Pengfei; Shen, Weidong

    2015-10-26

    Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats.

  4. Levodopa therapy with entacapone in daily clinical practice: results of a post-marketing surveillance study.

    Science.gov (United States)

    Kupsch, Andreas; Trottenberg, Thomas; Bremen, Dirk

    2004-01-01

    The catechol-O-methyl transferase inhibitor entacapone is given in combination with levodopa/dopa decarboxylase inhibitor for Parkinson's disease (PD) patients experiencing end-of-dose wearing-off. This 4-week post-marketing surveillance study was undertaken to assess patients' responses to levodopa combined with entacapone in a real clinical practice setting. Overall, 466 patients with idiopathic PD treated with levodopa and experiencing symptoms of wearing-off were recruited. Both physicians and patients recorded the response to therapy, including improvements and side-effects. Following initiation of entacapone treatment, the average daily levodopa dose was reduced from 510 to 453 mg. Physician assessment of entacapone efficacy was judged to be "very good" or "good" in 77.6% of the patients, and tolerability was considered to be "very good" or "good" in 92.4% of patients, with only 12 patients (2.6%) withdrawing from the study. Compared with baseline, there was a decrease in the mean duration of daily 'off' time from 3.0 to 1.3 h per day during the treatment period. Adverse events were in line with those previously reported, with diarrhoea being the most frequent event. The percentage of patients suffering from dyskinesia decreased from 46 to 34%, and of those patients still suffering from dyskinesia, the average daily duration of dyskinesia was reduced from 2.2 to 1.7 h. The use of adjunct dopamine agonists decreased from 67 to 59%. At study end, the percentage of patients who rated their quality of life (QoL) as "very good" or "good" increased from 12.1 to 51.7% and the percentage of patients who rated their QoL as "bad" or "very bad" decreased from 40 to 10.7%. In summary, the results of this survey conducted in real clinical practice support the findings of previous clinical trials demonstrating the efficacy and tolerability of entacapone, as well as the benefits of improved QoL, for patients achieved with entacapone.

  5. A Post-Marketing Surveillance Study to Evaluate Performance of the EXIMO™ Blood Glucose Monitoring System.

    Science.gov (United States)

    Chandnani, Sonia R; Ramakrishna, C D; Dave, Bhargav A; Kothavade, Pankaj S; Thakkar, Ashok S

    2017-05-01

    The performance of Blood Glucose Monitoring System (BGMS) is critical as the information provided by the system guide the patient or health care professional in making treatment decisions. However, besides evaluating accuracy of the BGMS in laboratory setting, it is equally important that the intended users (healthcare professionals and patients) should be able to achieve blood glucose measurements with similar level of high accuracy. To assess the performance of EXIMO™ (Meril Diagnostics Pvt. Ltd., Vapi, Gujarat, India) BGMS as per International Organization for Standardization (ISO) 15197:2013 section 8 user performance criteria. This was a non-randomized and post-marketing study conducted at a tertiary care centre of India. A total of 1005 patients with diabetes themselves performed fingertip blood glucose measurement using EXIMO™ BGMS. Immediately after capillary blood glucose measurement using the blood glucose monitoring system, venous blood sample from each patient was obtained by a trained technician which was assessed by reference laboratory method- Cobas Integra 400 plus (Roche Instrument Centre, Rotkreuz, Switzerland). All the blood glucose measurements assessed by EXIMO™ were compared with laboratory results. Performance of the system was assessed as per ISO 15197:2013 criteria using Bland-Altman plot, Parkes-Consensus Error Grid (CEG) and Surveillance Error Grid analyses (SEG). A total of 1005 patients participated in the study. Average age of the patients was 44.93±14.65 years. Evaluation of capillary fingertip blood glucose measurements demonstrated that 95.82% measurements fulfilled ISO 15197:2013 section 8 user performance criteria. All the results lie within clinically non-critical zones; Zone A (99.47%; n=1000) and Zone B (0.53%; n=05) of the CEG analysis. As per SEG analysis, majority of the results fell within "no-risk" zone (risk score 0 to 0.5; 90.42%). The result of the study confirmed that intended users are able to obtain accurate

  6. Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

    Science.gov (United States)

    Silva, Ivair R

    2017-09-25

    Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Comparative Experimental Study on the Inflammatory Mechanisms of Bronchial Asthma Amelioration by Montelukast and Methylprednisolone%孟鲁司特与甲泼尼龙缓解支气管哮喘炎症机制的对比实验研究

    Institute of Scientific and Technical Information of China (English)

    蔡畅; 周美茜; 陈成水; 李玉苹

    2013-01-01

    目的 探讨孟鲁司特(MK)和甲泼尼龙(MP)对白三烯代谢的作用机制.方法 选取BN大鼠在第1、8天用OVA致敏,建立哮喘模型并分组:A组致敏鼠+ NS注射;B组致敏鼠+OVA雾化;C组致敏鼠+OVA雾化+雾化前MK胃管注入;D组致敏鼠+ OVA雾化+雾化前MP肌内注射.检测气道反应曲线、肺泡灌洗液(BALF)白细胞总数和分类,ELISA法检测总白三烯量,HE染色观察炎症状况.另取致敏鼠肺组织制成碎片匀浆并分组:无OVA雾化肺碎片+NS(Ⅰ)、或MK(Ⅱ)或MP(Ⅲ)孵化,Ⅳ肺碎片(OVA雾化+NS注射)+OVA+ NS孵化,V肺碎片(OVA雾化+MK灌胃)+OVA+ MK孵化,Ⅵ肺碎片(OVA雾化+ MP注射)+OVA+ MP孵化.ELISA法检测上清白三烯量.结果 A组气道阻力无变化,B~D组气道阻力增高,MP对气道反应抑制强度大于MK(P =0.045).MK或MP干预后,C、D组白细胞计数均降低,程度相似(P =0.064).MK或MP干预后,C、D组白三烯量均降低,MP抑制作用强于MK(P =0.041).C、D两组白细胞计数和白三烯量间有相关性,r为0.735和0.796.CD组支气管黏膜下嗜酸性粒细胞、中性粒细胞浸润情况较AB组减轻.体外孵化分析:Ⅰ组与Ⅱ组总白三烯量差异有意义(P=0.035),Ⅰ组与Ⅲ组差异无意义(P =0.164).同Ⅳ组比较,Ⅴ、Ⅵ组白三烯量均明显下降.结论 MK可直接抑制白三烯合成;MP不能直接抑制,但可通过抑制气道炎性细胞浸润等间接途径减少其分泌.%Objective To investigate leukotriene metabolic mechanism by montelukast (MK) and methylprednisolone (MP). Methods Brown - Norway rats were selected, and active sensitization against OVA was performed at the 1st and 8st day. Models were divided into 4 groups. A group was sensitized rats with saline injection; B group was sensitized rats with OVA inhalation; C group was sensitized rats with OVA inhalation and MK gastric pretreatment; D group was sensitized rats with OVA inhalation and MP intramuscular pre-treatment. Airway responsive curve

  8. Montelukast as an episodic modifier for acute viral bronchiolitis: a randomized trial.

    Science.gov (United States)

    Zedan, Magdy; Gamil, Nareman; El-Assmy, Mohamed; Fayez, Engy; Nasef, Nehad; Fouda, Ashraf; Settin, Ahmed

    2010-01-01

    This study was designed to evaluate the effect of once-daily montelukast therapy on the clinical progress and the cytokine profile of patients with acute viral bronchiolitis. A randomized, double-blind, placebo-controlled trial included 85 patients (mean age, 3.5 +/- 2.35 months), clinically diagnosed as first-episode acute bronchiolitis in addition to 10 healthy controls of matched age and sex. Patients were randomly assigned to receive either montelukast (4-mg sachets; n = 47) or placebo (n = 38) daily from the time of admission until discharge. The primary outcome measure was the length of hospital stay (LOS), and clinical severity scores (CSs) and changes in plasma levels of interferon gamma and interleukin-4 were secondary outcomes. LOS for the montelukast group was found to be significantly lower than that of the placebo group (p viral bronchiolitis.

  9. Hallucination development with montelukast in a child with asthma: case presentation.

    Directory of Open Access Journals (Sweden)

    Aysen Kocyigit

    2013-12-01

    Full Text Available Leukotriene receptor antagonists(montelukast have been used for many years in the treatment of asthma both acute and chronic stages. They are accepted commonly as safe but mostly possible side effects are ignored. However, montelukast also could lead to important adverse reactions like hallucinations. In literature only 2 reports have been found about hallucinations with it. One is a study which reports 3 patients from 48 children and the other is a 29 year-old case report. In our case, psychiatric adverse reactions of montelukast,especially hallucinations are reported similarly. We are presenting a child who had visual hallucinations after starting to use montekulast and after stopping the medicine these complaints disappeared in 48 hours. Although it is a safe drug, it should not be forgotten that it has psychiatric side effects which may be missed easily especially in children.

  10. [Thought on several problems of post-marketing herbs clinical evaluation in special populations].

    Science.gov (United States)

    Zhou, Ai; Lian, Fengmei

    2011-10-01

    The re-evaluation of clinical post-marketing herbs in special populations, such as children, the aged, pregnant women, lactating women, has attracted attention in our country. The media is drug adverse reaction reports and package insert. The safety of combined administration in aged and children's growth should have been taken long-term follow-up study. Perfecting traditional chinese medicine FDA system will be beneficial to the re-evaluation of clinical postmarketing herbs in pregnant women. Dose-effect study in children also should cause the concern of researchers.

  11. Statement on the post-marketing monitoring of the use of lycopene

    DEFF Research Database (Denmark)

    Tetens, Inge

    information from the post-marketing monitoring programme imposed by the Commission Decisions authorising the use of synthetic lycopene, lycopene oleoresin from tomatoes and lycopene from Blakeslea trispora as a novel food ingredient in several foodstuffs. The marketing authorisation holders for the use...... manufacturers, food supplements appear to be the main source of lycopene after intake from natural occurrence. Since no new toxicological studies became available, there is no scientific basis on which the ADI established by EFSA in 2008 could be reconsidered. On the basis of previous intake assessments...

  12. DESIGN DEVELOPMENT AND EVALUATION OF MODIFIED RELEASE TABLET OF MONTELUKAST SODIUM USING ETHYL CELLULOSE AND TRAGACANTH

    Directory of Open Access Journals (Sweden)

    Patel Krunal M

    2011-01-01

    Full Text Available The purpose of this research was to prepare a modified release tablet of montelukast sodium. Montelukast sodium is Leukotriene antagonist which is rapidly absorbed after the oral administration. The drug was mixed with Ethyl Cellulose and Tragacanth as a dry binder and ethanol was used as solvent to perform the granulation in FBD by the bottom spray method. The granules obtain were mixed with the other ingredients and were compressed using 10 station tablet rotary press. The dissolution was carried out using USP paddle apparatus.

  13. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast

    DEFF Research Database (Denmark)

    Bisgaard, H; Loland, L; Oj, J A

    1999-01-01

    Nitric oxide in exhaled air (FENO) is increased in asthmatic children, probably reflecting aspects of airway inflammation. We have studied the effect of the leukotriene receptor antagonist (LTRA) montelukast on FENO with a view to elucidate potential anti-inflammatory properties of LTRAs. Twenty......-six asthmatic children 6 to 15 yr of age completed a double-blind crossover trial of 2 wk of treatment with 5 mg montelukast once daily versus placebo. FENO was measured during single-breath exhalation at a constant flow rate of 0.1 to 0.13 L/s against a resistance of 10 kPa/L/s. Eleven children were receiving...

  14. Results of European post-marketing surveillance of bosentan in pulmonary hypertension.

    Science.gov (United States)

    Humbert, M; Segal, E S; Kiely, D G; Carlsen, J; Schwierin, B; Hoeper, M M

    2007-08-01

    After the approval of bosentan for the treatment of pulmonary arterial hypertension (PAH), European authorities required the introduction of a post-marketing surveillance system (PMS) to obtain further data on its safety profile. A novel, prospective, internet-based PMS was designed, which solicited reports on elevated aminotransferases, medical reasons for bosentan discontinuation and other serious adverse events requiring hospitalisation. Data captured included demographics, PAH aetiology, baseline functional status and concomitant PAH-specific medications. Safety signals captured included death, hospitalisation, serious adverse events, unexpected adverse events and elevated aminotransferases. Within 30 months, 4,994 patients were included, representing 79% of patients receiving bosentan in Europe. In total, 4,623 patients were naïve to treatment; of these, 352 had elevated aminotransferases, corresponding to a crude incidence of 7.6% and an annual rate of 10.1%. Bosentan was discontinued due to elevated aminotransferases in 150 (3.2%) bosentan-naïve patients. Safety results were consistent across subgroups and aetiologies. The novel post-marketing surveillance captured targeted safety data ("potential safety signals") from the majority of patients and confirmed that the incidence and severity of elevated aminotransferase levels in clinical practice was similar to that reported in clinical trials. These data complement those from randomised controlled clinical trials and provide important additional information on the safety profile of bosentan.

  15. Post-marketing management of the use of non-narcotic analgesics.

    Science.gov (United States)

    Miettinen, O S

    1986-01-01

    While the use of non-narcotic analgesics is of considerable health benefit to people everywhere, they also represent a health problem. This problem has to do more with the risks associated with individual courses of treatment than with the commonality of those treatments. The public health challenge in post-marketing management of non-narcotic analgesic use, is to promote a pattern of use such that the risks are justifiable by the benefits and are the lowest that can be attained. To achieve such goals it is essential to have scientific knowledge about the benefits and risks and to be able to determine the quality of use in the population as to how proper it is. Current post-marketing management programmes focus largely on regulation, overlooking other equally important basic methods of public health intervention, namely education and service. If it is accepted that mass education is the key element in the proper management of non-narcotic analgesic use, the present emphasis on regulation needs amendment. Such changes will take time, but it is conceivable that ultimately the management goal can be achieved with minimal regulatory intervention.

  16. Bioequivalence studies of film-coated tablet and chewable tablet generic formulations of montelukast in healthy volunteers.

    Science.gov (United States)

    Cánovas, Mercedes; Arcabell, Marta; Martínez, Gemma; Canals, Mirela; Cabré, Francesc

    2011-01-01

    Two studies were conducted in order to assess the bioequivalence of montelukast (CAS 151767-02-1) 10 mg film-coated tablet (FCT) and 5 mg chewable tablet (CT) test formulations in comparison with the original brands. Under fasting conditions, healthy male and female volunteers received one 10 mg FCT or 5 mg CT orally as a single dose of a test or reference formulation. Both studies were designed as open-label, randomized, two-period, two-sequence, crossover studies with a 7-day washout interval. Plasma samples were collected up to 24 h after drug administration and montelukast levels were determined by a validated LC/ MS/MS method. Pharmacokinetic parameters were calculated using non-compartmental analysis and were statistically compared by analysis of variance for test and reference formulation. Bioequivalence between products was determined by calculating 90% confidence interval of the ratio test/reference of least-square means of logarithmically transformed Cmax and AUC0-t parameters. AUC0-infinity was also analysed to obtain additional information. The calculated 90% confidence intervals for the ratios of Cmax and AUC0-t parameters were 89.33-110.52 and 92.06-109.46, respectively, in the FCT study, and 91.58-101.86 and 92.15-98.83, respectively, in the CT study, which are all within the bioequivalence acceptance range of 80-125%. Based on the results, it can be concluded that the evaluated test FCT and CT formulations are bioequivalent to their respective reference formulation in terms of rate and extent of absorption.

  17. Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

    Science.gov (United States)

    Michel, Christiane; Scosyrev, Emil; Petrin, Michael; Schmouder, Robert

    2017-05-01

    Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

  18. 分析布地奈德联合孟鲁司特治疗小儿变异性哮喘的效果%Analysis of Therapeutic for Infantile Variant Asthma with Budesonide and Montelukast

    Institute of Scientific and Technical Information of China (English)

    董茂强

    2015-01-01

    目的 分析布地奈德联合孟鲁司特治疗小儿变异性哮喘的效果.方法 选取我院60例变异性哮喘患儿,将其随机分为观察组和对照组,每组30例,观察组使用布地奈德联合孟鲁司特治疗,对照组单纯使用布地奈德治疗,观察比较两组的临床疗效.结果 观察组的治疗总有效率为93.3%,对照组的总有效率为70%,两组对比有明显差异(P<0.05).结论 布地奈德联合孟鲁司特在治疗小儿变异性哮喘中具有显著疗效,值得临床的广泛应用.%Objective To analysis of budesonide combined Montelukast effect for the treatment of infantile asthma variant asthma.Methods60 patients with variant asthma of children, were randomly divided into observation group and control group, 30 cases in each group, the observation group USES budesonide combined Montelukast treatment, control group simply use Montelukast treatment, compare the clinical curative effect of two groups. Results Treatment group's total effective rate was 93.3%, control group's total effective rate was 70%, compared the two groups have significant difference (P < 0.05).Conclusion Budesonide combined Montelukast variant asthma in the treatment of pediatric asthma in has significant curative effect, worth clinical extensive application.

  19. 美国异维A酸上市后风险控制措施研究%Research on Isotretinoin Post-Marketing Risk Control in America

    Institute of Scientific and Technical Information of China (English)

    刘思齐; 刘文源; 杨悦

    2015-01-01

    目的:通过研究美国异维 A 酸上市后风险控制措施,以期为我国建立完善的药品上市后风险管理体系提供参考。方法通过查阅 FDA 药品上市后风险管理指南及法规,分析美国对异维 A 酸致畸和致抑郁甚至自杀风险的干预措施,并与我国采取的相关风险控制措施进行对比。结果美国实施一系列的风险管理措施,如随处方一起发放的用药指南,处方医生、患者、药房、批发商必须遵守一定的安全用药规定,定期评估风险控制效果并不断完善等,在很大程度上控制异维 A 酸使用风险。结论美国药品上市后风险管控思路和措施对我国具有一定的借鉴意义。%Objective To research isotretinoin post-marketing risk control in America, and make reference for developing sophisticated drug post -marketing risk management system in our country. Methods Drug post -marketing risk management regulation and guidance of America were looked up, the risk control measurements against teratogenesis and depression induced by isotretinoin were analyzed, and the risk control carried out by America and China were compared. Results FDA conducts a series of risk manage measures, such as medication guide dispensed with prescription, specific requirement which prescribers, patients, pharmacies and wholesalers must follow to assure safe use, evaluating the effect of risk mitigation periodically and improving accordingly, as a result, they control the risk to a large extent. Conclusion Drug post-marketing risk control concepts and designs are useful references for China.

  20. Effects of mometasone, fluticasone, and montelukast on bone mineral density in adults with asthma

    DEFF Research Database (Denmark)

    Maspero, Jorge; Backer, Vibeke; Yao, Ruji;

    2014-01-01

    asthma. METHODS: Adults with mild-moderate persistent asthma who did not receive ICS for ≥3 months were randomized to MF 400 μg once daily (QD) in the evening (pm), MF 200 μg QD pm, montelukast sodium (ML) 10 mg QD pm, or fluticasone propionate (FP) 250 μg twice daily. Included patients had 25-hydroxy...

  1. Montelukast modulates lung CysLT1 receptor expression and eosinophilic inflammation in asthmatic mice

    Institute of Scientific and Technical Information of China (English)

    Yan-jun ZHANG; Lei ZHANG; Shao-bin WANG; Hua-hao SHEN; Er-qing WEI

    2004-01-01

    AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT1 and CysLT2, in airway eosinophilic inflammation of OVA-induced asthmatic mice and the modulation by montelukast, a CysLT1 receptor antagonist.METHODS: Asthma model was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The eosinophils in bronchoalveolar lavage (BAL) fluid and lung tissues were counted, IL-5 level in BAL fluid was measured,and CysLT1 and CysLT2 receptor mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS:Montelukast (6 mg/kg, once per day for 20 d) significantly suppressed the increased eosinophils in BAL fluid and lung tissue, and increased IL-5 level in BAL fluid in OVA challenged mice. OVA challenge increased CysLT1 but decreased CysLT2 receptor mRNA expression. Montelukast inhibited the increased CysLT1 but not the reduced CysLT2 expression after OVA challenge. CONCLUSION: CysLT receptors are modulated immunologically, and montelukast inhibits up-regulation of CysLT1 receptor and airway eosinophilic inflammation in asthmatic mice.

  2. Montelukast, a leukotriene receptor antagonist, modulates lung CysLT1

    Institute of Scientific and Technical Information of China (English)

    ZHANGYan-Jun; ZHANGLei; WANGShao-Bin; SHENHua-Hao; WEIEr-Qing

    2004-01-01

    AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT, and CysLT2 , in airway eosinophilic inflammation of OVA-induced asthmatic mice and the modulation by montelukast, a CysLT1 receptor antagonist. METHODS: Asthma model was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The eosinophils in

  3. Role of Leukotriene receptor antagonist Montelukast in the treatment of chronic urticaria: A hospital based study

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2012-01-01

    Full Text Available Introduction: Chronic urticaria is a disabling disease which may be refractory to standard therapies. Leukotriene receptor antagonists like montelukast have been tried in allergic diseases like asthma and find mention as a therapeutic option in chronic urticaria. Purposes: A randomized single-blinded non-placebo controlled study to evaluate the role of montelukast, in addition to the adjunctive role of non-sedating antihistamine levocetirizine (H1, was conducted in patients with chronic urticaria.Methods: Thirty-five patients with chronic urticaria were enrolled. Medication was given for a period of twelve weeks. Montelukast 10mg/day in an adult and 5mg in the age group 6-13 years,4 mg 2-6 years and levocetirizine 5 mg once a day was added, if patient had new weals while on therapy. The improvement was monitored by estimating the episodes of wheals and pruritus in any two weeks period.Results: Twenty-two patients showed a good response with occasional wheals at the end of 2 weeks and no weals at the end of 12 weeks. These included all 8 patients on non-steroidal anti-inflammatory drugs (NSAIDS. Four of these patients relapsed on discontinuation of therapy.Conclusion: Montelukast is effective in chronic refractory urticaria especially in patients on non-steroidal anti-inflammatory drugs with occasional add-on use of a non-sedating anti-histamine.

  4. Formulation and evaluation of anti-asthmatic drug montelukast in mucoadhesive buccal patches

    Institute of Scientific and Technical Information of China (English)

    Magdy Ibrahim Mohamed; Mary Kamal Gad Mekhael

    2014-01-01

    Objective: To formulate and evaluate anti-asthmatic drug montelukast in mucoadhesive buccal patches. Methods:Buccal patches were formulated by using different hydrophilic polymers by solvent casting technique. Buccal patches were evaluated by seven physical appearances, in addition toin vitro drug release study. Results: All patches were uniform and translucent, and had smooth surface. In vitro release studies were conducted for montelukast buccal patches proved that release in the range of 75.26%-92.30% in 8 h. Emission of montelukast from all patches simulated zero order and diffusion mechanism. Finally it can be concluded that F3, F15 and F16 are the best formulation. Conclusions: The investigation concluded that patch of 5 mg of montelukast sodium were formulated by using sodium alginate with sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose K100M with sodium carboxy methyl cellulose, and hydroxy propyl methyl cellulose K100M with sodium alginate (F3, F15 and F16 formulations) were the best formulations.

  5. Safety and efficacy of adapalene gel 0.1% in acne vulgaris: Results of a post-marketing surveillance study

    Directory of Open Access Journals (Sweden)

    Percy S

    2003-07-01

    Full Text Available Introduction: Adapalene is a novel retinoid indicated for the topical treatment of acne vulgaris. The drug was introduced in India in 2001. Aims: A post-marketing surveillance study was conducted to assess the safety and efficacy of adapalene gel 0.1% when used as monotherapy or in combination with other anti-acne agents in Indian patients of acne vulgaris. Material and Methods: A 12-week, multicentre, open-label, non-comparative study involving 571 patients from 21 centers across India was conducted between January and September of 2002. Concomitant prescription of other anti-acne drugs was permitted, if needed. Results: Of the 571 patients, 441 completed the treatment as per protocol. At the end of therapy, 96.3% of patients showed an improvement in their acne from baseline, with greater than 75% improvement seen in two-thirds of patients. Adverse events were reported in 24% of the patients, none of which were serious. The tolerability of therapy was rated as excellent/good in 81% of patients by physicians and in 78% by the patients. Conclusion: Adapalene gel 0.1% is a safe and effective topical agent in the treatment of mild to moderate acne vulgaris in Indian patients. It may be safely combined with other topical and oral anti-acne agents.

  6. An update on the safety and tolerability of pimecrolimus cream 1%: evidence from clinical trials and post-marketing surveillance.

    Science.gov (United States)

    Langley, Richard G B; Luger, Thomas A; Cork, Michael J; Schneider, Dirk; Paul, Carle

    2007-01-01

    In this report, we review the data on the safety and tolerability of pimecrolimus cream 1% (Elidel) from clinical trials and post-marketing surveillance in patients with atopic dermatitis. These data demonstrate that topically applied pimecrolimus is minimally absorbed through the skin and has a favourable safety margin. The most common treatment-related adverse events are transient local reactions, particularly skin burning (16.1 and 12.9 events per 1,000 patient-months of follow-up in adults and children, respectively). When compared to the vehicle, the use of pimecrolimus cream 1% is associated with an increased incidence of herpes simplex virus infections in children (relative risk: 2.5; 95% confidence interval: 1.2-5.8; p = 0.017). However, pimecrolimus cream 1% does not increase the incidence of any skin infection in comparison with moderately potent topical corticosteroids and lacks other corticosteroid-related side effects such as skin atrophy. While cases of malignancy have been reported in patients who have used pimecrolimus cream 1%, there is no clinical evidence to establish that treatment with pimecrolimus cream 1% increases the risk of malignancy.

  7. Adherence to weight loss medications; post-marketing study from HMO pharmacy data of one million individuals.

    Science.gov (United States)

    Hemo, Beatriz; Endevelt, Ronit; Porath, Avi; Stampfer, Meir J; Shai, Iris

    2011-11-01

    Post-marketing data on weight-loss medications in free living population are a necessary adjunct to data from clinical trials. We conducted a population-based analysis of first-time medication users based on HMO pharmacy purchasing data serving > one million adults. During 5 years, usage of orlistat and sibutramine more than doubled and rates were higher during the months May-Aug. As compared to non-users (n = 1,038,828), annual weight-loss drug users (n = 7175) had higher women proportion, body-mass-index (BMI), bariatric surgery history, and usage of diabetes, depression, and cardiovascular medications (p analysis) reduced from 33.02 kg/m(2) to 32.04 kg/m(2) (p multivariate model, long-term adherence (≥ 4 months) to weight-loss medications was associated with use of sibutramine vs. orlistat (OR = 2.08; 95%CI: 1.76-2.45), and prevalence of diabetes (OR = 1.20; 95%CI: 1.01-1.25). Age, gender, and baseline BMI were not associated with long-term adherence. Usage of weight-loss drugs is higher among diabetes patients. However, the poor adherence to therapy is substantially below levels reported in clinical trials. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. [Post-marketing clinical study of traditional Chinese medicine--lessons learned from comprehensive evaluation of Fufang Zaoren capsule].

    Science.gov (United States)

    Qing, Shan; Gao, Lin; Zhang, Li; Jia, Jian-Ping; Liu, Xin-Min; Ji, Shao-Liang; Yang, Xiao-Hui

    2013-11-01

    By comprehensive review and analysis of post-marketing clinical research on the efficacy and safety,we concluded that Fufang Zaoren capsule has certain therapeutic effects for insomnia, although current clinical research design needs improving. The post-marketing clinical studies also showed that it causes several adverse reactions at the recommended doses, such as chills, fever, dizziness, nausea, shortness of breath, chest tightness and palpitations, whereas high doses of Fufang Zaoren capsule can cause delayed extrapyramidal symptoms. Health Canada government website also prompted the L-tetrahydropalmatine in Fufang Zaoren capsule caused liver damage in pregnant women. The authors summarized the risk points, factors and risk control in the clinical use of Fufang Zaoren capsule and also present their perspective on the research status, existing problems and corresponding countermeasures in the post-marketing clinical re-evaluation of traditional Chinese medicine.

  9. [Research about re-evaluation of screening of traditonal Chinese medicine symptoms item of post-marketing medicine Xuezhikang].

    Science.gov (United States)

    He, Wei; Xie, Yanming; Wang, Yongyan

    2011-10-01

    The purpose of post-marketing Chinese medicine re-evaluation is to identify Chinese medicine clinical indications, while designing scientific and rational of Chinese medicine symptoms items are important to the result of symptoms re-evaluation. This study give screening of traditional Chinese medicine(TCM) symptoms item of post-marketing medicine Xuezhikang re-evaluation as example that reference to principle dyslipidemia clinical research, academic dissertations, Xuezhikang directions, clinical expert practice experience etc. while standardization those symptom names and screening 41 dyslipidemia common symptoms. Furthermore, this paper discuss about the accoerdance and announcements when screening symptoms item, so as to providing a research thread to manufacture PRO chart for post-marketing medicine re-evaluation.

  10. Montelukast as Add-On Therapy to Inhaled Corticosteroids in the Management of Asthma (The SAS Trial

    Directory of Open Access Journals (Sweden)

    J Mark FitzGerald

    2009-01-01

    Full Text Available AIM: To evaluate the effectiveness of montelukast as add-on therapy for asthmatic patients who remain uncontrolled with low, moderate or high doses of inhaled corticosteroid monotherapy.

  11. Decision support methods for the detection of adverse events in post-marketing data.

    Science.gov (United States)

    Hauben, M; Bate, A

    2009-04-01

    Spontaneous reporting is a crucial component of post-marketing drug safety surveillance despite its significant limitations. The size and complexity of some spontaneous reporting system databases represent a challenge for drug safety professionals who traditionally have relied heavily on the scientific and clinical acumen of the prepared mind. Computer algorithms that calculate statistical measures of reporting frequency for huge numbers of drug-event combinations are increasingly used to support pharamcovigilance analysts screening large spontaneous reporting system databases. After an overview of pharmacovigilance and spontaneous reporting systems, we discuss the theory and application of contemporary computer algorithms in regular use, those under development, and the practical considerations involved in the implementation of computer algorithms within a comprehensive and holistic drug safety signal detection program.

  12. Composite sequential Monte Carlo test for post-market vaccine safety surveillance.

    Science.gov (United States)

    Silva, Ivair R

    2016-04-30

    Group sequential hypothesis testing is now widely used to analyze prospective data. If Monte Carlo simulation is used to construct the signaling threshold, the challenge is how to manage the type I error probability for each one of the multiple tests without losing control on the overall significance level. This paper introduces a valid method for a true management of the alpha spending at each one of a sequence of Monte Carlo tests. The method also enables the use of a sequential simulation strategy for each Monte Carlo test, which is useful for saving computational execution time. Thus, the proposed procedure allows for sequential Monte Carlo test in sequential analysis, and this is the reason that it is called 'composite sequential' test. An upper bound for the potential power losses from the proposed method is deduced. The composite sequential design is illustrated through an application for post-market vaccine safety surveillance data.

  13. The ability of animal studies to detect serious post marketing adverse events is limited.

    Science.gov (United States)

    van Meer, Peter J K; Kooijman, Marlous; Gispen-de Wied, Christine C; Moors, Ellen H M; Schellekens, Huub

    2012-12-01

    The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

    Science.gov (United States)

    Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

    2014-10-07

    Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied.

  15. The role of the Pharmaceuticals and Medical Devices Agency and healthcare professionals in post-marketing safety.

    Science.gov (United States)

    Mori, Kazuhiko; Watanabe, Meguru; Horiuchi, Naoya; Tamura, Atsushi; Kutsumi, Hiromu

    2014-04-01

    The development of drugs and medical devices is necessary for medical progress; however, safety measures need to be put in place to protect the health of the population. In order to ensure the safety of drugs and medical devices, it is important to determine measures for appropriate management of risks at any time during the development phase, the regulatory review and the post-marketing phase. Adverse events detected in clinical trials are limited due to the restricted numbers of patients enrolled in the trials. Therefore, it is almost impossible to predict rare serious adverse events during the post-marketing phase. The revised Pharmaceutical Affairs Act was established in Japan in November 20, 2013. The new act focuses on increased safety of drugs and medical devices. The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority in Japan that promotes safety measures from the development phase through to the post-marketing phase. In the post-marketing phase, the PMDA collects information from the medical product companies and healthcare professionals, as well as instructing and advising them with regard to post-marketing safety measures for each drug and medical device. Since Japan has a national health insurance system, a new drug or a medical device is available throughout the country when the drug price or medical fee is listed in the National Health Insurance price list. Healthcare professionals in medical institutions must learn about the drugs and medical devices they handle, and should make an effort to maintain patient safety. The PMDA medi-navi is a very useful electronic mail delivery service that provides critical information for protecting patients from health hazards caused by adverse events. The 'risk management plan' is also important as it contains important information about safety profile and post-marketing measures of a new drug.

  16. National post-market surveillance assessment of veterinary medicines in Korea during the past decade.

    Science.gov (United States)

    Kang, JeongWoo; Park, Hae-Chul; Jang, Yang Ho; Hossain, Md Akil; Jeong, Kyunghun; Jeong, Mi Young; Yun, Seon-Jong; Park, Sung-Won; Kim, Dae Gyun; Lee, Kwang-Jick

    2017-05-22

    Veterinary medicines have been widely used for the prevention and treatment of diseases, growth promotion, and to promote feeding efficacy in livestock. As the veterinary medicine industry has steadily grown, it is crucial to set up a baseline for the quality of medicine as well as the insufficiency or excessiveness of the active ingredients in drug products to ensure the compliance, safety and efficacy of these medicines. Thus, the 10 years data of post-marketing quality control study was summarized to determine the rate and extent of non-compliance of these medicines and to establish baseline data for future quality control measures of veterinary medicine. In this study, 1650 drugs for veterinary use were collected per year from each city and province in Korea and analysed for the quantity of active ingredients according to the "national post-market surveillance (NPMS) system" over the past decade. The NPMS assessment was performed using liquid and gas chromatography, titration, UV/Vis spectrophotometry, and bioassays. A total of 358 cases were deemed noncompliant, with the average noncompliance rate for all medicine types being 2.0%. The average noncompliance rates for antibiotics, biologics and other chemical drugs except antibiotics (OCD) were 1.1%, 1.2%, and 3.0%, respectively. The first leading cause for noncompliant products was insufficient quantity of major ingredients (283 cases), and the second leading cause was the existence of excess amount of active ingredients (60 cases). Tylosin, spiramycin, ampicillin, tetracyclines and penicillins were most frequently found to be noncompliant among antibiotics. Among the OCD, the noncompliance was found commonly in vitamin A. The overall trend presented gradually decreasing violation rates, suggesting that the quality of veterinary medicines has improved. Consistent application of the NPMS assessment and the establishment of the Korea Veterinary Good Manufacturing Practice (KVGMP) will help to maintain the good

  17. Comparisons of the complementary effect on exhaled nitric oxide of salmeterol vs montelukast in asthmatic children taking regular inhaled budesonide

    DEFF Research Database (Denmark)

    Buchvald, Frederik; Bisgaard, Hans

    2003-01-01

    was 20 ppb (95% confidence interval [CI], 15-27 ppb) after salmeterol, which was significantly higher than after montelukast (mean, 15 ppb; 95% CI, 11-18 ppb; P = 0.002) and placebo (mean, 15 ppb; 95% CI, 10-21 ppb; P = 0.03). There was no difference in FeNO between the montelukast and placebo groups...... with placebo in this group of children taking regular budesonide, 400 microg....

  18. [Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

    Science.gov (United States)

    Li, Hong-jiao; He, Li-yun; Liu, Bao-yan

    2015-06-01

    The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

  19. Clinical Effect of Montelukast Sodium in the Treatment of Children With Cough Variant Asthma%探讨孟鲁司特钠治疗小儿咳嗽变异性哮喘临床效果

    Institute of Scientific and Technical Information of China (English)

    赵丹

    2015-01-01

    Objective To evaluate the efficacy of montelukast sodium in patients with cough variant asthma. Methods Chose 90 cases of cough variant asthma in children from 2013 to 2014 in our hospital,these patients were divided into conventional therapy group and montelukast sodium in the treatment group,each were 45 cases,the conventional group used routine drug treatment,montelukast sodium treatment group used conventional drug plus montelukast sodium,on two groups of clinical treatment for comparative analysis.ResultsMontelukast special application of sodium in children with cough variant asthma clinical treatment with very high efficiency,than the conventional drug treatment effect more excelent clinical results were statisticaly significant difference(P< 0.05).Conclusion The treatment of children with cough variant asthma has a very good effect,and can be combined with conventional drugs in clinical practice.%目的:根据小儿咳嗽变异性哮喘患者接受孟鲁司特钠治疗的临床效果来进行探讨分析,对该种治疗方式应用于小儿咳嗽性变异性哮喘疾病的作用进行探讨。方法根据2013~2014年我院的90例咳嗽变异性哮喘患儿来进行分析,将这些患儿分成常规治疗组和孟鲁司特钠治疗组,每组均有45例患者,常规组使用常规药物治疗,孟鲁司特钠治疗组使用常规药物增加孟鲁司特钠治疗,对两组的临床治疗情况进行比较分析。结果孟鲁司特钠应用于小儿咳嗽变异性哮喘的临床治疗上具有非常高的有效率,比常规药物治疗效果更加优秀,临床结果存在统计学差异性,P<0.05。结论孟鲁司特钠对小儿咳嗽变异性哮喘的治疗具有非常好的效果,临床中可以和常规药物进行联合治疗,提升治疗有效率。

  20. A Validated RP-HPLC Method for theDetermination of Impurities in Montelukast Sodium

    Directory of Open Access Journals (Sweden)

    N. Rashmitha

    2010-01-01

    Full Text Available The present paper describes the development of a reverse phase chromatographic (RPLC method for montelukast sodium in the presence of its impurities and degradation products generated from forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of montelukast sodium was observed under acid and oxidative environment. The drug was found to be stable in other stress conditions studied. Successful separation of the drug from the process impurities and degradation products formed under stress conditions were achieved on an Atlantis dC18 (250 x 4.6 mm 5 μm column. The gradient LC method employs solution A and solution B as mobile phase. The solution A contains aqueous 0.1% OPA and solution B contains a mixture of water, acetonitrile (5:95 v/v. The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness.

  1. Response to montelukast among subgroups of children aged 2 to 14 years with asthma

    DEFF Research Database (Denmark)

    Meyer, Katie A; Arduino, Jean Marie; Santanello, Nancy C

    2003-01-01

    BACKGROUND: Determining who responds to asthma therapies, particularly leukotriene modifiers, continues to be explored. OBJECTIVE: We sought to identify patient characteristics predictive of response to montelukast. METHODS: We used data from 2 clinical trials in which children with asthma received...... either montelukast or placebo. Symptoms, beta-agonist use, and unanticipated health resource use caused by asthma were recorded in validated daily diaries for children 2 to 5 (n = 689) and 6 to 14 (n = 336) years old. We defined primary end points of days without asthma in 2- to 5-year-old patients (24...... hours without symptoms, beta-agonist use, or asthma attack) and change in percent predicted FEV(1) in 6- to 14-year-old children. Asthma attack was defined by the use of rescue oral corticosteroids or by an unscheduled visit to a medical provider. Patients were grouped according to baseline...

  2. 白三烯拮抗剂:儿童用Montelukast 咀嚼片%Leukotrien-Antagonisten Montelukast-Kautabletten fur Kinder

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    在美国,白三烯受体拮抗剂Montelukast(singularR)现在还有供学龄前儿童服用的新剂型.今年3月美国F D A批准4 m gMontelukast咀嚼片用于防治2-5岁儿童的支气管哮喘.在欧洲已提出本品用于该年龄组病人的申请.

  3. Effects of combination therapy with montelukast and carbocysteine in allergen-induced airway hyperresponsiveness and airway inflammation.

    Science.gov (United States)

    Takeda, K; Shiraishi, Y; Matsubara, S; Miyahara, N; Matsuda, H; Okamoto, M; Joetham, A; Gelfand, E W

    2010-07-01

    Montelukast and S-carbocysteine have been used in asthmatic patients as an anti-inflammatory or mucolytic agent respectively. S-carbocysteine also exhibits anti-inflammatory properties. Ovalbumin (OVA) sensitized BALB/c mice were challenged with OVA for 3 days followed by single OVA re-challenge (secondary challenge) 2 weeks later. Forty-eight hours after secondary challenge, mice were assessed for airway hyperresponsiveness (AHR) and cell composition in bronchoalveolar lavage (BAL) fluid. Suboptimal doses of 10 mg.kg(-1) of S-carbocysteine by intraperitoneal injection (ip), 20 mg.kg(-1) of montelukast by gavage, the combination of S-carbocysteine and montelukast or 3 mg.kg(-1) of dexamethasone as a control were administered from 1 day before the secondary challenge to the last experimental day. Isolated lung cells were cultured with OVA and montelukast to determine the effects on cytokine production. Treatment with S-carbocysteine or montelukast reduced both AHR and the numbers of eosinophils in BAL fluid. Neutralizing IFN-gamma abolished the effects of S-carbocysteine on these airway responses. Combination of the two drugs showed further decreases in both AHR and eosinophils in the BAL fluid. Goblet cell metaplasia and Th2-type cytokines, interleukin (IL)-4, IL-5 and IL-13, in BAL fluid were decreased with montelukast treatment. Conversely, S-carbocysteine increased Th1-type cytokines, IFN-gamma and IL-12 in BAL fluid. The combination of two agents, montelukast and S-carbocysteine, demonstrated additive effects on AHR and airway inflammation in a secondary allergen model most likely through independent mechanisms of action.

  4. [The role of drug registries in the post-marketing surveillance].

    Science.gov (United States)

    Traversa, Giuseppe; Sagliocca, Luciano; Magrini, Nicola; Venegoni, Mauro

    2013-06-01

    The aim of this article is to provide an introduction to issue of Recenti Progressi in Medicina, devoted to the role of drug registries in the post-marketing surveillance. We first motivate the need to implement registries as a tool in promoting the appropriateness of drug use and acquiring additional information on the risk-benefit profile of drugs. Then, the different role that can be played by registries in comparison with prescription monitoring systems and observational studies is clarified. The presentation of some of the most relevant registries established in Italy since the end of the '90s, with the analysis of their strengths and weaknesses, helps to understand some of the crucial issues that should be taken into account before a new registry is adopted. Specifically, we deal with the relationship between objectives - of appropriateness, effectiveness and safety - and methods; the overlapping between drug-based registries and disease-based ones; the duration and extension of data collection, which may be either exhaustive or based on a sampling frame; the importance of ensuring the quality of the data and to minimize the number of subjects who are lost to follow-up; the importance of infrastructures, and of ad hoc funding, for the functioning of a registry; the independence in data analysis and publication of findings.

  5. Effectiveness and tolerability of parenteral testosterone undecanoate: a post-marketing surveillance study.

    Science.gov (United States)

    Wolf, Jan; Keipert, Dieter; Motazedi, Heiko; Ernst, Michael; Nettleship, Joanne; Gooren, Louis

    2017-08-16

    This observational post-marketing study of parenteral testosterone undecanoate (TU) in a non-selected population aimed to: examine the effectiveness of TU as treatment of hypogonadism; record adverse drug reactions (ADR) quantitatively particularly regarding polycythemia, prostate safety and cardiovascular-related metabolic risk factors; and verify whether recommended injection intervals apply to routine clinical practice. Eight hundred and seventy subjects from 259 outpatient units scheduled to visit the clinic six times were included. Effectiveness and tolerability of TU administration were assessed on a 4-point scale. Body weight, waist girth, blood pressure, hemoglobin levels, hematocrit, prostate-specific antigen (PSA), and digital rectal prostate examination were assessed. Over 90% of subjects completed the observational duration of 52.8 ± 9.7 weeks (mean ± SD) and 56% judged effectiveness as very good, 30.8% as good. 63.1% judged tolerability as very good, and 24.4% as good. No adverse effects on indicators of cardiovascular risk were observed. Polycythemia occurred in one subject and a supranormal hematocrit in one subject. Four subjects developed supranormal PSA levels. Prostate carcinoma was found in one subject, one subject had recurrence of a previously surgically treated prostate carcinoma, and the other two showed no indication of malignancy. Parenteral TU is safe, effective, and well-tolerated in clinical practice proving a good therapeutic option for hypogonadism.

  6. Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.

    Science.gov (United States)

    Ninomiya, Haruhiko; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Nishiwaki, Kaichi; Matsumura, Itaru; Shichishima, Tsutomu; Okamoto, Shinichiro; Nishimura, Jun-Ichi; Ohyashiki, Kazuma; Nakao, Shinji; Ando, Kiyoshi; Kanda, Yoshinobu; Kawaguchi, Tatsuya; Nakakuma, Hideki; Harada, Daisuke; Akiyama, Hirozumi; Kinoshita, Taroh; Ozawa, Keiya; Omine, Mitsuhiro; Kanakura, Yuzuru

    2016-11-01

    Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 10(9)/L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.

  7. Post-marketing Surveillance for Combined Oral Contraceptive Containing Desogestrel (Marvelon?) in Chinese Rural Areas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective To assess the side effects and the continuation rate of combined oral contraceptive (COC) containing desogestrel (Marvelon ) during 12 months. Methods This was a post-marketing surveillance study on Marvelon COC among 870 healthy rural women in 5 different counties of Jiangsu Province during 12 months. Results About 24.02% of the women who used Marvelon COC experienced side effects during 12 months. Gastrointestinal disorder, bleeding/spotting and chloasma were ranked the first three in the side effects. The rate of side effects of Marvelon COC users during the first 3 months in southern area of Jiangsu was significantly higher than that of users in northern area of Jiangsu. Most of the users did not experience obvious weight changes i.e., loss or increase in weight of more than 5 kg during 12 months. Blood pressure and biochemical indicators of almost 99% among users were within the normal range. The gross cumulative continuation rate for 12 months was 83.14%; the most common medical reason for discontinuation was gastrointestinal disorder. There was an increased risk of discontinuation use among women with lower educational level.Conclusion Marvelon COC brought fewer side effects and was well accepted when applied in Chinese rural women.

  8. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast.

    Science.gov (United States)

    Mougey, E B; Lang, J E; Wen, X; Lima, J J

    2011-05-01

    Previously the authors found that a common polymorphism, rs12422149 (SLCO2B1{NM_007256.2}:c.935G>A), in the gene coding for OATP2B1, was associated with absorption of and response to montelukast in humans. In vitro studies showed that citrus juice could reduce the permeability of montelukast consistent with known inhibition of organic anion-transporting polypeptides. To study the clinical significance of c.935G>A, the authors conducted a single-dose, pharmacokinetic study of montelukast co-ingested with citrus juice. On average, co-ingestion with either orange juice or 4× concentrated grapefruit juice had a minimal effect on the area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC(0→∞)) of montelukast relative to co-ingestion with Gatorade control (n = 24). However when the data were stratified by genotype at c.935 (G/G n = 21, A/G n = 5), a significant reduction in AUC(0→∞) was detected with orange juice in G/G homozygotes (AUC(0→∞), G/G, Gatorade = 2560 ± 900 ng·h·mL(-1) vs AUC(0→∞), G/G, orange juice = 2010 ± 650 ng·h·mL(-1), P = .032). Significantly, A/G heterozygotes showed reduced AUC(0→∞) relative to G/G homozygotes, independent of treatment (AUC(0→∞), G/G, combined treatments = 2310 ± 820 ng·h·mL(-1) vs AUC(0→∞), A/G, combined treatments = 1460 ± 340 ng·h·mL(-1), P = 2.0 × 10(-5)) replicating previous observations.

  9. The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals.

    Science.gov (United States)

    Ponce, Loida; Arjona, Marjorie; Blanco, Gustavo; Alvarez, Stuart; Arcila, Eduardo; Ortega, Arnaldo; Nuñez, Dubelis; Verzura, Julie; Tovar, Robert; Bethencourt, Sarah; Riera, Ricardo; Mora-Orta, Sioly; Corado, José

    2011-03-01

    Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

  10. Simultaneous determination of montelukast and loratadine by HPLC and derivative spectrophotometric methods.

    Science.gov (United States)

    Radhakrishna, T; Narasaraju, A; Ramakrishna, M; Satyanarayana, A

    2003-02-26

    In this study, high performance liquid chromatography (HPLC) and second derivative spectrophotometry have been used and described for the simultaneous determination of montelukast and loratadine in pharmaceutical formulations. HPLC separation was achieved with a Symmetry C18 column and sodium phosphate buffer (pH adjusted to 3.7): acetonitrile (20:80, v/v) as eluent, at a flow rate of 1.0 ml/min. UV detection was performed at 225 nm. The LC method is simple, rapid, selective and stability indicating for the determination of montelukast. 5-Methyl 2-nitrophenol was used as internal standard for the purpose of quantification of both the drugs in HPLC. In the second-order derivative spectrophotometry, for the determination of loratadine the zero-crossing technique was applied at 276.1 nm, but for montelukast peak amplitude at 359.7 nm (tangent method) was used. Both methods were fully validated and a comparison was made for assay determination of selected drugs in formulations. The results confirm that the methods are highly suitable for its intended purpose.

  11. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

    Science.gov (United States)

    Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-01-01

    Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are

  12. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.

    Science.gov (United States)

    Spelsberg, Angela; Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-02-07

     To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.  Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.  Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.  Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.  Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.  Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the

  13. SIMULTANEOUS ESTIMATION OF FEXOFENADINE HYDROCHLORIDE AND MONTELUKAST SODIUM IN BULK DRUG AND MARKETED FORMULATION BY RP-HPLC METHOD

    Directory of Open Access Journals (Sweden)

    Ravisankar M

    2012-04-01

    Full Text Available A new simple and precise accurate RP-HPLC method has been developed and validated for simultaneous estimation of Montelukast Sodium and Fexofenadine in tablet formulations. The chromatographic separation was performed in Water symmetry C8 (150X4.6mm 5µm and mobile phase 0.05 m potassium di hydrogen ortho phosphate: acetonitrile in the ratio of 35:65 and the pH – 6 adjusted by triethylamine.The flow rate was 1.0ml/min and the wavelength selected for the quantization was 226 nm. The retention time was found to be 2.127 min for Fexofenadine and 5.650 min for Montelukast sodium .The linearity were found to be in the range of 4.8 - 28.8 µg/ml and 0.4 – 2.4 µg/ml for Fexofenadine and Montelukast respectively with the correlation co efficient of 0.999.The mean recoveries for Fexofenadine and Montelukast were 99.85 % and 100.19 % respectively, and relative standard deviation was less than 2%. Precision were performed as per ICH guidelines with the result shows relative standard deviation not more than 2%.The assay value for Fexofenadine and Montelukast were found to be 100.55 % and 100.40 % respectively.

  14. Statement on the post-marketing monitoring of the use of lycopene

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA

    2015-01-01

    Full Text Available Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to provide an update of its exposure assessment on lycopene as a novel food ingredient in the context of Regulation (EC No 258/97 taking into account the new additional information from the post-marketing monitoring programme imposed by the Commission Decisions authorising the use of synthetic lycopene, lycopene oleoresin from tomatoes and lycopene from Blakeslea trispora as a novel food ingredient in several foodstuffs. The marketing authorisation holders for the use of lycopene as a novel food ingredient jointly prepared and submitted a dossier containing sales data, product launch data, an intake estimate and toxicological information. On the basis of information on sales and new product launch data for the period from July 2009 to June 2012 provided by the lycopene manufacturers, food supplements appear to be the main source of lycopene after intake from natural occurrence. Since no new toxicological studies became available, there is no scientific basis on which the ADI established by EFSA in 2008 could be reconsidered. On the basis of previous intake assessments performed by EFSA and data on sales and product launch data provided for the period from July 2009 to June 2012, the Panel concludes that intakes of naturally occurring lycopene and from its use as a food colouring and as a novel food ingredient at permitted use levels do not lead to intakes above the ADI of 0.5 mg/kg bw/day.

  15. Environmental change challenges decision-making during post-market environmental monitoring of transgenic crops.

    Science.gov (United States)

    Sanvido, Olivier; Romeis, Jörg; Bigler, Franz

    2011-12-01

    The ability to decide what kind of environmental changes observed during post-market environmental monitoring of genetically modified (GM) crops represent environmental harm is an essential part of most legal frameworks regulating the commercial release of GM crops into the environment. Among others, such decisions are necessary to initiate remedial measures or to sustain claims of redress linked to environmental liability. Given that consensus on criteria to evaluate 'environmental harm' has not yet been found, there are a number of challenges for risk managers when interpreting GM crop monitoring data for environmental decision-making. In the present paper, we argue that the challenges in decision-making have four main causes. The first three causes relate to scientific data collection and analysis, which have methodological limits. The forth cause concerns scientific data evaluation, which is controversial among the different stakeholders involved in the debate on potential impacts of GM crops on the environment. This results in controversy how the effects of GM crops should be valued and what constitutes environmental harm. This controversy may influence decision-making about triggering corrective actions by regulators. We analyse all four challenges and propose potential strategies for addressing them. We conclude that environmental monitoring has its limits in reducing uncertainties remaining from the environmental risk assessment prior to market approval. We argue that remaining uncertainties related to adverse environmental effects of GM crops would probably be assessed in a more efficient and rigorous way during pre-market risk assessment. Risk managers should acknowledge the limits of environmental monitoring programmes as a tool for decision-making.

  16. Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk.

    Science.gov (United States)

    Raschi, Emanuel; De Ponti, Fabrizio

    2015-07-08

    Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent's management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as "signals"), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of post-marketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies. In this context, ongoing European/United States research consortia and novel pharmaco-epidemiological tools (e.g., specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities.

  17. [Results of a post-marketing surveillance of meropenem administered over 2 g/day for serious infectious diseases].

    Science.gov (United States)

    Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

    2015-10-01

    The post-marketing surveillance of meropenem (Meropen®) administered over 2g/day for serious infectious diseases was conducted between August 2011 and June 2013 to evaluate safety and efficacy under actual clinical use. There were 382 and 322 evaluable cases for safety and efficacy respectively, of 399 case cards collected from 87 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 19.1% (73/382 cases), and the main ADRs were hepatic function abnormal, aspartate aminotransferase increased, alanine aminotransferase increased, liver disorder, and diarrhoea, which were similar to these observed in the post-marketing surveillances of meropenem conducted before. In efficacy analysis, the efficacy was 73.6% (237/322 cases), which is as same as 71.4% (3214/4504 cases) of post-marketing surveillance of meropenem conducted after first approval under 2 g/day for infectious diseases. These results confirmed meropenem (Meropen®) is one of the useful antimicrobial agents for serious infectious diseases.

  18. Post-marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross-sectional study.

    Science.gov (United States)

    Zeitoun, Jean-David; Baron, Gabriel; Vivot, Alexandre; Atal, Ignacio; Downing, Nicholas S; Ross, Joseph S; Ravaud, Philippe

    2017-09-20

    Post-marketing research in oncology has rarely been described. We aimed to characterize post-marketing trials for a consistent set of anticancer agents over a long period. We performed a cross-sectional analysis of post-marketing trials registered at ClinicalTrials.gov through September 2014 for novel anticancer agents approved by both the US Food and Drug Administration and the European Medicines Agency between 2005 and 2010. All relevant post-marketing trials were classified according to indication, primary outcome, starting date, sponsors, and planned enrollment. Supplemental indications were retrieved from regulatory documents and publication rate was assessed by two different methods. Ten novel anticancer agents were eligible: five were indicated for hematologic malignancies and the remaining five for solid cancers (three for kidney cancer). We identified 2345 post-marketing trials; 1362 (58.1%) targeted an indication other than the originally approved one. We observed extreme variations among drugs in both number of post-marketing trials [range 8-530] and overall population to be enrolled per trial [1-8381]. Post-marketing trials assessed almost all types of cancers, the three most frequently studied cancers being leukemia, kidney cancer and myeloma. In all, 6.6% of post-marketing trials had a clinical endpoint as a primary outcome, and 35.9% and 54.1% had a safety or surrogate endpoint, respectively, as a primary outcome. Nine drugs obtained approval for supplemental indications. The publication rate at 10 years was 12.3% to 26.1% depending on the analysis method. In conclusion, we found that post-marketing research in oncology is highly heterogeneous and the publication rate of launched trials is low. This article is protected by copyright. All rights reserved. © 2017 UICC.

  19. Safety and efficacy of montelukast as adjunctive therapy for treatment of asthma in elderly patients

    Directory of Open Access Journals (Sweden)

    Scichilone N

    2013-10-01

    Full Text Available Nicola Scichilone, Salvatore Battaglia, Alida Benfante, Vincenzo BelliaDipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, ItalyAbstract: Asthma is a disease of all ages. This assumption has been challenged in the past, because of several cultural and scientific biases. A large body of evidence has accumulated in recent years to confirm that the prevalence of asthma in the most advanced ages is similar to that in younger ages. Asthma in the elderly may show similar functional and clinical characteristics to that occurring in young adults, although the frequent coexistence of comorbid conditions in older patients, together with age-associated changes in the human lung, may lead to more severe forms of the disease. Management of asthma in the elderly follows specific guidelines that apply to all ages, although most behaviors are pure extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. This review focuses specifically on the safety and efficacy of leukotriene modifiers, which represent a valid option in the treatment of allergic asthma, both as an alternative to first-line drugs and as add-on treatment to inhaled corticosteroids. Available studies specifically addressing the role of montelukast in the elderly are scarce; however, leukotriene modifiers have been demonstrated to be safe in this age group, even though cases of acute hepatitis and occurrence of Churg-Strauss syndrome have been described in elderly patients; whether this is associated with age is to be confirmed. Furthermore, leukotriene modifiers provide additional benefit when added to regular maintenance therapy, not differently from young asthmatics. In elderly patients, the simpler route of administration of leukotriene modifiers, compared with the inhaled agents, could represent a more effective strategy in improving the outcomes of asthma therapy

  20. [Importance of Post-Marketing Studies in Gathering of Clinical Evidences for Proper Usage of Anti-Cancer Drugs, and the StudyRequirements for Their Credibility].

    Science.gov (United States)

    Inagaki, Osamu

    2016-04-01

    Pharmaceutical companies recognize the importance of post-marketing studies because they are crucial in the generation of clinical evidences for the usage of new medicines. To generate clinical evidences, quality of post-marketing studies should be well controlled from view point of "ethical conduction" and "reliability of results". In addition, control of conflict of interest (COI) between researchers and industries is also indispensable and is requested for the transparency of the studies. Japan Pharmaceutical Manufacturers Association(JPMA)stresses its commitment to the progressof transparency in post-marketing studies.

  1. Non-clinical Post-Marketing Commitments for newly licenced pharmaceuticals.

    Science.gov (United States)

    Reeve, Lesley M

    2009-11-01

    There are clear minimum requirements for non-clinical (toxicology) studies which are needed prior to human exposure to a potential new pharmaceutical and additional studies are needed in an ongoing manner to support clinical development and marketing [ICH, 2009. ICH M3(R2) Non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals (CPMP/ICH/286/95). Adopted June 2009, effective December 2009.] The pharmaceutical industry is under increasing pressure to reduce costs and reduce, refine and replace the use of animals, as far as possible. Hence any increase in regulatory requirements for non-clinical safety data could have a significant impact both on the economic and ethical considerations of drug development. It is, therefore, of interest that further non-clinical studies are required by the Regulatory Authorities for a small but increasing proportion of drug product applications at the marketing approval/data review stage. These studies are known as Post-Marketing Commitments (PMCs). Available information on non-clinical PMCs was collated using drug product information from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA), resulting in a combined data set of 162 studies. Non-clinical PMCs comprised 9.8% and 6.5% of total PMCs for products authorised by the EMEA (Centralised Procedure) and FDA, respectively. Non-clinical PMCs increased with increasing date of approval, despite increased regulatory information available to guide Applicants. Furthermore, the increase reflected an increased proportion of applications with non-clinical PMCs, not an increase in overall numbers of applications. There was no clear correspondence between the publication dates of relevant guidelines and increases in specific non-clinical PMC study types, when the data were analysed by non-clinical study category, target population/indication or compound class. Possible exceptions were some

  2. Valutazione della qualitá dei dati in uno studio post marketing

    Directory of Open Access Journals (Sweden)

    D. D’Alessandro

    2003-05-01

    Full Text Available

    Obiettivo: misurare l'affidabilita nella segnalazione
    di eventi avversi a vaccino nell'ambito di uno studio post-marketing sulla tollerabilita della vaccinazione antipneumococcica (AP in associazione con la vaccinazione antinfluenzale (AI nella popolazione anziana.


    Metodi: e stato predisposto un modello di regressione
    logistica per stimare gli OR tra la segnalazione di almeno un effetto collaterale locale (y ed alcune variabili individuali dei vaccinati (x1: eta .75 anni; x2: sesso; x3: allergie; x4: associazione AI+AP; x5: vivere solo; x6: patologie croniche. I medici aderenti al progetto (229 sono stati stratificati in cinque categorie in funzione dellfincidenza media di eventi avversi da loro registrata: 0% (29, 1-5%
    (68, 6-10% (50, 11-50% (72, .50% (10. Lo stesso modello di regressione e stato applicato ai quattro
    sotto-gruppi di vaccinati afferenti alle categorie di medici che hanno segnalato sintomi, per valutare la coerenza degli OR registrati nei gruppi.

    Risultati: tra i 29.086 vaccinati, l'f11,3% (3.278 ha segnalato almeno un evento avverso locale nelle
    72 ore successive alla vaccinazione: 9,9% tra i soggetti vaccinati con AI e 13,9% tra i vaccinati con
    AI+AP. I fattori significativamente associati all'faumento di rischio sono: AI+AP (OR 1,4; allergie (OR 1,3; patologie croniche (OR 1,3. L' applicazione del modello di regressione ai sotto-gruppi di vaccinati ha mostrato un trend negli OR per le categorie di medici che hanno segnalato dall'f1-5% fino all'f11- 50%, mostrando un'effettiva differenza di rischio dei pazienti.

    Tale coerenza non si e evinta nell'ultima categoria (.50%, dove tali fattori appaiono addiritura protettivi nei riguardi dei sintomi (AI+AP: OR 0,5; allergie: OR 0,7, o non associati
    (patologie croniche: OR 1,0.

    Conclusioni: il 4,3% dei medici arruolati nello studio (10 su 229 ha

  3. Effects of tiotropium bromide combined with montelukast on blood rheology, pulmonary function and serum cytokine levels in patients with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Meng; Cheng-Hong Li; Xiao-Jiang Wang; Yi Shi; Qiong Feng

    2016-01-01

    Objective:To explore the effect of tiotropium bromide combined with montelukast on COPD patients’ blood rheology, pulmonary function and serum cytokine levels.Methods: A total of 82 COPD patients who were treated in our hospital from June 2015 to January 2016 were divided into control group and observation group randomly by half. All patients were given symptomatic and conventional treatment according to the specific circumstances, patients in the control group were treated with 10 mg montelukast with orally once per night on the basis of conventional treatment, and observation group patients was given 18 μg tiotropium bromide inhalation once per night on the basis of control group. All the patients were treated for 4 weeks, the blood rheology indexes, pulmonary function indexes and serum cytokines were measured and compared between the two groups before and after treatment.Results: Before treatment, there was no significant difference in blood rheology index of whole blood viscosity (high shear viscosity, shear viscosity, low shear viscosity), plasma viscosity, hematocrit and fibrinogen (P>0.05); After treatment, the blood rheology indexes of the two groups were significantly decreased compared with that in the same group before treatment (P0.05). After treatment, the indexes of pulmonary function in the two groups were significantly higher than that in the same group before treatment (P0.05); After treatment, the two groups’ serum IL-10, APN levels were significantly increased, IL-18 levels were significantly reduced (P<0.05). Meanwhile, serum IL-10, APN levels in Observation group were significantly increased, IL-18 levels were significantly lower than that in control group (P<0.05).Conclusions: The comibinition of tiotropium bromide with montelukas not only can improve the indexes of blood rheology in patients with COPD, and can significantly control the level of serum cytokines and control symptoms, improve lung function, so it is worth further clinical

  4. [Research on the issues in the process of post-market surveillance for medical devices based on the typical case analysis].

    Science.gov (United States)

    Zhang, Sumin; Zhang, Liang

    2011-11-01

    Regarding the information collected, analysis and actions that have been taken, the issues in the process of the Post-market Surveillance for Medical Device were analyzed, and some suggestions were given at the same time.

  5. Montelukast prevents microparticle-induced inflammatory and functional alterations in human bronchial smooth muscle cells.

    Science.gov (United States)

    Fogli, Stefano; Stefanelli, Fabio; Neri, Tommaso; Bardelli, Claudio; Amoruso, Angela; Brunelleschi, Sandra; Celi, Alessandro; Breschi, Maria Cristina

    2013-10-01

    Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation. Stimulation of human BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by inducing gene expression (COX-2 and IL-8), protein release in the supernatant (PGE2 and IL-8), and heterologous β2-adrenoceptor desensitization. The latter effect was most likely related to autocrine PGE2 since pre-treatment with COX inhibitors restored the ability of salbutamol to induce cAMP synthesis in desensitized cells. Challenge with MPs induced nuclear translocation of NF-κB and selective NF-κB inhibition decreased MP-induced cytokine release in the supernatant. Montelukast treatment prevented IL-8 release and heterologous β2-adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by blocking NF-κB nuclear translocation. These findings provide evidence on the role of human monocyte-derived MPs in the airway smooth muscle phenotype switch as a novel potential mechanism in the progression of chronic respiratory diseases and on the protective effects by montelukast in this setting.

  6. 孟鲁司特钠联合先声咳喘宁治疗感冒后咳嗽临床观察%Clinical observation on montelukast sodium tablets combined with Kechuanning for cough post infectious

    Institute of Scientific and Technical Information of China (English)

    王金陵

    2014-01-01

    Objective To observe the clincal effcet of montelukast sodium tablets combined with Kechuanning for cough post infectious(CPI). Methods 120 cases with CPI were randomly into two groups. In treatment group, 62 patients were treated with montelukast sodium tablets and Kechuanning; In control group, 58 patients were treated with Qiangli pipa syrup. the course of treatment lasted 7 days. The therapeutic effect was then compared between the two groups. Results The total e•ffective rate in treatment group was 90.3%, and that in control group was 75.9%, There was significant difference between the two groups(P<0.05). The treatment group was better than the control group. Conclusion Montelukast sodium tablets combined with Kechuanning is effective for CPI.%目的:观察孟鲁司特钠联合先声咳喘宁治疗感冒后咳嗽的临床疗效。方法:感冒后咳嗽120例随机分成两组,治疗组62例,给予孟鲁司特钠和先声咳喘宁治疗;对照组给予强力枇杷露治疗,疗程共7天,比较两组疗效。结果:治疗组总有效率90.3%,对照组总有效率75.9%,治疗组总有效率高于对照组,差异有统计学意义(P<0.05)。结论:孟鲁司特钠联合先声咳喘宁治疗感冒后咳嗽效果好。

  7. The clinical effect of montelukast sodium in the treatment of children with bronchial asthma%孟鲁司特钠治疗小儿支气管哮喘的临床疗效

    Institute of Scientific and Technical Information of China (English)

    姜国栋

    2015-01-01

    Objective:To explore the clinical effect of montelukast sodium in the treatment of children with bronchial asthma. Methods:70 children with bronchial asthma were selected,they were randomly divided into the treatment group and the control group with 35 cases in each.The control group was treated with conventional drugs,the treatment group was given montelukast sodium on the basis of routine treatment,we compared the treatment effect of the two groups.Results:The total effective rate of 91.4% in the treatment group was significantly higher than 77.1% of the control group(P<0.05).Conclusion:The clinical effect of montelukast sodium in the treatment of children with bronchial asthma was significant,the effect was quick,and the side effects were small.%目的:探讨孟鲁司特钠治疗小儿支气管哮喘的临床疗效.方法:收治小儿支气管哮喘患儿70例,随机分为对照组与治疗组各35例.对照组采用常规药物治疗,治疗组在常规用药的基础上加用孟鲁司特钠治疗,比较两组治疗效果.结果:治疗组总有效率91.4%,明显高于对照组的77.1%(P<0.05).结论:孟鲁司特钠治疗小儿支气管哮喘的临床疗效显著,见效快,不良反应小.

  8. Post-market drug evaluation research training capacity in Canada: an environmental scan of Canadian educational institutions.

    Science.gov (United States)

    Wiens, Matthew O; Soon, Judith A; MacLeod, Stuart M; Sharma, Sunaina; Patel, Anik

    2014-01-01

    Ongoing efforts by Health Canada intended to modernize the legislation and regulation of pharmaceuticals will help improve the safety and effectiveness of drug products. It will be imperative to ensure that comprehensive and specialized training sites are available to train researchers to support the regulation of therapeutic products. The objective of this educational institution inventory was to conduct an environmental scan of educational institutions in Canada able to train students in areas of post-market drug evaluation research. A systematic web-based environmental scan of Canadian institutions was conducted. The website of each university was examined for potential academic programs. Six core programmatic areas were determined a priori as necessary to train competent post-market drug evaluation researchers. These included biostatistics, epidemiology, pharmacoepidemiology, health economics or pharmacoeconomics, pharmacogenetics or pharmacogenomics and patient safety/pharmacovigilance. Twenty-three academic institutions were identified that had the potential to train students in post-market drug evaluation research. Overall, 23 institutions taught courses in epidemiology, 22 in biostatistics, 17 in health economics/pharmacoeconomics, 5 in pharmacoepidemiology, 5 in pharmacogenetics/pharmacogenomics, and 3 in patient safety/pharmacovigilance. Of the 23 institutions, only the University of Ottawa offered six core courses. Two institutions offered five, seven offered four and the remaining 14 offered three or fewer. It is clear that some institutions may offer programs not entirely reflected in the nomenclature used for this review. As Heath Canada moves towards a more progressive licensing framework, augmented training to increase research capacity and expertise in drug safety and effectiveness is timely and necessary.

  9. Construction and analysis of a human hepatotoxicity database suitable for QSAR modeling using post-market safety data.

    Science.gov (United States)

    Zhu, Xiao; Kruhlak, Naomi L

    2014-07-01

    Drug-induced liver injury (DILI) is one of the most common drug-induced adverse events (AEs) leading to life-threatening conditions such as acute liver failure. It has also been recognized as the single most common cause of safety-related post-market withdrawals or warnings. Efforts to develop new predictive methods to assess the likelihood of a drug being a hepatotoxicant have been challenging due to the complexity and idiosyncrasy of clinical manifestations of DILI. The FDA adverse event reporting system (AERS) contains post-market data that depict the morbidity of AEs. Here, we developed a scalable approach to construct a hepatotoxicity database using post-market data for the purpose of quantitative structure-activity relationship (QSAR) modeling. A set of 2029 unique and modelable drug entities with 13,555 drug-AE combinations was extracted from the AERS database using 37 hepatotoxicity-related query preferred terms (PTs). In order to determine the optimal classification scheme to partition positive from negative drugs, a manually-curated DILI calibration set composed of 105 negatives and 177 positives was developed based on the published literature. The final classification scheme combines hepatotoxicity-related PT data with supporting information that optimize the predictive performance across the calibration set. Data for other toxicological endpoints related to liver injury such as liver enzyme abnormalities, cholestasis, and bile duct disorders, were also extracted and classified. Collectively, these datasets can be used to generate a battery of QSAR models that assess a drug's potential to cause DILI.

  10. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  11. A data-capture system for post-marketing surveillance of drugs that integrates with hospital electronic health records

    Directory of Open Access Journals (Sweden)

    Yamamoto K

    2011-04-01

    Full Text Available Keiichi Yamamoto1, Shigemi Matsumoto2, Kazuhiro Yanagihara2, Satoshi Teramukai1, Masanori Fukushima1,2,31Department of Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, Japan; 2Outpatient Oncology Unit, Kyoto University Hospital, Kyoto, Japan; 3Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, JapanPurpose: In conventional clinical studies, the cost of data management for the purposes of quality control tend to be high and collecting paper-based case report forms (CRFs can be burdensome, because paper-based CRFs must be developed and filled out for each clinical study protocol. Use of electronic health records (EHRs for this purpose could reduce costs and improve data quality in clinical studies. Kyoto University Hospital launched an EHR system in January 2005. At the same time, a replicate of that database was established for other purposes. At the Outpatient Oncology Unit of Kyoto University Hospital we developed a data-capture system that includes a cancer clinical database system and a data warehouse for outcomes studies. This system allows us to accumulate data at low cost and apply it to various uses in clinical or outcomes studies. Here we report on the application of this system to the post-marketing surveillance of drugs.Methods: We evaluated the availability of this system and identified problems for future development. With this system investigators can register cases for post-marketing surveillance, and the registered cases are listed on a screen. When CRFs for a particular case are required, data can be extracted from the list and CRFs are produced in PDF format.Results and conclusion: In this study we confirmed the applicability of our new system to post-marketing surveillance in providing prompt and efficient data exchange. We expect it to reduce the cost of data management and analysis and to improve the quality of data in post-marketing

  12. 孟鲁司特钠咀嚼片细菌计数检查方法的比较与优化%Comparison and Optimization of Bacterial Counting Method for Montelukast Sodium Chew-able Tablets

    Institute of Scientific and Technical Information of China (English)

    廖燕萍

    2015-01-01

    Objective:To optimize bacterial counting method for Montelukast Sodium Chewable Tablets .Methods:Based on Chinese Pharmacopoeia (2010 edition), two types of diluents were used to prepare sample solutions that were applied for bacterial recovery as -say.In this study, the optimal bacterial counting method for the Montelukast Sodium Chewable Tablet was figured out by comparing the bacterial recovery rates using the two diluents .Results: The antibiotic activity of Montelukast Sodium Chewable Tablets was largely compromised by addition of 0.5%lecithin and 4%polysorbate80 to the sample solution.The bacterial recovery rate was shown higher than 70%with the routine plate counting method .On the other hand , the recovery rate for the sample without neutralization agents was less than 70%, it could be reached only if the sample solution was diluted to 1/1 000 as performed routinely.Conclusion:The bacte-rial counting method for Montelukast Sodium Chewable Tablets was set up optimally by adding 0.5%lecithin and 4%polysorbate80 to the diluent.%目的:优化孟鲁司特钠咀嚼片细菌计数检查方法。方法:用两种稀释剂分别制备供试液,按2010年版《中国药典》进行回收率试验,比较不同计数方法回收率的高低,以选择该药品最佳的细菌计数方法。结果:添加0.5%大豆卵磷脂和4%聚山梨酯80的稀释剂可去除孟鲁司特钠咀嚼片的抗菌活性,细菌计数检查方法为常规法回收率可达70%以上;未添加中和剂组细菌计数检查方法为常规法回收率低于70%,需用1∶1000稀释级常规法才能使回收率达到70%以上。结论:采用稀释剂中添加0.5%大豆卵磷脂和4%聚山梨酯80法可优化孟鲁司特钠咀嚼片的细菌计数检查方法。

  13. Immune reconstitution inflammatory syndrome Kaposi sarcoma in the liver manifesting as acute obstructive hepatitis: another potential role for montelukast?

    Science.gov (United States)

    Read, P J; Lucas, S; Morris, S; Kulasegaram, R

    2013-02-01

    Immune reconstitution inflammatory syndrome has been described in Kaposi sarcoma, but does not usually manifest as acute hepatitis. We describe a case of rapid obstructive jaundice after initiation of antiretroviral therapy, in which the liver biopsy confirmed hepatic Kaposi sarcoma, and the clinical course was altered by the addition of montelukast.

  14. Safety and tolerability of montelukast in placebo-controlled pediatric studies and their open-label extensions

    DEFF Research Database (Denmark)

    Bisgaard, H.; Skoner, D.; Boza, M.L.;

    2009-01-01

    Montelukast is a potent leukotriene-receptor antagonist administered once daily that provides clinical benefit in the treatment of asthma and allergic rhinitis in children and adults. Because of its wide use as a pediatric controller, there is a need for a further review of the safety...

  15. Comparison of Glucocorticoid (Budesonide) and Antileukotriene (Montelukast) Effect in Patients with Bronchial Asthma Determined with Body Plethysmography

    Science.gov (United States)

    Lajqi, Njomza; Ilazi, Ali; Kastrati, Bashkim; Islami, Hilmi

    2015-01-01

    Objective: Effect of glucocorticoids-budesonide and antileukotriene–montelukast in patients with bronchial asthma and bronchial increased reactivity was studied in this work. Methods: Parameters of the lung function are determined with Body plethysmography. Raw and ITGV were registered and specific resistance (SRaw) was also calculated. Results: Results of this research, in patients with bronchial asthma, indicate that glucocorticoids – budesonide (Pulmicort; 2 × 2 mg inh) has significant action (p< 0.01) on reduction of the specific resistance (SRaw) of airways, applied to the same patients 3 days after administration of montelukast, at home (2 × 10 mg). Three days after administration of the montelukast, antileukotriene medicine, at home, on the fourth day same patients administered a capsule of montelukast, 10 mg dose per os, and significantly (p < 0.05) reduced the increased bronchomotor tonus; and the effect of the control with salbutamol (beta2-adrenergic agonist) is effective in removal of the increased bronchomotor tonus, causing significant decrease of the resistance (Raw), respectively of the specific resistance (SRaw), (p < 0, 01). Conclusion: This suggests that the bronchodilator effect of glucocorticoids is more powerful than of the leukotriene, because glucocorticoids terminate the early stage of chemical mediator release (prostaglandins PgD2, SRS, and leukotriene LTC4, LTD4, LTE4 and Cytokinins also etc.) as powerful bronchoconstriction substances, whilst antileukotriene substances does not have this feature. PMID:26862243

  16. Clinical effectiveness and safety of montelukast in asthma. What are the conclusions from clinical trials and meta-analyses?

    Directory of Open Access Journals (Sweden)

    Hon KLE

    2014-06-01

    Full Text Available Kam Lun Ellis Hon,1 Ting Fan Leung,1 Alexander KC Leung21Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong; 2Department of Pediatrics, The University of Calgary, Calgary, AB, CanadaAbstract: Asthma is a common childhood atopic disease associated with chronicity and impaired quality of life. As there is no cure for this disease, treatment relies on avoidance of triggers such as food and aeroallergens, the use of inhaled bronchodilators/corticosteroids and antiallergic or immunomodulating therapies. Inhaled corticosteroids (ICSs and bronchodilators have been the mainstay. However, in Asia, myths and fallacies regarding Western medicine and corticosteroids are prevalent and lead to nonadherence to treatment. Also, use of traditional and proprietary herbal medicines is popular. In the past decades, a novel class of nonsteroidal immunomodulating montelukasts has become available. This article reviews the evidence for the effectiveness and clinical efficacy of these medications. A number of randomized and controlled trials have been performed over the years. The majority of studies confirm the usefulness of montelukast as monotherapy and add-on therapy to ICS in mild to moderate childhood asthma across all age groups. ICSs are generally superior to montelukasts for asthma management. However, montelukast has a place in the treatment of young children with viral-triggered wheezing diseases, exercise-induced asthma, and in children whose parents are steroid-phobic and find ICS unacceptable.Keywords: cysteinyl leukotriene receptor antagonist, inhaled corticosteroid, randomized control trial, meta analysis

  17. Treatment Evaluation with Mometasone Furoate, Alone or in Combination with Desloratadine/ Montelukast in Moderate Severe Allergic Rhinitis

    Directory of Open Access Journals (Sweden)

    Florincescu-Gheorghe Nona-Aura

    2014-06-01

    Full Text Available Introduction: Allergic rhinitis is one of the most common allergic diseases, characterized by the inflammation of the nasal mucosa. Eosinophils play a predominant pro-inflammatory role in allergic inflammation. This study assesses the effect of mometasone furoate alone or in combination with desloratadine/montelukast in patients with moderate-severe allergic rhinitis.

  18. Identification, synthesis, isolation and spectral characterization of potential impurities of montelukast sodium.

    Science.gov (United States)

    Saravanan, M; Siva Kumari, K; Pratap Reddy, P; Naidu, M N; Moses Babu, J; Srivastava, Alok Kumar; Lakshmi Kumar, T; Chandra Sekhar, B V V N; Satyanarayana, Bollikonda

    2008-11-04

    During the process development of montelukast sodium, three polar impurities and one non-polar impurity with respect to montelukast sodium were detected by simple reverse phase high-performance liquid chromatography (HPLC). Initially, all the four impurities were identified by the liquid chromatography-mass spectrometry (LC-MS) data and out of four impurities, three have been prepared by the synthetic method and remaining one is isolated by preparative HPLC. Based on the spectral data (IR, (1)H NMR, (13)C NMR and MS), the structure of these impurities 1-4 were characterised as 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropane acetamide (impurity-1), {1-[1-{3-[2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-3-(2-isopropenyl-phenyl)-propylsulfanylmethyl]-cyclopropyl}-acetic acid (impurity-2), 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-3) and 1-[[[(1R)-1-[3-[(1E)-2-(2-quinolinyl)ethenyl]phenyl-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid (impurity-4).

  19. [Skin test: guide of post-marketed re-evaluation of clinical safety in traditional Chinese medicine injection].

    Science.gov (United States)

    Wei, Xu; Xie, Yanming; Wang, Yongyan

    2011-10-01

    Anaphylaxis is the most common adverse reaction caused by traditional Chinese medicine (TCM) injection, the most serious of which is type I, so post-marketed safety re-evaluation is necessary. Skin test can be used to screen type I allergy reaction, which is of great significance for TCM injection safe use. Skin test is not only able to find the population sensitization situation of TCM injection, but also is a way of understanding the mechanism of allergy reaction. TCM injection varieties that often occur type I anaphylaxis are applicable to skin test, and study population include healthy volunteers and patients whose disease is listed in the drug specification, intracutaneous test and prick test are the alternative method. The concentration of skin-test solution may influence the positive rate of skin test, penicillin skin-test solution preparation method can be used as the reference in TCM injection. Different doses of TCM injection skin-test solution,glucose injection and normal saline, histamine hydrochloride are comprised in comparison. Given the characteristics of type I allergy reaction,we should be pay close attention to skin test reaction in half an hour, and observation index need be designed based on post-marketed re-evaluation of clinical safety.

  20. Drug- and herb-induced liver injury: Progress, currentchallenges and emerging signals of post-marketing risk

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Drug-induced liver injury (DILI) and herb-inducedliver injury is a hot topic for clinicians, academia, drugcompanies and regulators, as shown by the steadilyincreasing number of publications in the past 15 years.This review will first provide clues for clinicians tosuspect idiosyncratic (unpredictable) DILI and succeedin diagnosis. Causality assessment remains challengingand requires careful medical history as well as awarenessof multifaceted aspects, especially for herbs.Drug discontinuation and therapy reconciliation remainthe mainstay in patent's management to minimizeoccurrence of acute liver failure. The second section willaddress novel agents associated with liver injury in 2014(referred to as "signals"), especially in terms of clinical,research and drug development implications. Insightswill be provided into recent trends by highlighting thecontribution of different post-marketing data, especiallyregistries and spontaneous reporting systems. Thisliterature scrutiny suggests (1) the importance of postmarketingdatabases as tools of clinical evidence todetect signals of DILI risk; and (2) the need for joiningefforts in improving predictivity of pre-clinical assays,continuing post-marketing surveillance and design adhoc post-authorization safety studies. In this context,ongoing European/United States research consortia andnovel pharmaco-epidemiological tools (e.g. , specialistprescription event monitoring) will support innovation inthis field. Direct oral anticoagulants and herbal/dietarysupplements appear as key research priorities.

  1. Efficacy of Add-on Montelukast in Nonasthmatic Eosinophilic Bronchitis: The Additive Effect on Airway Inflammation, Cough and Life Quality

    Institute of Scientific and Technical Information of China (English)

    Wuping Bao; Ping Liu; Zhongmin Qiu; Li Yu; Jingqing Hang; Xiaohua Gao; Xin Zhou

    2015-01-01

    Background:The efficacy of montelukast (MONT),a cysteinyl leukotriene receptor antagonist,in nonasthmatic eosinophilic bronchitis (NAEB),especially its influence on cough associated life quality is still indefinite.We evaluated the efficacy of MONT combined with budesonide (BUD) as compared to BUD monotherapy in improving life quality,suppressing airway eosinophilia and cough remission in NAEB.Methods:A prospective,open-labeled,multicenter,randomized controlled trial was conducted.Patients with NAEB (aged 18-75 years) were randomized to inhaled BUD (200 μg,bid) or BUD plus oral MONT (10 μg,qn) for 4 weeks.Leicester cough questionnaire (LCQ) life quality scores,cough visual analog scale (CVAS) scores,eosinophil differential ratio (Eos),and eosinophil cationic protein (ECP) in induced sputum were monitored and compared.Results:The control and MONT groups contained 33 and 32 patients,respectively,with similar baseline characteristics.Significant with-in group improvement in CVAS,LCQ scores,Eos,and ECP was observed in both groups during treatment.After 2-week treatment,add-on treatment of MONT was significantly more effective than BUD monotherapy for CVAS decrease and LCQ scores improvement (both P < 0.05).Similar results were seen at 4-week assessment (both P < 0.05).4-week add-on therapy of MONT also resulted in a higher percentage of patients with normal sputum Eos (<2.5%) and greater decrease of ECP (both P < 0.05).Conclusions:MONT combined with BUD was demonstrated cooperative effects in improvement of life quality,suppression ofeosinophilic inflammation,and cough remission in patients with NAEB.

  2. Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia.

    Science.gov (United States)

    Regan, Annette K; Tracey, Lauren; Gibbs, Robyn

    2015-11-17

    In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV.

  3. ["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

    Science.gov (United States)

    Wu, Shu-Xin; Sun, Hong-Feng; Yang, Xiao-Hui; Long, Hong-Zhu; Ye, Zu-Guang; Ji, Shao-Liang; Zhang, Li

    2014-08-01

    We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in

  4. Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist

    Directory of Open Access Journals (Sweden)

    James P Kemp

    2009-11-01

    Full Text Available James P KempClinical Professor of Pediatrics, Division of Immunology and Allergy, University of California School of Medicine, San Diego, CA, USAAbstract: Exercise-induced bronchoconstriction (EIB is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting β2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled β2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB

  5. Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results.

    Science.gov (United States)

    Hanafusa, Norio; Isoai, Ayako; Ishihara, Tomoaki; Inoue, Tetsuya; Ishitani, Ken; Utsugisawa, Taiju; Yamaka, Toshihiko; Ito, Tetsuya; Sugiyama, Hiroshi; Arakawa, Atsushi; Yamada, Yosuke; Itano, Yasuo; Onodera, Hirokazu; Kobayashi, Ryosuke; Torii, Naoko; Numata, Toyoko; Kashiwabara, Taihei; Matsuno, Yoshihiro; Kato, Michio

    2017-01-01

    We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine volume, body weight and abdominal circumference were significantly improved after CART. Body temperature increased significantly, by 0.3°C on average. Concomitant steroids and/or NSAIDs use before reinfusion was significantly and negatively associated with increases in body temperature. Most adverse events were fever and chills. This study examined a large number of patients compared with previous studies, and showed that CART is an effective and relatively safe treatment for refractory ascites, such as malignant ascites.

  6. Technical challenges in designing post-marketing eCRFs to address clinical safety and pharmacovigilance needs.

    Science.gov (United States)

    Lu, Zhengwu

    2010-01-01

    To identify key challenges and propose technical considerations in designing electronic case report form (eCRF) for post-marketing studies, the author undertakes a comprehensive literature review of peer reviewed and grey literature to assess the key aspects, processes, standards, recommendations, and best practices in designing eCRFs based on industry experience in designing and supporting electronic data capture (EDC) studies. Literature search using strings on MEDLINE and PUBMED returned few papers directly related to CRF design. Health informatics and general practice journals were searched and results reviewed. Many conference, government commission, health professional and special interests group websites provide relevant information from practical experience - summarization of this information is presented. Further, we presented a list of concrete technical considerations in dealing with EDC technology/system limitations based on literature assessment and industry implementation experience. It is recognized that cross-functional teams be involved in eCRF design process and decision making. To summarize the keys in designing eCRFs to address post-market study safety and pharmacovigilance needs, the first is to identify required data elements from the study protocol supporting data analyses and reporting requirements. Secondly, accepted best practices, CDASH & CDISC guidelines, and company internal or therapeutic unit standard should be considered and applied. Coding (MedDRA & WHODD) mapping should be managed and implemented as well when possible. Finally, we need to be on top of the EDC technologies, challenge the technologies, drive EDC improvement via working with vendors, and utilize the technologies to drive clinical effectiveness. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  7. Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

    Science.gov (United States)

    Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

    2013-06-01

    Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

  8. Formulation and evalution of montelukast sodium - chitosan based spray dried microspheres for pulmonary drug delivery

    Directory of Open Access Journals (Sweden)

    Rushi Panchal

    2012-01-01

    Full Text Available The objective of present work was to prepare microspheres of montelukast sodium using a natural polymer- chitosan by spray drying method by using glutaraldehyde as a cross linking agent. The microspheres were characterized for size, shape, dissolution, swelling and mucoadhesion. It was observed that, all microspheres were spherical in shape with narrow size distribution. Microspheres had mean particle size of 7-12 μm, with % encapsulation efficiency of 78-86%. The % yield was 32-49% and drug load was 48-53%. With the increase in proportion of chitosan in formulation mucoadhesive strength was increase and also increased in particle size of microspheres. As the drug:polymer ratio increase drug loading was increase and % encapsulation efficiency was also increase.

  9. A Case of Montelukast-Induced Churg-Strauss Syndrome Associated with Liver Dysfunction

    Directory of Open Access Journals (Sweden)

    Keiji Matsui

    2011-01-01

    Full Text Available A 64-year-old woman was admitted to hospital due to protracted diarrhea and liver dysfunction. The patient was diagnosed as Churg-Strauss syndrome (CSS due to asthma, paranasal sinusitis, hypereosinophilia, and polyneuropathy. There was a history of taking montelukast, a leukotriene receptor antagonist (LTRA, which is thought to have some relationship with CSS. The liver biopsy specimen showed eosinophilic infiltration and centrolobular fatty change. In this paper, we review the relationship between LTRA and CSS. Several lines of evidence suggest that leukotriene plays an important role in maintaining neural tissues. We also review the potential relationship between centrolobular fatty change and pivoxil-containing antibiotics, which was prescribed for sinusitis before admission. Carnitine deficiency induced by pivoxil-containing agents may cause impaired fatty acid oxidation in mitochondria.

  10. Important statistical considerations in the evaluation of post-market studies to assess whether opioids with abuse-deterrent properties result in reduced abuse in the community.

    Science.gov (United States)

    By, Kunthel; McAninch, Jana K; Keeton, Stephine L; Secora, Alex; Kornegay, Cynthia J; Hwang, Catherine S; Ly, Thomas; Levenson, Mark S

    2017-08-23

    Abuse, misuse, addiction, overdose, and death associated with non-medical use of prescription opioids have become a serious public health concern. Reformulation of these products with abuse-deterrent properties is one approach for addressing this problem. FDA has approved several extended-release opioid analgesics with abuse-deterrent labeling, the bases of which come from pre-market studies. As all opioid analgesics must be capable of delivering the opioid in order to reduce pain, abuse-deterrent properties do not prevent abuse, nor do pre-market evaluations ensure that there will be reduced abuse in the community. Utilizing data from various surveillance systems, some recent post-market studies suggest a decline in abuse of extended-release oxycodone after reformulation with abuse-deterrent properties. We discuss challenges stemming from the use of such data. We quantify the relationship between the sample, the population, and the underlying sampling mechanism and identify the necessary conditions if valid statements about the population are to be made. The presence of other interventions in the community necessitates the use of comparators. We discuss the principles under which the use of comparators can be meaningful. Results based on surveillance data need to be interpreted with caution as the underlying sampling mechanisms can bias the results in unpredictable ways. The use of comparators has the potential to disentangle the effect due to the abuse-deterrence properties from those due to other interventions. However, identifying a comparator that is meaningful can be very difficult. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  11. Comparison of Glucocorticoid (Budesonide) and Antileukotriene (Montelukast) Effect in Patients with Bronchial Asthma Determined with Body Plethysmography

    OpenAIRE

    Lajqi, Njomza; Ilazi, Ali; Kastrati, Bashkim; Islami, Hilmi

    2015-01-01

    Objective: Effect of glucocorticoids-budesonide and antileukotriene–montelukast in patients with bronchial asthma and bronchial increased reactivity was studied in this work. Methods: Parameters of the lung function are determined with Body plethysmography. Raw and ITGV were registered and specific resistance (SRaw) was also calculated. Results: Results of this research, in patients with bronchial asthma, indicate that glucocorticoids – budesonide (Pulmicort; 2 × 2 mg inh) has significant act...

  12. 白三烯受体拮抗剂孟鲁司特治疗变应性鼻炎的荟萃分析%Meta-analysis of leukotriene receptor antagonist montelukast in the treatment of allergic rhinitis

    Institute of Scientific and Technical Information of China (English)

    陆忆; 殷敏; 程雷

    2014-01-01

    鲁司特或氯雷他定.%Objective To evaluate the treatment outcomes of leukotriene receptor antagonists (LTRA) as monotherapy or combined with the second-generation oral H1-histamines in the treatment of allergic rhinitis (AR),and to provide a basis for optimizing clinical therapeutic strategies.Methods PubMed,EMBASE,CBMdisc and CJFD databases,retrieving randomized controlled trials (RCTs) of AR therapy literatures were searched.Based on the literature inclusion and exclusion criteria,the related literatures were selected and the quality was evaluated by using the Jadad scale.Meta-analysis was performed by Stata 12.1 software.For continuous outcomes,the weighted mean difference (WMD) and its 95% confidence intervals (CI) were calculated.The forest plots were drawn.The treatment outcomes included daytime nasal symptom scores (DNSS),nighttime symptom scores (NSS),composite symptom scores (CSS),daytime eye symptom scores (DESS),and the rhinoconjunctivitis quality of life questionnaire (RQLQ) were used to evaluate the therapeutic effects of LTRA on seasonal and perennial AR.Results Eleven of clinical RCTs including 14 809 cases of AR patients,aged 15 to 85 years old,were available for Meta-analysis.Montelukast,a drug of LTRA,was primarily evaluated in the study.The results of Metaanalysis showed:(1) Compared with the placebo,montelukast statistically significantly reduced the DNSS,NSS,CSS,and RQLQ scores in patients with seasonal and perennial AR,as well as the DESS in patients with seasonal AR.(2) There were no statistical differences in the improvement of the CSS,DESS,and RQLQ scores in patients with seasonal AR after the treatment by montelukast compared with loratadine,a secondgeneration oral H1-histamine.(3) Montelukast statistically significantly reduced the NSS,but not DNSS,in patients with seasonal AR compared with loratadine.(4) The combination therapy of montelukast and loratadine statistically significantly improved the CSS compared with either montelukast or loratadine monotherapy

  13. Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

    Science.gov (United States)

    Swank, Kimberley A; Wu, Eileen; Kortepeter, Cindy; McAninch, Jana; Levin, Robert L

    The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to

  14. Salmeterol plus fluticasone propionate versus fluticasone propionate plus montelukast: a randomised controlled trial investigating the effects on airway inflammation in asthma

    Directory of Open Access Journals (Sweden)

    Woodcock Ashley

    2007-09-01

    Full Text Available Abstract Background Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP (Seretide™; SFC and FP plus montelukast (FP/M on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics. Methods Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function. Results Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94. Conclusion Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC. Study number SAM40030 (SOLTA

  15. Magnesium sulfate and montelukast for treatment of asthma in adult:a meta-analysis%孟鲁司特与硫酸镁联合治疗成人支气管哮喘的meta分析

    Institute of Scientific and Technical Information of China (English)

    马康; 赵宇

    2016-01-01

    Objective To systemically review the efficacy and safety of magnesium sulfate for asthma.Methods Such databases as Pubmed,Cochrane Library,CNKI,VIP from inception to January 201 6 for randomized controlled trials (RCTs)concerning magnesium sulfate and montelukast for adult asthma.Two reviewers screened literature according to the inclusion and exclusion criteria,extracted data,and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.3 software.Results A total of 12 RCTs involving 1 992 patients were included.The results of meta-analysis showed that magnesium sulfate and montelukast had higher remission rate of clinical signs compared with control group (OR = 5.50,95% CI = 3.73-8.1 1,P < 0.01 ).And magnesium sulfate and montelukast could significantly reduce the relief time of cough (SMD = -1.66,95% CI =-1.92--1.40,P <0.01),gasp (SMD =-1.42,95% CI =-1.68--1.16,P <0.01),chest congestion (SMD =-1.54,95% CI = -1.73--1.34,P < 0.01 ).Compared with control group,magnesium sulfate and montelukast could obviously reduce the recurrence rate of asthma (OR =0.26,95% CI =0.1 5-0.43,P <0.01).And magnesium sulfate and montelukast could significantly improve lung function index:PEF (SMD =0.85,95% CI =0.11-1.59,P <0.01),FEV1 % (SMD =7.65,95% CI =2.60-12.71,P <0.01),FEV1/FVC% (SMD =6.31,95% CI =5.47-7.14,P <0.01).Magnesium sulfate and montelukast could cause more adverse drug reactions (OR =4.43,95% CI =1.87-10.49,P =0.0007).Funnel plot of the remission rate of clinical signs is asymmetric that indicates publication bias.Conclusion Magnesium sulfate and montelukast can obviously improve the clinical signs,pulmonary function of patients with asthma,and reduce the recurrence rate,but increase adverse drug reactions.Due to limited quantity and quality of the included studies,the above conclusion should be further verified by conducting more high quality,large scale,multicentre RCTs.%目的:系统评价孟鲁司特与硫酸镁联合治

  16. Biosimilars in inflammatory bowel disease: A review of post-marketing experience.

    Science.gov (United States)

    Deiana, Simona; Gabbani, Tommaso; Annese, Vito

    2017-01-14

    Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods. A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined "boundaries of tolerance": differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited.

  17. [Investigation of the factors that contribute to the onset of insomnia in hypertensive patients by using a post-marketing surveillance database].

    Science.gov (United States)

    Tanabe, Naoto; Fujita, Toshiharu; Fujii, Yosuke; Orii, Takao

    2011-01-01

    Many factors contribute to the onset of insomnia. However, few studies have identified the factors related to the onset of insomnia in hypertensive patients. We conducted a pharmacoepidemiologic study to examine the incidence of insomnia in hypertensive patients by using a post-marketing surveillance database. The insomnia onset was defined as the time of first prescription of hypnotics. The insomnia incidence rate in hypertensive patients under antihypertensive therapy was 0.77/100 person-years. The median insomnia onset date was 5 weeks. The insomnia type in 50.2% of the patients was difficulty in initiating sleep. We assessed the factors contributing to insomnia by using a nested case-control design. We selected 10 time-matched controls for every case. The hypotensive effect induced by antihypertensive therapy on the case group was lesser than that on the control group (p4-4.98), β blockers (OR, 1.54; 95% CI, 0.99-2.39), and calcium channel blockers (OR, 0.62; 95% CI, 0.43-0.90) compared with angiotensin-converting enzyme inhibitors; female sex (OR, 1.76; 95% CI, 1.27-2.44); complication of gastric/duodenal disorders (OR, 2.35; 95% CI, 1.14-4.86) or musculoskeletal system/connective tissue disorders (OR, 2.43; 95% CI, 1.23-4.79); and concomitant antihypertensive therapy (OR, 0.44; 95% CI, 0.31-0.63). This study identified the potential factors that may help to predict insomnia onset in hypertensive patients under antihypertensive therapy.

  18. Post-marketing safety surveillance conducted in Korea (2008–2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™)

    Science.gov (United States)

    Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

    2016-01-01

    ABSTRACT Purpose: According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). Methods: During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. Results: A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. Conclusions: We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice. PMID:27494163

  19. Real-life versus package insert: a post-marketing study on adverse-event rates of the virosomal hepatitis A vaccine Epaxal® in healthy travellers.

    Science.gov (United States)

    Hatz, Christoph; Beck, Bernhard; Steffen, Robert; Genton, Blaise; d'Acremont, Valérie; Loutan, Louis; Hartmann, Katharina; Herzog, Christian

    2011-07-12

    There are various methods to collect adverse events (AEs) in clinical trials. The methods how AEs are collected in vaccine trials is of special interest: solicited reporting can lead to over-reporting events that have little or no biological relationship to the vaccine. We assessed the rate of AEs listed in the package insert for the virosomal hepatitis A vaccine Epaxal(®), comparing data collected by solicited or unsolicited self-reporting. In an open, multi-centre post-marketing study, 2675 healthy travellers received single doses of vaccine administered intramuscularly. AEs were recorded based on solicited and unsolicited questioning during a four-day period after vaccination. A total of 2541 questionnaires could be evaluated (95.0% return rate). Solicited self-reporting resulted in significantly higher (p<0.0001) rates of subjects with AEs than unsolicited reporting, both at baseline (18.9% solicited versus 2.1% unsolicited systemic AEs) and following immunization (29.6% versus 19.3% local AEs; 33.8% versus 18.2% systemic AEs). This could indicate that actual reporting rates of AEs with Epaxal(®) may be substantially lower than described in the package insert. The distribution of AEs differed significantly between the applied methods of collecting AEs. The most common AEs listed in the package insert were reported almost exclusively with solicited questioning. The reporting of local AEs was more likely than that of systemic AEs to be influenced by subjects' sex, age and study centre. Women reported higher rates of AEs than men. The results highlight the need for detailing the methods how vaccine tolerability was reported and assessed.

  20. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  1. [Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

    Science.gov (United States)

    Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

    2014-04-01

    The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

  2. Automatic signal extraction, prioritizing and filtering approaches in detecting post-marketing cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Xu, Rong; Wang, Quanqiu

    2014-02-01

    Targeted drugs dramatically improve the treatment outcomes in cancer patients; however, these innovative drugs are often associated with unexpectedly high cardiovascular toxicity. Currently, cardiovascular safety represents both a challenging issue for drug developers, regulators, researchers, and clinicians and a concern for patients. While FDA drug labels have captured many of these events, spontaneous reporting systems are a main source for post-marketing drug safety surveillance in 'real-world' (outside of clinical trials) cancer patients. In this study, we present approaches to extracting, prioritizing, filtering, and confirming cardiovascular events associated with targeted cancer drugs from the FDA Adverse Event Reporting System (FAERS). The dataset includes records of 4,285,097 patients from FAERS. We first extracted drug-cardiovascular event (drug-CV) pairs from FAERS through named entity recognition and mapping processes. We then compared six ranking algorithms in prioritizing true positive signals among extracted pairs using known drug-CV pairs derived from FDA drug labels. We also developed three filtering algorithms to further improve precision. Finally, we manually validated extracted drug-CV pairs using 21 million published MEDLINE records. We extracted a total of 11,173 drug-CV pairs from FAERS. We showed that ranking by frequency is significantly more effective than by the five standard signal detection methods (246% improvement in precision for top-ranked pairs). The filtering algorithm we developed further improved overall precision by 91.3%. By manual curation using literature evidence, we show that about 51.9% of the 617 drug-CV pairs that appeared in both FAERS and MEDLINE sentences are true positives. In addition, 80.6% of these positive pairs have not been captured by FDA drug labeling. The unique drug-CV association dataset that we created based on FAERS could facilitate our understanding and prediction of cardiotoxic events associated with

  3. Post-marketing safety surveillance conducted in Korea (2008-2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™).

    Science.gov (United States)

    Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

    2016-10-02

    According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice.

  4. Long-term efficacy of sirolimus-eluting stent for small vessel disease--subanalysis of Cypher Stent Japan Post-Marketing Surveillance Registry.

    Science.gov (United States)

    Fujimoto, Hajime; Ikari, Yuji; Nakamura, Masato

    2013-01-01

    Percutaneous coronary intervention for lesions with small vessel diameter may have high event rates. Although drug-eluting stents reduce the risk of restenosis, the long-term efficacy of drug-eluting stent implantation in small vessels is unclear. We reviewed the data of Cypher Stent Japan Post-Marketing Surveillance Registry including 2356 lesions of 1959 patients, and retrospectively investigated the angiographic outcomes at 8 months, and the clinical outcomes at 1800 days after sirolimus-eluting stent (SES) implantation in vessels with diameter less than 2.5mm (small vessel group) compared to that with diameter of 2.5mm or more (non-small vessel group). The rate of major adverse cardiac events (MACE) at 1800 days was slightly higher in the small vessel group than in the non-small vessel group, but not statistically significant (24.4% vs 21.0%, p=0.086). The rate of target lesion revascularization was higher in the small vessel group than in the non-small vessel group (10.2% vs 6.4%, p=0.004). The rate of stent thrombosis was almost the same in the two groups. Multivariate Cox hazard model analysis revealed that a vessel diameter less than 2.5mm was not an independent risk factor for MACE. SES implantation for vessels with diameter less than 2.5mm is safe and provides good long-term outcomes. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  5. [Safety and efficacy of docetaxel in prostate cancer patients: based on the post-marketing surveillance in Japan].

    Science.gov (United States)

    Mera, Takeshi; Saijo, Nagahiro; Akaza, Hideyuki

    2012-04-01

    The safety and efficacy of docetaxel in prostate cancer were evaluated based on the results of post-marketing surveillance. 149 patients were enrolled between September 2008 and May 2010. The starting dose of docetaxel was 75 mg/m² in 53 patients(36%), 70 mg/m² in 55 (37%), and ≤ 60 mg/m² in 41(28%). The median number of treatment cycles was 8 (range, 1 to 10). There was no age difference observed in the starting doses and the treatment cycles. The most common ≥ grade 3 adverse drug reactions (ADRs) were neutropenia (71%)and leukocytopenia (51%), and they occurred more frequently in patients receiving ≥ 70 mg/m². However, the multi-variate analyses revealed that ≥ grade 3 ADRs did not correlate with the starting doses. Infection-related events (≥ grade 3) and interstitial pneumonia were observed in 15% and 1% of patients, respectively. Prostate-specific-antigen (PSA) flare appeared in 19% of 95 evaluable patients at median period of 26 days from treatment initiation. It continued with median duration of 39. 5 days. PSA response rate as defined ≥ 50% level decline was 37%(95%confidence interval: 27-47) in evaluable patients. It was low in patients receiving ≤ 60 mg/m² (18%). There was no notable difference between patients with initial dose of 75 and 70 mg/m². Further investigation for the longer term is warranted.

  6. Monitoring biomedical literature for post-market safety purposes by analyzing networks of text-based coded information.

    Science.gov (United States)

    Botsis, Taxiarchis; Foster, Matthew; Kreimeyer, Kory; Pandey, Abhishek; Forshee, Richard

    2017-01-01

    Literature review is critical but time-consuming in the post-market surveillance of medical products. We focused on the safety signal of intussusception after the vaccination of infants with the Rotashield Vaccine in 1999 and retrieved all PubMed abstracts for rotavirus vaccines published after January 1, 1998. We used the Event-based Text-mining of Health Electronic Records system, the MetaMap tool, and the National Center for Biomedical Ontologies Annotator to process the abstracts and generate coded terms stamped with the date of publication. Data were analyzed in the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment to evaluate the intussusception-related findings before and after the release of the new rotavirus vaccines in 2006. The tight connection of intussusception with the historical signal in the first period and the absence of any safety concern for the new vaccines in the second period were verified. We demonstrated the feasibility for semi-automated solutions that may assist medical reviewers in monitoring biomedical literature.

  7. Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study – PRIME study

    Science.gov (United States)

    Shah, Kshitij; Chaudhari, Omvijay B; Gupta, Palash; Chaudhuri, R Hom; Kamilya, Ranjan; Kulkarni, Shreedhar S; Subbaiah, S; Sorathia, Zubair H; Billa, Gauri

    2017-01-01

    Objective To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician’s routine clinical practice. Materials and methods In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18–60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. Results A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (pTramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions. PMID:28579825

  8. Safety and effectiveness of certolizumab pegol in patients with rheumatoid arthritis: Interim analysis of post-marketing surveillance.

    Science.gov (United States)

    Kameda, Hideto; Nishida, Keiichiro; Nannki, Toshihiro; Watanabe, Akira; Oshima, Yukiya; Momohara, Shigaki

    2017-01-01

      Objective: To evaluate the safety and effectiveness of certolizumab pegol (CZP) in a real-world setting among Japanese patients with rheumatoid arthritis. Post-marketing surveillance data from 2,579 patients treated with CZP were analyzed. Adverse events (AEs) observed during the 24-week CZP treatment period were recorded. Disease activity was evaluated using DAS28-ESR and DAS28-CRP at baseline, Week 12, Week 24, or at withdrawal. The total period of exposure to CZP was 1313.8 patient-years (PY). AEs were reported in 658 (25.5%) patients, at an event rate (ER) of 73.68/100 PY. The most frequent serious AEs were pneumonia, herpes zoster, and interstitial lung disease, at ER per 100 PY of 2.06, 1.29, and 1.22, respectively. Mean disease activity scores at baseline, as measured by DAS28-ESR and DAS28-CRP, were 4.77 ± 1.34 and 4.21 ± 1.27, respectively. Mean changes from baseline at the last observation were -1.29 ± 1.46 and -1.30 ± 1.42, respectively. EULAR good or moderate responses were achieved in 65% of patients. Longer disease duration, prior biologics use, and treatment without MTX co-therapy were associated with EULAR no response. In this interim analysis, no new safety signals were observed. Clinical response to CZP was observed in approximately two thirds of patients.

  9. Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.

    Science.gov (United States)

    Shah, Kshitij; Chaudhari, Omvijay B; Gupta, Palash; Chaudhuri, R Hom; Kamilya, Ranjan; Kulkarni, Shreedhar S; Subbaiah, S; Sorathia, Zubair H; Billa, Gauri

    2017-01-01

    To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (pevents of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.

  10. Development of a drug safety ePlatform for physicians, pharmacists, and consumers based on post-marketing adverse events

    Directory of Open Access Journals (Sweden)

    Keith B. Hoffman

    2013-07-01

    Full Text Available Rigorous clinical trials under the watchful eye of regulators remain the cornerstone of drug safety. However, the emergence of serious and life-threatening Adverse Events (AEs across best-selling drug classes [sometimes many years after winning Food and Drug Administration (FDA approval] underscores the limitations of current clinical trial processes and reinforces the need for careful post-approval pharmacovigilance. The FDA’s sizeable repository of patient case reports linking AEs to approved drugs is the Adverse Event Reporting System (FAERS. We believe that open and user-friendly access to the millions of case reports in FAERS would help advance the field of post-marketing pharmacovigilance. However, FAERS data are virtually inaccessible to most physicians, pharmacists, and consumers. Accordingly, we have recently launched a big data platform (www.AdverseEvents.com that, unlike previous efforts, provides on-demand, user-friendly, and high-impact access to FAERS data. Bringing the power of big data to regular users, such as clinicians, pharmacists, and patients, is the logical next step in the transformation of health care to a model of shared decision making between consumers and the system.

  11. Biosimilars in inflammatory bowel disease: A review of post-marketing experience

    Science.gov (United States)

    Deiana, Simona; Gabbani, Tommaso; Annese, Vito

    2017-01-01

    Biologic compounds are obtained from living organisms or cell cultures by means of biotechnology methods. A similar biologic drug, commonly called biosimilar, is a product copied by a native approved biologic drug whose license has expired. Biosimilar drugs usually are marketed at a lower price and provide important financial savings for public healthcare systems. Some differences between biosimilars and original biologic drugs might exist but they are acceptable if they fall within defined “boundaries of tolerance”: differences in some features between the two molecules are considered important only if clinical relevant. Considering that the efficacy of the innovator biologic drug has already been established, the clinical studies required for approval of a biosimilar could be reduced compared with those required for the approval of the originator. In this review, real life data available in inflammatory bowel disease patients treated with biosimilars are reported, documenting in general satisfactory outcomes, sustained efficacy and no sign of increased immunogenicity, although, further controlled data are awaited. PMID:28127193

  12. Use of celecoxib immediately post marketing in Canada: acute or chronic pain?

    Science.gov (United States)

    Kozyrskyj, Anita L; Raymond, Colette; Racher, Amber

    2007-01-01

    The diffusion of innovations theory suggests that early users of innovations influence others. This study was undertaken to apply the diffusion of innovations theory to the prescribing of celecoxib and to determine if prescriber and patient characteristics differed amongst early use of celecoxib for acute pain versus chronic musculoskeletal conditions. Using Manitobaâs population-based prescription and health care databases, diffusion time from market availability to first prescription for celecoxib was determined for each prescriber. The diffusion of prescribing curves for celecoxib in acute pain versus chronic musculoskeletal conditions were compared. Separately for acute and chronic conditions, the likelihood of being an early or late prescriber or user of celecoxib was determined according to physician factors (specialty and place of training) and patient demographics. This multivariate analysis was completed using polytomous logistic regression, with majority prescribers as the reference. The use of celecoxib for chronic musculoskeletal conditions demonstrated faster diffusion than for acute pain. The majority of early use of celecoxib was for chronic conditions; however 36% of first prescriptions were for acute pain, including the treatment of back pain and injuries. Early prescribers of celecoxib for acute pain were more likely than majority prescribers to be general practitioners (OR = 2.24, 95%CI: 1.53-3.29) and have hospital affiliations (OR=1.54, 95%CI: 1.04-2.27). Early users of celecoxib for chronic conditions were less likely to be low income (OR=0.56, 95%CI: 0.35-0.91). Immediately after market release in Canada, celecoxib was commonly prescribed for the treatment of acute pain; these prescriptions were associated with general practitioners and hospital affiliation status.

  13. Impact of Chronic Renal Failure on Safety and Effectiveness of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: Subgroup Analysis from Zilver PTX Post-Market Surveillance Study in Japan.

    Science.gov (United States)

    Ogawa, Yukihisa; Yokoi, Hiroyoshi; Ohki, Takao; Kichikawa, Kimihiko; Nakamura, Masato; Komori, Kimihiro; Nanto, Shinsuke; O'Leary, Erin E; Lottes, Aaron E; Saunders, Alan T; Dake, Michael D

    2017-05-09

    Favorable long-term outcomes of the Zilver PTX drug-eluting stent (DES) in femoropopliteal lesions have been demonstrated. Chronic renal failure (CRF) has been shown to be a risk factor for restenosis and decreased limb salvage. The results of the DES in patients with CRF have not previously been reported. This study compares the results with the DES in patients with CRF and those without CRF. This retrospective analysis from the Zilver PTX Japan Post-Market Surveillance Study included 321 patients with CRF and 584 patients without CRF. Outcomes included freedom from target lesion revascularization (TLR) and patency. Of the patients included in this subgroup analysis, 2-year data were available for 209 patients in the CRF group and 453 patients in the non-CRF group. The two groups were similar in terms of lesion length and the frequency of in-stent restenosis. Critical limb ischemia, severe calcification, and diabetes were more common in patients with CRF, whereas total occlusion was more common in patients without CRF. Freedom from TLR rates were 81.4 versus 84.9% (p = 0.24), and patency rates were 70.7 versus 70.3% (p = 0.95) in patients with and without CRF at 2 years, respectively. This is the first comparative study of the DES in femoropopliteal artery lesions in patients with and without CRF. These results indicate that the DES placed in femoropopliteal artery lesions of CRF patients is safe and effective with similar patency and TLR rates to patients without CRF. Level 3, Post-Market Surveillance Study.

  14. Post-marketing access to orphan drugs: a critical analysis of health technology assessment and reimbursement decision-making considerations

    Directory of Open Access Journals (Sweden)

    Iskrov G

    2014-01-01

    Full Text Available Georgi Iskrov, Rumen Stefanov Department of Social Medicine and Public Health, Medical University of Plovdiv, Plovdiv, Bulgaria Abstract: This study aims to explore the current rationale of post-marketing access to orphan drugs. As access to orphan medicinal products depends on assessment and appraisal by health authorities, this article is focused on health technology assessment (HTA and reimbursement decision-making considerations for orphan drugs. A critical analysis may identify important factors that could predetermine the combined outcomes of these two processes. Following this objective, an analytical framework was developed, comprising three overlaying issues: to outline what is currently done and what needs to be done in the field of HTA of orphan drugs, to synthesize important variables relevant to the reimbursement decision-making about orphan drugs, and to unveil relationships between theory and practice. Methods for economic evaluation, cost-effectiveness threshold, budget impact, uncertainty of evidence, criteria in reimbursement decision-making, and HTA research agenda are all explored and discussed from an orphan drug perspective. Reimbursement decision-making for orphan drugs is a debate of policy priorities, health system specifics, and societal attitudes. Health authorities need to pursue a multidisciplinary analysis on a range of criteria, ensuring an explicit understanding of the trade-offs for decisions related to eligibility for reimbursement. The only reasonable way to accept a higher valuation of orphan drug benefits is if these are demonstrated empirically. Rarity means that the quality of orphan drug evidence is not the same as for conventional therapies. Closing this gap is another crucial point for the timely access to these products. The generation of evidence goes far beyond pre-market authorization trials and requires transnational cooperation and coordination. Early constructive dialogue among orphan drug

  15. Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

    Science.gov (United States)

    Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

    2017-07-03

    Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

  16. Safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension: Japanese post-marketing surveillance data.

    Science.gov (United States)

    Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Murakami, Masahiro

    2017-05-01

    To evaluate the long-term safety and effectiveness of tadalafil in patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This prospective, multicenter, noninterventional, post-marketing surveillance included patients with PAH who were observed for up to 2 years after initiation of tadalafil. Safety was assessed by analyzing the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included the assessment of the change in World Health Organization (WHO) functional classification of PAH, 6-minute walk test, cardiac catheterization, and echocardiography. Among 1676 patients analyzed for safety, the overall incidence of ADRs was 31.2%. The common ADRs (≥1.0%) were headache (7.0%), diarrhea (1.9%), platelet count decreased (1.8%), anemia, epistaxis, and nausea (1.6% each), flushing (1.3%), hepatic function abnormal (1.1%), hot flush, and myalgia (1.0% each). The common SADRs (≥0.3%) were cardiac failure (0.7%), interstitial lung disease, worsening of PAH, and platelet count decreased (0.3% each). Among 1556 patients analyzed for effectiveness, the percentages of patients with improvement of WHO functional class at 3 months, 1 year, and 2 years after the initiation of tadalafil, and last observation were 17.1%, 24.8%, 28.9%, and 22.5%, respectively. At all observation points (except pulmonary regurgitation pressure gradient at end diastole at 3 months), the mean 6-minute walk distance, cardiac catheterization, and echocardiogram measurements showed statistically significant improvement. This surveillance demonstrated that tadalafil has favorable safety and effectiveness profiles for long-term use in patients with PAH in Japan.

  17. Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

    Science.gov (United States)

    Nakayama, Tetsuo; Onoda, Kazumasa

    2007-01-05

    General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in

  18. Increased pain catastrophizing associated with lower pain relief during spinal cord stimulation: results from a large post-market study.

    Science.gov (United States)

    Rosenberg, Jason C; Schultz, David M; Duarte, Luis E; Rosen, Steven M; Raza, Adil

    2015-06-01

    Pain catastrophizing is a negative cognitive distortion to actual or anticipated pain. Our aim was to determine if greater catastrophizing has a deleterious relationship with pain intensity and efficacy outcomes in patients receiving SCS. As part of an ongoing Institutional Review Board-approved, multi-site, single arm post-market study, 386 patients were implanted with an Eon Mini™ SCS system and had follow-up visits at 3, 6, and 12 months post-implant. Outcomes collected during the study included, but were not limited to pain intensity using the numeric rating scale (NRS), patient reported pain relief (PRP), satisfaction with their SCS system, quality of life (QOL), pain catastrophizing scale (PCS) and state-trait anxiety index (STAI). NRS scores were associated with higher PCS scores at six months (r = 0.50, p < 0.001). The PCS was a strong predictor of the NRS when controlled for known confounders. Patients with PCS ≥30 at 6-months post-implant had a lower six-month PRP (p < 0.001) and were five times more likely to report dissatisfaction with their SCS device (p < 0.001, OR = 5.46, 95% CI: 2.51-6.35). Additionally, at six months, those who were clinically catastrophizing were three times more likely to report deterioration in QOL (p < 0.002, OR = 3.12, 95% CI: 1.62-5.51). These findings were similar at the 12 months follow visit. Our results indicate that patients with greater catastrophizing, post-implant, were more likely to report higher pain intensity and lower pain relief, quality of life and satisfaction with SCS. These results indicate that associations between pain intensity and pain-related mental health may contribute to influence the overall efficacy of SCS. © 2015 International Neuromodulation Society.

  19. The clinical efficacy of a clarithromycin-based regimen for Mycobacterium avium complex disease: A nationwide post-marketing study.

    Science.gov (United States)

    Kadota, Jun-Ichi; Kurashima, Atsuyuki; Suzuki, Katsuhiro

    2017-05-01

    The revised 2007 American Thoracic Society/Infectious Diseases Society of America statement recommend clarithromycin-based combination therapy for treatment of Mycobacterium avium complex lung disease and stipulates approximately 1 year of continuous treatment after bacilli negative conversion. However, supporting data are insufficient. Our objective was to obtain data on the clinical outcome of clarithromycin-based daily regimens by conducting a nationwide retrospective post-marketing study of M. avium complex lung disease. In accordance with the Japanese guidelines, patients were enrolled in this survey according to their chest radiographic findings and microbiologic test results. They were treated with a multidrug regimen including clarithromycin, rifampicin, and ethambutol (clarithromycin-based regimen) until bacilli negative conversion, and the treatment was continued for approximately 1 year after the initial conversion. Data were collected before administration, at the time of bacilli negative conversion, at the end of treatment, and at 6 months after the end of treatment. Of the 466 subjects enrolled in the study, 271 patients who received clarithromycin at 800 mg/day underwent evaluation for M. avium complex disease. The final bacilli negative conversion rate in those patients was 94.7%. The bacteriological relapse rate was 5.0% (5/100 patients). Bacteriological relapse was noted in patients treated for less than 15 months after conversion. No life-threatening or serious adverse drug reactions were observed. This study demonstrated that a clarithromycin-based daily regimen can yield a high bacteriological conversion rate in M. avium complex disease. After conversion, treatment for less than 15 months might be insufficient to prevent bacteriological relapse. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. Post-marketing of disease modifying drugs in multiple sclerosis: an exploratory analysis of gender effect in interferon beta treatment.

    Science.gov (United States)

    Trojano, M; Pellegrini, F; Paolicelli, D; Fuiani, A; Zimatore, G B; Tortorella, C; Simone, I L; Patti, F; Ghezzi, A; Portaccio, E; Rossi, P; Pozzilli, C; Salemi, G; Lugaresi, A; Bergamaschi, R; Millefiorini, E; Clerico, M; Lus, G; Vianello, M; Avolio, C; Cavalla, P; Iaffaldano, P; Direnzo, V; D'Onghia, M; Lepore, V; Livrea, P; Comi, G; Amato, M P

    2009-11-15

    There are a few and conflicting results from randomised controlled trials (RCTs) pertaining to the influence of gender in response to currently used disease modifying drugs in Multiple Sclerosis (MS). Observational studies may be especially valuable for answering effectiveness questions in subgroups not studied in RCTs. To conduct a post-marketing analysis aimed to evaluate the gender effect on Interferon beta (IFNbeta) treatment response in a cohort of relapsing (RR) MS patients. A cohort of 2570 IFNbeta-treated RRMS was prospectively followed for up to 7 years in 15 Italian MS Centers. Cox proportional hazards regression models were used to assess gender differences for risk of reaching 1st relapse and risk of progression by 1 point on Expanded Disability Status Scale (EDSS) score. Gender effects were also explored by a propensity score (PS) matching algorithm, and a tree-growing technique. The multivariate Cox Regression analyses showed that male patients had a significant (p=0.0097) lower risk for 1st relapse and a trend (p=0.0897) for a higher risk to reach 1 point EDSS progression than females. The PS matched multivariate Cox Regression confirmed these results. The RECPAM analysis showed that male sex conferred a significant reduction in the risk for 1st relapse (HR=0.86; 95% CI=0.76-0.98; p=0.0226) in the subgroup with a low pre-treatment number of bouts, and a significant increase in the risk for 1 point EDSS progression (HR=1.33; 95% CI: 1.00-1.76; panalysis seem to suggest that male patients do not respond to IFNbeta treatment in the same way of females.

  1. [Study on building index system of risk assessment of post-marketing Chinese patent medicine based on AHP-fuzzy neural network].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming; Fu, Yingkun

    2011-10-01

    Currently massive researches have been launched about the safety, efficiency and economy of post-marketing Chinese patent medicine (CPM) proprietary Chinese medicine, but it was lack of a comprehensive interpretation. Establishing the risk evaluation index system and risk assessment model of CPM is the key to solve drug safety problems and protect people's health. The clinical risk factors of CPM exist similarities with the Western medicine, can draw lessons from foreign experience, but also have itself multi-factor multivariate multi-level complex features. Drug safety risk assessment for the uncertainty and complexity, using analytic hierarchy process (AHP) to empower the index weights, AHP-based fuzzy neural network to build post-marketing CPM risk evaluation index system and risk assessment model and constantly improving the application of traditional Chinese medicine characteristic is accord with the road and feasible beneficial exploration.

  2. Therapeutic effect of Montelukast combined with Glucocorticoid on childhood cough variant asthma%孟鲁司特联合糖皮质激素治疗儿童咳嗽变异型哮喘疗效研究

    Institute of Scientific and Technical Information of China (English)

    刘卫周

    2011-01-01

    目的:评估应用孟鲁司特联合糖皮质激素对咳嗽变异性哮喘患儿的疗效.方法:将我院2006年1月~2010年6月咳嗽变异性哮喘86例患儿随机分为对照组和观察组,各43例,对照组患儿吸入丙酸氟地卡松125μg/次,每天早晚各1次,观察组除予糖皮质激素吸人治疗外,同时睡前予口服孟鲁司特4 mg 1次,连续治疗8周,观察治疗前和治疗后咳嗽症状和咳嗽对患儿睡眠、日常行为的影响.结果:孟鲁司特联合糖皮质激素总有效率为95.35%.与对照组有效率(74.42%)比较差异有统计学意义(x2=42.742,P<0.05),治疗前对照组和观察组症状评分比较差异无统计学意义(t=0.716,P>0.05),治疗后对照组和观察组症状评分比较差异有统计学意义(t=5.321,P<0.05),且未增加药物的副作用.结论:孟鲁司特联合糖皮质激素在咳嗽变异性哮喘患儿治疗中能有效提高治疗的有效率.明显改善患儿的临床症状,值得推广应用.%Objective: To evaluate the therapeutic effect of the combined treatment by the oral Montelukast and inhaled Glucocorticoid on the childhood cough variant asthma.Methods: 86 cases children with cough variant asthma were selected in our hospital from January 2006 to June 2010 and divided into observation group and control group evenly.The control group only inhaled 125 μg Fluticasone propionate per time, twice a day with one in the morning and the other in the night.In the regular treatment with the inhaled Glucocorticoid, observation group was added with Montelukast orally taken 4 mg once daily before bedtime.After eight weeks with the continuous therapy, the clinical efficacy before and after treatment were compared in order to find out the influence of asthma symptom and asthma itself on the sleeping quality and daily behavior of sick children.Results: Total efficiency rate of Montelukast combined with Glucocorticoid was 95.35%, compared with the efficiency rate of control group (74.42

  3. Post-marketing Safety Evaluation of S-1 in Patients with Inoperable or Recurrent Breast Cancer: Especially in Patients Treated with S-1 + Trastuzumab

    OpenAIRE

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-01-01

    Objective The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. Methods A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Resu...

  4. Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.

    Science.gov (United States)

    Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi

    2016-07-01

    A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma. © 2015 Japanese Dermatological Association.

  5. 孟鲁司特钠联合糖皮质激素吸入治疗小儿支气管哮喘临床对照研究%A Clinical Study of Inhaled Corticosteroids United Montelukast Sodium for Treatment of Asthma in Children

    Institute of Scientific and Technical Information of China (English)

    白爱宁; 郭红梅

    2015-01-01

    Objective :To evaluate the clinical efficacy of inhaled corticosteroids united Montelukast sodium for Monte‐lukast of asthma in children .Methods :From January 2013 to December 2014 ,98 children with mild to moderate acute bronchial asthma ,were randomly divided in two groups .One group with 51 cases was taken inhaled corticosteroids unit‐ed Montelukast sodium (Montelukast group) ,the other group with 47 cases was taken inhaled corticosteroids only (control group) .The pulmonary function(FEVl% ,PEF% )were recorded before and after Montelukast at day of 3 ,7 , 10 and 14 .Results:Compared to pretreatment ,the FEV1% and PEF% were obviously improved in both groups (P0 .05) .After 14 days treatment ,the asthma control rate was much higher in Montelukast group(94 .1% ) than that in control group (78 .7% ) ,P<0 .05 .Conclusion:The clinical efficacy of inhaled corticosteroids united Montelukast sodium for treatment of asthma in children was much better than only use of inhaled corticosteroids .%目的:评价糖皮质激素吸入联合孟鲁司特钠治疗小儿急性轻中度支气管哮喘的临床疗效。方法:2013年1月-2014年12月,我院儿科收治轻中度急性支气管哮喘患儿98例,采用随机数字表法分为糖皮质激素吸入联合孟鲁司特钠(孟鲁司特钠组)51例,单用糖皮质激素吸入组(对照组)47例,记录患儿用药前和用药后第3、7、10、14天的肺功能变化。结果:用药后两组患儿肺功能(FEVl%,PEF%)较治疗前明显好转(P<0.05);用药后第3、7、10、14天,两组患儿肺功能指标FEV1%和PEF%比较差别无统计学意义( P>0.05);用药14d后,孟鲁司特钠组患儿哮喘控制率为94.1%显著高于对照组的78.7%( P<0.05)。结论:糖皮质激素吸入联合孟鲁司特钠对小儿急性轻中度支气管哮喘控制率明显好于单用激素。

  6. Meta-analysis of studies on inhaled corticosteroids and montelukast in children with asthma%吸入性糖皮质激素与孟鲁司特治疗儿童哮喘疗效的M eta分析

    Institute of Scientific and Technical Information of China (English)

    郭梅; 符州

    2014-01-01

    Objective To compare the effect of inhaled corticosteroids and montelukast in children with asthma .Methods Data were obtained from Pubmed ,Embase and Central databases ,CNKI and VIP .Only randomized controlled trials (RCT ) that evalua-ting inhaled corticosteroids and montelukast for children were included .The Cochrane collaboration risk bias tools was used to eval-uated the quality of literature .Results The patients with inhaled corticosteroids had a better effect in FEV 1% and PEF than pa-tients with montelukast ,the incidences of adverse drug reactions had no statistically significant difference .The patients with inhaled corticosteroids combined with montelukast had a better effect in FEV 1% or PEF than patients with inhaled corticosteroids only . Conclusion The effect of inhaled corticosteroids is better than montelukast ,the effect of inhaled corticosteroids combined with montelukast is better than inhaled corticosteroids only ,and has drug safety .%目的:比较吸入性糖皮质激素与孟鲁司特或吸入性糖皮质激素联合孟鲁司特与吸入性糖皮质激素治疗儿童轻中度哮喘的疗效。方法检索Pubmed、Embase、Central databases、CNKI、VIP等数据库自建库至今的关于吸入性糖皮质激素与孟鲁司特治疗儿童哮喘的随机对照试验(RCT ),对纳入研究根据Cochrane协作网推荐的风险偏倚工具进行文献质量评价。结果接受吸入性糖皮质激素治疗的患者的一秒用力呼气容积(FEV1)变化量占预计值百分比、呼气峰流量(PEF)的改善均优于接受孟鲁司特治疗的患者,两种治疗方法药物不良反应事件发生率无差异。接受吸入性糖皮质激素联合孟鲁司特治疗的患者FEV1、PEF的改善明显优于接受吸入性糖皮质激素治疗的患者。结论吸入性糖皮质激素的治疗效果优于孟鲁司特,吸入性糖皮质激素联合孟鲁司特的治疗效果优于单纯吸入性糖皮质激素治疗,且药物安全性较好。

  7. 口服孟鲁司特钠咀嚼片治疗小儿慢性咳嗽的疗效观察%Efficacy of Montelukast Sodium Chewable Tablets for Oral Treatment of Children With Chronic Cough

    Institute of Scientific and Technical Information of China (English)

    吴岚

    2016-01-01

    Objective To investigate the clinical effect of the treatment of chronic cough in children with oral montelukast sodium.Methods 148 children with chronic cough in our hospital were randomly divided into treatment group and control group, the clinical treatment effect of the two groups was compared.Results The total effective rate of the treatment group was higher than that of the control group, the difference was statistically signiifcant (χ2=5.436,P<0.05).Conclusion The clinical application of oral administration of the oral administration of the oral administration of montelukast chewable tablet for the treatment of children with chronic cough can signiifcantly increase the effciency of the clinical treatment.%目的:探讨小儿慢性咳嗽口服孟鲁司特钠咀嚼片的临床治疗效果。方法选取我院收治的小儿慢性咳嗽患者148例,随机均分为治疗组和对照组,比较两组的临床治疗效果。结果治疗组治疗总有效率高于对照组,具有统计学差异(χ2=5.436,P<0.05)。结论小儿慢性咳嗽在常规综合治疗的基础上口服孟鲁司特钠咀嚼片能增加患儿的临床治疗有效率。

  8. Observation of Montelukast Sodium in Treatment of Children with Light,Moderate Persistent Asthma Effect%孟鲁司特纳治疗小儿轻、中度持续性哮喘的效果观察

    Institute of Scientific and Technical Information of China (English)

    朴仙花

    2014-01-01

    Objective To observe the clinical effect of montelukast sodium in treatment of children with light, moderate persistent asthma. Methods Select 74 cases of light, moderate persistent asthma in children in our hospital as the research object, then they were randomly divided into observation group and control group, the control group was given the treatment of Budesonide aerosol agent, the observation group in the control group based on the use of secretary Meng Lu Turner tablets in the treatment, the clinical efficacy was compared between two groups. Results The observation group with clinical efficacy than the control group (P<0.05), there is statistical significance. Conclusion The clinical effect of montelukast sodium in treatment of children with light, moderate persistent asthma significantly, worthy of clinical popularization.%目的观察孟鲁司特纳治疗小儿轻、中度持续性哮喘的临床效果。方法选取我院收治的74例轻、中度持续性哮喘患儿为研究对象,将其随机分为观察组与对照组,对照组给予布地奈德气雾剂治疗,观察组在对照组基础上加用孟鲁司特纳片治疗,比较两组患儿的临床疗效。结果观察组患儿临床疗效优于对照组(P<0.05),有统计学意义。结论孟鲁司特纳治疗小儿轻、中度持续性哮喘的临床效果显著,值得在临床上推广。

  9. 酮替芬联合孟鲁司特治疗慢性喘息型支气管炎的疗效分析%Analysis of curative effect by ketotifen combined with montelukast in the treatment of chronic asthmatic bronchitis

    Institute of Scientific and Technical Information of China (English)

    李艳春

    2016-01-01

    Objective To analyze clinical effect by ketotifen combined with montelukast in the treatment of chronic asthmatic bronchitis. Methods A total of 105 patients with chronic asthmatic bronchitis were divided by different therapy into observation group (60 cases) and control group (45 cases). Both groups received conventional therapy, and the control group received additional montelukast, while the observation group received ketotifen combined with montelukast for treatment. Curative effects were compared between the two groups. Results The observation group had higher total effective rate as 95.00% than 80.00% of the control group, and the difference had statistical significance (P<0.05). Conclusion Implement of ketotifen combined with montelukast shows remarkably clinical effect in treating chronic asthmatic bronchitis. This method is safe and creditable, and it is worth clinical promotion.%目的:分析酮替芬联合孟鲁司特治疗慢性喘息型支气管炎的临床疗效。方法105例慢性喘息型支气管炎患者,根据治疗方法的不同分为观察组(60例)和对照组(45例 )。两组均给予常规治疗,对照组在常规治疗基础上加用孟鲁司特治疗,观察组在常规治疗基础上加用酮替芬联合孟鲁司特治疗。比较两组治疗效果。结果观察组总有效率为95.00%高于对照组的80.00%,差异具有统计学意义(P<0.05)。结论采用酮替芬联合孟鲁司特治疗慢性喘息型支气管炎的临床疗效显著,安全可靠,值得临床推广。

  10. Montelukast Disposition: No Indication of Transporter-Mediated Uptake in OATP2B1 and OATP1B1 Expressing HEK293 Cells

    Science.gov (United States)

    Brännström, Marie; Nordell, Pär; Bonn, Britta; Davis, Andrew M.; Palmgren, Anna-Pia; Hilgendorf, Constanze; Rubin, Katarina; Grime, Ken

    2015-01-01

    Clinical studies with montelukast show variability in effect and polymorphic OATP2B1-dependent absorption has previously been implicated as a possible cause. This claim has been challenged with conflicting data and here we used OATP2B1-transfected HEK293 cells to clarify the mechanisms involved. For montelukast, no significant difference in cell uptake between HEK-OATP2B1 and empty vector cell lines was observed at pH 6.5 or pH 7.4, and no concentration-dependent uptake was detected. Montelukast is a carboxylic acid, a relatively potent inhibitor of OATP1B1, OATP1B3, and OATP2B1, and has previously been postulated to be actively transported into human hepatocytes. Using OATP1B1-transfected HEK293 cells and primary human hepatocytes in the presence of OATP inhibitors we demonstrate for the first time that active OATP-dependent transport is unlikely to play a significant role in the human disposition of montelukast. PMID:26694455

  11. Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and Ocular Hypertension: Effectiveness and Treatment Persistence.

    Science.gov (United States)

    Kuwayama, Yasuaki; Hashimoto, Masako; Kakegawa, Reiko; Nomura, Akio; Shimada, Fumiki

    2017-06-01

    The aim of this study was to investigate the long-term intraocular pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin analogue, in actual clinical practice and to determine persistency of tafluprost as an indicator of its benefit-risk balance. This was a large-scale, post-marketing, multicenter, non-interventional, open-label, long-term study. Patients with glaucoma or ocular hypertension who initiated tafluprost treatment were registered and prospectively observed over a 2-year period in the real-world setting in Japan. Long-term IOP and safety data were collected. Of the 4502 patients registered from 553 medical institutions, 4265 patients were analyzed. The majority of patients had normal-tension glaucoma (44.4%) and primary open-angle glaucoma (37.8%), and patients with ocular hypertension constituted 7.0%. Treatment patterns with tafluprost during the study period were as follows: naïve monotherapy (48.1%), switching monotherapy (18.4%), and concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly reduced from 18.6 ± 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2-year observation period after initiation of tafluprost. Significant IOP-lowering effects were shown in various treatment patterns and disease types. Adverse reactions were observed in 795 patients (18.64%). Major adverse reactions included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6% and 76.1% of patients were persistent on tafluprost for 1 and 2 years, respectively, when discontinuation due to insufficient efficacy or adverse events was defined as a treatment failure event. Furthermore, among treatment-naïve patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0% for 1 year and 67.0% for 2 years. Tafluprost showed significant long-term IOP-lowering effects regardless of treatment patterns or diagnosis, with

  12. Novel LC Method Development and Validation for Simultaneous Determination of Montelukast and Doxofylline in Bulk and Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    Gadapa Nirupa

    2013-01-01

    Full Text Available A novel rapid HPLC method was developed for simultaneous determination of montelukast and doxofylline in bulk and pharmaceutical dosage forms. Development of an analytical method for simultaneous estimation of drugs requires a lot of efforts and of course it is a challenging task. The method was developed by using C18 (150 mm×4.6 mm, 5 μm column; mobile phase consisting of methanol and phosphate buffer at pH 4.5; the flow rate of 1.0 mL/min and ultraviolet detection at 280 nm. Both drugs were sufficiently resolved having retention time of 4.7 min and 1.9 min for montelukast and doxofylline, respectively. The method was validated as per ICH Guidelines for various parameters like precision, linearity, accuracy, ruggedness, and robustness. The validated method was applied to the commercially available pharmaceutical dosage form and obtained the desired result.

  13. Development and validation of a rapid RP-UPLC method for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium from tablets

    Directory of Open Access Journals (Sweden)

    R Yanamandra

    2012-01-01

    Full Text Available A rapid, simple, sensitive and selective analytical method was developed by using reverse phase ultra performance liquid chromatographic technique for the simultaneous estimation of bambuterol hydrochloride and montelukast sodium in combined tablet dosage form. The developed method is superior in technology to conventional high performance liquid chromatography with respect to speed, resolution, solvent consumption, time, and cost of analysis. Elution time for the separation was 6 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm Acquity UPLC column using 0.025% (v/v trifluoro acetic acid in water and acetonitrile as organic solvent in a linear gradient program. Resolutions between bambuterol hydrochloride and montelukast sodium were found to be more than 31. The active pharmaceutical ingredient was extracted from tablet dosage from using a mixture of methanol, acetonitrile and water as diluent. The calibration graphs were linear for bambuterol hydrochloride and montelukast sodium in the range of 6.25-37.5 μg/ml. The percentage recoveries for bambuterol hydrochloride and montelukast sodium were found to be in the range of 99.1-100.0% and 98.0-101.6%, respectively. The test solution was found to be stable for 7 days when stored in the refrigerator between 2-8Ί. Developed UPLC method was validated as per International Conference on Harmonization specifications for method validation. This method can be successfully employed for simultaneous estimation of bambuterol hydrochloride and montelukast sodium in bulk drugs and formulations.

  14. [Discussion about relativity between post-marketed safety outcome and treatment course of traditional Chinese medicine drugs on basis of reinforced urn processes].

    Science.gov (United States)

    Zhong, Cheng-Liang; Hu, Si-Yuan; Xie, Yan-Ming; Wang, Yong-Yan

    2013-09-01

    Based on relevant research and development, the possibility of applying the reinforced urn processes (RUPs) statistical approach to traditional Chinese medicine(TCM) drugs safety research is discussed in this paper, primarily through theoretical discussion and simulations. Also introduced are work flows and the key points for the application of the RUPs approach. This potentially new approach has recently been applied to the target estimation of phase I human tolerance clinical trials. A traditional RUPs approach has also been widely applied in the precise point-estimation of allowable longest treatment courses, according to the particular safety outcomes of post-marketed TCM.

  15. [Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

    Science.gov (United States)

    Shimada, Yasuhiro

    2016-04-01

    The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

  16. Formulation and in vitro and in vivo evaluation of film-coated montelukast sodium tablets using Opadry® yellow 20A82938 on an industrial scale

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2013-02-01

    Full Text Available Abdel Naser Zaid,1 Salam Natur,2 Aiman Qaddumi,2 Abeer Abu Ghoush11Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Pharmacare PLC, Ramallah, PalestinePurpose: The aim of this study was to formulate stable film-coated montelukast sodium (MS tablets using Opadry® yellow 20A82938 (Montikast® tablets and to evaluate their in vitro and in vivo release profile.Methods: MS core tablets were manufactured using a direct compression method. Opadry yellow 20A82938 aqueous coating dispersion was used as the film-coating material. Dissolution of the film-coated tablets was tested in 900 mL of 0.5% sodium lauryl sulfate solution and the bioequivalence of the tablets was tested by comparing them with a reference formulation – Singulair® tablets. In vitro–in vivo correlation was evaluated. The stability of the obtained film-coated tablets was evaluated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines.Results: The efficiency of the film coating was determined by subjecting the coated tablets to gastric pH and drug release was analyzed using high-performance liquid chromatography. The coated tablets had no obvious defects. MS release met the study criterion of not less than 80% dissolved after 30 minutes in 0.5% sodium lauryl sulfate solution. Statistical comparison of the main pharmacokinetic parameters clearly indicated no significant difference between test and reference in any of the calculated pharmacokinetic parameters. Level A correlation between in vitro drug release and in vivo absorption was found to be satisfactory.Conclusion: These findings suggest that aqueous film coating with Opadry yellow 20A82938 is an easy, reproducible, and economical approach for preparing stable MS film-coated tablets without affecting the drug-release characteristics.Keywords: coating, stability, aqueous

  17. Montelukast treatment (cysteinyl leukotriene receptor antagonist in a model of food allergy: modifications in lymphatic cell population from rectal mucosa

    Directory of Open Access Journals (Sweden)

    M. Vinuesa

    Full Text Available Objective: the aim is to determine immunopathological modifications in rectal mucosa from rabbits after local challenge in ovalbumin (OVA sensitized animals previously treated with montelukast. Material and methods: experimental design: thirty two rabbits divided into four groups: G1: normal; G2: subcutaneously OVA sensitized; G3: sensitized, locally OVA challenged and sampled 4 hours after challenge; and G4: sensitized, locally OVA challenged and treated 4 hours before challenge with montelukast (0.15 mg/kg. Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA. In each group 200 high microscopical power fields (HPF were counted. Results were expressed as arithmetic mean and SE. Anti -CD4, CD5, µ chain monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. Results: CD 4: G1: 8.3 ± 0.06; G2: 13.4 ± 0.08, G3: 8.25 ± 0.06, G4: 11.8 ± 0.02. CD 5: G1: 7.3 ± 0.05; G2: 9.4 ± 0.05, G3: 11.3 ± 0.06, G4: 8.1 ± 0.06. μ chain: G1: 10.4 ± 0.06; G2: 3.8 ± 0.02, G3: 6.0 ± 0.10, G4: 2.2 ± 0.10. In all cases, experimental groups (G3 vs. G4 presented statistical significant differences (p < 0.05. CD4+, CD5+ cells and μ chain+ decrease in experimental group (G4, probably due to lymphocyte migration inhibition to challenged mucosa. μ chain+ cell decrease could be based on B cell activation and expression of different surface immunoglobulins. Cells expressing μ chain decreased in G2 and G3 likely due to activation of B cells and subsequent expression of other immunoglobulin chains in cell surface. Conclusions: we conclude that obtained data are important to elucidate immunopathology of local anaphylactic reaction in rectal mucosa from systemic sensitized animals after treatment with montelukast.

  18. Optimal Implantation Depth and Adherence to Guidelines on Permanent Pacing to Improve the Results of Transcatheter Aortic Valve Replacement With the Medtronic CoreValve System: The CoreValve Prospective, International, Post-Market ADVANCE-II Study.

    Science.gov (United States)

    Petronio, Anna S; Sinning, Jan-Malte; Van Mieghem, Nicolas; Zucchelli, Giulio; Nickenig, Georg; Bekeredjian, Raffi; Bosmans, Johan; Bedogni, Francesco; Branny, Marian; Stangl, Karl; Kovac, Jan; Schiltgen, Molly; Kraus, Stacia; de Jaegere, Peter

    2015-05-01

    The aim of the CoreValve prospective, international, post-market ADVANCE-II study was to define the rates of conduction disturbances and permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement with the Medtronic CoreValve System (Minneapolis, Minnesota) using optimized implantation techniques and application of international guidelines on cardiac pacing. Conduction disturbances are a frequent complication of transcatheter aortic valve replacement. The rates of PPI in the published reports vary according to bioprosthesis type and the indications for PPI. The primary endpoint was the 30-day incidence of PPI with Class I/II indications when the Medtronic CoreValve System was implanted at an optimal depth (≤6 mm below the aortic annulus). The timing and resolution of all new-onset conduction disturbances were analyzed. A total of 194 patients were treated. The overall rate of PPI for Class I/II indications was 18.2%. An optimal depth was reached in 43.2% of patients, with a nonsignificantly lower incidence of PPI in patients with depths ≤6 mm, compared with those with deeper implants (13.3% vs. 21.1%; p = 0.14). In a paired analysis, new-onset left bundle branch block and first-degree atrioventricular block occurred in 45.4% and 39.0% of patients, respectively, and resolved spontaneously within 30 days in 43.2% and 73.9%, respectively. In patients with new PPI, the rate of intrinsic sinus rhythm increased from 25.9% at 7 days to 59.3% at 30 days (p = 0.004). Optimal Medtronic CoreValve System deployment and adherence to international guidelines on cardiac pacing are associated with a lower rate of new PPI after transcatheter aortic valve replacement, compared with results reported in previous studies. (CoreValve Advance-II Study: Prospective International Post-Market Study [ADVANCE II]; NCT01624870). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. Evaluación clínica y funcional en niños asmáticos tratados con montelukast Clinical and functional evaluation in asthmatic children treated with montelukast

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    Concepción Sánchez Infante

    2011-09-01

    Full Text Available Introducción: el asma bronquial es una enfermedad que se considera puede ser controlable, aunque no puede curarse, pero sus manifestaciones clínicas, que son las que afectan al paciente, pueden desaparecer o disminuir hasta lograr una vida normal, o casi normal, para este y sus familiares, con una serie de medidas medicamentosas y no medicamentosas. Objetivo: evaluar la eficacia del montelukast en el tratamiento de niños asmáticos persistentes. Métodos: se realizó un estudio en 65 niños asmáticos persistentes en el Hospital Pediátrico Universitario "William Soler". Se evaluaron los síntomas, pruebas funcionales respiratorias, días perdidos en la escuela, y control de la enfermedad, inicialmente, y un año después de la introducción del montelukast. Se observó la posibilidad de efectos secundarios. Resultados: 55 pacientes (84,6 % tenían tos nocturna diaria antes del tratamiento. Al año, la tos nocturna diaria se observó solo en 9 (13,9 %; 43 (66,1 % presentaban sibilancias al reírse, mientras que al año 1 (1,6 % mantenía sibilancias diarias con la risa; 41 (63,0 % tenían, inicialmente, afectación de la actividad física, mientras que al año 51 (78,4 % no tenían limitaciones. El 100 % tenía ausencias escolares. Durante el año de tratamiento 34 (57,0 % no presentaron días perdidos; 42 (64,6 % tenían crisis diarias, sin embargo, al reevaluar, 38 (58,5 % no tuvieron crisis. Habían tenido ingresos hospitalarios 23 (35,4 %, pero posteriormente solo 5 necesitaron hospitalización. Antes del tratamiento, 49 (75,0 % necesitaron tratamiento de rescate, en cambio, durante el año disminuyó a 27 (41,0 %. 19 niños (38,0 % tenían inicialmente el volumen espiratorio forzado en 1 s menor del 80 %, y solamente 8 (16,0 % posteriormente. Antes del tratamiento el 100 % de los pacientes tenían asma no controlada o parcialmente controlada, mientras que al año el 57 % tenía el asma controlada. No se observaron reacciones adversas

  20. Effect of montelukast on excessive airway narrowing response to methacholine in adult asthmatic patients not on controller therapy

    DEFF Research Database (Denmark)

    Ulrik, Charlotte Suppli; Diamant, Zuzana

    2009-01-01

    2-agonists p.r.n. only with a twice-documented absence of dose-response plateau, participated in a double-blind, parallel study with Mont (10 mg) or placebo once daily for 12 weeks. Mtc dose-response curves (0.03-256 mumol or >40% FEV(1) decline) were repeated every 4 weeks. The primary objective......Excessive airway narrowing is an important determinant of fatal asthma. This pathophysiological feature is characterized by the absence of a dose-response plateau to methacholine (Mtc). We investigated if the leukotriene receptor antagonist (LTRA) montelukast (Mont) can induce a dose-response.......9%, respectively, with no differences between the groups. After 12 weeks, a dose-response plateau was observed in two patients (Mont) and one patient (placebo) (NS), and comparison of changes from baseline in maximal decline in FEV(1) or PD(20) revealed no significant differences between groups. Twelve weeks...

  1. Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats.

    Science.gov (United States)

    Kalonia, H; Kumar, P; Kumar, A; Nehru, B

    2010-11-24

    The present study has been designed to explore the protective effect of montelukast (leukotriene receptor antagonist) against intrastriatal quinolinic acid (QA; 300 nmol) and malonic acid (MA; 6 μmol) induced Huntington's like symptoms in rats. Quinolinic acid has been reported to induce excitotoxicity by stimulating the N-methyl-D-aspartate receptor, causing calcium overload which in turn leads to the neurodegeneration. On the other hand, MA, being a reversible inhibitor of mitochondrial enzyme complex-II, leads to energy crisis and free radical generation. Recent studies have reported the therapeutic potential of leukotriene receptor antagonists in different neurodegenerative disorders. However, their exact role is yet to be established. The present study accordingly, is an attempt to investigate the effect of montelukast against QA and MA induced behavioral, biochemical and molecular alterations in rat striatum. Oxidative stress, mitochondrial enzyme complex and tumor necrosis factor-alpha (TNF-α) were evaluated on day 21st and 14th post intrastriatal QA and MA treatment, respectively. Findings of the present study demonstrate significant alteration in the locomotor activity and motor coordination as well as oxidative burden (increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidants), mitochondrial enzyme complex (I, II and IV) activities and TNF-α level, in both intrastriatal QA and MA treated animals. Further, montelukast (0.4, 0.8 mg/kg p.o.) treatment for 21 and 14 days respectively, attenuated the behavioral alterations, oxidative stress, mitochondrial dysfunction and TNF-α level in these models of Huntington's disease in a significant manner. In conclusion, the present study emphasizes the neuroprotective potential of montelukast in the therapeutic management of Huntington like symptoms.

  2. Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan.

    Science.gov (United States)

    Takeuchi, Tsutomu; Ishida, Kota; Shiraki, Katsuhisa; Yoshiyasu, Takashi

    2017-06-26

    Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.

  3. Effect of montelukast sodium combined with budesonide in the treatment of asthma in children%孟鲁司特钠联合布地奈德治疗小儿哮喘的效果

    Institute of Scientific and Technical Information of China (English)

    李峥嵘; 张烁

    2015-01-01

    Objective To investigate the effect of montelukast sodium combined with budesonide in the treatment of asthma in children. Methods 131 children with asthma diagnosed and treated in our hospital from April 2012 to April 2014 were chosen and they were randomly divided into the control group(n=65)and the treatment group(n=66).The con-trol group only was given budesonide,while the treatment group was given budesonide combined with montelukast sodi-um.The curative effect,the change of lung function and peripheral blood eosinophil in the two groups were compared. Results The total effective rate of the treatment group and the control group was 97.0%,87.7% respectively,the total ef-fective rate of the treatment group was higher than that in the control group (P<0.05);lung function indictors (FEV1,PEF) and the level of peripheral blood Eos of the two groups after treatment were better than before treatment (P<0.05),and the treatment group improved more significantly (P<0.05). Conclusion Montelukast sodium combined with budesonide in the treatment of asthma in children can better recover lung function of children,and obviously improve peripheral blood Eos leve.Its effect is significant,and it is worthy of promotion.%目的:探讨孟鲁司特钠联合布地奈德治疗小儿哮喘的效果。方法选取2012年4月~2014年4月本院诊治的小儿哮喘患者共131例,将其随机分为对照组65例和治疗组66例。对照组单用布地奈德,治疗组加用孟鲁司特钠治疗。比较两组的疗效、肺功能和外周血Eos的变化情况。结果治疗组、对照组的总有效率分别为97.0%、87.7%,治疗组的总有效率高于对照组(P<0.05);两组治疗后的肺功能指标(FEV1、PEF)和外周血Eos水平均优于治疗前(P<0.05),且治疗组改善更显著(P<0.05)。结论孟鲁司特钠联合布地奈德治疗小儿哮喘可较好地恢复患儿的肺功能,明显改善其外周血Eos水平,效果显著,值得推广。

  4. Diffuse large B-cell lymphoma associated with the use of biologic and other investigational agents: the importance of long-term post-marketing safety surveillance.

    Science.gov (United States)

    Goddard, Allison; Borovicka, Judy H; West, Dennis P; Evens, Andrew M; Laumann, Anne

    2011-01-01

    This case report describes a patient who developed diffuse large B-cell lymphoma (DLBCL) after receiving courses of two investigational biologic agents and cyclosporine followed by more than four years of subcutaneous efalizumab for the treatment of extensive chronic plaque psoriasis. Three years later, the patient remains free of lymphoma and his psoriasis is well controlled with thrice-weekly narrow-band ultraviolet phototherapy. This case emphasizes the importance of continued long-term post-marketing safety surveillance and the early reporting of all possible serious side effects, including cancers, related to the use of any newly available product. In particular, surveillance should focus on the immunomodulating biologic agents in order to identify possible dangerous sequelae.

  5. A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER Database and Association Analysis.

    Directory of Open Access Journals (Sweden)

    Masakazu Fujiwara

    Full Text Available Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender has not been proposed.We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA. We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male.Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions

  6. Safety and effectiveness of tofogliflozin in elderly Japanese patients with type 2 diabetes mellitus: A post-marketing study (J-STEP/EL Study).

    Science.gov (United States)

    Utsunomiya, Kazunori; Shimmoto, Naoki; Senda, Masayuki; Kurihara, Yuji; Gunji, Ryoji; Fujii, Shoko; Kakiuchi, Seigo; Fujiwara, Hisataka; Kameda, Hiroyuki; Tamura, Masahiro; Kaku, Kohei

    2017-01-20

    Although sodium-glucose cotransporter 2 inhibitors are a promising treatment for type 2 diabetes mellitus, they are associated with concerns about specific adverse drug reactions. We carried out a 1-year post-marketing study of tofogliflozin, a novel agent in this class, in Japanese elderly patients with type 2 diabetes mellitus. This was a prospective, observational and multicenter post-marketing study carried out in the context of routine clinical practice. The study included all type 2 diabetes patients aged ≥65 years who started treatment with tofogliflozin during the first 3 months after its launch on 23 May 2014. Of 1,535 patients registered, 1,507 patients whose electronic case report forms were collected and who had at least one follow-up visit were included in the safety analysis. A total of 270 of 1,507 patients (17.92%) had at least one adverse drug reaction to tofogliflozin. The incidences of adverse drug reactions of special interest, namely, polyuria/pollakiuria, volume depletion-related events, urinary tract infection, genital infection, hypoglycemia and skin disorders were 2.92, 3.85, 2.06, 1.33, 1.06 and 2.39%, respectively. Among those patients evaluable for clinical effectiveness, the mean change in glycated hemoglobin and bodyweight from baseline to last visit was -0.46% (P < 0.0001) and -2.71 kg (P < 0.0001), respectively. The present study showed that the incidence of adverse drug reactions to tofogliflozin in this study of elderly patients aged ≥65 years differed little from the incidence in the preapproval clinical trials. It was shown that tofogliflozin significantly decreased glycated hemoglobin levels. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  7. Children with mild to moderate asthma efficacy of montelukast therapy%孟鲁司特钠治疗小儿轻、中度哮喘的疗效观察

    Institute of Scientific and Technical Information of China (English)

    李杰; 王啟燕; 唐晓燕; 罗洁

    2015-01-01

    Objective To study suffering from mild or moderate asthma symptoms in children with the use of montelukast treatment is feasible. Methods Randomly selected between March 2013 to March 2014 in our hospital for treatment of mild or moderate asthma symptoms in children 82 cases. The first 41 patients to the hospital pediatric divided into experimental group and 41 cases of pediatric hospital later the inclusion of a control group. To control drug budesonide alone, children in the experimental group also received budesonide and montelukast pharmaceutical agents for the treatment. Comparative efficacy. Results The data confirm that children in the experimental group and the effective control of lung function recovery situations are better than children in the control group P<0.05. Conclusion In order to improve the therapeutic effect in children with mild or moderate asthma symptoms, the choice of drug sodium Meng Lute better efficacy, and therefore should be universal primary health care institutions in the treatment program.%目的:研究对身患轻度或中度哮喘病症的小儿使用孟鲁司特钠进行治疗的可行性。方法随机抽选在2013年3月至2014年3月之间在本院接受诊治的轻度或中度哮喘病症的小儿82例。把先来院的41例小儿划分为实验组,后来院的41例小儿则列入对照组。给对照组单独使用布地奈德药剂,实验组的小儿同时接受布地奈德药剂以及孟鲁司特钠药剂治疗。对比疗效。结果数据证实,实验组的小儿在有效控制以及肺部机能复原情况皆比对照组小儿更好P<0.05。结论为提高轻度或中度哮喘病症的小儿治疗效果,选用孟鲁特钠药剂疗效更佳,因此基层医疗机构应普及该治疗方案。

  8. 新药Ⅳ期临床试验与药品上市后再评价的异同点以及存在的问题%Similarities and differences of new drug phase Ⅳ clinical trials and post -marketing drug evaluation as well as existing problems

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    With the retrospection of the background information of new drug phase Ⅳ clinical trials and post -marketing drug evaluation , this paper compared their similarities and differences and explored the exist-ing problems.Meanwhile , it illustrated the characteristics of clinically verified trials having inclination to pharmaceutical promotion , anticipating helping clinicians and clinical pharmacists clarify the purpose and range of clinical trials, and providing data for clinical rational drug use by dis-tinguishing among new drug phase IV clinical trial , post-marketing drug evaluation and clinical trials having inclination to pharmaceutical promotion.%本文将新药Ⅳ期临床试验与药品上市后再评价的相关政策背景进行了追溯,对两者的异同点进行了比较,并对存在的问题进行了探讨;同时,对具“药品促销倾向”的临床验证试验的特点进行了阐述,期望通过比较三者的区别,为临床医师与药师等明确临床试验的研究目的与范围、为临床合理用药提供研究数据。

  9. The risk of bleeding with duloxetine treatment in patients who use nonsteroidal anti-inflammatory drugs (NSAIDs: analysis of placebo-controlled trials and post-marketing adverse event reports

    Directory of Open Access Journals (Sweden)

    Perahia DG

    2013-11-01

    Full Text Available David G Perahia,1 Mark E Bangs,2 Qi Zhang,2 Yingkai Cheng,2 Jonna Ahl,2 Elijah P Frakes,2 Michael J Adams,2 James M Martinez2 1Neurosciences, Lilly Research Centre, Windlesham, Surrey, UK; 2Neurosciences, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To assess the safety of duloxetine with regards to bleeding-related events in patients who concomitantly did, versus did not, use nonsteroidal anti-inflammatory drugs (NSAIDs, including aspirin. Methods: Safety data from all placebo-controlled trials of duloxetine conducted between December 1993 and December 2010, and post-marketing reports from duloxetine-treated patients in the US Food and Drug Administration Adverse Event Reporting System (FAERS, were searched for bleeding-related treatment-emergent adverse events (TEAEs. The percentage of patients with bleeding-related TEAEs was summarized and compared between treatment groups in all the placebo-controlled studies. Differences between NSAID user and non-user subgroups from clinical trial data were analyzed by a logistic regression model that included therapy, NSAID use, and therapy-by-NSAID subgroup interaction. In addition, to determine if higher duloxetine doses are associated with an increased incidence of bleeding-related TEAEs, and whether the use of concomitant NSAIDs might influence the dose effect if one exists, placebo-controlled clinical trials with duloxetine fixed doses of 60 mg, 120 mg, and placebo were analyzed. Also, the incidence of bleeding-related TEAEs reported for duloxetine alone was compared with the incidence in patients treated with duloxetine and concomitant NSAIDs. Finally, the number of bleeding-related cases reported for duloxetine in the FAERS database was compared with the numbers reported for all other drugs. Results: Across duloxetine clinical trials, there was a significantly greater incidence of bleeding-related TEAEs in duloxetine- versus placebo-treated patients overall and also in those patients who

  10. Value of leukotrienes C4 in exhaled breath condensate and the anti-inflammatory effect of montelukast in asthma%哮喘患者呼出气冷凝液白三烯检测及孟鲁司特的抗炎作用

    Institute of Scientific and Technical Information of China (English)

    秦娥; 沈巨信; 周国忠; 孙健

    2013-01-01

    Objective: To investigate the level of leukotrienes C4(LTC4) in exhaled breath condensate (EBC) of patients with asthma and the effect of inflammatory factors after montelukast treatment. Methods: Thirty patients with asthma were enrolled and given 10 mg montelukast once each night for one month. Before therapy and one month later, the levels of LTC4 in EBC were measured. Another 30 healthy controls were selected as control group. Results: LTC4 levels were significantly higher in the asthma patients before and after treatment compared with the control subjects. The level of LTC4 was significantly decreased in patients with asthma after treatment. Conclusion: Detecting the LTC4 level in EBC can monitor asthmatic airway inflammation, which is convenient, noninvasive and safe. Montelukast can decrease the level of LTC4, which is an effective anti - inflammatory reagent.%目的:观察支气管哮喘患者呼出气冷凝液(EBC)中半胱氨酰白三烯C4 (LTC4)水平及孟鲁司特治疗后的变化.方法:选择哮喘非急性发作期患者30例,均予孟鲁司特10 mg,每晚一次口服,疗程1月,分别于治疗前及治疗后检测EBC中LTC4水平,同时测定肺功能,另选择30例健康人为对照组.结果:哮喘组治疗前LTC4水平(55.17±17.02) ng/ml,显著高于正常对照组(17.15±7.48)ng/ml,差异有统计学意义(P<0.01).哮喘组治疗后LTC4水平为(38.36±14.03) ng/ml,仍高于正常对照组,差异有统计学意义(P<0.0l).哮喘组治疗前LTC4水平显著高于治疗后,差异有统计学意义(P<0.01).结论:检测哮喘患者EBC中LTC4水平可简便安全监测哮喘的气道炎症,孟鲁司特是一种有效的气道炎症抑制剂.

  11. 丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎60例临床分析%Clinical analysis of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis in 60 cases

    Institute of Scientific and Technical Information of China (English)

    郭书霞

    2015-01-01

    目的:探讨丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎的临床效果。方法:收治重症毛细支气管炎患儿60例,随机分为对照组和观察组,对照组采用常规对症支持治疗,观察组在常规治疗的基础上加用丙种球蛋白+沙丁胺醇+孟鲁司特钠治疗,比较两组的治疗效果及不良反应。结果:观察组总有效率显著高于对照组(P<0.05)。结论:丙种球蛋白、沙丁胺醇联合孟鲁司特钠治疗重症毛细支气管炎总有效率显著高于常规治疗,不良反应少,使用方便。%Objective:To explore the clinical effect of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis.Methods:60 children with severe bronchiolitis were selected.They were randomly divided into the control group and the observation group.The control group was given conventional symptomatic and supportive treatment.The observation group was given gamma globulin,salbutamol combined with montelukast sodium treatment on the basis of conventional treatment.The treatment effects and adverse reactions of two groups were compared.Results:The total effective rate of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The total effective rate of gamma globulin,salbutamol combined with montelukast sodium in the treatment of severe bronchiolitis is significantly higher than that of the conventional treatment.Its adverse reaction is less.It is easy to use.

  12. 孟鲁司特联合鼻内激素治疗儿童腺样体肥大的临床观察%Clinical efficacy of combined treatment with montelukast and intranasal steroid for chronic adenoid hypertrophy in children

    Institute of Scientific and Technical Information of China (English)

    陈超; 刘大波; 刘少峰; 仇书要

    2013-01-01

    Objectives To observe the clinical efficacy of combined treatment with montelukast and intranasal steroid for chronic adenoid hypertrophy in children. Methods 47 children with chronic adenoid hypertrophy were selected and ran-domly divided into drug combination group (n=23) treated with montelukast combined with intranasal steroids for two months and control group (n=24) treated with intranasal steroids only for two months. Clinical efficacy was compared between two groups by clinical score and the result of fibronasopharyngoscopy. Results The clinical scores were 0 (0, 1.0) and 0(0, 0) at 2 weeks and 2 months after treatment in combination group, and 1.0 (1.0, 1.0) and 0 (0, 1.0) in control group. There were sig-nificant differences between two groups (Z=2.404, P<0.05;Z=2.069, P<0.05). Conclusions The clinical efficacy of combined treatment with Montelukast and intranasal steroid is better than that of treatment with intranasal steroid only in children with chronic adenoid hypertrophy.%  目的观察孟鲁司特联合鼻内激素治疗儿童腺样体肥大的短期疗效。方法选取腺样体肥大患儿47例,随机分成2组。联合用药组23例,采用孟鲁司特与鼻内激素联合治疗;对照组24例,单用鼻内激素治疗;连续治疗2个月。根据纤维鼻咽镜检查和改进的Bitar临床评分方法比较两组疗效。结果联合用药组治疗2周和2个月的临床评分分别为0(0,1.0);0(0,0),优于对照组的临床评分1.0(1.0,1.0);0(0,1.0),差异具有统计学意义(Z=2.404、2.069,P均<0.05)。结论孟鲁司特联合鼻内激素治疗腺样体肥大的疗效优于单纯使用鼻内激素。

  13. A Comparative Study of Treatment-Emergent Adverse Events Following Use of Common Bowel Preparations Among a Colonoscopy Screening Population: Results from a Post-Marketing Observational Study.

    Science.gov (United States)

    Anastassopoulos, Kathryn; Farraye, Francis A; Knight, Tyler; Colman, Sam; Cleveland, Mark vB; Pelham, Russell W

    2016-10-01

    Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP(®) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). This real-world, observational study used de-identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. Among patients ≥45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non-OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non-OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations.

  14. Optimal implantation depth and adherence to guidelines on permanent pacing to improve the results of transcatheter aortic valve replacement with the medtronic corevalve system: The CoreValve prospective, international, post-market ADVANCE-II study

    NARCIS (Netherlands)

    A.S. Petronio (Anna S.); J.-M. Sinning (Jan-Malte); N.M. van Mieghem (Nicolas); G. Zucchelli (Giulio); G. Nickenig (Georg); R. Bekeredjian (Raffi); B. Bosmans; F. Bedogni (Francesco); M. Branny (Marian); K. Stangl (Karl); J. Kovac (Jan); M. Schiltgen (Molly); S. Kraus (Stacia); P.P.T. de Jaegere (Peter)

    2015-01-01

    textabstractObjectives The aim of the CoreValve prospective, international, post-market ADVANCE-II study was to define the rates of conduction disturbances and permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement with the Medtronic CoreValve System (Minneapolis, Minnes

  15. Optimal implantation depth and adherence to guidelines on permanent pacing to improve the results of transcatheter aortic valve replacement with the medtronic corevalve system: The CoreValve prospective, international, post-market ADVANCE-II study

    NARCIS (Netherlands)

    A.S. Petronio (Anna S.); J.-M. Sinning (Jan-Malte); N.M. van Mieghem (Nicolas); G. Zucchelli (Giulio); G. Nickenig (Georg); R. Bekeredjian (Raffi); B. Bosmans; F. Bedogni (Francesco); M. Branny (Marian); K. Stangl (Karl); J. Kovac (Jan); M. Schiltgen (Molly); S. Kraus (Stacia); P.P.T. de Jaegere (Peter)

    2015-01-01

    textabstractObjectives The aim of the CoreValve prospective, international, post-market ADVANCE-II study was to define the rates of conduction disturbances and permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement with the Medtronic CoreValve System (Minneapolis, Minnes

  16. Fast Disintegrating Combination Tablet of Taste Masked Levocetrizine Dihydrochloride and Montelukast Sodium: Formulation Design, Development, and Characterization

    Directory of Open Access Journals (Sweden)

    M. M. Gupta

    2014-01-01

    Full Text Available The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC. The tablets were prepared using microcrystalline cellulose (MCC PH 102 as diluent along with crospovidone (CP, croscarmellose sodium (CCM, and sodium starch glycolate (SSG as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT, and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.

  17. Protective effect of high-dose montelukast on salbutamol-induced homologous desensitisation in airway smooth muscle.

    Science.gov (United States)

    Fogli, Stefano; Stefanelli, Fabio; Martelli, Alma; Daniele, Simona; Testai, Lara; Calderone, Vincenzo; Trincavelli, Maria Letizia; Martini, Claudia; Breschi, Maria Cristina

    2013-12-01

    Montelukast (MK) is a potent cysteinyl-leukotriene receptor antagonist that causes dose-related improvements in chronic asthma. We sought to determine whether MK was able to prevent salbutamol-induced tolerance in airway smooth muscle. Homologous β2-adrenoceptor desensitisation models were established in guinea-pigs and in human bronchial smooth muscle cells (BSMC) by chronic salbutamol administration. Characterisation tools included measurement of the response of tracheal smooth muscle tissues to salbutamol, analysis of gene expression and receptor trafficking, evaluation of intracellular cAMP levels and phosphodiesterase (PDE) activity in human bronchial smooth muscle cells. Salbutamol-induced β2-adrenoceptor desensitisation was characterised by β2-agonist hyporesponsiveness (-30%, p salbutamol. Prolonged salbutamol treatment significantly decreased cAMP synthesis, induced a complete removal of the β2-adrenoceptor from plasma membrane with a parallel increase in the cytosol and increased PDE4D5 gene transcription and PDE activity in human bronchial smooth muscle cells. In homologously desensitised BSMC, MK 30 μM for 24 h was able to prevent salbutamol subsensitivity and such an effect was associated with inhibition of salbutamol-induced PDE4 activity and restoration of membrane β2-adrenoceptor expression and function. These findings suggest the presence of a favourable interaction between MK and β2-adrenoceptor agonists that might improve the therapeutic index of bronchodilators in patients with chronic respiratory diseases.

  18. Following-up study on efficacy of different preventive montelukast sodium programs in the prevention of wheezing and asthma of atopic children with asthmatic bronchitis%不同孟鲁司特钠方案预防特应质喘息性支气管炎患儿发作的研究

    Institute of Scientific and Technical Information of China (English)

    郭玉兰; 郦银芳; 张莉

    2015-01-01

    Objective To observe and explore the clinical efficacy of different preventive montelukast sodi-um programs in the prevention of wheezing and asthma of atopic children with asthmatic bronchitis. Methods 150 atopic children with asthmatic bronchitis from Jan. 2012 to June. 2014 were selected and randomly divided into the 3-month preventive medicine group ( group A ) , the 6-month preventive medicine group ( group B ) and the control group, 50 cases in each group. The 3-month preventive medicine group was treated with montelukast sodium for 3 months to prevent wheezing and asthma, and the 6-month preventive medicine group was treated with montelukast so-dium for 6 months, while the control group was not given preventive medicine intervention. After 6 months of follow-up, the blood serum IgE, leukotriene E4 and other inflammatory mediators were examined, and the incidence of wheezing and asthma of the 3 groups during follow-up were compared. Results After 6 months' follow-up, the serum levels of IgE, LTE4, IL-4, IL-8 and IL-10 were significantly different from each group (P0. 05). Conclusion Stable atopic asthmatic bronchitis children with preventive montelukast sodium programs can effectively reduce the incidence of wheezing and asthma, and the 6-month program has comparative advantages.%目的:观察并探讨不同孟鲁司特钠服药方案预防特异质喘息性支气管炎患儿喘息及哮喘发作的临床疗效。方法入选2012年1月~2014年6月收治的150例喘息性支气管炎患儿为研究对象,患儿治疗稳定后根据随机数字表分为3个月服药组、6个月服药组和对照组,每组各50例,3个月服药组给予口服孟鲁司特钠3个月预防性服药方案,6个月服药组给予口服孟鲁司特钠6个月服药方案,对照组不给于药物干预,随访6个月后采血检测血清IgE、白三烯E4等炎性介质,比较三组随访期间喘息及哮喘发生率。结果随访6个月后三组患儿血清IgE、LTE4、IL-4、IL-8

  19. Bioequivalence studies for two different strengths of montelukast in healthy volunteers: 10 mg film-coated tablets and 5 mg chewable tablets.

    Science.gov (United States)

    Pedroso, P; Almeida, S; Filipe, A; Neves, R I; Boudreault, S; Jiménez, C

    2013-09-01

    In order to assess the bioequivalence of 2 different formulations of montelukast, a pivotal trial for the montelukast 10 mg film-coated tablets formulation and a pivotal trial for the montelukast 5 mg chewable tablets formulation were conducted.For the 10 mg study, 34 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days, while for the 5 mg study, 42 healthy subjects were included in another study with a similar design. For both studies, plasma samples were collected up to 24 h post-dosing and drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection.Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and from time zero to infinity (AUC0-inf) and maximum observed concentration (Cmax), were determined from the drug concentration data using non-compartmental analysis.In the 10 mg study, the 90% confidence intervals obtained by analysis of variance were 99.62-120.51% for Cmax, 102.25-117.37% for AUC0-t and 101.96-116.67% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.In the 5 mg study, the 90% confidence intervals were 91.14-98.46% for Cmax, 93.02-98.42% for AUC0-t and 93.09-98.63% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.Bioequivalence between formulations was concluded both in terms of rate and extent of absorption for both strengths.

  20. Evaluation of Aryoseven Safety (Recombinant Activated Factor VII) in Patients with Bleeding Disorders (An Observational Post-Marketing Surveillance Study)

    Science.gov (United States)

    Toogeh, Gholamreza; Abolghasemi, Hassan; Eshghi, Peyman; Managhchi, Mohammadreza; Shaverdi-niasari, Mohammadreza; Karimi, Katayoon; Roostaei, Samin; Emran, Neda; Abdollahi, Alireza

    2016-01-01

    Background: Recombinant activated factor VII induces hemostasis in patients with coagulopathy disorders. AryoSeven™ as a safe Iranian Recombinant activated factor VII has been available on our market. This study was performed to establish the safety of AryoSeven on patients with coagulopathy disorder. Methods: This single-center, descriptive, cross sectional study was carried out in Thrombus and Homeostasis Research Center ValiAsr Hospital during 2013-2014. Fifty one patients with bleeding disorders who received at least one dose of Aryoseven were enrolled. Patients’ demographic data and adverse effect of drug and reaction related to Aryoseven or previous usage of Recombinant activated FVII were recorded in questionnaires. Finally data were analyzed to compare side effects of Aryoseven and other Recombinant activated FVII brands. Results: Aryoseven was prescribed for 51 Patients. Of all participants with mean age 57.18+21.38 yr, 31 cases were male and 26 subjects had past history of recombinant activated FVII usage. Glanzman was the most frequent disorder followed by congenital FVII deficiency, hemophilia with inhibitors, factor 5 deficiency, acquired hemophilia, hemophilia A with inhibitor, and hemophilia A or B with inhibitor. The majority of bleeding episodes had occurred in joints. Three patients (5.9%) complained about adverse effects of Aryoseven vs. 11.5 % about adverse effects of other brands. However this difference was not significant, statistically. Conclusion: Based on monitor patients closely for any adverse events, we concluded that Aryoseven administration under careful weighing of benefit versus potential harm may comparable with other counterpart drugs. PMID:27799968

  1. 欧盟药品上市后抽验模式分析与启示%A look into the EU post-marketing sampling and testing model and its inspiration to China

    Institute of Scientific and Technical Information of China (English)

    孙苓苓; 毕开顺

    2012-01-01

    Due to the large number of pharmaceutical manufacturers and intermediate links in China as well as the incomplete market security system, there are many factors that affect drug quality, and drug safety problems have attracted more and more attention. Compared with our country, European Union ( EU) has already set up a full equipped marketing sampling and testing system. This article gives an introduction of their surveillance and testing bodies and studies the Centrally Authorised Products (CAP) sampling and testing and the Mutual Recognition Procedure (MRP)/Decentralised Procedure (DCP) products post-marketing surveillance models, thus to provide reference for our own work.%由于我国药品生产企业数目众多,流通环节众多,市场保障体系建立尚不完全,因而影响药品安全的风险因素也较多,药品质量问题越来越引起了国家与公众的重视.与我国相比,欧盟已经建立了完善的药品抽验体系,本文通过对欧盟上市后药品抽验监管机构及技术机构的介绍,并对集中抽验和市场监督抽验两种模式进行研究,为我国上市后药品的评价性抽验和市场监督抽验提供借鉴.

  2. Safety and Effectiveness of Once-Daily Tadalafil (5 mg) Therapy in Korean Men with Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms in a Real-World Clinical Setting: Results from a Post-Marketing Surveillance Study.

    Science.gov (United States)

    Won, Ji Eon; Chu, Ji Yeon; Choi, Hyunah Caroline; Chen, Yun; Park, Hyun Jun; Dueñas, Héctor José

    2017-09-06

    The aim of this study was to investigate the safety and effectiveness of tadalafil 5 mg once daily (quaque die [everyday], QD) among Korean men with benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) in a real-world clinical setting. This was a single-country, prospective, observational cohort study in which patients newly prescribed tadalafil 5 mg QD for the treatment of BPH/LUTS were followed-up for 12±2 or 24±2 weeks, or to the last treatment, during post-marketing surveillance. Safety was evaluated in terms of the frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Effectiveness was assessed by changes in the International Prostate Symptom Score (IPSS) from baseline to each endpoint. All patients receiving ≥1 dose of tadalafil 5 mg QD (N=637) were included in the safety population. Two percent of patients (n=13) experienced 15 TEAEs of mild (n=10; 66.7%) or moderate (n=5; 33.3%) severity. No severe TEAEs and no SAEs were reported. Effectiveness evaluations included all patients receiving tadalafil who had both baseline and endpoint observations (12-week, N=265; 24-week, N=44). Compared with baseline, mean the IPSS total score (±standard error) significantly improved by 4.7±0.3 and 6.4±0.7 points at the 12- and 24-week endpoints, respectively (p<0.0001), with significant improvements also observed on the storage, voiding, and quality of life subscores. In total, 69.1% of the patients had a clinically meaningful ≥3-point improvement in the IPSS total score. Tadalafil 5 mg QD was well tolerated and effective in Korean men with BPH/LUTS in a real-world clinical setting.

  3. Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea.

    Science.gov (United States)

    Kim, Tae Heon; Lee, Sang Eun; Lee, Hahn-Ey; Lee, Kyu-Sung

    2016-08-01

    The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz ) in Korean patients with overactive bladder (OAB) in routine clinical practice. This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator's discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy. A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24 hours decreased by 4.0, 2.4, and 0.8, respectively (all p fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.

  4. Post-marketing safety evaluation of S-1 in patients with inoperable or recurrent breast cancer: especially in patients treated with S-1 + trastuzumab.

    Science.gov (United States)

    Saito, Yuki; Oshitanai, Risa; Terao, Mayako; Terada, Mizuho; Tsuda, Banri; Okamura, Takuho; Suzuki, Yasuhiro; Tokuda, Yutaka

    2011-09-01

    The purpose of this study was to assess the safety of S-1 in Japanese in inoperable or recurrent breast cancer patients. A prospective post-marketing surveillance was performed at 313 sites in Japan in patients with inoperable or recurrent breast cancer treated with S-1. We examined 1361 patients between January 2006 and December 2007 with regard to the incidence of adverse drug reactions graded by the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. At least one adverse drug reaction was encountered by 858 patients, with an overall incidence of 63.0% (858/1361). The incidence of Grade 3 or higher adverse drug reactions in a descending order was 14.7% (200/1361). In this study, the most common combination drug was trastuzumab. The overall incidence of adverse drug reactions was 63.5% (431/679 patients) in patients treated with S-1 alone, and 55.9% (66/118 patients) in patients treated with S-1 + trastuzumab. Monotherapy with S-1 or combination therapy with S-1 + trastuzumab was well tolerated for inoperable or recurrent breast cancer patients.

  5. [Response of Pharmaceutical Companies to the Crisis of Post-Marketing Clinical Trials of Anti-Cancer Agents -- Results of Questionnaires to Pharmaceutical Companies].

    Science.gov (United States)

    Nakajima, Toshifusa

    2016-04-01

    Investigator-oriented post-marketing clinical trials of anti-cancer agents are faced to financial crisis due to drastic decrease in research-funds from pharmaceutical companies caused by a scandal in 2013. In order to assess the balance of research funds between 2012 and 2014, we made queries to 26 companies manufacturing anti-cancer agents, and only 10 of 26 responded to our queries. Decrease in the fund was observed in 5 of 10, no change in 1, increase in 3 and no answer in 1. Companies showed passive attitude to carry out doctor-oriented clinical trials of off-patent drugs or unapproved drugs according to advanced medical care B program, though some companies answered to proceed approved routines of these drugs if clinical trials showed good results. Most companies declined to make comments on the activity of Japan Agency for Medical Research and Development (AMED), but some insisted to produce good corroboration between AMED and pharmaceutical companies in order to improve the quality of trials. Further corroboration must be necessary for this purpose among researchers, governmental administrative organs, pharmaceutical companies, patients' groups, and mass-media.

  6. Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

    Science.gov (United States)

    Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

    2017-06-01

    The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

  7. Practical synthesis of methyl (E)-2-(3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-oxopropyl)benzoate, a key intermediate of Montelukast

    Institute of Scientific and Technical Information of China (English)

    Liang He; Yang Hui Guo; Ya Ping Wang; Xiang Jing Wang; Ji Zhang; Wen Sheng Xiang

    2012-01-01

    A novel and practical synthetic route is presented for the preparation of methyl-(E)-2-(3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-oxopropyl)benzoate,the key intermediate of Montelukast,a leukotriene antagonist.The main diarylpropane framework was prepared via a polarity conversation reaction resulting in an acyl anion equivalent followed by a nucleophilic substitution reaction.The overall yield of this approach was 61%.This method is simple for operation and suitable for industrial production.

  8. A post-marketing assessment of major bleeding in total hip and total knee replacement surgery patients receiving rivaroxaban.

    Science.gov (United States)

    Kwong, Louis M; Turpie, Alexander G G; Tamayo, Sally; Peacock, W Frank; Yuan, Zhong; Sicignano, Nicholas; Hopf, Kathleen Pillsbury; Patel, Manesh R

    2017-09-01

    Rivaroxaban is a novel oral anticoagulant indicated for prophylaxis against deep vein thrombosis and pulmonary embolism in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. To evaluate major bleeding (MB) in THR/TKR patients receiving post-operative rivaroxaban. Electronic medical records of nearly 10 million US Department of Defense (DoD) beneficiaries were queried from 1 January 2013 through 30 June 2015. Using the validated Cunningham case-finding algorithm, post-surgical MB events in rivaroxaban users were identified and analyzed. The incidence of MB was determined, and descriptive statistics were used to compare patient characteristics and other covariates in those with and without MB. Two additional methods were used to explore and identify bleeding cases that were not considered MB events per the study case-finding algorithm. A total of 12,429 patients received THR and/or TKR surgery, and were post-operatively prescribed rivaroxaban. Nine patients had MB, yielding an incidence proportion of 0.07% (95% CI 0.02-0.13). The alternative case-finding methods found bleeding incidences of 0.46% and 0.21%, though it is not clear whether these are clinical MB cases, since the alternative methods were not validated. The incidence of MB in this retrospective analysis is lower than that observed in the clinical trials of rivaroxaban. Whether this is due to lower real-world MB rates or challenges with case-finding algorithms is unclear.

  9. Tocilizumab use in pregnancy: Analysis of a global safety database including data from clinical trials and post-marketing data.

    Science.gov (United States)

    Hoeltzenbein, Maria; Beck, Evelin; Rajwanshi, Richa; Gøtestam Skorpen, Carina; Berber, Erhan; Schaefer, Christof; Østensen, Monika

    2016-10-01

    Analyze the cumulative evidence for pregnancy outcomes after maternal exposure to tocilizumab, an anti-interleukin-6-receptor monoclonal antibody used for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. At present, published experience on tocilizumab use during pregnancy is very limited. We have analyzed all pregnancy-related reports documented in the Roche Global Safety Database until December 31, 2014 (n = 501). After exclusion of ongoing pregnancies, duplicates, and cases retrieved from the literature, 399 women were found to have been exposed to tocilizumab shortly before or during pregnancy, with pregnancy outcomes being reported in 288 pregnancies (72.2%). Of these 288 pregnancies, 180 were prospectively reported resulting in 109 live births (60.6%), 39 spontaneous abortions (21.7%), 31 elective terminations of pregnancy (17.2%), and 1 stillbirth. The rate of malformations was 4.5%. Co-medications included methotrexate in 21.1% of the prospectively ascertained cases. Compared to the general population, an increased rate of preterm birth (31.2%) was observed. Retrospectively reported pregnancies (n = 108) resulted in 55 live births (50.9%), 31 spontaneous abortions (28.7%), and 22 elective terminations (20.4%). Three infants/fetuses with congenital anomalies were reported in this group. No increased risks for adverse pregnancy outcomes were observed after paternal exposure in 13 pregnancies with known outcome. No indication for a substantially increased malformation risk was observed. Considering the limitations of global safety databases, the data do not yet prove safety, but provide information for physicians and patients to make informed decisions. This is particularly important after inadvertent exposure to tocilizumab, shortly before or during early pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

    Science.gov (United States)

    Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

    2017-06-22

    Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

  11. Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study

    Science.gov (United States)

    Yan, Ying-Ying; Yang, Yi-Heng; Wang, Wei-Wei; Pan, Yu-Ting; Zhan, Si-Yan; Sun, Ming-Yang; Zhang, Hong; Zhai, Suo-Di

    2017-01-01

    Background Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. Objective To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. Methods This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. Results Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50–73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk

  12. Post-Marketing Safety Surveillance of the Salvia Miltiorrhiza Depside Salt for Infusion: A Real World Study.

    Science.gov (United States)

    Yan, Ying-Ying; Yang, Yi-Heng; Wang, Wei-Wei; Pan, Yu-Ting; Zhan, Si-Yan; Sun, Ming-Yang; Zhang, Hong; Zhai, Suo-Di

    2017-01-01

    Salvia Miltiorrhiza Depside Salt for Infusion (SMDS) is made of a group of highly purified listed drugs. However, its safety data is still reported limitedly. Compared with the clinical trials, its safety in the real world setting is barely assessed. To investigate the safety issues, including adverse events (AEs), adverse events related to SMDS (ADEs), and adverse drug reactions (ADRs) of the SMDS in the real world clinical practice. This is a prospective, multicenter, pharmacist-led, cohort study in the real world setting. Consecutive patients prescribed with SMDS were all included in 36 sites. Pharmacists were well trained to standardized collect the patients information, including demographics, medical history, prescribing patterns of SMDS, combined medications, adverse events, laboratory investigations, outcomes of the treatment when discharge, and interventions by pharmacists. Adverse events and adverse drug reactions were collected in details. Multivariate possion regression analysis was applied to identify risk factors associated with ADEs using the significance level (α) 0.05. ClinicalTrials.gov Identifier: NCT01872520. Thirty six hospitals were participated in the study and 30180 consecutive inpatients were included. The median age was 62 (interquartile range [IQR], 50-73) years, and male was 17384 (57.60%) among the 30180 patients. The incidences of the AEs, ADEs and ADRs were 6.40%, 1.57% and 0.79%, respectively. There were 9 kinds of new ADEs which were not on the approved label found in the present study. According to the multivariate analysis, male (RR = 1.381, P = 0.009, 95%CI [1.085~1.759]), more concomitant medications (RR = 1.049, P<0.001, 95%CI [1.041~1.057]), longer duration of SMDS therapy (RR = 1.027, P<0.001, 95%CI [1.013~1.041]), higher drug concentration (RR = 1.003, P = 0.014, 95%CI [1.001~1.006]), and resolvent unapproved (RR = 1.900, P = 0.002, 95%CI [1.260~2.866]) were the independent risk factors of the ADEs. Moreover, following the

  13. Sensitive LC-MS/MS-ESI method for simultaneous determination of montelukast and fexofenadine in human plasma: application to a bioequivalence study.

    Science.gov (United States)

    Muppavarapu, Rajendraprasad; Guttikar, Swati; Rajappan, Manavalan; Kamarajan, Kannan; Mullangi, Ramesh

    2014-08-01

    A rapid, simple, sensitive and selective LC-MS/MS method was developed and validated for simultaneous quantification of montelukast (MT) and fexofenadine (FF) in human plasma (200 μL) using montelukast-d6 (MT-d6 ) and fexofenadine-d10 (FF-d10 ), respectively as an internal standard (IS) as per the US Food and Drug Administration guidelines. The chromatographic resolution was achieved on a Chromolith RP18e column using an isocratic mobile phase consisting of 20 mm ammonium formate-acetonitrile (20:80, v/v) at flow rate of 1.2 mL/min. The LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The total run time of analysis was 4 min and elution of MT, FF, MT-d6 and FF-d10 occurred at 2.5, 1.2, 2.4 and 1.2 min, respectively. The standard curve found to be linear in the range 2.00-1000 ng/mL with a coefficient of correlation of ≥0.99 for both the drugs. The intra- and inter-day accuracy and precision values for MT and FF met the acceptance as per FDA guidelines. MT and FF were found to be stable in a battery of stability studies viz., bench-top, auto-sampler and repeated freeze-thaw cycles. The validated assay was applied to an oral bioequivalence study in humans.

  14. The impact of neutralizing antibodies on the risk of disease worsening in interferon β-treated relapsing multiple sclerosis: a 5 year post-marketing study.

    Science.gov (United States)

    Paolicelli, D; D'Onghia, M; Pellegrini, F; Direnzo, V; Iaffaldano, P; Lavolpe, V; Trojano, M

    2013-06-01

    The impact of neutralizing antibodies (NAbs) on interferon β (IFNβ) efficacy in MS patients is still an object of controversy. To evaluate the clinical response to IFNβ during NAb-positive (NAb+) and NAb-negative (NAb-) statuses on a large population of relapsing remitting (RR) MS patients were followed up to 5 years. Sera from 567 RR MS patients treated with IFNβ for 2-5 years were collected every 6-12 months and evaluated for NAb presence by a cytopathic effect assay. The relapse rate and expanded disability status scale (EDSS) score were assessed at baseline and every 6 months for each patient. A NAb+ status was defined after two consecutive positive titers of NAbs >/= 20 neutralizing units (NU)/mL. Multivariate models were used to analyze the relapse rate, the time to first relapse, the time to confirmed EDSS score 4 during NAb+ and NAb- statuses. A propensity score (PS) matching analysis was performed to assess the robustness of the multivariate models. Fourteen percent of patients became NAb+ during the follow-up. A significant increase of the relapse rate (IRR = 1.38; p = 0.0247) and decrease of the time to 1st relapse (IRR = 1.51; p = 0.0111) were found during NAb+ periods. The PS matching analysis, in a selected cohort of patients, demonstrated a negative trend of NAbs on the time to reach the milestone EDSS 4 (IRR = 2.94; p = 0.0879). This long-term post-marketing observational study further confirms that the occurrence of NAbs significantly affects the risk of disease worsening in IFNβ- treated RRMS.

  15. Examining the Quality of Medicines at Kenyan Healthcare Facilities: A Validation of an Alternative Post-Market Surveillance Model That Uses Standardized Patients.

    Science.gov (United States)

    Wafula, Francis; Dolinger, Amy; Daniels, Benjamin; Mwaura, Njeri; Bedoya, Guadalupe; Rogo, Khama; Goicoechea, Ana; Das, Jishnu; Olayo, Bernard

    2017-03-01

    Promoting access to medicines requires concurrent efforts to strengthen quality assurance for sustained impact. Although problems of substandard and falsified medicines have been documented in low- and middle-income countries, reliable information on quality is rarely available. The aim of this study was to validate an alternative post-market surveillance model to complement existing models. The study used standardized patients or mystery clients (people recruited from the local community and trained to pose as real patients) to collect medicine samples after presenting a pre-specified condition. The patients presented four standardized conditions to 42 blinded facilities in Nairobi, Kenya, resulting in 166 patient-clinician interactions and dispensing of 300 medicines at facilities or nearby retail pharmacies. The medicine samples obtained thus resemble those that would be given to real patients. Sixty samples were selected from the 300, and sent for analysis at the Kenya National Quality Control Laboratory. Of these, ten (17%) did not comply with monograph specifications (three ibuprofen, two cetirizine, two amoxicillin/clavulanic acid combinations, and one each for prednisone, salbutamol and zinc). Five of the ten samples that failed had been inappropriately prescribed to patients who had presented symptoms of unstable angina. There was no association between medicine quality and ownership, size or location of the facilities. The study shows that the standardized patient model can provide insights into multiple dimensions of care, thus helping to link primary care encounters with medicine quality. Furthermore, it makes it possible to obtain medicines from blinded sellers, thus minimizing the risk of obtaining biased samples.

  16. Confirmation of in vitro and clinical safety assessment of behentrimonium chloride-containing leave-on body lotions using post-marketing adverse event data.

    Science.gov (United States)

    Cameron, D M; Donahue, D A; Costin, G-E; Kaufman, L E; Avalos, J; Downey, M E; Billhimer, W L; Gilpin, S; Wilt, N; Simion, F A

    2013-12-01

    Behentrimonium chloride (BTC) is a straight-chain alkyltrimonium chloride compound commonly used as an antistatic, hair conditioning, emulsifier, or preservative agent in personal care products. Although the European Union recently restricted the use of alkyltrimonium chlorides and bromides as preservatives to ≤0.1%, these compounds have been safely used for many years at ≤5% in hundreds of cosmetic products for other uses than as a preservative. In vitro, clinical, and controlled consumer usage tests in barrier-impaired individuals were conducted to determine if whole body, leave-on skin care products containing 1-5% BTC cause dermal irritation or any other skin reaction with use. BTC-containing formulations were predicted to be non-irritants by the EpiDerm® skin irritation test and the bovine corneal opacity and permeability (BCOP)/chorioallantoic membrane vascular assay (CAMVA) ocular irritation test battery. No evidence of allergic contact dermatitis or cumulative dermal irritation was noted under the exaggerated conditions of human occlusive patch tests. No clinically assessed or self-reported adverse reactions were noted in adults or children with atopic, eczematous, and/or xerotic skin during two-week and four-week monitored home usage studies. These results were confirmed by post-marketing data for five body lotions, which showed only 0.69 undesirable effects (mostly skin irritation) reported per million shipped consumer units during 2006-2011; a value consistent with a non-irritating body lotion. No serious undesirable effects were reported during in-market use of the products. Therefore, if formulated in appropriate conditions at 1-5%, BTC will not cause dermal irritation or delayed contact sensitization when used in a whole-body, leave-on product.

  17. 参麦注射液上市后再评价系列研究%Series of Studies on Post-marketing Evaluation of Shenmai Injection

    Institute of Scientific and Technical Information of China (English)

    王连心; 谢雁鸣; 艾青华; 姜俊杰

    2014-01-01

    Shenmai injection is commonly used for treatment of shock,coronary heart disease,viral myocarditis,chronic pulmonary heart disease and neutropenia.After going on market drugs can have effectiveness and safety that differ from our expectation.Thus, post-marketing evaluation is both necessary and essential.The research will summarize series of studies of Shenmai injection conducted by our team (bibliometric analysis,systems analysis,electronic medical data analysis and safety data analysis of spontaneous reporting system),to provide scientific basis for proper use.%参麦注射液临床上常用于休克、冠心病、病毒性心肌炎、慢性肺心病、粒细胞减少症的治疗。药品上市后在临床真实世界的使用中,其有效性与安全性往往会与已知情况有所不同,因而,药品上市后临床再评价非常必须与必要。本文从本团队进行的参麦注射液上市后文献计量分析、系统评价以及基于电子医疗数据分析和自发呈报系统安全性数据分析等方面,进行系列研究综述,以为临床安全合理用药提供依据。

  18. Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).

    Science.gov (United States)

    Sakaida, Isao; Terai, Shuji; Kurosaki, Masayuki; Yasuda, Moriyoshi; Okada, Mitsuru; Bando, Kosuke; Fukuta, Yasuhiko

    2017-10-01

    Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings. Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure. Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%). In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained. © 2016 The Japan Society of Hepatology.

  19. Assessment of safety and efficacy of lamotrigine over the course of 1-year observation in Japanese patients with bipolar disorder: post-marketing surveillance study report.

    Science.gov (United States)

    Terao, Takeshi; Ishida, Atsuko; Kimura, Toshifumi; Yoshida, Mitsuhiro; Hara, Terufumi

    2017-01-01

    A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD). Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton's Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4-6 months post treatment initiation, and 10-12 months post treatment initiation. A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10-12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10-12 months post treatment. The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice.

  20. Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

    Science.gov (United States)

    Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

    2017-07-27

    Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

  1. Efficacy and safety of cross-linked hyaluronic acid single injection on osteoarthritis of the knee: a post-marketing phase IV study

    Directory of Open Access Journals (Sweden)

    Bashaireh K

    2015-04-01

    Full Text Available Khaldoon Bashaireh,1 Ziad Naser,2 Khaled Al Hawadya,2 Sorour Sorour,2 Rami Nabeel Al-Khateeb3 1Department of Orthopedics Surgery, King Abdullah University Hospital, Jordan University of Science and Technology, Irbid, Jordan; 2Private Clinic, 3Elaf Medical Supplies Company, Amman, Jordan Purpose: The primary objective of this study was to evaluate the efficacy, safety, and duration of action of viscosupplementation with Crespine® Gel over a 9-month period.Materials and methods: The study was a post-marketing phase IV study. A total of 109 participants with osteoarthritis of the knee (grades 1–4 in the tibio–femoral compartment were recruited in Jordan. Data were collected from each participant during the baseline visit. Each participant received Crespine® Gel injection, and follow-up visits took place at 3 months, 6 months, and 9 months post-injection.Main outcome measure(s: An assessment of participants by phone was conducted at 1 month, 2 months, 4 months, 5 months, 7 months, and 8 months post-injection. Western Ontario and McMaster Universities Arthritis Index questionnaires were completed during each visit. A 72-hour visit questionnaire was used to assess the safety of the injection. Statistical analysis included a two-sided 95% confidence interval for the difference between pain scores across visits, and the percent change from baseline was calculated.Main results: The full analysis included 84 participants who gave their informed consent and finished the necessary baseline and follow-up visits needed to assess efficacy and safety. Peak improvement was noted at 5 months post-injection, when pain and physical performance scores had decreased to 2.60 and 9.90, respectively, and the stiffness score was 0.33. The peak improvement in stiffness was noted at 8 months post-injection, when the stiffness score had decreased to 0.32. Significant improvements were still apparent at 9 months post-injection, when the pain score was 3

  2. Clinical evaluation of recombinant factor VIII preparation (Kogenate) in previously treated patients with hemophilia A: descriptive meta-analysis of post-marketing study data.

    Science.gov (United States)

    Yoshioka, A; Fukutake, K; Takamatsu, J; Shirahata, A

    2006-08-01

    The safety and efficacy of Kogenate, a recombinant factor VIII (rFVIII) preparation for the treatment of bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of Kogenate were evaluated for FVIII inhibitor antibodies, antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11 PTPs investigated (PTP-I) developed antibodies against baby hamster kidney protein and mouse immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855 bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that Kogenate is safe and very effective for the treatment of bleeding in PTPs with hemophilia A.

  3. Clinical study of budesonide combined with montelukast sodium in the treatment of children with asthma%布地奈德联合孟鲁司特钠治疗儿童哮喘的临床研究

    Institute of Scientific and Technical Information of China (English)

    李麒; 邓成华; 袁伟芳; 薛萍芳; 张涛

    2015-01-01

    目的:布地奈德气雾剂联合孟鲁司特钠咀嚼片在支气管哮喘患儿中的应用效果评价。方法将2013年5月~2014年5月深圳市龙岗区第三人民医院儿科门诊接治的70例轻-中度慢性持续期支气管哮喘患儿按照随机数字表法均分2组,在相同常规治疗及护理基础上:研究组35例患儿给予布地奈德气雾剂及口服孟鲁司特钠咀嚼片联合治疗,对照组35例患儿给予布地奈德气雾剂治疗,对两组患儿治疗1个疗程后的哮喘症状评分及随访期间哮喘控制情况进行综合比较。结果治疗1个疗程后,两组患儿日、夜间哮喘症状评分均有明显下降(P<0.05);研究组较对照组下降幅度更为显著(P<0.05);随访期间,研究组哮喘急性发作次数明显少于对照组(P<0.05);研究组无症状天数比例(87.50%)明显高于对照组(71.43%)(P<0.05);两组患儿均无严重药物不良反应情况发生。结论在常规治疗基础上给予慢性持续期支气管哮喘患儿布地奈德气雾剂联合孟鲁司特钠咀嚼片治疗可明显减轻患儿哮喘症状,有利于哮喘症状的长期控制,值得临床推广应用。%Objective To evaluate the application effect of inhaled budesonide combined with montelukast sodium chewable tablets in the treatment of children with bronchial asthma. Methods 70 children with mild to moderate chronic persistent bronchial asthma treated in our hospital from May 2013 to May 2014 were selected and randomly di-vided into two groups.35 cases of patients in study group were treated with inhaled budesonide combined with oral montelukast sodium chewable tablets on the bases of the same routine treatment and nursing care while 35 cases of the patients in control group were treated with inhaled budesonide.The asthma symptoms score and the asthma control of the patients between two groups during the follow-up period were compared after one course of drug treatment. Results After one

  4. 孟鲁司特钠对轻度持续哮喘患儿疗效和安全性的随机双盲安慰剂对照试验%Efficacy and safety of montelukast in children with mild persistent asthma: a randomized double-blind, placebo-controlled trial

    Institute of Scientific and Technical Information of China (English)

    董文芳; 周小建; 洪建国

    2011-01-01

    were enrolled and randomly allocated to placebo or monterlukast sodium groups.Patients received either montelukast ( 5 mg chewable tablet ) or matching-image placebo once daily at bed-time for 12 consecutive weeks.All the patients were assessed at week 4.week 8 and week 12 according to the asthma daily cards, which included following measurements : daytime and nighttime asthma symptom score , short acting beta agonist ( SABA ) usage, medical resource utilization for asthma and peak expiratory flow rates( PEF ).Spirometry was performed before and after treatment.Side effects were also judged during the 12 weeks of therapy.Results A total of 126 suhjects were reruited in the trial.and 112 subjects completed the study, with 35 from the placebo group and 77 from the montelukast sodium group.Compared with placebo group, PEF and lung function were significantly improved after 12 weeks treatment in montelukast group( P =0.039 ).Daytime and nighttime asthma symptom score , SABA usage and medical resource utilization for asthma were significantly reduced after 12 weeks treatment ( Ps≤0.002 7 ).Significant clinical improvement( P = 0.049.0.037 ) was also noted after 4 weeks treatment.No adverse eve.nts were observed in the two groups.Conclusions These results suggested that montelukast was an effective and safe controller as monotherapy in children with mild persistent asthma.

  5. Therapeutic effect of N-acetylcysteine and montelukast sodium in patients with idiopathic pulmonary fibrosis%N-乙酰半胱氨酸联合孟鲁司特钠治疗特发性肺纤维化临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    王传海; 李承红

    2016-01-01

    Objective To investigate the effect of N-acetylcysteine (NAC) and montelukast sodium in pa-tients with idiopathic pulmonary fibrosis (IPF). Methods A total of 64 patients with IPF confirmed by clinical data and imaging examination from January 2008 to June 2014 were selected in our hospital. According to random number table, the patients were randomly divided into the observation group and the control group with 32 patients in each group. The control group applied conventional glucocorticoids treatment, while the observation group used NAC and montelukast sodium based on glucocorticoids treatment. All patients were treated for 3 months. The therapeutic effect, vital capacity (VC), diffusion capacity for carbon monoxide (DLco), pH value, oxygen partial pressure (PaO2), oxygen saturation (SaO2), partial pressure of carbon dioxide (PaCO2) and medication safety were compared between the two groups. Results In the observation group, the total effective rate was 81.25%, which was significantly higher than 57.60%in the control group (P0.05). After treatment, the differences in VC, DLco between the two groups were statistical-ly significant (P0.05). After treatment, the dif-ferences in PaO2, SaO2 between the two groups were statistically significant (P0.05). No serious adverse reaction was found in the two groups. Conclusion The conventional glucocorticoids therapy added with NAC and montelukast sodium in the treatment of IPF can effectively improve the symptoms of patients, and slow down the decrease of VC, DLco, PaO2, SaO2.%目的 探讨N-乙酰半胱氨酸(NAC)联合孟鲁司特钠治疗特发性肺纤维化(IPF)的临床疗效.方法 选择我院2008年1月至2014年6月经临床-影像证实的IPF患者64例,按随机数字表法分为观察组和对照组,每组32例,观察组在口服常规激素治疗基础上加用NAC联合孟鲁司特钠,对照组口服常规糖皮质激素治疗,疗程3个月.比较两组患者的临床疗效、肺活量(VC)、一氧化碳弥

  6. Building up Evidence Body for Post-marketing Chinese Medicines Research%构建中药上市后安全性评价证据体的思考

    Institute of Scientific and Technical Information of China (English)

    廖星; 谢雁鸣

    2014-01-01

    Safety surveillance is the most important aspect for post-marketing research of Chinese medicine.However,passive monito-ring systems or phase four clinical trials or large sample epidemiology studies were historically the common ways of surveillance of post-marketing Chinese medicine.However those studies can no longer meet the expectations,and there are many more evidence sources for post-marketing Chinese medicine safety evaluation,eg.active surveillance from observational cohort study and study on hospital informa-tion system.These data and study can provide adequate source data for post-marketing Chinese medicine research.The most prominent problem is how to integrate different evidences from multiple sources.This article suggests we should build an evidence-based system to evaluate post-marketing Chinese medicines safety.%中药上市后安全性评价关乎用药患者在临床应用中的生命安全,关系着国家医疗卫生政策的导向,以及药厂对药品开发规划设计。上市后药品的安全监测无疑是所有上市后药品的重要内容,而监测主要关注药品在上市前未曾发现的那些潜在的不良反应/事件。既往,上市后药物监测习惯以被动监测模式或者是四期的临床试验或者是大型的流行病学调查,这些统被称之为安全性监测或药物警戒研究。现今,研究者们发现这些方法或方式远远不能满足当下对于上市后药品安全性评价的证据需求。为此,为了能够弥补这些证据积累的不足,目前亟需发展新的证据研究模式,比如转向大样本大范围的主动监测,采用队列观察性研究方法,基于真实世界医疗电子数据库等等。本文基于上市后中药的特点,从循证医学证据理念出发,提出构建中药上市后安全性评价证据体的设想来对未来中药上市后安全性评价研究提供参考。

  7. Montelukast treatment (cysteinyl leukotriene receptor antagonist in a model of food allergy: modifications in lymphatic cell population from rectal mucosa Tratamiento con Montelukast (antagonista cisteinílico del receptor de leucotrienos en un modelo de alergia alimentaria: cambios en la población linfocítica de la mucosa renal

    Directory of Open Access Journals (Sweden)

    M. Vinuesa

    2010-07-01

    Full Text Available Objective: the aim is to determine immunopathological modifications in rectal mucosa from rabbits after local challenge in ovalbumin (OVA sensitized animals previously treated with montelukast. Material and methods: experimental design: thirty two rabbits divided into four groups: G1: normal; G2: subcutaneously OVA sensitized; G3: sensitized, locally OVA challenged and sampled 4 hours after challenge; and G4: sensitized, locally OVA challenged and treated 4 hours before challenge with montelukast (0.15 mg/kg. Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA. In each group 200 high microscopical power fields (HPF were counted. Results were expressed as arithmetic mean and SE. Anti -CD4, CD5, µ chain monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. Results: CD 4: G1: 8.3 ± 0.06; G2: 13.4 ± 0.08, G3: 8.25 ± 0.06, G4: 11.8 ± 0.02. CD 5: G1: 7.3 ± 0.05; G2: 9.4 ± 0.05, G3: 11.3 ± 0.06, G4: 8.1 ± 0.06. μ chain: G1: 10.4 ± 0.06; G2: 3.8 ± 0.02, G3: 6.0 ± 0.10, G4: 2.2 ± 0.10. In all cases, experimental groups (G3 vs. G4 presented statistical significant differences (p < 0.05. CD4+, CD5+ cells and μ chain+ decrease in experimental group (G4, probably due to lymphocyte migration inhibition to challenged mucosa. μ chain+ cell decrease could be based on B cell activation and expression of different surface immunoglobulins. Cells expressing μ chain decreased in G2 and G3 likely due to activation of B cells and subsequent expression of other immunoglobulin chains in cell surface. Conclusions: we conclude that obtained data are important to elucidate immunopathology of local anaphylactic reaction in rectal mucosa from systemic sensitized animals after treatment with montelukast.

  8. Evaluación clínica y funcional en niños asmáticos tratados con montelukast

    Directory of Open Access Journals (Sweden)

    Concepción Sánchez Infante

    2011-09-01

    Full Text Available Introducción: el asma bronquial es una enfermedad que se considera puede ser controlable, aunque no puede curarse, pero sus manifestaciones clínicas, que son las que afectan al paciente, pueden desaparecer o disminuir hasta lograr una vida normal, o casi normal, para este y sus familiares, con una serie de medidas medicamentosas y no medicamentosas. Objetivo: evaluar la eficacia del montelukast en el tratamiento de niños asmáticos persistentes. Métodos: se realizó un estudio en 65 niños asmáticos persistentes en el Hospital Pediátrico Universitario "William Soler". Se evaluaron los síntomas, pruebas funcionales respiratorias, días perdidos en la escuela, y control de la enfermedad, inicialmente, y un año después de la introducción del montelukast. Se observó la posibilidad de efectos secundarios. Resultados: 55 pacientes (84,6 % tenían tos nocturna diaria antes del tratamiento. Al año, la tos nocturna diaria se observó solo en 9 (13,9 %; 43 (66,1 % presentaban sibilancias al reírse, mientras que al año 1 (1,6 % mantenía sibilancias diarias con la risa; 41 (63,0 % tenían, inicialmente, afectación de la actividad física, mientras que al año 51 (78,4 % no tenían limitaciones. El 100 % tenía ausencias escolares. Durante el año de tratamiento 34 (57,0 % no presentaron días perdidos; 42 (64,6 % tenían crisis diarias, sin embargo, al reevaluar, 38 (58,5 % no tuvieron crisis. Habían tenido ingresos hospitalarios 23 (35,4 %, pero posteriormente solo 5 necesitaron hospitalización. Antes del tratamiento, 49 (75,0 % necesitaron tratamiento de rescate, en cambio, durante el año disminuyó a 27 (41,0 %. 19 niños (38,0 % tenían inicialmente el volumen espiratorio forzado en 1 s menor del 80 %, y solamente 8 (16,0 % posteriormente. Antes del tratamiento el 100 % de los pacientes tenían asma no controlada o parcialmente controlada, mientras que al año el 57 % tenía el asma controlada. No se observaron reacciones adversas

  9. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2015-09-01

    Full Text Available Abdel Naser Zaid,1 Murad N Abualhasan,1 David G Watson,2 Ayman Mousa,3 Nadia Ghazal,4 Rana Bustami5 1Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; 2Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK; 3R&D Department, Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd., Riyadh, Kingdom of Saudi Arabia; 4Naratech Pharmaceutical Consultancy, 5Pharmaceutical Research Unit, Amman, Jordan Background: Montelukast (MT is a leukotriene D4 antagonist. It is an effective and safe medicine for the prophylaxis and treatment of chronic asthma. It is also used to prevent acute exercise-induced bronchoconstriction and as a symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis.Objective: The aim of this study was to evaluate the bioequivalence (BE of two drug products: generic MT 5 mg chewable tablets versus the branded drug Singulair® pediatric 5 mg chewable tablets among Mediterranean volunteers.Methods: An open-label, randomized two-period crossover BE design was conducted in 32 healthy male volunteers with a 9-day washout period between doses and under fasting conditions. The drug concentrations in plasma were quantified by using a newly developed and fully validated liquid chromatography tandem mass spectrometry method, and the pharmacokinetic parameters were calculated using a non-compartmental model. The ratio for generic/branded tablets using geometric least squares means was calculated for both the MT products.Results: The relationship between concentration and peak area ratio was found to be linear within the range 6.098–365.855 ng/mL. The correlation coefficient (R2 was always greater than 0.99 during the course of the validation. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between the generic and branded products. The point estimates (ratios of

  10. Safety and efficacy of a novel drug elores (ceftriaxone + sulbactam + disodium edetate in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study

    Directory of Open Access Journals (Sweden)

    Manu Chaudhary

    Full Text Available Abstract Objective: In India, Elores (CSE-1034: ceftriaxone + sulbactam + disodium edetate was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. Methods: This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034. Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs associated with the treatment were recorded. Results: A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4% patients. The major AEs reported were vomiting (3.0%, pain at injection site (2.5%, nausea (2.3%, redness at site (1.96%, thrombophlebitis (1.4%. Of total reported AEs, 40 (5.3% AEs were reported in pediatric, 310 (20.6% in adult, and 59 (23.6% in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4% patients were cured, 501 (20.1% patients showed clinical improvement and 5 (0.2% patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. Conclusion: In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR bacterial infections under routine ward settings.

  11. Safety and efficacy of a novel drug elores (ceftriaxone+sulbactam+disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study.

    Science.gov (United States)

    Chaudhary, Manu; Mir, Mohd Amin; Ayub, Shiekh Gazalla

    In India, Elores (CSE-1034: ceftriaxone+sulbactam+disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  12. Six-year multi-centre, observational, post-marketing surveillance of the safety of the HPV-16/18 AS04-adjuvanted vaccine in women aged 10-25 years in Korea.

    Science.gov (United States)

    Kim, Chul-Jung; Song, Rok; Chen, Jing; Tavares Da Silva, Fernanda; Gopala, Kusuma B; Kim, Joon Hyung; Bi, Dan; Park, Jong Sup

    2017-07-01

    To evaluate the safety of HPV-16/18 AS04-adjuvanted vaccine when administered as per the PI in Korea. A total of 3084 women aged 10-25 years were enrolled in this post-marketing surveillance from 2008 to 2014. Subjects were invited to receive three doses of the vaccine (0, 1 and 6 months), and participants who received at least one dose were included in the analysis. Adverse events (AEs), adverse drug reactions (ADRs) and serious AEs (SAEs) were recorded after each dose. All AEs, ADRs and SAEs were presented with exact 95% confidence intervals (CI) (NCT01101542). Injection-site pain was the most frequent AE and ADR reported by 322 subjects (10.4% [95%CI: 9.4-11.6]); the local pain was transient and lasted 4-7 days in most cases. Dysmenorrhoea and vaginitis were the most common unexpected AEs reported by 30 (1.0% [95%CI: 0.7-1.4]) and 16 subjects (0.7% [95%CI: 0.3-0.8]), respectively. Pain (toe pain, leg pain and body pain [one case each]; foot pain [two cases]) was the most common unexpected ADR reported by five subjects (0.2% [95%CI: 0.1-0.4]). Four subjects reported a single SAE (one case each of exostosis, gastroenteritis, abortion and tonsillitis); none were fatal. All SAEs were assessed as unlikely to be related to vaccination; gastroenteritis, exostosis and tonsillitis resolved during the study period. This is the first post-marketing surveillance study in Korea that provides 6-year safety data for HPV-16/18 AS04-adjuvanted vaccine. The vaccine showed an acceptable safety profile and favourable benefit/risk ratio when given to women aged 10-25 years in Korea. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  13. Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels.

    Science.gov (United States)

    Bentli, Recep; Ciftci, Osman; Cetin, Asli; Otlu, Ali

    2016-05-01

    This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor α and interleukin 1β levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD. © The Author(s) 2013.

  14. The clinical observation of budesonide and montelukast in treatment of children cough variant asthma%布地奈德及孟鲁斯特治疗小儿咳嗽变异性哮喘的疗效观察

    Institute of Scientific and Technical Information of China (English)

    闻丽; 王海霞

    2014-01-01

    目的:观察布地奈德与孟鲁斯特治疗小儿咳嗽变异性哮喘的疗效与差异。方法研究纳入2013年1月~2014年1月入院治疗咳嗽变异性哮喘共102例患儿,按照治疗方法分为两组,51例患儿使用布地奈德治疗2周,51例患儿使用孟鲁斯特治疗2周,两组患者气喘发作时同时给予雾化沙丁胺醇缓解,观察两组患儿2周后咳嗽症状缓解率、肺功能指标(FEV1、FEV1/FVC、PEF)和不良反应。结果孟鲁斯特组症状缓解率为88.2%(45/51),布地奈德组为86.2%(44/51),两组缓解率相似(P>0.05);孟鲁斯特组1周缓解显效率为52.9%(27/51),布地奈德组为47.1%(24/51),孟鲁斯特组较高(P<0.05)。两组患者治疗后FEV1、FEV1/FVC和PEF指标较治疗前均明显改善(P<0.05);布地奈德组和孟鲁斯特组治疗后FEV1、FEV1/FVC和PEF指标变化结果相似(P>0.05)。结论布地奈德与孟鲁斯特在控制小儿咳嗽变异性哮喘的症状缓解、肺功能指标均相似,但孟鲁斯特在治疗第1周的症状缓解显效率较高。%Objective To observe the effect and difficult of Budesonide and Montelukast in treatment of children cough variant asthma.Methods 102 patients with children cough variant asthma in our hospital from January 2013 to January 2014 were divided into two groups based on treatment ways.51 patients used Budesonide with two weeks treatment,51 patients used Montelukast with two weeks treatment,patients of two group were used Salbutamol when asthma attack, the cough response rate,lung function indices(FEV1、FEV1/FVC,PEF) and adverse reaction were observed after two weeks.Resultsthe cough response rate of Budesonide group was 88.2%(45/51),the cough response rate of Montelukast group was 86.2%(44/51),there was no different of two groups(P>0.05);the cough response rate of Budesonide group after 1 week was 52.9%(27/51),the cough response rate of Montelukast group after 1 week was 47

  15. The impact of montelukast combined with Ketotifen on the levels of serum TGF-β1 , MCP-1, SDF-1 in asthma suffe- rers%孟鲁司特联合酮替芬对哮喘患者血清TGF-β1、MCP-1、SDF-1水平的影响

    Institute of Scientific and Technical Information of China (English)

    王昕华; 韩曙光; 吕蕾; 赵弘卿

    2016-01-01

    Objective To investigate the impact of montelukast combined with Ketotifen on the levels of transforming growth factor-β1(TGF-β1), monocyte chemoattractant protein-1 (MCP-1), stromal cell derived factor-1 ( SDF-1) in asthma sufferers.Methods 128 cases of asthma patients in Department of Respiration, Wuxi Second People's Hospital Affiliated to Nanjing Medical University from October 2014 to October 2015 were selected and randomly divided into observation group (n =64) and control group ( n =64).Patients of two groups were given symptomatic treatment;patients of the observation group were treated with montelukast combined with Ketotifen orally, while patients of the control group were treated with mon-telukast orally, and both for three months.The levels of TGF-β1 , MCP-1, SDF-1 of two groups before and after treatment were compared.Results The total effective rate of observation group( 96.9%) were higher than control group (84.4%) ( P <0.05).The Asthma Control Test table (ACT) score of observation group (24.25 ±3.98) was significantly higher than control group (20.12 ±4.02) ( P <0.05).The levels of expiratory volume in one second (FEV1) and peak expiratory flow rate (PEF) of observation group were (80.25 ±4.25)%, (7.25 ±0.69) L/min were higher than control group (75.02 ± 3.96)%, (5.82 ±0.70) L/min ( P <0.05).The levels of serum TGF-β1, MCP-1, SDF-1 of observation group (42.2 ± 6.0) ng/ml, (48.6 ±4.0) ρg/ml, (252.4 ±32.2) ng/L after treatment were lower than the control group (48.9 ±5.2) ng/ml, (59.0 ±4.2) ρg/ml, (425.3 ±40.6) ng/L, the difference was statistically significant ( P <0.05).Conclusion Montelukast combined with Ketotifen can effectively reduce serum TGF-β1 , MCP-1, SDF-1 levels in asthmatic patients and improve clinical symptoms, lung function and improve patient outcomes.%目的 观察孟鲁司特联合酮替芬对哮喘患者血清转化生长因子-β1(TGF-β1)、单核细胞趋化蛋白-1(MCP-1)、基质细胞衍生因子-1(SDF-1)

  16. The Clinical Research of Montelukast Sodium for the Treatment of Pediatric Asthmatic Bronchitis%应用孟鲁司特钠治疗小儿喘息性支气管炎的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘金联

    2015-01-01

    ObjectiveTo investigate the clinical effect of application of montelukast sodium in treatment of children with asthmatic bronchitis. MethodsTo our hospital for 76 children with asthmatic bronchitis patients treated cases selected in accordance with the different treatment methods for the observation group and the control group, patients in the control group using conventional methods of treatment, patients in the observation group based on the treatment in control group were treated with montelukast sodium.Results After treatment, the patients in observation group were signiifcantly better than the treatment effect of patients in the control group, P<0.05.Conclusion The addition of montelukast sodium in the process of traditional therapy in treatment can signiifcantly improve the treatment effect.%目的探讨应用孟鲁司特钠治疗小儿喘息性支气管炎的临床治疗效果。方法选取来我院进行治疗的小儿喘息性支气管炎患者76例,按照治疗方式的不同分为对照组和观察组,对照组患者使用常规方式进行治疗,观察组患者在对照组治疗的基础上加用孟鲁司特钠进行治疗。结果经过治疗后,观察组患者的治疗效果明显优于对照组患者, P<0.05。结论在传统治疗的过程中加入孟鲁司特钠进行治疗能够明显提高治疗的效果。

  17. Montelukast inhibition of resting and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under flow conditions appears independent of cysLT(1)R antagonism.

    Science.gov (United States)

    Robinson, Alexander J; Kashanin, Dmitry; O'Dowd, Frank; Williams, Vivienne; Walsh, Garry M

    2008-06-01

    Montelukast (MLK) is a cysteinyl leukotriene receptor-1 (cysLT(1)R) antagonist with inhibitory effects on eosinophils, key proinflammatory cells in asthma. We assessed the effect of MLK on resting and GM-CSF-stimulated eosinophil adhesion to recombinant human (rh)VCAM-1 at different flow rates using our novel microflow system. At 1 or 2 dyn cm(-2), shear-stress unstimulated eosinophils tethered immediately to rhVCAM-1, "rolled" along part of the channel until they tethered, or rolled without tethering. At flow rates greater than 2 dyn cm(-2), adherent eosinophils began to be displaced from rhVCAM-1. MLK (10 nM and 100 nM) gave partial ( approximately 40%) but significant (PMLK observed. This effect appeared specific for MLK, as the analog (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid, sodium salt, had no significant effect on eosinophil adhesion to VCAM-1. The possibility that LTC(4), released from unstimulated or GM-CSF-treated eosinophils, contributed to their adhesion to VCAM-1 was excluded as the LT biosynthesis inhibitor 3-[1-(p-Chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethylpropanoic acid had no inhibitory effect, and exogenously added LTC(4) did not enhance eosinophil adhesion. In contrast, LTD(4) enhanced eosinophil adhesion to VCAM-1, an effect blocked by MLK (10 and 100 nM). These findings demonstrate that MLK-mediated inhibition of unstimulated and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under shear-stress conditions appears independent of cysLT(1)R antagonism.

  18. Effectiveness and adverse events of tolvaptan in octogenarians with heart failure. Interim analyses of Samsca Post-Marketing Surveillance In Heart faiLurE (SMILE study).

    Science.gov (United States)

    Kinugawa, Koichiro; Inomata, Takayuki; Sato, Naoki; Yasuda, Moriyoshi; Shimakawa, Toshiyuki; Bando, Kosuke; Mizuguchi, Kazuki

    2015-01-01

    The vasopressin receptor 2 (V2) receptor antagonist tolvaptan is an aquaretic agent that has been found to improve symptoms in patients with congestive heart failure. In this study (SMILE study), we administered tolvaptan to patients aged ≥ 80 years with heart failure accompanied by congestive symptoms and compared its effectiveness and safety profiles in this group with those in patients < 80 years (U-80). The results showed that the effectiveness of tolvaptan in the aged patients was similar to that in U-80 patients. In the safety profile, the incidence rate of thirst was lower in the aged patients than that in U-80 patients (9.6% versus 11.6%, P = 0.0023). Furthermore, the incidence of hypernatremia, defined as ≥ 150 mEq/L in aged patients, was comparable with that in U-80 patients (2.9% versus 3.6%, respectively, P = 0.3657). Based on these findings, tolvaptan has similar effectiveness and safety profiles in aged patients compared with U-80 patients. In addition, we found that a higher starting dose of tolvaptan was markedly associated with the occurrence of hypernatremia exclusively in the aged population; therefore, we recommend that tolvaptan should be started at lower doses in aged patients.

  19. 孟鲁斯特钠联合匹多莫德治疗儿童哮喘临床疗效观察%Observation on clinical efficacy of Montelukast sodium combined with Pidotimod for children with asthma

    Institute of Scientific and Technical Information of China (English)

    柴若楠; 林小平

    2011-01-01

    目的 探讨孟鲁斯特钠联合匹多莫德治疗儿童哮喘的应用价值.方法 将117例非急性发作期哮喘息儿,随机分为观察Ⅰ组、Ⅱ组和对照组.观察Ⅰ组给予孟鲁斯特钠4 mg,1次/晚,口服,匹多莫德400 mg,1次/晚,口服;Ⅱ组给予孟鲁斯特钠4mg,1次/晚,口服;对照组经常规止咳、平喘及必要时抗感染治疗.三组均观察12周.结果 无哮喘症状的天数、医生评价明显好转率、有1次以上哮喘发作的例数以及需全身用糖皮质激素治疗的例数,观察Ⅰ组与Ⅱ组优于对照组(P<0.01),观察Ⅰ组优于观察Ⅱ组(P<0.01或0.05).每周日、夜间哮喘症状计分:观察Ⅰ、Ⅱ组优于对照组,观察Ⅰ组优于观察Ⅱ组(P<0.01或0.05).结论 孟鲁斯特钠联合匹多莫德治疗儿童哮喘疗效显著,高于孟鲁斯特钠单独应用和常规治疗方法.%Objective To discuss the application value of Montelukast sodium combined with Pidotimod for children with asthma. Methods 117 cases of patients with non-acute attack of asthma randomly divided into observation group Ⅰ , Ⅱ and control group. For observation I group, oral intake Montelukast sodium 4mg and Pidotimod 400mg one time per night; for group Ⅱ , oral intake Montelukast sodium 4mg one time per night; the control group was treated with relieving cough and asthma and anti-infection treatment. 3 groups were observed for 12 weeks. Results The number of days without asthma symptoms, the obvious recovery rate of doctor' s evaluation, the cases of asthma attack more than once and the cases of asthma of systemic corticosteroid therapy, observation group Ⅰ, Ⅱ are superior to control group ( P < 0.01). Observation group Ⅰ is superior to observation group Ⅱ ( P < 0.01 or 0.05 ). Asthma symptoms score of day and night weekly: observation group Ⅰ, Ⅱ are superior to control group, observation group Ⅰ is superior to observation group Ⅱ (P<0.01 orO. 05). Conclusion The therapy of

  20. Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study.

    Science.gov (United States)

    Yokote, Koutaro; Terauchi, Yasuo; Nakamura, Ichiro; Sugamori, Haruko

    2016-10-01

    To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM). Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015. Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. The PMS included 8505 patients (4181 males/4324 females). The mean age and diabetes duration were 72.3 years and 10.6 years, respectively. In 84.3% of patients, ipragliflozin was prescribed at 50 mg/day, which was continued unchanged. Overall, 16.91% of patients experienced 1880 ADRs, and 165 ADRs were classified as serious in 127 patients (1.49%). ADRs of special interest included skin complications, volume depletion, polyuria/pollakiuria, genital infection, urinary tract infection, renal disorders, hypoglycemia, cerebrovascular disease, cardiovascular disease, malignant tumor, fracture, and ketone body-related events. This 1-year PMS revealed probable ADRs in elderly Japanese patients with T2DM prescribed ipragliflozin in real-world settings, with no new safety concerns. The risk factors for ADRs varied but could be rationalized. The results should help physicians to identify possible treatment-emergent ADRs in ipragliflozin-treated patients.

  1. Safety and effectiveness of 24-week treatment with iguratimod, a new oral disease-modifying antirheumatic drug, for patients with rheumatoid arthritis: interim analysis of a post-marketing surveillance study of 2679 patients in Japan.

    Science.gov (United States)

    Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

    2017-09-01

    To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.

  2. Use of endpoint adjudication to improve the quality and validity of endpoint assessment for medical device development and post marketing evaluation: Rationale and best practices. A report from the cardiac safety research consortium.

    Science.gov (United States)

    Seltzer, Jonathan H; Heise, Ted; Carson, Peter; Canos, Daniel; Hiatt, Jo Carol; Vranckx, Pascal; Christen, Thomas; Cutlip, Donald E

    2017-08-01

    This white paper provides a summary of presentations, discussions and conclusions of a Thinktank entitled "The Role of Endpoint Adjudication in Medical Device Clinical Trials". The think tank was cosponsored by the Cardiac Safety Research Committee, MDEpiNet and the US Food and Drug Administration (FDA) and was convened at the FDA's White Oak headquarters on March 11, 2016. Attention was focused on tailoring best practices for evaluation of endpoints in medical device clinical trials, practical issues in endpoint adjudication of therapeutic, diagnostic, biomarker and drug-device combinations, and the role of adjudication in regulatory and reimbursement issues throughout the device lifecycle. Attendees included representatives from medical device companies, the FDA, Centers for Medicare and Medicaid Services (CMS), end point adjudication specialist groups, clinical research organizations, and active, academically based adjudicators. The manuscript presents recommendations from the think tank regarding (1) rationale for when adjudication is appropriate, (2) best practices establishment and operation of a medical device adjudication committee and (3) the role of endpoint adjudication for post market evaluation in the emerging era of real world evidence. Copyright © 2017. Published by Elsevier Inc.

  3. Scientific Opinion on the annual post-market environmental monitoring (PMEM report from Monsanto Europe S.A. on the cultivation of genetically modified maize MON 810 in 2012

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Genetically Modified Organisms (GMO

    2014-06-01

    Full Text Available Following a request from the European Commission, the Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA GMO Panel assessed the post-market environmental monitoring (PMEM report for the 2012 growing season of maize MON 810 provided by Monsanto Europe S.A. The EFSA GMO Panel noted that the applicant used a similar methodology as the one previously established for monitoring maize MON 810 in 2009, 2010 and 2011. The EFSA GMO Panel therefore focused its assessment on the novel datasets specific to the 2012 growing season of maize MON 810, and not on the methodology. The data submitted by the applicant in its 2012 PMEM report do not indicate any adverse effects on human and animal health or the environment arising from maize MON 810 cultivation in 2012. However, having already highlighted the poor sensitivity of the methodology followed by the applicant, the EFSA GMO Panel strongly reiterates its previous recommendations for the improvement of the methodology. In addition, the EFSA GMO Panel recommends that the applicant: (1 further investigates effects observed during the monitoring of baseline susceptibility of target pests in Spain; (2 follow-up possible adverse effects of maize MON 810 on rove beetles.

  4. Scientific Opinion on the annual Post-Market Environmental Monitoring (PMEM report from Monsanto Europe S.A. on the cultivation of genetically modified maize MON 810 in 2011

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Genetically Modified Organisms (GMO

    2013-12-01

    Full Text Available Following the request from the European Commission, the Panel on Genetically Modified Organisms of the European Food Safety Authority (EFSA GMO Panel assessed the monitoring report for the 2011 growing season of maize MON 810 provided by Monsanto Europe S.A. The EFSA GMO Panel already assessed the 2009 and 2010 monitoring reports and followed the same approach as for the assessment of the methodology applied by the applicant for monitoring maize MON 810 in 2011. The EFSA GMO Panel considered the plan for insect-resistant management and addressed the comments raised by the applicant on its previous recommendations for improving the methodology of the resistance monitoring of target pests. The EFSA GMO Panel also paid particular attention to the design and analysis of the farmer questionnaires. The EFSA GMO Panel notes similar shortcomings in the overall methodology for the post-market environmental monitoring of maize MON 810 as in the previous monitoring reports. Hence, while the EFSA GMO Panel reiterates its previous recommendations for the improvement of the methodology, it also clarifies and elaborates on those related to the monitoring of resistance evolution in target pests. However, from the data submitted by the applicant, the EFSA GMO Panel does not identify adverse effects on the environment, human and animal health due to maize MON 810 cultivation during the 2011 growing season. The outcomes of the 2011 monitoring report do not invalidate the previous EFSA GMO Panel’s scientific opinions on maize MON 810.

  5. A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

    Science.gov (United States)

    Outteryck, O; Ongagna, J C; Brochet, B; Rumbach, L; Lebrun-Frenay, C; Debouverie, M; Zéphir, H; Ouallet, J C; Berger, E; Cohen, M; Pittion, S; Laplaud, D; Wiertlewski, S; Cabre, P; Pelletier, J; Rico, A; Defer, G; Derache, N; Camu, W; Thouvenot, E; Moreau, T; Fromont, A; Tourbah, A; Labauge, P; Castelnovo, G; Clavelou, P; Casez, O; Hautecoeur, P; Papeix, C; Lubetzki, C; Fontaine, B; Couturier, N; Bohossian, N; Clanet, M; Vermersch, P; de Sèze, J; Brassat, D

    2014-01-01

    BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

  6. Benefit-risk assessment in a post-market setting: a case study integrating real-life experience into benefit-risk methodology.

    Science.gov (United States)

    Hallgreen, Christine E; van den Ham, Hendrika A; Mt-Isa, Shahrul; Ashworth, Simon; Hermann, Richard; Hobbiger, Steve; Luciani, Davide; Micaleff, Alain; Thomson, Andrew; Wang, Nan; van Staa, Tjeerd P; Downey, Gerald; Hirsch, Ian; Hockley, Kimberley; Juhaeri, Juhaeri; Metcalf, Marilyn; Mwangi, Jeremiah; Nixon, Richard; Peters, Ruth; Stoeckert, Isabelle; Waddingham, Ed; Tzoulaki, Ioanna; Ashby, Deborah; Wise, Lesley

    2014-09-01

    Difficulties may be encountered when undertaking a benefit-risk assessment for an older product with well-established use but with a benefit-risk balance that may have changed over time. This case study investigates this specific situation by applying a formal benefit-risk framework to assess the benefit-risk balance of warfarin for primary prevention of patients with atrial fibrillation. We used the qualitative framework BRAT as the starting point of the benefit-risk analysis, bringing together the relevant available evidence. We explored the use of a quantitative method (stochastic multi-criteria acceptability analysis) to demonstrate how uncertainties and preferences on multiple criteria can be integrated into a single measure to reduce cognitive burden and increase transparency in decision making. Our benefit-risk model found that warfarin is favourable compared with placebo for the primary prevention of stroke in patients with atrial fibrillation. This favourable benefit-risk balance is fairly robust to differences in preferences. The probability of a favourable benefit-risk for warfarin against placebo is high (0.99) in our model despite the high uncertainty of randomised clinical trial data. In this case study, we identified major challenges related to the identification of relevant benefit-risk criteria and taking into account the diversity and quality of evidence available to inform the benefit-risk assessment. The main challenges in applying formal methods for medical benefit-risk assessment for a marketed drug are related to outcome definitions and data availability. Data exist from many different sources (both randomised clinical trials and observational studies), and the variability in the studies is large. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Pregabalin as mono- or add-on therapy for patients with refractory chronic neuropathic pain: a post-marketing prescription-event monitoring study.

    Science.gov (United States)

    Lampl, Christian; Schweiger, Christine; Haider, Bernhard; Lechner, Anita

    2010-08-01

    This observational study examined the outcome of two different therapeutic strategies in the treatment of chronic neuropathic pain by including pregabalin (PGB) as mono- or add-on therapy in one of two treatment options. Patients with a pain score of > or =4, refractory to usual care for neuropathic pain for at least 6 months, were allocated consecutively to one of two treatment strategies according to the decision of the physician: complete switch to a flexible-dosage, monotherapeutic or add-on therapy with pregabalin (PGB group), or change established doses and combinations of pre-existing mono- or combination therapy without pregabalin (non-PGB group). After 4 weeks (primary endpoint) a significant improvement in pain reduction was documented in both intention-to treat (ITT) analysis (PGB group, n = 85: mean pain score reduction of 3.53, SD 2.03, p < 0.001; non-PGB group, n = 102; mean pain score reduction of 2.83, SD 2.23, p < 0.001) and per-protocol (PP) analysis (PGB group, n = 79: mean pain score reduction 3.53 vs. 2.83, p < 0.05; non-PGB group, n = 81; 3.5 vs. 2.9, p < 0.05) compared to baseline. Comparison of the results observed in the two groups shows that patients in the PGB group achieved significantly greater pain reduction. These results demonstrate that PGB administered twice daily is superior to treatment regimes without PGB in reducing pain and pain-related interference in quality of life.

  8. The occurrence rate of cerebrovascular and cardiac events in patients receiving antihypertensive therapy from the post-marketing surveillance data for valsartan in Japan (J-VALID).

    Science.gov (United States)

    Yamazaki, Tsutomu; Kohro, Takahide; Chujo, Mitsuaki; Ishigaki, Masahide; Hashimoto, Takafumi

    2013-02-01

    It is well known that blood pressure (BP) management reduces the incidence of cerebrovascular and cardiovascular events. However, it is unclear how many of these events occur in hypertensive patients who receive pharmacological treatment. The aim of this survey was to evaluate the occurrence rate of both types of events in patients receiving valsartan-based treatment. Of 30 366 patients treated with valsartan, 28 356 patients were observed for 2.93 years. Antihypertensive drugs other than valsartan were used in 56.8% of patients. After the administration of valsartan, the systolic and diastolic BP significantly decreased from 161.1±19.1/90.4±13.1 to 139.9±18.1/79.6±11.9 mm Hg. Cerebrovascular events were observed in 550 patients (1.94%, 9.29/1000 patient-years), and cardiac events were observed in 576 patients (2.03%, 9.73/1000 patient-years). A comparative analysis of the hazard ratios for cerebrovascular and cardiac events according to the BP level at the endpoint showed a BP-dependent reduction of risk for cerebrovascular events, and the change in risk exhibited a J-curve phenomenon in the relationship between cardiac events and systolic BP. The J-curve phenomenon was not observed in patients aged marketing surveillance data for valsartan showed the outcomes for treated hypertensive patients in a large population in Japan who were followed for up to 3 years. These data will add important knowledge regarding the treatment of hypertension in Japan.

  9. Comparative Effectiveness of Biosimilar, Reference Product and Other Erythropoiesis-Stimulating Agents (ESAs) Still Covered by Patent in Chronic Kidney Disease and Cancer Patients: An Italian Population-Based Study

    NARCIS (Netherlands)

    Y. Ingrasciotta (Ylenia); F. Giorgianni (Francesco); I. Marcianò (Ilaria); J. Bolcato (Jenny); R. Pirolo (Roberta); A. Chinellato (Alessandro); V. Ientile (Valentina); D. Santoro (Domenico); A.A. Genazzani (Armando A.); A. Alibrandi (Angela); A. Fontana (Andrea); A.P. Caputi (Achille); G. Trifirò (Gianluca)

    2016-01-01

    textabstractBackground Since 2007 biosimilars of erythropoiesis-stimulating agents (ESAs) are available on the Italian market. Very limited post-marketing data exist on the comparative effectiveness of biosimilar and originator ESAs. Aim This population-based study was aimed to compare the effects o

  10. 孟鲁司特联合沙丁胺醇气雾剂治疗咳嗽变异性哮喘的临床疗效及对IL-6 TNF-α的影响%Influence of montelukast combined with salbutamol aerosol on IL-6、T NF-αand clinical efficacy in patients with asthma

    Institute of Scientific and Technical Information of China (English)

    朱明辉; 胡广奋; 陆婉晖; 黎靖麟

    2015-01-01

    Objective To evaluate the clinical efficacy of montelukast combined with salbutamol aerosol in the treatment of cough variant asthma.Methods 128 patients with cough variant asthma were randomly divided into control group and observation group.Monte-lukast combined with salbutamol aerosol were administrated to the 64 patients in the observation group,and salbutamol aerosol alone was used in the control group.The clinical efficacy,pulmonary function,cough disappeared time,and serum cytokine level of patients in the two groups were assessed and compared.Results The efficacy rate in the observation group was significant higher than that of the control group (94.8% vs 75.0%,χ2 =4.267,P<0.05).The forced expiratory volume in 1 s (FEV1 )and forced expiratory volume in 1 s /forced vital capacity (FEV1/FVC)in the observation group were also significantly higher than those of the control group,and the difference was statisti-cally significant (P<0.05 ).But the average cough disappeared time,serum IL-6 and TNF-αlevel in the observation group were significant-ly lower than the control group,with significant difference between the two groups (P<0.05 ).Conclusion Treatment with montelukast combined with salbutamol aerosol in patients with cough variant asthma is safe and effective,and is worthy of clinical application and promo-tion.%目的:探讨孟鲁司特联合沙丁胺醇气雾剂在治疗咳嗽变异性哮喘的临床疗效。方法选取128例咳嗽变异性哮喘患者,随机分为观察组和对照组,对照组仅给予沙丁胺醇气雾剂,观察组采用孟鲁司特联合沙丁胺醇气雾剂治疗,比较两组患者临床疗效、肺功能、咳嗽消失时间及血清细胞因子变化。结果观察组治疗有效率(94.8%)显著优于对照(75.0%),差异有统计学意义(χ2=4.267,P<0.05)。观察组第一秒用力呼气容积(FEV1)、第一秒用力呼气容积/用力肺活量(FEV1/FVC)均显著高于对照组,

  11. Innovations in Post-Marketing Safety Research

    NARCIS (Netherlands)

    Stefánsdóttir, G.

    2012-01-01

    Safety surveillance is important during the entire life cycle of a drug. Pre-marketing trials have been shown to be ineffective in establishing the full safety profile of the drug, mainly due to their relatively small sample size and characteristics of the patients, which are usually younger and hea

  12. Innovations in Post-Marketing Safety Research

    NARCIS (Netherlands)

    Stefánsdóttir, G.

    2012-01-01

    Safety surveillance is important during the entire life cycle of a drug. Pre-marketing trials have been shown to be ineffective in establishing the full safety profile of the drug, mainly due to their relatively small sample size and characteristics of the patients, which are usually younger and

  13. The clinical observation of Montelukast in the treatment of 32 cases with atypical asthma%孟鲁司特钠治疗儿童非典型哮喘32例临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    贾洪礼; 贾苗; 刘志桢; 潘兆永; 刘国志; 王凤莲; 杨晓菲; 李成柏

    2011-01-01

    Objective To explore the clinical effect of Montelukast sodium in the treatment of atypical asthma. Methods Thirty- two cases of atypical asthma received routine laboratory examination and took Montelukast sodium chewable tablets once per night with the following instructions: <2 - year - old children 2.5 mg/times; 3~4 years old, 3.5 mg/times; 5~ 14 - year- old,5 mg/times. Results Coughing of 12 cases disappeared after 7 days, 10 cases' symptoms disappeared after 14 - day treatment, and 4 patients' symptoms disappeared with persistent medication as long as 45 days. Six cases improved on the forth day with inhaled corticosteroids, and pulmonary sputum together with tone and voice bubbles disappeared on the sixth day. Conclusion Montelukast sodium has a good preventive effect on pneumonia with atypical asthma.%目的 探讨孟鲁司特钠治疗儿童非典型哮喘的临床疗效.方法 32例非典型哮喘患儿行常规实验室检查后,服用孟鲁司特钠咀嚼片,每晚服1次,<2岁的患儿2.5 mg/次;3岁~4岁的患儿,3.5 mg/次;5岁~14岁的患儿,5 mg/次.结果 12例治疗7 d后咳嗽消失;10例用药14 d症状消失;4例持续用药45 d咳嗽消失;6例患儿加入糖皮质激素吸入第4天其症状改善,6 d后肺部痰鸣音和水泡音消失.结论 孟鲁司特钠对呈肺炎表现的非典型哮喘具有良好的防治作用.

  14. Establishing a Post Market Surveillance System under ISO 13485:2016%基于 ISO13485:2016构建医疗器械生产企业上市后监督体系

    Institute of Scientific and Technical Information of China (English)

    王红漫; 陈小红; 陈刚

    2016-01-01

    With the rapid development of medical device industry and the emergence of innovative medical devices, post-marketing surveillance (PMS) is being paid more and more attention by manufacturers, certification bodies and regulatory agency. ISO 13485:2016 has been published lately, and this new standard also reflected this trend. Many PMS requirements are included in the new standard to bet er harmonize with existing regulatory system (e.g FDA). The author analyzed the gap of PMS between new and old version of ISO 13485, and provided recommendations on establishment of PMS system under framework of the new standard.%随着医疗器械行业的飞速发展和创新医疗器械的不断涌现,产品的上市后监督(PMS)越来越受到企业、认证组织和政府监管部门的重视。最近发布的 ISO 13485:2016也反映了这个趋势,在多个条款上增加和细化了对上市后监督的要求,加强了与主流法规体系(例如美国 FDA)的协调性。本文分析了新版 ISO13485在上市后监督方面与旧版的差异,并就如何在新标准的框架下构建上市后监督管理体系作了探讨。

  15. Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis.

    Science.gov (United States)

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2014-02-15

    Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA), an observational, non-interventional, 24-week post-marketing surveillance study in Japanese patients with type 2 diabetes (T2DM) having uncontrolled glycemic control, demonstrated that basal supported oral therapy (BOT) with insulin glargine was an effective and safe treatment in real-life clinical practice. We performed subgroup analysis to identify incidence and predictors associated with risk of hypoglycemia. Among 4219 patients with T2DM, 3732 patients were insulin-naïve and 487 patients were insulin non-naïve who switched from other insulin to insulin glargine. All hypoglycemic episodes were counted by physicians' documentation based on patients' reports. Relationships between baseline patient characteristics and glargine-related hypoglycemic episodes were examined by univariate and multivariate analysis. Among 4219 patients, 44 (1.0%) patients experienced hypoglycemic episodes (41 insulin-naïve patients; 3 insulin non-naïve patients), with a rate of incidence 0.035 episodes/patient-years. Majority of patients with hypoglycemia (37 of 44) had just one hypoglycemic episode during study period. Among insulin-naïve patients, incidence of hypoglycemia differed significantly depending on age, diabetic complications, estimated glomerular filtration rate (eGFR), and postprandial plasma glucose (P multivariate adjusted model, poor renal function (eGFR <60 mL/min/1.73 m2) was a statistically significant risk factor (P < 0.05). Our results suggest that BOT using insulin glargine is an option of insulin therapy with 1% risk of hypoglycemia in patients with T2DM with inadequate glycemic control. Patients with low renal function might need a careful follow-up.

  16. A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance.

    Science.gov (United States)

    Akaza, Hideyuki; Oya, Mototsugu; Iijima, Masafumi; Hyodo, Ichinosuke; Gemma, Akihiko; Itoh, Hiroshi; Adachi, Masatoshi; Okayama, Yutaka; Sunaya, Toshiyuki; Inuyama, Lyo

    2015-10-01

    Real-life safety and efficacy of sorafenib in advanced renal cell carcinoma in a nationwide patient population were evaluated by post-marketing all-patient surveillance. All patients with unresectable or metastatic renal cell carcinoma in Japan who started sorafenib therapy from February 2008 to September 2009 were registered and followed for up to 12 months. Baseline characteristics, treatment status, tumor response, survival and safety data were recorded by the prescribing physicians. Safety and efficacy were evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800 mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued the treatment by 12 months, half of which (52.0% of discontinued patients) were due to adverse events. The most common adverse drug reactions were hand-foot skin reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase (23%). The median progression-free survival was 7.3 months (95% confidence intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5-77.1). Prognostic factors for overall survival were mostly consistent with those in previous clinical trials in the univariate analysis and largely similar to those for progression-free survival and duration of treatment in the multivariate analysis. Sorafenib for the treatment of advanced renal cell carcinoma under the labeled dose was feasible in daily medical practice, for its acceptable toxicity profile and favorable clinical benefit that were consistent with those in clinical trials. © The Author 2015. Published by Oxford University Press.

  17. The impact of coronary calcification on angiographic and 3-year clinical outcomes of everolimus-eluting stents: results of a XIENCE V/PROMUS post-marketing surveillance study.

    Science.gov (United States)

    Shiode, Nobuo; Kozuma, Ken; Aoki, Jiro; Awata, Masaki; Nanasato, Mamoru; Tanabe, Kengo; Yamaguchi, Junichi; Kusano, Hajime; Nie, Hong; Kimura, Takeshi

    2017-07-19

    Coronary calcification (CCA) is one of the independent predictors for major adverse cardiac events (MACEs) in coronary intervention. Post-marketing surveillance study Japan is a prospective registry designed to evaluate the safety and efficacy of the everolimus-eluting stent (EES, XIENCE V/PROMUS Stent) in routine clinical practice at 47 centers. In this study, 1848 lesions (1546 patients) were assessed using quantitative coronary angiography. In these 1546 patients, renal function data were unknown in 26 patients. Three patients in 70 patients with dialysis and 56 patients in 1450 patients with no dialysis were excluded, because they had multiple lesions with mixed calcification lesions. We evaluated the effects of CCA on 8-month angiographic and 3-year clinical outcomes in dialysis and non-dialysis patients. Moderate-to-severe (Ca group) and none-to-mild CCA (non-Ca group) were observed in 33 lesions (30 patients) and 48 lesions (37 patients) in dialysis patients, and these were observed in 306 lesions (286 patients) and 1303 lesions (1108 patients) in non-dialysis patients, respectively. In non-dialysis patients, the ischemic-driven target lesion revascularization (ID-TLR) and MACE rate over the 3 years were significantly higher in the Ca group than in the non-Ca group (5.8 vs. 3.1%, p = 0.025 and 10.0 vs. 5.0%, p = 0.0011). In dialysis patients, ID-TLR and MACE rates were high in both groups (14.3 vs. 17.9%, p = 0.85 and 17.5 vs. 36.1%, p = 0.16). In non-dialysis patients, 8-month angiographic and 3-year clinical outcomes were worse in the Ca group. However, in dialysis patients, both outcomes were worse regardless of CCA.Clinical Trial registration https://clinicaltrials.gov/ct2/show/NCT01086228 .

  18. 布地奈德福莫特罗干粉吸入剂联合孟鲁司特对中重度支气管哮喘肺功能的影响%The Effect on Lung Function of Budesonide and Fomoterol Fumarate Powder for Inhalation in Combination with Montelukast in the Treatment of Moderate and Severe Bronchial Asthma

    Institute of Scientific and Technical Information of China (English)

    区秀燕; 袁小玲; 郭伟洪

    2014-01-01

    Inhalation only (160 μg/4.5 μg/snuff, AZN, twice daily), 12 weeks for each treatment.The clinical control effect and lung function were compared between the two groups before and after treatment in the 4, 8 and 12 weeks.Results There were no significant differences in control rate and ACT scores in the two groups before treatment (P>0.05).The control rate of observation group after 4 and 8 weeks is 91.11%and 93. 33%respectively, and the ACT scores are 23.17±4.87 and 25.31±3.61 respectively, which are significantly higher than those of the control group.There were significant differences in the two groups (P0.05).By the end of the course, there had been significant differences in FEV1, FEV1% and PEF% compared with the prior treatment ( P>0.05 ) , but there were no significant differences in the two groups ( P>0.05 ) .Conclusion Budesonide and Fomoterol Fumarate Powder for Inhalation in combination with Montelukast, with the unique advantages, prove to be obviously effective in controlling asthma in the early stage, improving the symptoms and reducing the recurrence rate.

  19. Scientific Opinion on the annual Post-Market Environmental Monitoring (PMEM report from BASF Plant Science Company GmbH on the cultivation of genetically modified potato EH92-527-1 in 2011

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Genetically Modified Organisms (GMO

    2012-12-01

    Full Text Available Following a request from the European Commission, the Panel on Genetically Modified Organisms of the European Food Safety Authority(EFSA GMO Panel assessed the monitoring report for the 2011 growing season, provided by BASF, on the genetically modified (GM potato EH92-527-1 (variety Amflora. On 26 January 2012, the EFSA GMO Panel had adopted a scientific opinion on the 2010 monitoring report on potato EH92-527-1. The EFSA GMO Panel followed the same approach as for the assessment of the 2010 monitoring report and assessed, in close collaboration with the EFSA Unit for Scientific Assessment Support, the methodology used by the applicant in 2011 for the case-specific studies, the general surveillance of potato EH92-527-1 and the field study to monitor potential adverse effects on potato-feeding organisms as required in the related Commission Decision. The EFSA GMO Panel notes similar shortcomings in the methodology for general surveillance and for the specific field study on potato-feeding organisms as were found in the 2010 monitoring report. Hence, the EFSA GMO Panel reiterates the same recommendations for improvement of the methodology for the post-market environmental monitoring of potato EH92-527-1 as it did in its scientific opinion on the 2010 monitoring report. The EFSA GMO Panel also assessed the methodology of a new study monitoring GM volunteers within and around fields cropped with potato EH92-527-1 in 2010. The EFSA GMO Panel identified flaws in that study and therefore makes recommendations to the applicant to improve the study design. However, from the overall dataset submitted by the applicant, the EFSA GMO Panel did not identify adverse effects on the environment or human and animal health due to potato EH92-527-1 cultivation. The outcomes of the 2011 monitoring report do not invalidate the conclusions of the EFSA GMO Panel’s previous opinions on potato EH92-527-1.

  20. 中药上市后临床再评价及Ⅳ期临床试验的基本要求%Basic requirements on post-marketing clinical re-evaluation of Chinese medicine and phase Ⅳ clinical trials

    Institute of Scientific and Technical Information of China (English)

    谢雁鸣; 王燕平; 田峰; 王永炎

    2011-01-01

    As information on safety and effectiveness is not comprehensive, gained from the researches for listing approval of Chinese medicine, it is very necessary to conduct post-marketing clinical re-evaluation of Chinese medicine. Effectiveness, safety and economic evaluation are three main aspects of post-marketing clinical re-evaluation. In this paper, the difference and relations between the post-marketing clinical re-evaluation and the phase IV clinical trials were discussed, and the basic requests and suggestions were proposed, according to the domestic and foreign relevant regulations and experts' suggestions, and discussed the requirements of the phase IV clinical trials on indications, design methods, inclusion and exclusion criteria, sample size, etc.%鉴于药品上市前临床试验获得的药品安全性和有效性数据的局限性,开展中药上市后临床再评价是非常必要的.该文讨论中药上市后临床再评价与Ⅳ期临床试验的共同点与区别;根据国内外相关法规,结合专家建议,提出中药上市后临床再评价的基本要求和建议;讨论Ⅳ期临床试验在适应证范围、设计方法、病例入选和排除标准、样本含量等方面的具体要求.

  1. 地氯雷他定联合孟鲁斯特钠治疗慢性荨麻疹疗效评价%Assessment of desloratadine combined with montelukast in the treatment of chronic urticaria

    Institute of Scientific and Technical Information of China (English)

    刘麟; 郑海霞

    2015-01-01

    目的::评价地氯雷他定联合孟鲁斯特钠治疗慢性荨麻疹( chronic urticaria,CU)的疗效。方法:68例慢性荨麻疹患者随机分为联合用药组( CTT组)和对照组( CTL组),每组34例,CTT组给予地氯雷他定(5 mg,1次/d)联合孟鲁斯特钠(0.1 g,3次/d)进行治疗,CTL组仅给予地氯雷他定(5 mg,1次/d)治疗,两组患者均连续服药8周。根据患者瘙痒程度、风团大小(最大直径)、风团数目等对两组患者进行疗效评价。结果: CTT 组有效率为94.12%, CTL 组73.53%,差异有统计学意义( P<0.05)。随访28周,CTT组和CTL组复发率分别为21.88%和56.00%,差异有统计学意义( P<0.01)。结论:地氯雷他定联合孟鲁斯特钠治疗CU不仅可获得更高的有效率且可降低患者的复发率。%Objective:To assess the efficacy of desloratadine combined with montelukast in the treatment of chronic urticaria ( CU) . Methods:Sixty-eight patients with CU were divided into the control ( CTL) group and the combined treatment ( CTT) group randomly ( 34 patients in each group) . All the patients were treated with desloratadine 5 mg, once a day and the patients in the CTT group were given additional leukotrienes re-ceptor antagonist of montelukast 0.1 g, three times a day, for 8 weeks. The efficacies in the two groups were assessed according to the itch degree, numbers and sizes of urticaria. Results: The effective rate in the CTT group was 94.12%, which was higher than that in the CTL group (73.53%), with a significant difference (P<0.05). The recurrent rate in the CTT group was 21.88%, which was lower than that in the CTL group ( 56.00%) after the 28 weeks follow-up, with a significant difference ( P<0.01) . Conclusion:Desloratadine combined with montelukast is more effective and lower recurrent rate than desloratadine alone in the treatment of CU.

  2. 孟鲁司特钠治疗小儿过敏性紫癜疗效观察%Clinical Effect of Montelukast Soudium in Treating Children with Henoch-Sch(o)nlein Purpura

    Institute of Scientific and Technical Information of China (English)

    赵素香

    2013-01-01

    目的:探讨孟鲁司特钠治疗小儿过敏性紫癜(HSP)的临床疗效.方法:96例HsP患儿随机分为治疗组和对照组各48例.两组患儿均予抗组胺药物、钙剂、维生素C治疗,并停止服用可能引起过敏的食物、药物,避免接触可疑过敏物,有感染征象的给予抗生素治疗,消化道出血者卧床休息,暂禁食,给予西咪替丁及胃粘膜保护剂,腹痛、关节肿痛者加用激素,治疗组在此基础上给予孟鲁司特钠咀嚼片口服,<10岁患儿每次5 mg,≥10岁患儿每次10 mg,每晓睡前服1次,疗程1个月.观察比较两组疗效.结果:治疗组总有效率95.8%(46/48),对照组总有效率85.4% (41/48),治疗组高于对照组,但两组总有效率比较差异无统计学意义(x2=3.065,P>0.05);治疗组皮肤紫癜、消化道病变、关节肿痛、肾脏病变消失时间等方面均比对照组明显缩短,两组比较差异均有统计学意义(P<0.05).结论:孟鲁司特钠治疗小儿HSP,疗效确切,能较快缓解症状、缩短病程,未发现明显不良反应,值得临床推广使用.%Objective: To explore the clinical effect of montelukast soudium in treating children with Henoch-Schonlein Puipura ( HSP). Methods: Ninety six cases of children with HSP were randomly divided into a treatment group and a control group equally. Patients in the two groups were given anlihistamine drugs, calcium, vitamin C, and antibiotic treatment to those with signs of infection. All patients stopped taking food and medications that may cause allergy, and avoided contacting with suspicious allergens. Patients with gastrointestinal bleeding received cimetidine and mucosa protective agent, and had bed rest and fasting. Patients with abdominal pain, joint swelling and pain were given glucocorticoids. Based on the comprehensive therapy, the treatment group was given montelukast soudium chewing tablets, 5 mg/day for 0. 05). The durations of cutaneous purpura, gastrointestinal lesions, joint

  3. Analysis of Effect of Montelukast Sodium combined with BCG-PSN on Sick Children with Chronic Urticaria.%孟鲁司特联合卡介菌素治疗儿童慢性荨麻疹

    Institute of Scientific and Technical Information of China (English)

    吕广秀; 曹勇; 陈青青

    2012-01-01

      Objective The efficacy of the concept Chameng Lu Special Secretary and BCG polysaccharide nucleic acid injection treatment of chronic urticaria. Methods Control group with BCG Polysaccharide Nucleic Acid Injection 0.5mg every other day, intramuscular injection, 10d1 courses, a total of three courses, the experimental group add services on the basis of montelukast oral daily 5mg, per nightorally once. Results Results of 117 cases ,the 59 was for test group , and 58 for control group .The effective rate of test group was 88.1%, while 70.7% for control group ,the difference had statistically significant (P<0.05).Conclusion BCG-PSN was effective for treatment chronic urticaria in children ,and BCG-PSN combined with Montelukast could raise the treating effect of sick children with chronic urticaria ,and reduce the recurrence .%  目的观察孟鲁司特和卡介菌多糖核酸注射液治疗慢性荨麻疹的疗效.方法对照组单用卡介菌多糖核酸注射液0.5mg,隔日一次,肌内注射,10d1个疗程,共计3个疗程,实验组在此基础上加服孟鲁司特口服,每天5mg,每晚一次口服.结果共治疗117例,实验组59例,对照组58例,实验组有效率为88.1%,对照组有效率为70.7%,两组比较差异有统计学意义(P <0.05).结论孟鲁司特联合卡介菌素多糖核酸注射液治疗可提高儿童慢性荨麻疹病的疗效,以减少复发率.

  4. The effects of montelukast on antioxidant enzymes and proinflammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture-induced sepsis.

    Science.gov (United States)

    Coskun, Ali Kagan; Yigiter, Murat; Oral, Akgun; Odabasoglu, Fehmi; Halici, Zekai; Mentes, Oner; Cadirci, Elif; Atalay, Fadime; Suleyman, Halis

    2011-07-07

    We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)-induced tissue injury in vital organs - liver, heart, kidneys, and especially lungs - through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

  5. The Effects of Montelukast on Antioxidant Enzymes and Proinflammatory Cytokines on the Heart, Liver, Lungs, and Kidneys in a Rat Model of Cecal Ligation and Puncture–Induced Sepsis

    Directory of Open Access Journals (Sweden)

    Ali Kagan Coskun

    2011-01-01

    Full Text Available We investigated the potential protective effects of montelukast (MLK on cecal ligation and puncture (CLP–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS in rats. The rat groups were (1 a 10-mg/kg MLK-treated CLP group; (2 a 20-mg/kg MLK-treated CLP group; (3 a 20-mg/kg MLK-treated, sham-operated group; (4 a CLP control group; and (5 a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6 cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.

  6. Clinical observation of Montelukast combined with Procaterol in treating pediatric asthmat-ic bronchitis%孟鲁司特联合丙卡特罗佐治小儿喘息性支气管炎的临床观察

    Institute of Scientific and Technical Information of China (English)

    严淑颜; 戴汝均

    2015-01-01

    AIM:To evaluate the efficacy of Montelukast com-bined with Procaterol in treating pediatric asthmatic bronchitis. METHODS:60 cases with asthmatic bronchitis were divided into treatment group (30 cases)and control group (30 cases)ran-domly.The control group received routine treatment,while the treatment group received oral Montelukast and Procaterol on the basic of routine therapy.RESULTS:The disappeared time of symptoms and signs in treatment group was significantly better than that in control group.CONCLUSION:Oral Montelukast combined with Procaterol has significantly curative effect in the treatment of pediatric asthmatic bronchitis.%目的:观察孟鲁司特联合丙卡特罗治疗小儿喘息性支气管炎的疗效。方法:选择喘息性支气管炎患儿60例,随机分为治疗组(30例)和对照组(30例)。对照组接受常规治疗,治疗组在常规治疗的同时口服孟鲁司特与丙卡特罗治疗。结果:治疗组症状、体征消失时间等方面均明显优于对照组。结论:口服孟鲁司特联合丙卡特罗治疗小儿喘息性支气管炎疗效显著。

  7. 盐酸二甲双胍肠溶片上市后人体生物等效性再评价%Post-Marketing Reevaluation of Bioequivalénce of Metformin Hydrochloride Enteric-Coated Tablets

    Institute of Scientific and Technical Information of China (English)

    张丹; 王振龙; 王涛; 刘会臣; 杨漫; 韩静; 王晓琳; 张丽娜; 张娅喃; 肖雪; 杜爱华; 刘曼

    2012-01-01

    , not only conducting pre-marketing bioequivalence study with proper reference preparation, but also enhancing post-marketing surveillance and re-evaluation of bioequivalence are very important for maintaining the consistency of drugs quality.%目的 对已上市的盐酸二甲双胍肠溶片的人体生物等效性进行再评价.方法 采用转篮法和紫外分光光度法考察4个厂家(A、B、C、D)的盐酸二甲双胍肠溶片的体外释放度,选择其中2个厂家的盐酸二甲双胍肠溶片作为受试制剂(受试制剂1和受试制剂2),以原研药盐酸二甲双胍片(格华止)为参比制剂.21名健康男性受试者随机分组,于3个周期交叉服用受试制剂1、受试制剂2和参比制剂500 mg,采用LC-MS/MS测定血浆样本中二甲双胍的浓度,计算药动学参数及2种受试制剂相对于参比制剂的平均相对生物利用度,采用(1-2α)置信区间法评价2种受试制剂与参比制剂的生物等效性,以及2种受试制剂之间的生物等效性.结果 除A厂家的盐酸二甲双胍肠溶片在酸中释放度不符合2010年版《中国药典》增补本拟新增品种公示中的规定外,其他3个厂家的产品均符合规定,且4个厂家的盐酸二甲双胍肠溶片在缓冲液中释放度均符合规定.选择A和D厂家的盐酸二甲双胍肠溶片作为受试制剂1和受试制剂2.受试制剂1的平均相对生物利用度F0-t和F0-∞分别为(72.8±9.7)%、(73.2±10.0)%,受试制剂2的平均相对生物利用度F0-t和F0-∞分别为(45.5±16.2)%、(46.2±16.0)%.受试制剂1、受试制剂2和参比制剂的ρmax、AUC0-t和AUC0-∞分别经对数转换后进行(1-2α)置信区间检验,不能判定受试制剂1与参比制剂不具有生物等效性,受试制剂2与参比制剂不具有生物等效性,2种受试制剂之间也不具有生物等效性.结论 盐酸二甲双胍肠溶片为生物不等效风险高的品种,建议不仅应在上市前选择合适的参比制剂进行规范

  8. Progress of Post-marketing Surveillance on Adverse Events Following Immunization of the Pandemic Influenza A(H1N1) Vaccine%甲型H1N1流行性感冒疫苗疑似预防接种异常反应监测进展

    Institute of Scientific and Technical Information of China (English)

    吴冰冰; 刘大卫; 李克莉; 武文娣; 许涤沙; 贾磊

    2011-01-01

    甲型H1N1流行性感冒(甲流)疫苗上市后,疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)监测是评价甲流疫苗安全性的重要方法.文章对各国甲流疫苗的监测概况和监测结果 进行了综述.%Post-marketing surveillance on Adverse Events Following Immunization (AEFI)is crucial for evaluating the safety of vaccines against the pandemic influenza A (H1N1)virus.Progress of postmarketing surveillance of AEFI of the pandemic influenza A(H1N1 )vaccine among countries has been reviewed in this article.

  9. 孟鲁斯特治疗小儿喘息性支气管炎的临床观察%Clinical Observation of Montelukast in the Treatment of Children With Asthmatic Bronchitis

    Institute of Scientific and Technical Information of China (English)

    魏晓峰

    2016-01-01

    目的:探讨孟鲁斯特治疗小儿喘息性支气管炎的时效性。方法我院2013年5月~2015年4月确诊的小儿喘息性支气管炎患儿62例,均给予常规治疗。观察组睡前口服孟鲁司特,对照组睡前口服安慰剂。结果观察组喘息症状缓解时间(t=6.416,P=0.00)、肺部哮鸣音和啰音消失时间(t=4.190,P=0.00)、平均住院天数(t=4.111,P=0.00)短于对照组,疗效优于对照组(χ2=6.7721,P=0.0338)。结论孟鲁司特钠可加速喘息性支气管炎患儿的症状和体征的改善,提高临床效果。%Objective To investigate the effectiveness of montelukast in the treatment of children with asthmatic bronchitis. Methods 62 cases of children with asthmatic bronchitis in our hospital from May 2013 to April 2015 were treated with routine treatment. The observation group was oral before bedtime, and the control group received placebo before bedtime. Results In the observation group,the asthmatic symptoms remission time(t=6.416, P=0.00),pulmonary wheezing sound tone and rales disappearance time(t=4.190,P=0.00),the average hospitalization days(t=4.111,P=0.00) shorter than the control group,the curative effect was better than that of the control group(χ 2=6.772 1,P=0.033 8). Conclusion The effect of the improvement of the symptoms and signs of the patients with acute wheezing bronchitis can be improved by the conclusion of the conclusion.

  10. Clinical study on montelukast treatment for adenoidal hypertrophy in children%孟鲁司特钠治疗儿童腺样体肥大的临床疗效

    Institute of Scientific and Technical Information of China (English)

    汤海玲; 曹园园

    2013-01-01

    目的 探讨孟鲁司特钠治疗儿童腺样体肥大(AH)的可行性及临床疗效.方法 选择2010年6月至2012年6月我院收治的上气道咳嗽综合征合并AH患儿120例,依据随机对照原则分为观察组(60例)与对照组(60例),所有病例使用抗生素治疗及对症治疗,观察组给予孟鲁司特钠治疗16周,对照组同期给予安慰剂.观察两组患儿治疗前后咳嗽持续天数、呼吸相关睡眠障碍症状指标评分及腺样体/鼻咽比值(A/N比值)的改变.结果 所有患者均顺利完成16周治疗.观察组治疗前后咳嗽持续天数、呼吸相关睡眠障碍症状指标评分及A/N比值比较差异有统计学意义(P0.05);观察组与对照组治疗前上述指标比较差异无统计学意义,与治疗后比较差异有统计学意义(P 0. 05 ); before the therapy, there was no significant difference for all the above-mentioned index between the experiment group and the control group, while after the therapy,there were significant differences between the two groups( P < 0. 05 ). Conclusion Montelukast has good clinical effect in children with upper respiratory cough syndrome complicated with adenoidal hypertrophy, it is able to reduce cough days, and improve the sleep disorder and reduced the size of the adenoid.

  11. Phase 0 clinical trials and post-marketed re-evaluation of clinical safety in injection of traditional Chinese medicine%0期临床试验与中药注射剂上市后临床安全性再评价

    Institute of Scientific and Technical Information of China (English)

    谢雁鸣; 魏戌; 张占军; 王永炎

    2011-01-01

    中药注射剂不良反应时有发生,临床安全性问题亟待解决,需要进行上市后临床安全性再评价,过敏反应是不良反应评价的主要内容之一.对含有毒药材的中成药、有安全问题的中药注射剂需要开展0期临床试验,0期临床试验使用“微剂量”研究周期内收集必要的药物安全性及药代动力学试验数据,微剂量可以反映中药注射剂的致敏情况.0期临床试验为上市后中药注射剂的安全性再评价提供了新的方法,是否进行0期临床试验,应依据品种是否有安全性问题而定,中药注射剂初始剂量以及样本含量的确定是研究设计的关键问题.%Adverse drug reaction induced by injection of traditional Chinese medicine ( TCM ) often occurs. Post-marketed re-evaluation of clinical safety in injection of TCM is indispensable, in order to solve the clinical safety problems. It is necessary to conduct Phase 0 clinical trials for containing toxic medicine and injection of TCM. Phase 0 clinical trials, involving very limited human exposure, and using microdose of drugs,are intended to collect the necessary safety and pharmacokinetic data in limited period. Microdose reflects allergies of injection of TCM. Phase 0 clinical trials provide a new method for post-marketed re-evaluation of safety in injection of TCM. Its use depends on whether there is a safety problem for injection of TCM, and the determination of initial dose and sample size are key questions in study design.

  12. Effectiveness and Persistence of Liraglutide Treatment Among Patients with Type 2 Diabetes Treated in Primary Care and Specialist Settings: A Subgroup Analysis from the EVIDENCE Study, a Prospective, 2-Year Follow-up, Observational, Post-Marketing Study.

    Science.gov (United States)

    Martinez, Luc; Penfornis, Alfred; Gautier, Jean-Francois; Eschwège, Eveline; Charpentier, Guillaume; Bouzidi, Amira; Gourdy, Pierre

    2017-03-01

    The objective of this subgroup analysis is to investigate the effectiveness of liraglutide in people with type 2 diabetes (T2D) treated within the primary care physician (PCP) and specialist care settings. EVIDENCE is a prospective, observational study of 3152 adults with T2D recently starting or about to start liraglutide treatment in France. We followed patients in the PCP and specialist settings for 2 years to evaluate the effectiveness of liraglutide in glycemic control and body weight reduction. Furthermore, we evaluated the changes in combined antihyperglycemic treatments, the reasons for prescribing liraglutide, patient satisfaction, and safety of liraglutide in these two treatment settings. After 2 years of follow-up, 477 out of 1209 (39.0%) of PCP and 297 out of 1398 (21.2%) of specialist-treated patients still used liraglutide and maintained the glycated hemoglobin (HbA1c) target of <7.0%. Significant reductions from baseline were observed in both PCP- and specialist-treated cohorts in mean HbA1c (-1.22% and -0.8%, respectively), fasting plasma glucose (FPG) concentration (-39 and -23 mg/dL), body weight (-4.4 and -3.8 kg), and body mass index (BMI) (-1.5 and -1.4 kg/m(2)), all p < 0.0001. Reductions in HbA1c and FPG were significantly greater among PCP- compared with specialist-treated patients, p < 0.0001 for both. Patient treatment satisfaction was also significantly increased in both cohorts. Reported gastrointestinal adverse events were less frequent among PCP-treated patients compared with specialist-treated patients (4.5% vs. 16.1%). Despite differences in demography and clinical characteristics of patients treated for T2D in PCP and specialty care, greater reduction in HbA1c and increased glycemic control durability were observed with liraglutide in primary care, compared with specialist care. These data suggest that liraglutide treatment could benefit patients in primary care by delaying the need for further treatment intensification

  13. Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

    Science.gov (United States)

    Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

    2017-08-01

    To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

  14. Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine%FDA风险控制计划指南及其对我国中药上市后风险管理的启示

    Institute of Scientific and Technical Information of China (English)

    黎元元; 谢雁鸣

    2011-01-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine and promote the evaluation of risk management of the drug development and improvement.%该文介绍了FDA风险控制计划(risk evaluation and mitigation strategy,REMS)指南,并结合实例芬太尼的FOCUS风险控制计划进行分析REMS的内容组成.我国可借鉴美国的相关经验,建立科学的药品再评价机制,强化风险意识,促进合理用药,将中药上市前和上市后评价有机结合,促进我国药品风险管理的发展与完善.

  15. Impact of insulin-treated diabetes and hemodialysis on long-term clinical outcomes following sirolimus-eluting stent deployment. Insights from a sub-study of the Cypher Stent Japan Post-Marketing Surveillance(Cypher J-PMS) Registry.

    Science.gov (United States)

    Nakamura, Masato; Yokoi, Hiroyoshi; Hamazaki, Yuji; Watarai, Masato; Kijima, Mikihiro; Mitsudo, Kazuaki

    2010-11-01

    Long-term clinical outcomes of diabetes mellitus (DM) patients who underwent drug-eluting stent deployment has not well investigated. A total of 2,050 cases were enrolled consecutively from 50 sites in Japan into the Cypher stent Japan Post-Marketing Surveillance (Cypher J-PMS) registry, and the 3-year outcomes of DM patients were analyzed. Subjects were divided into 2 groups based on the treatment of DM (insulin-treated diabetes (IT) group, n=207; and non insulin-treated diabetes (NIT) group, n=682). Major adverse cardiac event (MACE) rates in the IT group and the NIT group were 26.0% and 14.5% at 3 years, respectively (PMultivariate analysis suggested that hemodialysis and insulin-treated DM were independent predictors for MACE, and insulin-treated DM, hemodialysis and long lesions were strong independent predictors for target-lesion revascularization (TLR). Hemodialysis and insulin-treated DM were strong independent predictors of mortality and TLR in DM patients. These results might suggest that special attention to patients with hemodialysis and insulin-treated DM is warranted in the setting of sirolimus-eluting stent deployment for DM patients.

  16. Olestra consumption does not predict serum concentrations of carotenoids and fat-soluble vitamins in free-living humans: early results from the sentinel site of the olestra post-marketing surveillance study.

    Science.gov (United States)

    Thornquist, M D; Kristal, A R; Patterson, R E; Neuhouser, M L; Rock, C L; Neumark-Sztainer, D; Cheskin, L J

    2000-07-01

    In 1996, the U.S. Food and Drug Administration approved olestra, a fat substitute, for use in snack foods. Previous studies had shown that olestra consumption could reduce absorption of carotenoids and fat-soluble vitamins. To determine the association between consumption of olestra-containing snack foods and serum concentrations of carotenoids and fat-soluble vitamins in a free-living population, we interviewed independent population-based cross-sectional samples of 1043 adults before olestra was available and 933 adults 9 mo after olestra snacks were introduced into the marketplace in Marion County, IN, the first major test market for olestra. A cohort composed of 403 adults from the first survey, oversampling those most frequently reporting olestra consumption during follow-up telephone interviews, completed a second survey. We assessed diet, lifestyle factors and olestra consumption, and collected blood for assays for the serum concentrations of six carotenoids, four fat-soluble vitamins and lipids. Nine months after the introduction of olestra into the marketplace, 15.5% of Marion County residents reported consuming an olestra-containing snack in the previous month, with a median frequency among consumers of 3.0 times per month. There were no significant associations or consistent trends for decreased serum carotenoids or fat-soluble vitamins associated with olestra consumption, although cohort members consuming >/=2 g/d of olestra had adjusted total serum carotenoids 15% lower compared with baseline. There were increases in serum vitamin K concentrations associated with olestra consumption (P = 0.03 in the cross section and P = 0.06 in the cohort). In summary, there was no statistically significant evidence in this free-living population of associations between olestra consumption and decreased serum concentrations of carotenoids and fat-soluble vitamins.

  17. Monitoring risk: post marketing surveillance and signal detection.

    Science.gov (United States)

    Dart, Richard C

    2009-12-01

    The primary goal of postmarketing surveillance is to provide information for risk assessment of a drug. Drugs affecting the central nervous system form a unique group of products for surveillance because they are often misused, abused, and diverted. These medications include opioid analgesics, stimulants, sedative-hypnotics, muscle relaxants, anticonvulsants and other drug classes. Their adverse events are difficult to monitor because the perpetrator often attempts to conceal the misuse, abuse and diversion of the product. A postmarketing surveillance system for prescription drugs of abuse in the U.S. should include product specific information that is accurate, immediately available, geographically specific and includes all areas of the country. Most producers of branded opioid analgesic products have created systems that measure abuse from multiple vantage points: criminal justice, treatment professionals, susceptible patient populations and acute health events. In the past, the U.S. government has not established similar requirements for the same products produced by generic manufacturers. However, the Food and Drug Administration Amendments Act of 2007 includes generic opioid analgesic products by requiring that all products containing potent opioid drugs perform rigorous surveillance and risk management. While general risk management guidance has been developed by FDA, more specific analyses and guidance are needed to improve surveillance methodology for drugs which are misused, abused, diverted.

  18. Clinical outcomes with the STENTYS self-apposing coronary stent in patients presenting with ST-segment elevation myocardial infarction: two-year insights from the APPOSITION III (A Post-Market registry to assess the STENTYS self-exPanding COronary Stent In AcuTe MyocardIal InfarctiON) registry.

    Science.gov (United States)

    Lu, Huangling; Grundeken, Maik J; Vos, Nicola S; IJsselmuiden, Alexander J J; van Geuns, Robert-Jan; Wessely, Rainer; Dengler, Thomas; La Manna, Alessio; Silvain, Johanne; Montalescot, Gilles; Spaargaren, René; Tijssen, Jan G P; Amoroso, Giovanni; de Winter, Robbert J; Koch, Karel T

    2017-08-04

    The APPOSITION III registry evaluated the feasibility and performance of the STENTYS self-apposing stent in an ST-segment elevation myocardial infarction (STEMI) population. This novel self-apposing stent device lowers stent strut malapposition rates and therefore carries the potential to prevent stent undersizing during primary percutaneous coronary intervention (PCI) in STEMI patients. To date, no long-term data are available using this device in the setting of STEMI. We aimed to evaluate the long-term clinical outcomes of the APPOSITION III registry. This was an international, prospective, multicentre post-marketing registry. The study population consisted of 965 STEMI patients. The primary endpoint, major adverse cardiac events (MACE), was defined as the composite of cardiac death, recurrent target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularisation (CD-TLR). At two years, MACE occurred in 11.2%, cardiac death occurred in 2.3%, TV-MI occurred in 2.3% and CD-TLR in 9.2% of patients. The two-year definite stent thrombosis (ST) rate was 3.3%. Incremental event rates between one- and two-year follow-up were 1.0% for TV-MI, 1.8% for CD-TLR, and 0.5% for definite ST. Post-dilation resulted in significantly reduced CD-TLR and ST rates at 30-day landmark analyses. Results were equivalent between the BMS and PES STENTYS subgroups. This registry revealed low rates of adverse events at two-year follow-up, with an incremental ST rate as low as 0.5% in the second year, demonstrating that the self-apposing technique is feasible in STEMI patients on long-term follow-up while using post-dilatation.

  19. Post-marketing Evaluation of Clinical Application of St. John's Wort Extract(Neurostan®) in China%圣•约翰草提取物片(路优泰®)国内上市后临床应用评价

    Institute of Scientific and Technical Information of China (English)

    贡联兵

    2016-01-01

    目的:评价圣•约翰草提取物片(路优泰®)上市后国内临床应用情况,为临床用药提供借鉴。方法:查阅国内外相关文献,对路优泰上市后国内临床使用的适应证、有效性、安全性、经济学等方面进行评价。结果与结论:路优泰目前已在国内广泛用于治疗轻、中度抑郁症,焦虑和烦躁不安等疾病,其临床应用在不断扩展。鉴于路优泰不良反应轻微、价格相对便宜,路优泰的应用前景将会更加广阔。%Objective: To do the post-marketing evaluation ofclinical application of St. John's Wort Extracts (Neurostan®) in China, and provide the reference for clinical practice.Method: We searched the relevantliterature at domestic and abroad, and reviewed the indications, treatment efficacy, safety and cost-benefit of Neurosta after listing in China. Result andConclusion: Neurostan has been widely used to treat mild to moderate depression, anxiety and restlessness in China. And its clinical applications are expanding. Due to less side effect and cheaper cost, applications of Neurostan will be broader in the future.

  20. 孟鲁斯特治疗对慢阻肺患者肺功能及 Th1、Treg 平衡的调节作用%Lung function and Th1/Treg balance regulation of Montelukast on patients with COPD

    Institute of Scientific and Technical Information of China (English)

    唐朝晖; 李永兰; 孟英龙; 王常林; 曾杰

    2016-01-01

    目的:观察慢阻肺患者加用孟鲁斯特钠片治疗后肺功能的改善情况及对机体 Th1/Treg 平衡的影响。方法:以2011~2013年期间来我院就诊的90名慢阻肺患者为研究对象,随机分成实验组和对照组,实验组在对照组治疗方案基础上加用孟鲁斯特钠片,两组患者都在治疗前和治疗3个月后进行肺功能测定和血清细胞炎症因子检测。结果:治疗后两组患者的肺通气功能都有所改善,治疗后实验组 FEV1/FVC 明显升高且改善程度优于对照组,血清细胞因子 IL-10显著升高,对照组则无明显变化。结论:在慢性阻塞性肺疾病的临床治疗中加用孟鲁特斯,能有效抑制气道炎症,并能调节介导自身免疫的 Th1/Treg 失衡状态,从而改善肺通气功能,减少发作。%Objective patients after addition of montelukast sodium tablets in the treatment of lung function improvement and observe the effect of chronic obstructive pulmonary disease on the body Th1 / Treg balance. Methods period 2011~2013 to our hospital for 90 COPD patients in this study were randomly divided into experimental group and control group, the experi-mental group were treated with montelukast sodium tablets in the control group treatment program based on two patients before treatment and after 3 months spirometry, and serum cytokine detection. Results After treatment, the two groups of patients with pulmonary function has improved after treatment in the experimental group FEV1 / FVC and the degree of improvement was significantly higher than the control group, IL-10 significantly increased serum cytokines in the control group did not change significantly. Conclusion In patients with chronic obstructive pulmonary disease clinical treatment plus montelukast Benitez, can effectively suppress airway inflammation, and can regulate autoimmune-mediated Th1 / Treg imbalance, thereby improving pulmonary function and reduce seizures.

  1. The Effect of Montelukast on the Levels of IL-6,IL-8 and IL-10 in Patients with Bronchial Asthma%孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10水平的影响

    Institute of Scientific and Technical Information of China (English)

    许成

    2012-01-01

    Objective To explore the effect of Montelukaat on serum IL-6,IL-8 and IL-10 levels in patients with bronchial asthma. Methods Serum TL-6,TLS (with RIA) ,IL-10 (with ELISA) levels were measured in 31 patients after Montelukast treatment with bronchial asthma as well as in 35 normal healthy controls. Result Before treatment serum IL-6, IL-8 levels in the asthma group were significantly higher than those in controls (P<0.01). While the IL-10 level was undoubtedly lower than that in the controls (P <0.01). After treatment, the serum IL-6, IL-8 and IL-10 levels were still significantly (P<0.05). Conclusion Montelukast treatment could bring about some regulatory effect on serum IL-6, IL-8 and IL-10 levels in patients with asthma and furthermore reducing the severity of inflammation and enhancing remission.%目的 探讨孟鲁司特在支气管哮喘患者体内IL-6、IL-8和IL-10水平的影响.方法 应用放射免疫分析和酶联法对31例支气管哮喘患者应用孟鲁司特治疗前后血清IL-6、IL-8和IL-10水平的变化,并与35名正常健康人作比较.结果 支气管哮喘患者在治疗前血清IL-6、IL-8水平非常显著地高于正常人组(P<0.01),而IL-10水平显著地低于正常人组(P<0.01),经治疗2周后与正常人组比较仍有显著性差异(P<0.05).结论 孟鲁司特对支气管哮喘患者血清IL-6、IL-8和IL-10有一定程度的调节作用,从而降低患者体内的炎症水平,促进病情缓解和好转.

  2. 孟鲁司特钠联和氟替卡松鼻喷雾剂治疗变应性鼻炎合并支气管哮喘患者血清C反应蛋白的影响%The influence on serum C reactive protein in patients with allergic rhinitis and bronchial asthma treated by Montelukast sodium and Fluticasone nasal spray

    Institute of Scientific and Technical Information of China (English)

    郭良斌; 江永琴

    2016-01-01

    目的:研究孟鲁司特钠联和氟替卡松鼻喷雾剂治疗变应性鼻炎(AR)合并支气管哮喘患者血清C反应蛋白的影响。方法选取2010年2月~2015年2月我院接诊的100例AR合并支气管哮喘患者作为本次研究对象。按照随机数表法分为观察组和对照组,对照组给予孟鲁司特钠治疗,观察组给予孟鲁司特钠联和氟替卡松鼻喷雾剂治疗,观察两组患者治疗后血清c反应蛋白水平、临床症状和体征消失时间、治疗疗效情况。结果观察组C反应蛋白水平(5.03±1.02)mg/L小于对照组(18.92±3.02)mg/L,差异具有统计学意义(P<0.05);观察组喘憋消失时间、啰音消失时间、咳嗽消失时间、退热时间、住院时间(2.52±0.71、4.56±0.63、6.93±1.31、4.52±1.01、7.53±1.24)d均小于对照组(3.92±1.03、5.80±0.82、10.39±2.04、5.31±1.30、12.49±2.05)d,差异具有统计学意义(P<0.05);观察组总有效率98.00%(49/50)优于对照组80.00%(40/50),差异具有统计学意义(P<0.05)。结论孟鲁司特钠联和氟替卡松鼻喷雾剂治疗AR合并支气管哮喘疗效显著,能够降低c反应蛋白水平。%Objective To investigate the influence on serum C reactive protein in patients with allergic rhinitis and bronchial asthma treated by montelukast sodium and flutica-sone nasal spray. Methods 100 cases of allergic rhinitis with bronchial asthma were enrolled in this study from Febru-ary 2010 to February 2015. According to the random number table,patients were divided into observation group and control group. The control group was treated with montelukast sodi-um,while the observation group was treated with montelukast sodium and fluticasone nasal spray. Serum C reactive protein level,clinical symptoms,signs disappeared time and treat-ment efficacy were observed. Results C reactive protein level in the observation group(5.03±1.02)mg/L was less than that of the control

  3. Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines.

    Science.gov (United States)

    Pane, Josep; Coloma, Preciosa M; Verhamme, Katia M C; Sturkenboom, Miriam C J M; Rebollo, Irene

    2017-01-01

    Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit-risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features

  4. 糠酸莫米松鼻喷剂和孟鲁司特钠联合治疗儿童腺样体肥大的疗效观察%The treatment of adenoidal hypertrophy by mometasone furoate combined with montelukast

    Institute of Scientific and Technical Information of China (English)

    于亚峰; 吴文璎; 刘济生; 孙朋; 李满意; 肖根生

    2014-01-01

    目的:探讨儿童腺样体肥大的非手术治疗方法及其疗效。方法联合使用糠酸莫米松鼻喷剂和孟鲁司特钠治疗儿童腺样体肥大30例,按照腺样体大小分为轻度12例、中度11例、重度7例三组,同时按照有无变应性鼻炎分为伴变应性鼻炎组19例和不伴变应性鼻炎组11例。患者的症状评分根据Carlos O’Connor-Reina的家长调查问卷获得。结果轻度组中有效率91.7%(11/12),中度组有效率63.6%(7/11),重度组有效率14.3%(1/7)。伴变应性鼻炎组有效率73.7%(14/19),不伴变应性鼻炎组有效率36.4%(4/11)。结论糠酸莫米松鼻喷剂联合孟鲁司特钠是非手术治疗腺样体肥大一个较好的方法,但各组效果不一。轻度腺样体肥大效果较好,重度腺样体肥大效果较差。对于伴有变应性鼻炎的腺样体肥大治疗效果明显优于不伴有变应性鼻炎的。%Objective To explore the non-surgical treatment and efficacy of adenoidal hypertrophy in children. Methods 30 cases of adenoidal hypertrophy were treated with mometasone furoate (Nasonex) combined with montelukast (Singulair). All patients were divided into three groups (mild, moderate, severe) according to the size of adenoid. They were also divided into two groups according to the presence or absence of allergic rhinitis. Symptom scores of patients were acquired by Carlos O'Connor-Reina questionnaire. Results The efficiency in the mild group was 91.7% (11/12), in the moderate group was 63.6% (7/11) and in the severe group was 14.3% (1/7). The efficiency of adenoidal hypertrophy with allergic rhinitis group was 73.7% (14/19) and not with allergic rhinitis group was 36.4% (4/11). Conclusion Mometasone furoate combined with montelukast is a good non-surgical treatment of adenoidal hypertrophy. However, the effect is different for different patients. The efficiency is better for mild and moderate adenoid hypertrophy but poor for severe

  5. 孟鲁司特联合沙美特罗替卡松治疗218例支气管炎哮喘的可行性探究%The Feasibility Study of the Treatment of 218 Cases of Bronchitis Asthma by Montelukast Combined with Salmeterol

    Institute of Scientific and Technical Information of China (English)

    高晓婷

    2015-01-01

    目的:探讨孟鲁司特联合沙美特罗替卡松治疗支气管炎哮喘临床疗效。方法选取218例支气管炎患者作为研究对象,分为观察组对照组,各109例。观察组采用孟鲁斯特联合沙美特罗替卡松;对照组采用沙美特罗替卡松。比较两组肺功能情况和不良反应情况。结果观察组治疗有效率为94.4%,对照组为82.6%,差异具有统计学意义(P <0.05)。观察组治疗后肺功能改善情况优于对照组。结论采用孟鲁司特联合沙美特罗替卡松治疗支气管炎哮喘具有临床效果。%Objective To study clinical curative effect of montelukast combined with Shah Mette Lo Tikason to treat bronchitis asthma.MethodsTo choose 218 cases of bronchitis patients as the research object.They were divided into the observation group and the control group.The observation group treated with meng LuSi combined with salmeterol. The control group used salmeterol .Results The observation group treatment effective rate was 94.4%,the control group was 82.6%,and the difference statisticaly significant(P < 0.05).Conclusion The meng LuSi combined with salmeterol for treatment of bronchitis asthma is worthy of popularization and application.

  6. Clinical study on treatment of sensitive isolate homemade cream combined with montelukast sodium in prevention and treatment of allergic rhinitis%自制治敏隔离膏联合孟鲁司特钠治疗过敏性鼻炎的临床研究

    Institute of Scientific and Technical Information of China (English)

    贺荣莉; 欧仁兵; 高雅; 杨芳; 李刚; 付蓉

    2015-01-01

    Objective To explore the safety and effectiveness of treatment of sensitive self isolation agent combined with montelukast sodium in prevention and treatment of allergic rhinitis, a new way to search for the effective prevention and treatment of allergic rhinitis. Method 122 cases of children with allergic rhinitis in children methods selection standard, were randomly divided into two groups, treatment group 62 cases, using the self-made isolation agent applied daily to treat allergic nasal 1~3 times per night, oral montelukast sodium 4~5mg a. The control group of 60 cases, Fluticasone Propionate Nasal Spray every morning and evening of 1, per oral ketotifen 0.5~1mg. Two groups all take 1 months for a course of treatment. The changes were observed in the two groups during the treatment, the symptoms of rhinitis symptoms score, drug daily integral, recurrence rate and adverse reaction of index.Results In 1 months of treatment, the efficacy of the two groups were not significant (P > 0.05), the control group symptoms improved time was shorter in the treatment group (P < 0.01); but the 6 and 12 months after the treatment group the recurrence rate is low (P < 0.01), the long-term curative effect is better than that of the control group; the treatment group no adverse reaction while in the control group the incidence of adverse reactions was 51.7%.Conclusions Treatment of allergic isolation agent in combination with montelukast treatment of children allergic rhinitis curative effect, good safety, and less recurrence, opened up a new way of prevention and treatment of allergic rhinitis, is worth the clinical promotion.%目的:探索自制治敏隔离膏联合孟鲁司特钠治疗过敏性鼻炎的安全性、有效性,旨在寻找有效的治疗过敏性鼻炎的新途径。方法:择符合标准的小儿过敏性鼻炎患儿122例,随机分为两组,治疗组62例,采用自制治敏隔离膏每日涂鼻腔1~3次,每晚口服孟鲁司特钠4~5m g

  7. The In fluence of Sla meterol Fluticasone Joint with Montelukast on the IL-4 IN F-γIgE EOS of Asthmatic Children%沙美特罗替卡松联合孟鲁斯特对哮喘患儿IL-4 INF-γIgE EOS 影响研究

    Institute of Scientific and Technical Information of China (English)

    王艳军

    2015-01-01

    Ob jective:To investigate the clinical efficacy and immune function of salmeterol fluticasone joint with montelukast on asthmatic children .Method:From January 2011 to December 2013, 102 cases of asthmatic children were divided into test group and control group according to different treatment methods , each had 51 cases.The control group accepted salmeterol fluticasone inhalants ,while the test group accepted montelukast on the basis of control group .Result:The total effective rate of test group was 96.1%,while the control group was 82.4%,the difference was statistically significant ( P 0.05) . But at he treatment of 3 months and after 3 months,the compliance rates of lung function of text group were all better than the control group ( P IgE,EOS between the two groups before the treatment (P>0.05).But at he treatment of 3 months and after 3 months,the levels of IL-4,IgE and EOS of two groups were all lower than before ,and the levels of the INF-γwas higher than before ( P<0.05) .The difference was statistically significant between the two groups ( P<0. 05).Con clusion:The treatment of salmeterol fluticasone joint with montelukast on asthmatic children have significant effect , good safety .It is worthy of being popularizing on clinical .%目的:探讨沙美特罗替卡松联合孟鲁斯特治疗支气管哮喘患儿对临床疗效、免疫功能的影响。方法:选取我院自2011年1月至2013年12月收治的哮喘患儿102例,按治疗方法的不同分为试验组及对照组,各51例。对照组患儿给予沙美特罗替卡松粉吸入剂,试验组在此基础上给予口服孟鲁司特钠。观察患儿治疗前后临床疗效及免疫功能的情况。结果:试验组患儿治疗总有效率为96.1%,对照组患儿治疗后总有效率为82.4%,试验组患儿治疗后总有效率显著优于对照组,差异有统计学意义(P<0.05)。两组患儿治疗前肺功能达标率,差异无统计学意义(P>0.05

  8. Comparing outcomes in patients with persistent asthma: a registry of two therapeutic alternatives.

    Science.gov (United States)

    O'Connor, Richard D; Gilmore, Amanda S; Manjunath, Ranjani; Stanford, Richard H; Legorreta, Antonio P; Jhingran, Priti M

    2006-03-01

    Clinical trials have demonstrated improved efficacy of fluticasone propionate/salmeterol (100/50 mcg) in a single device (FSC) compared with montelukast (10 mg) (MON). This study was designed to assess asthma control, asthma-related quality of life, asthma-related emergency department (ED) visit/hospitalization, treatment-related satisfaction, and productivity losses in patients newly started on FSC or MON. Patients who were newly prescribed FSC or MON during a regularly scheduled office visit were enrolled in a prospective observational study by nearly 500 physicians from eight managed care plans. Patient survey data were collected at baseline and at months 1, 3, 6, and 12, to measure study outcomes. ED visits/inpatient stays were reported from commercial claims data. Multivariate analyses assessed 12-month outcomes, controlling for several baseline patient characteristics. A total of 1414 patients >or= 15 years old were enrolled in the registry (FSC, n = 1061; MON, n = 353), 90% of which completed a 12-month survey. FSC patients had significantly greater improvement in both asthma control and quality of life, and reported significantly higher satisfaction with their medication (p = 0.003) and fewer days at work/school with asthma symptoms (p = 0.04) than MON. Other parameters of productivity losses such as missed work/school days due to asthma were not significantly different between the two groups. FSC use was also significantly associated with a lower risk of an asthma-related ED visit/hospitalization compared with MON (odds ratio = 0.35, 95% confidence interval: 0.15-0.92). In a 12-month office-based observational study, patients age 15 and older with persistent asthma, newly started on FSC, improved in symptom, quality of life, treatment, and utilization-related outcomes compared with patients newly started on MON. These results should be interpreted in light of the inherent limitations of non-randomized, uncontrolled studies.

  9. Hospital Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Hospital Compare has information about the quality of care at over 4,000 Medicare-certified hospitals across the country. You can use Hospital Compare to find...

  10. Value of leukotrienes C4, 8-isoprostane, nitrite/nitrate in exhaled breath condensate and the effect of montelukast on inflammatory factors in asthma%呼出气冷凝液白三烯、8异前列腺素、硝酸盐/亚硝酸盐检测在哮喘中的应用及孟鲁司特对炎症指标的影响

    Institute of Scientific and Technical Information of China (English)

    沈巨信; 秦娥; 李明晖; 孙健; 周国忠

    2012-01-01

    AIM: To investigate the levels of leukotrienes C4 ( LTC4 ), 8-isoprostane, nitrite / nitrate(NO2/NO3) in exhaled breath condensate of patients with asthma and the effect of inflammatory factors after montelukast treatment. METHODS: 30 patients with asthma were enrolled. They were given 10 mg montelukast once each night for one month. Before starting therapy and one month later, the levels of LTC4, 8-isoprostane, NO2/NO3 in exhaled breath condensate were measured. RESULTS: The levels of LTC4(55 + 17) ng/mL, 8-isoprostane (13 + 9) ng/mL, and NO2/NO3 (4.2 + 1.2) ng/mL were significantly higher in the asthma group than those in the control group (17 + 17) ,(7 + 6) ,(3. 2 + 0. 6) ng/mL(P 0. 05). CONCLUSION: Detecting the LTC4, 8-isoprostane and NO2/NO3 in EBC can be used to monitor asthmatic airway inflammation, which are convenient, noninvasive and safe. Montelukast can decrease the level of LTC4 , which is an effective anti-inflammatory a-gent.%目的:观察支气管哮喘患者呼出气冷凝液(EBC)中半胱氨酰白三烯C4(LTC4)、8异前列腺素(8-isoprostane)、硝酸盐/亚硝酸盐(NO2/NO3)水平及孟鲁司特干预前后炎症指标的变化.方法:选择哮喘非急性发作期患者30例,均予孟鲁司特10 mg,每晚一次口服,疗程1月,分别于治疗前及治疗后检测EBC中LTC4、8-isoprostane、NO2/NO3水平,另选择30例健康人为健康对照组.结果:哮喘组LTC4( 55±17) ng/mL、8-isoprostane( 13±9)ng/mL、NO2/NO3(4.2±1.2) ng/mL显著高于正常对照组(17±17)、(7±6)、(3.2±0.6) ng/mL(均P<0.01).哮喘组治疗前LTC4 (55±17) ng/mL显著高于治疗后(38±14) ng/mL,P<0.01.哮喘组治疗前8- isoprostane (13±9)ng/mL,高于治疗后(11±6) ng/mL,但差异无统计学意义(P>0.05).哮喘组治疗前NO2 /NO3 水平为(4.2±1.2) ng/mL,治疗后为(4.1±1.4) ng/mL,差异无统计学意义(P>0.05).结论:检测哮喘患者EBC中LTC4、8-isoprostane、NO2/NO3水平可简便安全监测哮喘的气道炎

  11. Physician Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Physician Compare, which meets Affordable Care Act of 2010 requirements, helps you search for and select physicians and other healthcare professionals enrolled in...

  12. Comparative Advantage

    DEFF Research Database (Denmark)

    Zhang, Jie; Jensen, Camilla

    2007-01-01

    that are typically explained from the supply-side variables, the comparative advantage of the exporting countries. A simple model is proposed and tested. The results render strong support for the relevance of supply-side factors such as natural endowments, technology, and infrastructure in explaining international...

  13. Comparative hemorheology

    OpenAIRE

    Başkurt, Oğuz K.; Meiselman, Herbert J.

    2013-01-01

    Comparative data on blood composition and blood flow properties indicate different levels of interspecies variation for several parameters. Hematocrit and hemoglobin levels have relatively low variability among mammals, while mean cell volume and red blood cell (RBC) count are more variable. There is also a difference of variability between high and low shear rate blood viscosity in mammals, with low shear rate viscosity having a higher degree of interspecies variation. This observation paral...

  14. Comparative evaluations.

    Science.gov (United States)

    Bibace, Roger

    2008-03-01

    My response to Engelmann (2008) will be based on several questions that will allow both its author and the general reader to determine whether the assumptions I make as an interpreter of this complex paper are congruent or incongruent with their own interpretations of the text. The interpretations by the writer, by any commentator, and the diverse interpretations of a general audience together with my own interpretations will, I hope, facilitate some fruitful 'comparative evaluations.' I articulate my inferences of the most dense part of the paper, namely the 'concrete immediate Consciousness and the developing absent outside.' My hope is to address Engelmann's question: "Am I in a better disposition to judge modern theories of consciousness?" The last section of my response spells out more personal comments to my all too brief and single encounter with Arno Engelmann. It is there that Arno Engelmann's fascinating statement "I am a citizen of the world" is addressed through its counterparts in my life.

  15. The effect of comparative effectiveness research on drug development innovation: a 360° value appraisal

    Directory of Open Access Journals (Sweden)

    Doyle JJ

    2011-03-01

    Full Text Available John J DoyleQuintiles, NY, USAAbstract: The drug development process is in dire need of transformation. Even after achieving regulatory approval, pharmaceutical companies are increasingly seeing their products subjected to health technology assessments (HTAs by public and private payers. The cornerstone of HTA value appraisal, and thus reimbursability, is comparative effectiveness research (CER, a ‘real-world’ comparison of a new product with the existing standard of care. Burgeoning demand for CER will fundamentally transform drug development by forcing biopharmaceutical manufacturers to view drug innovation from a holistic, 360° perspective. Specifically, drug and device developers must alter their existing approach to R&D by: adapting experimental research design methods to address multiple stakeholder demands; demonstrating real-world value through a suite of post-market observational research methods; and creating a transparent CER evaluation protocol based on standard principles. In the long-term, CER is forecast to propel innovation by focusing R&D on products that deliver real-world value to multiple customers and market stakeholders.Keywords: comparative effectiveness research, comparative effectiveness balance sheet, health technology assessment, large simple trial, moderator, observational studies, patient randomized clinical trial, registry, ‘real-world’ value

  16. 孟鲁司特联合噻托溴铵对稳定期COPD患者肺功能与呼吸困难症状的影响%Effect of Montelukast combined Tiotropium on lung function and dyspnea in stable COPD

    Institute of Scientific and Technical Information of China (English)

    糜晓光

    2015-01-01

    目的:探讨孟鲁斯特联合噻托溴铵对稳定期慢性阻塞性肺疾病( COPD)患者肺功能与呼吸困难症状的影响。方法将2010年1月至2013年1月180例稳定期COPD患者随机分作观察组与对照组,每组90例,观察组给予孟鲁司特(10 mg/次,每天1次,晚间口服)联合噻托溴铵(18μg/次,每天1次,吸入)治疗,对照组仅予以孟鲁司特(10 mg/次,每天1次,晚间口服)治疗。观察比较两组患者肺功能与呼吸困难症状的变化。结果治疗后两组肺功能指标1秒用力呼气量(FEV1)、FEV1/预计值百分比及FEV1/用力肺活量(FVC)均较治疗前有所改善,治疗后1个月观察组FEV1显著高于对照组( P0.05),治疗后3个月观察组FEV1、FEV1/预计值及FEV1/FVC均明显高于对照组(P0.05),而观察组治疗后3个月时显著低于对照组(P0. 05), FEV1, FEV1/predicted value and FEV1/FVC of observation group were significantly higher than control group (P<0. 05) 3 months after treatment;FRC in observation group and control group reduced and IC increased 1 month after treatment, and there was significant difference (P<0. 05), but there was no significant difference between the two groups;FRC in observation group and con-trol group reduced further and IC increased further 3 months after treatment (P<0. 05), there was significant difference between the two groups (P<0. 05); dyspnea score in two groups patients before treatment had no significant difference, dyspnea score reduced in two groups 1 month after treatment,but there was no significant difference,while 3 months dyspnea scores of observation group were significantly lower than control group after treatment for(P<0. 05). Conclusions Mon-telukast combined tiotropium can relieve lung hyperinflation in stable COPD patients, improve lung function, relieve diffi-culty breathing symptoms,increase exercise tolerance and improve quality of life.

  17. Interpreting the quality of health care database studies on the comparative effectiveness of oral anticoagulants in routine care

    Directory of Open Access Journals (Sweden)

    Schneeweiss S

    2013-09-01

    Full Text Available Sebastian Schneeweiss, Krista F Huybrechts, Joshua J Gagne Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Background: Dabigatran, an oral direct thrombin inhibitor, has now been available for 2 years in the US for the prevention of stroke in patients with nonvalvular atrial fibrillation, and direct Xa inhibitors are also starting to enter the market. Studies examining the effects of new oral anticoagulants in health care databases are beginning to emerge. The purpose of this study was to describe the validity of early published observational studies on the comparative safety and effectiveness of new oral anticoagulants in patients with atrial fibrillation. Methods: We identified published nonrandomized post-marketing studies (articles or conference abstracts or posters and critically appraised their internal validity, with a particular focus on their ability to control confounding and other biases. Results: Two full-length journal articles, three conference posters, two conference presentation abstracts, and a US Food and Drug Administration analysis form the basis of the early comparative effectiveness and safety experience with new oral anticoagulants. Some published studies exhibit substantial biases and have insufficient precision for several important endpoints. Several studies suffer from biases arising from comparing ongoing users of the older drug, warfarin, who seem to tolerate it, to initiators of the new treatment who may have switched from warfarin or have had no prior experience with anticoagulants. Analyses tended to not adjust or not adjust adequately for confounding, and unsound propensity score application was also observed. Several studies introduced selection bias by excluding patients who died during follow-up and by restricting the study population to those with continuous database enrollment following cohort entry. We

  18. Comparative authentication of Hypericum perforatum herbal products using DNA metabarcoding, TLC and HPLC-MS.

    Science.gov (United States)

    Raclariu, Ancuta Cristina; Paltinean, Ramona; Vlase, Laurian; Labarre, Aurélie; Manzanilla, Vincent; Ichim, Mihael Cristin; Crisan, Gianina; Brysting, Anne Krag; de Boer, Hugo

    2017-05-02

    Many herbal products have a long history of use, but there are increasing concerns over product efficacy, safety and quality in the wake of recent cases exposing discrepancies between labeling and constituents. When it comes to St. John's wort (Hypericum perforatum L.) herbal products, there is limited oversight, frequent off-label use and insufficient monitoring of adverse drug reactions. In this study, we use amplicon metabarcoding (AMB) to authenticate 78 H. perforatum herbal products and evaluate its ability to detect substitution compared to standard methods using thin-layer chromatography (TLC) and high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Hypericum perforatum was detected in 68% of the products using AMB. Furthermore, AMB detected incongruence between constituent species and those listed on the label in all products. Neither TLC nor HPLC-MS could be used to unambiguously identify H. perforatum. They are accurate methods for authenticating presence of the target compounds, but have limited efficiency in detecting infrageneric substitution and do not yield any information on other plant ingredients in the products. Random post-marketing AMB of herbal products by regulatory agencies could raise awareness among consumers of substitution and would provide an incentive to manufacturers to increase quality control from raw ingredients to commercialized products.

  19. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

    Science.gov (United States)

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged measles-containing vaccines used in Anhui Province of China are safe.

  20. Labour Market Structure in Malaysia: Pre- and Post-Market Gender Comparison

    OpenAIRE

    Chung-Khain Wye; Rahmah Ismail

    2012-01-01

    Gender inequality in Malaysian labour market can be observed through labour force participation, unemployment, occupational distribution, top management employment involving decision making, and average monthly salary. Such an inequality generally works to the disadvantage of females, notwithstanding their outperformance of educational attainment over their males’ counterparts. Case study in the ICT services subsector points to the importance of imparting employability skills among females to...

  1. [Post-marketing surveillance of Tanreqing injection in children: a real world study].

    Science.gov (United States)

    Li, X X; Zhuo, L; Yang, Y H; Zhan, S Y; Zhai, S D

    2017-02-10

    Objective: To evaluate the safety of Tanreqing injection among children in the real world. Methods: A multicenter, large sample, ambispective cohort study, with registration-type clinical safety monitoring. A total of 6 188 inpatients and patients from the emergency units, aged ≤ 14 years who all had been using Tanreqing injection in 59 secondary and tertiary hospitals in China, were recruited between January, 2014 and May, 2015. The main outcomes would include incidence and severity of adverse drug reaction (ADR)/adverse drug event (ADE) of Tanreqing injection. Univariate analysis was used to explain the risk factors of ADR. Results: The overall incidence of ADE was 4.20‰ (26 cases), including 4 serious ones. The incidence of ADR was 3.07‰ (19 cases), including 17 cases of general ADR and 2 cases of new ADR. All the ADR cases were mild or moderate, mostly showing damages in skin and appendages. The onset of disease happened in 24 hours after the Tanreqing injection but all the ADR cases got improved or cured. Having histories of allergies to drugs or foods would increase the incidence of ADR. Conclusion:Tanreqing injection caused low incidence of ADR in children. Progams as stratifying high-risk patients and improving administrative management could further increase the safety level of Tanreqing injection.

  2. Effectiveness and safety of dydrogesterone in regularization of menstrual cycle: a post-marketing study.

    Science.gov (United States)

    Trivedi, Nilesh; Chauhan, Naveen; Vaidya, Vishal

    2016-08-01

    Oral administration of dydrogesterone during second half of menstrual cycle has been shown to reduce menstrual irregularities. This prospective, observational study aimed to determine continued effectiveness of dydrogesterone (prescribed between 1 and 6 cycles or longer) in menstrual cycle regularization in Indian women aged ≥18 years with irregular menstrual cycle for at least 3 months. Those achieving regular cycles (21 to 35 days, inclusive) during treatment were followed up for 6 months after cessation of dydrogesterone treatment. Of the 910 women completing dydrogesterone treatment, 880 (96.7%) achieved cycle regularization (pevent (appendicitis) and three non-serious adverse events were reported. Dydrogesterone regularizes and improves the duration of the menstrual cycle, reduces the amount of bleeding, relieves menstrual pain and prevents relapse of irregular cycles at six months after discontinuation of treatment.

  3. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China

    Science.gov (United States)

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe. PMID:28192490

  4. Labour Market Structure in Malaysia: Pre- and Post-Market Gender Comparison

    Directory of Open Access Journals (Sweden)

    Chung-Khain Wye

    2012-10-01

    Full Text Available Gender inequality in Malaysian labour market can be observed through labour force participation, unemployment, occupational distribution, top management employment involving decision making, and average monthly salary. Such an inequality generally works to the disadvantage of females, notwithstanding their outperformance of educational attainment over their males’ counterparts. Case study in the ICT services subsector points to the importance of imparting employability skills among females to have its bearing on wagedetermination. As such, future research is expected to analyse gender wage decomposition taking into considerations of different types of labour market discrimination, occupational preferences, and gender differences in employability skills.

  5. Labour Market Structure in Malaysia: Pre- and Post-Market Gender Comparison

    OpenAIRE

    Chung-Khain Wye; Rahmah Ismail

    2012-01-01

    Gender inequality in Malaysian labour market can be observed through labour force participation, unemployment, occupational distribution, top management employment involving decision making, and average monthly salary. Such an inequality generally works to the disadvantage of females, notwithstanding their outperformance of educational attainment over their males’ counterparts. Case study in the ICT services subsector points to the importance of imparting employability skills among females to...

  6. Hepatoxicity associated with weight-loss supplements: A case for better post-marketing surveillance

    Institute of Scientific and Technical Information of China (English)

    Ano Lobb

    2009-01-01

    There is a growing number of case reports of hepatoxicity from the widely marketed weight-loss supplement Hydroxycut, which contains the botanical ingredient Garcinia cambogia. These case reports may substantially undercount the true magnitude of harm. Based on the past experience with harmful dietary supplements, US regulators should assume the more precautionary approach favored by Canada and Europe. Lacking effective adverse event surveillance for supplements, or the requirements to prove safety prior to coming to the market, case reports such as those summarized here assume added importance.

  7. Hepatoxicity associated with weight-loss supplements: a case for better post-marketing surveillance.

    Science.gov (United States)

    Lobb, Ano

    2009-04-14

    There is a growing number of case reports of hepatoxicity from the widely marketed weight-loss supplement Hydroxycut, which contains the botanical ingredient Garcinia cambogia. These case reports may substantially undercount the true magnitude of harm. Based on the past experience with harmful dietary supplements, US regulators should assume the more precautionary approach favored by Canada and Europe. Lacking effective adverse event surveillance for supplements, or the requirements to prove safety prior to coming to the market, case reports such as those summarized here assume added importance.

  8. [Analysis and thinking on the post marketing quality of the disposable sterilized syringe].

    Science.gov (United States)

    Li, Jingli; Yang, Wanjuan; Hao, Qing; Ji, Yuan; Zhu, Bijun

    2012-11-01

    By scattered-sampling testing the disposable sterilized syringe according to legal inspection and explorative research methods of vitro cytotoxicity and easy oxide etc. testing, this article comprehensively evaluated and analyzed the product quality and found the potential risk. The results will help to improve the work process and product quality.

  9. [Literature review of post-marketing clinical evaluation of Xiaoke pill].

    Science.gov (United States)

    Liu, Huan; Xie, Yanming

    2011-10-01

    The literatures of clinical application showed that Xiaoke pill has exact effect on type 2 diabetes. Because Xiaoke pills contain glyburide, most adverse reactions are resulted from inappropriate use. Clinical scientific and medical treatment can be guided by strengthening the mission, improving the instructions of medicines, improving pharmaceutical production technology, strengthening clinical research to further explore the relationship between blood glucose levels and dose, and clearing indications and contraindications. These also can improve security together with the good economy, and will benefit the sustainable development of Xiaoke pill.

  10. [A perspective for the role of drug registries in the post-marketing surveillance].

    Science.gov (United States)

    Traversa, Giuseppe; Sagliocca, Luciano; Magrini, Nicola; Venegoni, Mauro

    2013-06-01

    Drug registries are implemented after the authorization of new products and represent a tool for systematic collection of data aimed at obtaining additional knowledge on appropriateness, effectiveness and safety. The design of registries needs to be coherent with the main objective and a study protocol is required before the implementation. A registry aimed at the appropriateness of drug use should be primarily considered for high cost drugs when there is a risk, either for the patients' safety or for public expenditure, in using the drug outside the approved indications. Since the registry is a condition for the access to drugs, and all users are included, an extremely simplified data collection is required. However, the data should be available at regional level to allow record linkage procedures with other databases for conducting outcome studies. When registries are aimed at acquiring new information on the risk profile, the duration and the regional extension of data collection should be coherent with the expected incidence of events of interest. A great attention should be devoted in preventing that patients are lost to follow-up, since the reasons for being lost are frequently associated with harmful outcomes, such as adverse drug reactions. In a registry focused on effectiveness, the main aim consists in ascertaining the reasons (the prognostic factors), for possible discrepancies between premarketing studies and clinical practice. Taking into account the greater incidence of the expected events, there are fewer reasons for extending data collection to all users, whereas the main attention should focus on quality controls and the ascertainment of confounding factors. Given the relevance of the validity issues, in the set out of a registry it is important to think about ad hoc resources and the adequacy of infrastructures. As for any epidemiological study, an adequate qualification of the researcher/clinician in charge of conducting a registry should be guaranteed, together with independence in data analysis and freedom to publish all findings.

  11. Comparative tolerability and efficacy of treatments for impotence.

    Science.gov (United States)

    Meinhardt, W; Kropman, R F; Vermeij, P

    1999-02-01

    Modern pharmacological treatment of impotence is determined by the presenting symptoms. Since this involves symptomatology with a heterogenous aetiology, many different drugs are involved in the treatment of impotence. Drugs used for libido and arousal problems include testosterone, yohimbine, trazodone and apomorphine. Since patient self-assessment is the only parameter that can be used to measure the result of treatment and positive results are seldom affirmed, no positive benefit of these agents can be assumed at present. Oral medications for erectile dysfunction include yohimbine, trazodone, apomorphine, phentolamine, arginine and sildenafil. Of these drugs, sildenafil has been the most systematically studied for effectiveness, but long term safety data await the results of post-marketing surveillance. Of the ejaculation disorder therapies, treatments for premature ejaculation are the best studied. Favourable results have been obtained with clomipramine, paroxetine and fluoxetine. The safety of these medications has been assessed through their long term use in psychiatry. Intracavernous self-injections for erectile disorders are performed using a variety of drugs and drug mixtures. Only alprostadil and the combination of papaverine with phentolamine are widely used. Alprostadil is very well tolerated; however, penile pain is a serious problem in a significant proportion of patients. Papaverine in combination with phentolamine is effective, but penile fibrosis and priapism occur more often than with the use of alprostadil. Several new developments in this area are currently under way. Alternative routes for medication for erectile dysfunction include ointments and patches to the penile skin and the glans. Only transurethral alprostadil, 'MUSE' (medicated urethral system for erection) has been shown to be effective in large trials. Long term safety still has to be demonstrated, but the 1-year safety profile is encouraging. In general, the end points of impotence

  12. Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines

    NARCIS (Netherlands)

    Pane, J. (Josep); P.M. Coloma (Preciosa); K.M.C. Verhamme (Katia); M.C.J.M. Sturkenboom (Miriam); Rebollo, I. (Irene)

    2017-01-01

    textabstractRecent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our obje

  13. A Comparative Study of Teaching Comparative Education

    OpenAIRE

    2007-01-01

    The purpose of this paper is to characterize the comparative education subjects offered in different programs in different foreign universities. As a subject, comparative education has not been firmly institutionalized in education programs in Japanese universities. There was a movement which aimed at making comparative education as one of the mandatory subjects in the teacher training program, however it was not successful. To date, comparative education subject has been offered in various p...

  14. AirCompare

    Data.gov (United States)

    U.S. Environmental Protection Agency — AirCompare contains air quality information that allows a user to compare conditions in different localities over time and compare conditions in the same location...

  15. From Comparatism to Comparativity: Comparative Reasoning Reconsidered

    Directory of Open Access Journals (Sweden)

    Svend Erik Larsen

    2015-07-01

    Full Text Available Comparative literature was born with the national paradigm of literary historiography in the early nineteenth century when literary studies, together with other historical and comparative studies, were institutionalized as a particular field of research and higher education. The cognitive pattern generated by this paradigm comprises both national literary studies and comparative literature. They are both instances of comparatism, solidly anchored in a national context as its basic and indispensable point of reference rather than in the border crossing life of literary texts. In contrast, the comparative reasoning of the twenty first century, as exemplified by the emerging interest in world literature studies, attempts to cultivate the comparativity of the literary texts themselves – their potential to engage with several possible contexts of comparison beyond the standard theories and methods of comparatism and without giving an axiomatic priority to one of them. In the traditional aesthetics of imitation, European and non European, the double nature of any text as being organized around both an external centre and a domestic centre is already an integral part of the definition of literature in view, first of all, of their degree of canonicity. Today, more radically, all literary texts, irrespective of canonical position but as part of their status and function as literary texts, are assumed to possess the capacity to be part of several textual and cultural contexts beyond that of their place and time of origin. The paper traces the history of comparative reasoning, leading both to the national paradigm and the nineteenth century inspired comparatism and to the consequences for modern literary studies, opening a broader view of the comparative potentials of texts across time and space.

  16. A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors.

    Science.gov (United States)

    Shah, Rashmi R; Roberts, Samantha A; Shah, Devron R

    2013-09-01

    We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison. The FDA had granted priority review to 12 TKIs but the EMA/CHMP did not grant the equivalent accelerated assessment to any. The FDA granted accelerated approvals to six (38%) and CHMP granted (the equivalent) conditional approvals to four (29%) of these agents. On average, the review and approval times were 205.3 days in the US compared with 409.6 days in the European Union (EU). The active review times, however, were comparable (225.4 days in the EU and 205.3 days in the US). Since oncology drug development lasts about 7 years, the 20 days difference in review times between the two agencies is inconsequential. Clock stops during review and the time required to issue an approval had added the extra 184.2 days to review time in the EU. We suggest possible solutions to expedite the EU review and approval processes. However, post-marketing emergence of adverse efficacy and safety data on gefitinib and lapatinib, respectively, indicate potential risks of expedited approvals. We challenge the widely prevalent myth that early approval translates into early access or beneficial impact on public health. Both the agencies collaborate closely but conduct independent assessments and make decisions based on distinct legislation, procedures, precedents and societal expectations.

  17. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

    This document includes the specification on the IEA task of evaluation building energy simulation computer programs for the Double Skin Facades (DSF) constructions. There are two approaches involved into this procedure, one is the comparative approach and another is the empirical one. In the comp....... In the comparative approach the outcomes of different software tools are compared, while in the empirical approach the modelling results are compared with the results of experimental test cases. The comparative test cases include: ventilation, shading and geometry....

  18. Dialysis Facility Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Dialysis Facility Compare helps you find detailed information about Medicare-certified dialysis facilities. You can compare the services and the quality of care that...

  19. Ezra Pound's Comparative Poetics

    OpenAIRE

    2001-01-01

    In his paper, "Ezra Pound's Comparative Poetics," Naikan Tao concentrates on Pound's theories regarding comparison and examines the significance of his comparative studies to the formulation of his poetics, an aspect that has not been sufficiently investigated. On the basis of Pound's work, Tao observes that the conception of comparison Pound shaped through his comparative studies is the internal principle that governs the presentation of details and particulars, the method Pound advocated as...

  20. Towards Comparative Leadership

    DEFF Research Database (Denmark)

    Jensen, Merete Storgaard

    2015-01-01

    Globalization is the imitation and adaptation of knowledgesolutions or innovations, as they are diffused from one country to another” (Peter Jarvis 2007) Conducting comparative, educational research of school leadership that effects student achievement in an international perspective...... is of scientific value in qualifying the international and national knowledgebase on effective school leadership. In a methodological perspective comparative analysis in an international setting creates specifically a scientific demand of comparability and a theory based leadership - framework to guide...

  1. Comparative Test Case Specification

    DEFF Research Database (Denmark)

    Kalyanova, Olena; Heiselberg, Per

     This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....... This document includes a definition of the comparative test cases DSF200_3 and DSF200_4, which previously described in the comparative test case specification for the test cases DSF100_3 and DSF200_3 [Ref.1]....

  2. Contesting Citizenship: Comparative Analyses

    DEFF Research Database (Denmark)

    Siim, Birte; Squires, Judith

    2007-01-01

    . Comparative citizenship analyses need to be considered in relation to multipleinequalities and their intersections and to multiple governance and trans-national organisinf. This, in turn, suggests that comparative citizenship analysis needs to consider new spaces in which struggles for equal citizenship occur...

  3. Nursing Home Compare Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — These are the official datasets used on the Medicare.gov Nursing Home Compare Website provided by the Centers for Medicare and Medicaid Services. These data allow...

  4. Nursing Home Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — The data that is used by the Nursing Home Compare tool can be downloaded for public use. This functionality is primarily used by health policy researchers and the...

  5. Comparative State Politics.

    Science.gov (United States)

    Brooks, Gary H.

    1981-01-01

    Describes a college course dealing with comparative state politics. Students learn about the way in which political scientists employ the study of American state politics as a "laboratory" for the development of scientific explanations of political phenomena. (RM)

  6. Home Health Compare Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — These are the official datasets used on the Medicare.gov Home Health Compare Website provided by the Centers for Medicare and Medicaid Services. These data allow...

  7. Dialysis Facility Compare Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — These are the official datasets used on the Medicare.gov Dialysis Facility Compare Website provided by the Centers for Medicare and Medicaid Services. These data...

  8. Comparative Packaging Study

    Science.gov (United States)

    Perchonok, Michele; Antonini, David

    2008-01-01

    This viewgraph presentation describes a comparative packaging study for use on long duration space missions. The topics include: 1) Purpose; 2) Deliverables; 3) Food Sample Selection; 4) Experimental Design Matrix; 5) Permeation Rate Comparison; and 6) Packaging Material Information.

  9. Home Health Compare

    Data.gov (United States)

    U.S. Department of Health & Human Services — Home Health Compare has information about the quality of care provided by Medicare-certified home health agencies throughout the nation. Medicare-certified means the...

  10. Hospital Compare - Archived Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Hospital Compare is a consumer-oriented website that provides information on how well hospitals provide recommended care to their patients. This information can help...

  11. Hospital Compare Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — These are the official datasets used on the Medicare.gov Hospital Compare Website provided by the Centers for Medicare and Medicaid Services. These data allow you to...

  12. Physician Compare Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — This is the official dataset associated with the Medicare.gov Physician Compare Website provided by the Centers for Medicare and Medicaid Services (CMS). These data...

  13. Comparing Political Communication

    OpenAIRE

    Pfetsch, Barbara; Esser, Frank

    2012-01-01

    This chapter describes the maturation of comparative political communications as a sub-discipline and defines its conceptual core. It then lays out the concept of “political communication system”. At the macro-level, this model captures the patterns of interaction between media and politics as social systems; at the micro-level it captures the interactions between media and political actors as individuals or organizations. Comparative research in this tradition focuses on the structure of pol...

  14. Virtual Optical Comparator

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Greg

    2008-10-20

    The Virtual Optical Comparator, VOC, was conceived as a result of the limitations of conventional optical comparators and vision systems. Piece part designs for mechanisms have started to include precision features on the face of parts that must be viewed using a reflected image rather than a profile shadow. The VOC concept uses a computer generated overlay and a digital camera to measure features on a video screen. The advantage of this system is superior edge detection compared to traditional systems. No vinyl charts are procured or inspected. The part size and expensive fixtures are no longer a concern because of the range of the X-Y table of the Virtual Optical Comparator. Product redesigns require only changes to the CAD image overlays; new vinyl charts are not required. The inspection process is more ergonomic by allowing the operator to view the part sitting at a desk rather than standing over a 30 inch screen. The procurement cost for the VOC will be less than a traditional comparator with a much smaller footprint with less maintenance and energy requirements.

  15. Determination of Sodium Benzoate and Potassium Sorbate in “Doogh” Samples in Post Market Surveillance in Iran 2012

    Directory of Open Access Journals (Sweden)

    B. Akbari-adergani

    2013-06-01

    Full Text Available Sodium benzoate and potassium sorbate are two major chemical preservatives which are used in Doogh (Iranian traditional dairy drink. In this study, a total of 27 commercial brands of highly consumed of Doogh samples were analyzed. The means and standard deviation for concentration of these preservatives based on HPLC results for analysis of benzoate and sorbate were 195·9 (SD 1·8 and 328·8 (SD 2·1 mg.Kg-1 respectively. The minimum and maximum of benzoate content in various brands were 18.3 and 2345.1 mg.Kg-1 and for sorbate were not detected and 4961.3 mg.Kg-1 respectively. The study revealed that there was not significant difference in preservative concentration in the samples that belonged to various dates. However, a few samples had a high preservative concentration, which could be a risk factor for human health, especially when their intake was being occurred by various foodstuffs simultaneously.

  16. Efficacy, tolerability and safety of nebivolol in patients with hypertension and diabetes: a post-marketing surveillance study.

    Science.gov (United States)

    Van Bortel, L M

    2010-09-01

    Hypertension is a widely prevalent condition of elevated blood pressure (BP) and is the leading risk factor for the development of cardiovascular disease (CVD). Many patients have additional risk factors such as diabetes mellitus (DM) or previous history of CVD. Nebivolol is a third-generation beta (beta)-blockers which has been shown not to influence metabolic parameters in patients with DM. This postmarketing surveillance study aimed to collect information on the efficacy, safety and tolerability of nebivolol in hypertensive patients with concomitant DM. Hypertensive patients with DM followed by 52 cardiologists, internal medicine specialists and general practitioners, between 24 August 2003 and 9 January 2007 in The Netherlands were included in this study. Physicians were asked to survey nebivolol treatment for 6 months. A total of 510 patients were enrolled. Overall, 93.3% of patients were diagnosed with essential hypertension and 6.7% with secondary hypertension. All patients were co-diagnosed with DM. Nebivolol therapy was associated with a significant reduction in both systolic blood pressure (BP) and diastolic BP versus baseline (p hypertension, resistance or intolerance to previous antihypertensive medication, or other reasons). A significant improvement in blood glucose was seen at 4 months (-0.6 mmol/L; p = 0.021). Significant reductions in total cholesterol (-1.45 mmol/L; p = 0.006), low density lipoprotein (LDL) cholesterol (-1.32 mmol/L; p = 0.003) and LDL/high density lipoprotein (HDL) cholesterol ratio (-0.77; p = 0.011) were observed at 2 months. No significant changes were seen in HDL cholesterol and triglycerides. Nebivolol treatment was associated with a significantly reduced BP, improved blood glucose and LDL cholesterol levels and was well tolerated in hypertensive patients with concomitant DM.

  17. Italian post-marketing surveillance for adverse event reports after MF59-adjuvanted H1N1v vaccination.

    Science.gov (United States)

    Parretta, Elisabetta; Ianniello, Benedetta; Ferrazin, Fernanda; Rossi, Francesco; Capuano, Annalisa

    2011-05-09

    According to European recommendations, the Italian Medicines Agency (AIFA) required close monitoring of the safety of the MF59-adjuvanted H1N1v vaccine, which was the only vaccine available in Italy for prophylaxis of the A/H1N1 (2009) pandemic influenza. From October 2009 to June 2010, the Italian Pharmacovigilance Adverse Event (AE) Spontaneous Reporting System [Rete Nazionale Farmacovigilanza] (RNF) received 1330 reports of AEs temporally related with the pandemic influenza vaccination out of a total of 924,057 doses administered. Among these, 1,162 (87.37%) AE reports were classified 'non serious', 91 (6.84%) 'serious', 3 (0.23%) had a fatal outcome and 74 (5.56%) did not include the degree of seriousness. Among the serious AE reports, some unexpected AEs emerged. Even though some typical vaccine safety issues which emerged should be further explored, such as vaccination in pregnancy, the analysis of all AE reports sent to RNF shows that the vaccine has a well-tolerated safety profile which resembles that of the already available seasonal influenza vaccines. This contrasts with the widespread public concern about its safety, which has been one of the major causes of the low vaccination rate observed in Italy, as well as in other countries.

  18. Post-marketing assessment of neuropsychiatric adverse events in influenza patients treated with oseltamivir: an updated review.

    Science.gov (United States)

    Toovey, Stephen; Prinssen, Eric P; Rayner, Craig R; Thakrar, Bharat T; Dutkowski, Regina; Koerner, Annette; Chu, Tom; Sirzen-Zelenskaya, Alexandra; Britschgi, Markus; Bansod, Sudhir; Donner, Barbara

    2012-10-01

    A 2008 review by our group concluded that the risk of neuropsychiatric adverse events (NPAEs) in influenza patients was not increased by oseltamivir exposure, and did not identify any mechanism by which oseltamivir or its metabolites could cause or worsen such events. The current article reviews new information on this topic. Between September 16, 2007 and May 15, 2010, 1,805 spontaneously-reported NPAEs were identified in 1,330 patients receiving oseltamivir: 767 (42.5%) from Japan, 296 (16.4%) from the USA, and 742 (41.1%) from other countries. NPAEs were more common in children: 1,072 (59.4%) events were in those aged ≤16 years. NPAEs often occurred within 48 h of treatment initiation (953 events; 52.8%). Nearly half of the events were serious in nature (838; 46.4%). The three largest categories of events were abnormal behavior (457 events, 25.3%), miscellaneous psychiatric events (370; 20.5%), and delusions/perceptual disturbances (316 events, 17.5%). A total of 1,545 events (85.6%) in eight different categories were considered to be delirium or delirium-like. Twenty-eight suicide-related events were reported. A US healthcare claims database analysis showed that the risk of NPAEs in 7,798 oseltamivir-treated patients was no higher than that in 10,411 patients not on antivirals, but a study on oseltamivir and abnormal behavior in Japan was less conclusive. NPAE frequency in oseltamivir-exposed Japanese and Taiwanese children with influenza was the same as in unexposed children. New analysis of the UK General Practice Research Database showed that the relative adjusted risk of NPAEs in influenza patients was 2.18-times higher than in the general population. Other epidemiology studies report frequent occurrence of encephalitis and similar disorders in influenza patients independently of oseltamivir exposure. The new data support the findings of the original assessment. Evidence suggests that influenza-related encephalopathies are caused by influenza-induced inflammatory responses, but more work is needed to confirm the underlying mechanisms.

  19. Post-marketing surveillance study to assess the safety and tolerability of an Inactivated Poliomyelitis Vaccine in Indian children.

    Science.gov (United States)

    Sharma, Hitt; Dhere, Rajeev; Parekh, Sameer; Shewale, Sunil

    2017-08-28

    To evaluate the incidence of adverse events following administration of an Inactivated poliomyelitis vaccine (IPV) manufactured by Serum Institute of India Pvt. Ltd., Pune, India. A single 0.5 ml dose of the IPV was administered intramuscularly to children attending private clinics or out-patient department of hospitals for routine immunization across different cities in India. They were observed over a period of 30 days for local or systemic adverse events and rare case of anaphylaxis, if any. A total of 2210 children were enrolled of which 2120 children received the vaccine within primary immunization series and 90 children received booster dose. The common adverse events reported were pain, erythema, swelling and fever. No serious adverse event was reported during the study period. Poliomyelitis vaccine (Inactivated) manufactured by Serum Institute of India Pvt. Ltd., Pune can be safely administered to children following the Expanded Programme on Immunization or World Health Organization recommended immunization schedule.

  20. Post-Marketing Regulation of Medicines Withdrawn from the Market Because of Drug-Attributed Deaths: An Analysis of Justification.

    Science.gov (United States)

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2017-05-01

    Several medicinal products have been withdrawn from the market because of drug-attributed deaths. However, there has been no investigation of whether such withdrawals were justified, and the extent to which confirmatory studies are used to investigate drug-adverse event relationships when deaths are reported is uncertain. We documented medicinal products withdrawn from the market because of drug-attributed deaths, identified confirmatory studies investigating the drug-adverse event relationships, examined whether withdrawals of medicinal products because of drug-attributed deaths after marketing were justified based on a mechanistic analysis, and examined the trends over time. We searched electronic and non-electronic sources to identify medicinal products that were withdrawn because of drug-attributed deaths. We used a previously published algorithm to examine whether the withdrawals of products were justified. We then searched PubMed and Google Scholar to identify studies investigating the drug-adverse event relationships, used the Oxford Centre for Evidence-Based Medicine criteria to document the levels of evidence, and assessed whether the evidence of an association was confirmed. We included 83 medicinal products. The reasons for withdrawal appeared to have been justified in 80 cases (96%). The median interval between the first reported adverse reaction that was related to the cause of death and the first reported death was 1 year (interquartile range = 1-3); products were withdrawn sooner when the interval between the first reported relevant adverse reaction and the first death was shorter. Confirmatory studies were conducted in 57 instances (69%), and there was evidence of an association in 52 cases (63%). Four products (5%) were re-introduced after initial withdrawal. Regulatory authorities have been justified in making withdrawal decisions when deaths have been attributed to medicinal products, using the precautionary principle when alternative decisions could have been made. Medicinal products are likely to be quickly withdrawn from the market when there is a short interval to the first reported deaths. The use of an algorithm such as we have used in this study could help to expedite the process of decision making.

  1. Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use

    Directory of Open Access Journals (Sweden)

    Plaizier-Vercammen Jacqueline

    2007-01-01

    Full Text Available Abstract Background Artemisinin-derivative formulations are now widely used to treat falciparum malaria. However, the dry powder suspensions developed for children are few and/or are of poor quality. In addition to the active compound, the presence of a suitable preservative in these medicines is essential. In this study, an evaluation of the preservative content and efficacy in some dry suspensions available on the Kenyan market was performed. Method UV spectrophotometry was used to identify the preservatives in each sample while HPLC-UV was used for quantification. After reconstitution of the powders in water, the dissolution of the preservatives was followed for 7 days. Antimicrobial efficacy of the preservatives was assessed by conducting a preservative efficacy test (PET following the European pharmacopoeia standards. Results Four different preservatives were identified namely methylparahydroxybenzoate (MP, propylparahydroxybenzoate (PP, benzoic acid and sorbic acid. MP and PP were identified in Artesiane® (artemether 300 mg/100 ml, Alaxin® (dihydroartemisinin 160 mg/80 ml andGvither ® (artemether 300 mg/100 ml respectively. Sorbic acid was presentin Artenam® (artemether 180 mg/60 ml while benzoic acid was identified in Santecxin® (dihydroartemisinin 160 mg/80 ml andArtexin® (dihydroartemisinin 160 mg/80 ml respectively. Cotecxin® (dihydroartemisinin 160 mg/80 ml did not contain any of the above preservatives. After reconstitution in water, preservativesin 50%(3/6 of the products did not completely dissolve and the PET results revealed that only Artenam® and Gvither® met the requirements for antimicrobial efficacy. The other products did not conform. Conclusion These results show that paediatric antimalarial dry powder formulations on the market may contain ineffective or incorrect amounts of preservatives. This is a potential risk to the patient. Studies conducted on the dry powder suspensions should include the analysis of both the active ingredient and the preservative, including the efficacy of the latter.

  2. Methodological approaches to developing and establishing the body of evidence on post-marketing Chinese medicine safety.

    Science.gov (United States)

    Liao, Xing; Robinson, Nicola

    2013-07-01

    Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, postmarketing surveillance (PMS) has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions (ADRs). Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detect ADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.

  3. Comparative oncology today.

    Science.gov (United States)

    Paoloni, Melissa C; Khanna, Chand

    2007-11-01

    The value of comparative oncology has been increasingly recognized in the field of cancer research, including the identification of cancer-associated genes; the study of environmental risk factors, tumor biology, and progression; and, perhaps most importantly, the evaluation of novel cancer therapeutics. The fruits of this effort are expected to be the creation of better and more specific drugs to benefit veterinary and human patients who have cancer. The state of the comparative oncology field is outlined in this article, with an emphasis on cancer in dogs.

  4. Comparative Nivkh Dictionary

    DEFF Research Database (Denmark)

    Fortescue, Michael David

    This dictionary undertakes to reconstruct the lexis and morphology of the Nivkh proto-language by marshaling and organizing all the data available in published form on the contemporary dialects. It builds upon a considerable body of descriptive and comparative work carried out by scholars who have...... World is a subject of continuing interest to both linguists and anthropologists. The dictionary does not address this question directly. Reconstructing the proto-language is an essential step, however, to any further comparative work – in particular to sorting out the relationship between Nivkh...

  5. Ebolavirus comparative genomics

    DEFF Research Database (Denmark)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms...

  6. Comparative genomics of Eukaryotes

    NARCIS (Netherlands)

    Noort, Vera van

    2007-01-01

    This thesis focuses on developing comparative genomics methods in eukaryotes, with an emphasis on applications for gene function prediction and regulatory element detection. In the past, methods have been developed to predict functional associations between gene pairs in prokaryotes. The challenge

  7. Dermatologia comparativa Comparative Dermatology

    Directory of Open Access Journals (Sweden)

    Hiram Larangeira de Almeida Jr

    2005-06-01

    Full Text Available Demonstra-se o quadro exuberante dos angiofibromas faciais em paciente do sexo masculino, de 32 anos, com esclerose tuberosa, os quais podem ser comparados com amoras.The impressive facial angiofibromas, from a 32 year-old male paciente, with the classical features of tuberous sclerosis, were compared with mulberries.

  8. Comparing Information Access Approaches.

    Science.gov (United States)

    Chalmers, Matthew

    1999-01-01

    Presents a broad view of information access, drawing from philosophy and semiology in constructing a framework for comparative discussion that is used to examine the information representations that underlie four approaches to information access--information retrieval, workflow, collaborative filtering, and the path model. Contains 32 references.…

  9. Comparative and Translatorly

    Directory of Open Access Journals (Sweden)

    Anna Rosen Guercio

    2011-12-01

    Full Text Available World literature’s natural home is comparative literature, a discipline born from and shaped by, as Vilashini Cooppan elegantly puts it, “scholarly engagements with the categories of migration, exile, diaspora, and globalization” (15. However, world literature has frequently been framed as a problem for the discipline, in large part because of its dependence on the ever-vexing and still mistrusted specter of translation. In light of the long-standing anxiety toward both world literature and translation, I propose here that comparatists do ourselves a terrible disservice if we do not urgently take up the questions raised by this disciplinary tension. Translation – in all of its attendant struggles with ethics, aesthetics, appropriation, authority – is not the problem, but, rather, should be understood as a key critical lens for comparative and world literature.In order to establish academia’s frustration with this subject, one need look no further than the “Three Reports to the America Comparative Literature Association on ‘Professional Standards’” (dating from 1965, 1975, and 1993, which return repeatedly to the problem of reading translated literature, circling around it with intense ambivalence. The moral of their story seems to be that translated texts are integral to comparative literature at the same time that they threaten its existence by undermining disciplinary exclusivity in foreign language expertise and by shining a sort of spotlight on all that literature which comparative literature may sometimes “condone” (as one of the reports puts it but to which it does not often actively attend. Even Goethe had Western European languages and literatures firmly in mind when he coined the term, “Weltliteratur.” Translations can’t help but point up the limits of the “four [likely European] languages” proposed as minimal standards for graduate students by the Green and Bernheimer reports, and on the strength of

  10. Protein Models Comparator

    CERN Document Server

    Widera, Paweł

    2011-01-01

    The process of comparison of computer generated protein structural models is an important element of protein structure prediction. It has many uses including model quality evaluation, selection of the final models from a large set of candidates or optimisation of parameters of energy functions used in template free modelling and refinement. Although many protein comparison methods are available online on numerous web servers, their ability to handle a large scale model comparison is often very limited. Most of the servers offer only a single pairwise structural comparison, and they usually do not provide a model-specific comparison with a fixed alignment between the models. To bridge the gap between the protein and model structure comparison we have developed the Protein Models Comparator (pm-cmp). To be able to deliver the scalability on demand and handle large comparison experiments the pm-cmp was implemented "in the cloud". Protein Models Comparator is a scalable web application for a fast distributed comp...

  11. The Beetle comparator implementation

    CERN Document Server

    Van Beuzekom, M G

    2003-01-01

    Measurements of the comparator thresholds on a Beetle 1.1 chip show large variations. The width of the threshold distribution is several tenths of a MIP signal for a 300 µm silicon detector, which is more than can be corrected for by individual threshold settings. Monte Carlo simulations of the production-process parameters have been performed to track the cause of this large offset spread. The main cause of the offset variation is the spread in the threshold voltage of the MOSFETs. Since this cannot easily be solved by a change in the design of the comparator as such, the solution is to increase the range of the individual threshold settings while maintaining the same resolution. This implies an increase in the number of bits for the individual thresholds. The note describes measurements and simulations for the Beetle versions 1.1 and 1.2, and the changes in the design for the Beetle 1.3.

  12. Comparing Point Clouds

    Science.gov (United States)

    2004-04-01

    Point clouds are one of the most primitive and fundamental surface representations. A popular source of point clouds are three dimensional shape...acquisition devices such as laser range scanners. Another important field where point clouds are found is in the representation of high-dimensional...framework for comparing manifolds given by point clouds is presented in this paper. The underlying theory is based on Gromov-Hausdorff distances, leading

  13. Fast Holographic Comparator

    Science.gov (United States)

    Vahey, D. W.

    1982-01-01

    Comparator is integrated-optical system constructed on a LiNb03sub. waveguide chip. Only the laser, lens and detector are external to chip. Aluminized surface gratings serve as input coupler and beam splitter. Light beams striking edges are returned by ordinary total internal reflection. Three operating modes are possible: A "screening" mode, an "identification" mode and a novel "self-subtraction" mode.

  14. Comparing apples and pears?

    DEFF Research Database (Denmark)

    Waite, Sue; Bølling, Mads; Bentsen, Peter

    2016-01-01

    Using a conceptual model focused on purposes, aims, content, pedagogy, outcomes, and barriers, we review and interpret literature on two forms of outdoor learning: Forest Schools in England and udeskole in Denmark. We examine pedagogical principles within a comparative analytical framework...... and consider how adopted pedagogies reflect and refract the culture in which they are embedded. Despite different national educational and cultural contexts, English Forest Schools and Danish udeskole share several commonalities within a naturalistic/progressive pedagogical tradition; differences appear...

  15. Comparative pharmacognosy of Pashanbhed

    Directory of Open Access Journals (Sweden)

    Poonam Verma

    2014-01-01

    Full Text Available Background: Pashanbhed is a commercially available diuretic and lithotropic drug, used to treat renal problems. It is a controversial name as it is assigned to various plants such as Bergenia ligulata, Kalanchoe pinnata, Coleus aromaticus and Rotula aquatica. Objective: To perform the comparative preliminary phytochemical screening, diuretic activity, and thin layer chromatography (TLC finger printing profile of three plants (B. ligulata, C. aromaticus, and K. pinnata, most commonly used as Pashanbhed. Materials and Methods: Diuretic potential of methanolic extract (ME of three plants were evaluated at two dose levels (500 and 1,000 mg/kg p.o., using normal Wistar rats (Lipschitz method. Furosemide (20 mg/kg p.o. was used as a standard drug. The effect on urine output and electrolyte changes were measured for 24 h and compared. All MEs were screened preliminarily for their constituents and their TLC finger printing profiles were prepared. One-way analysis of variance (ANOVA followed by Bonferroni′s multiple comparison test. P < 0.05 was considered statistically significant. Results: The MEs of all three plants have shown diuresis in normal rats. However, in intercomparison of the ME C. aromaticus (1,000 mg/kg p.o. produced more significant diuresis (P < 0.05 and electrolyte excretion compared to other test groups, the effect was at par with furosemide. The ME of these plants showed presence of alkaloids, glycosides, steroids, terpenoids, saponins, flavonoids, etc. Conclusion: The ME of C. aromaticus (1,000 mg/kg p.o. has showed highest diuretic action (4.2 among the tested extracts. This suggests the use of C. aromaticus leaves as "Pashanbhed"; the most effective diuretic drug.

  16. Comparing East and West

    DEFF Research Database (Denmark)

    Razeto, Anna

    2014-01-01

    This chapter explores the archaeological and literary evidence for marketplaces and urban forms connected to the manufacturing of bricks and metalworking in the capital cities of the contemporary empires of Rome and Han China (ca. 200 BC-200 AD). The comparative analysis of the physical aspects...... of these urban structures and the following discussion of the impact of the political, practical, ideological and economic circumstances of the two empires on the distribution and features of the architecture and industries presented, will highlight the extent to which the urban architecture of the capitals...

  17. Cosmetic outcome and surgical site infection rates of antibacterial absorbable (Polyglactin 910) suture compared to Chinese silk suture in breast cancer surgery: a randomized pilot research

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhong-tao; Jessica Shen; Martin Weisberg; ZHANG Hong-wei; FANG Xue-dong; WANG Li-ming; LI Xiao-xi; LI Ya-fen; SUN Xiao-wei; Judith Carver; Dorella Simpkins

    2011-01-01

    Background The primary objective of this multicenter post-market study was to compare the cosmetic outcome of triclosan-coated VICRYL* Plus sutures with Chinese silk sutures for skin closure of modified radical mastectomy. A secondary objective was to assess the incidence of surgical site infection (SSI).Methods Patients undergoing modified radical mastectomy were randomly assigned to coated VICRYL* Plus antibacterial (Polyglactin 910) suture or Chinese silk suture. Cosmetic outcomes were evaluated postoperatively at days 12 (±2) and 30 (±5), and the evidence of SSI was assessed at days 3, 5, 7, 12 (±2), 30 (±5), and 90 (±7). Cosmetic outcomes were independently assessed via visual analogue scale (VAS) score evaluations of blinded incision photographs (primary endpoint) and surgeon-assessed modified Hollander Scale (mHCS) scores (secondary endpoint).SSI assessments used both CDC criteria and ASEPSIS scores.Results Six Chinese hospitals randomized 101 women undergoing modified radical mastectomy to closure with coated VICRYL* Plus suture (n=51) or Chinese silk suture (n=50). Mean VAS cosmetic outcome scores for antibacterial suture (67.2) were better than for Chinese silk (45.4) at day 30 (P<0.0001)). Mean mHCS cosmetic outcome total scores, were also higher for antibacterial suture (5.7) than for Chinese silk (5.0) at day 30 (P=0.002).Conclusions Patients using coated VICRYL* Plus suture had significantly better cosmetic outcomes than those with Chinese silk sutures. Patients using coated VICRYL* Plus suture had a lower SSI incidence compared to the Chinese silk sutures, although the difference did not reach statistical significance. (ClinicalTrials.gov NCT 00768222)

  18. Comparing pedigree graphs.

    Science.gov (United States)

    Kirkpatrick, Bonnie; Reshef, Yakir; Finucane, Hilary; Jiang, Haitao; Zhu, Binhai; Karp, Richard M

    2012-09-01

    Pedigree graphs, or family trees, are typically constructed by an expensive process of examining genealogical records to determine which pairs of individuals are parent and child. New methods to automate this process take as input genetic data from a set of extant individuals and reconstruct ancestral individuals. There is a great need to evaluate the quality of these methods by comparing the estimated pedigree to the true pedigree. In this article, we consider two main pedigree comparison problems. The first is the pedigree isomorphism problem, for which we present a linear-time algorithm for leaf-labeled pedigrees. The second is the pedigree edit distance problem, for which we present (1) several algorithms that are fast and exact in various special cases, and (2) a general, randomized heuristic algorithm. In the negative direction, we first prove that the pedigree isomorphism problem is as hard as the general graph isomorphism problem, and that the sub-pedigree isomorphism problem is NP-hard. We then show that the pedigree edit distance problem is APX-hard in general and NP-hard on leaf-labeled pedigrees. We use simulated pedigrees to compare our edit-distance algorithms to each other as well as to a branch-and-bound algorithm that always finds an optimal solution.

  19. Comparing dependent robust correlations.

    Science.gov (United States)

    Wilcox, Rand R

    2016-11-01

    Let r1 and r2 be two dependent estimates of Pearson's correlation. There is a substantial literature on testing H0  : ρ1  = ρ2 , the hypothesis that the population correlation coefficients are equal. However, it is well known that Pearson's correlation is not robust. Even a single outlier can have a substantial impact on Pearson's correlation, resulting in a misleading understanding about the strength of the association among the bulk of the points. A way of mitigating this concern is to use a correlation coefficient that guards against outliers, many of which have been proposed. But apparently there are no results on how to compare dependent robust correlation coefficients when there is heteroscedasicity. Extant results suggest that a basic percentile bootstrap will perform reasonably well. This paper reports simulation results indicating the extent to which this is true when using Spearman's rho, a Winsorized correlation or a skipped correlation.

  20. Comparing Measures of Sparsity

    CERN Document Server

    Hurley, Niall P

    2008-01-01

    Sparsity of representations of signals has been shown to be a key concept of fundamental importance in fields such as blind source separation, compression, sampling and signal analysis. The aim of this paper is to compare several commonlyused sparsity measures based on intuitive attributes. Intuitively, a sparse representation is one in which a small number of coefficients contain a large proportion of the energy. In this paper six properties are discussed: (Robin Hood, Scaling, Rising Tide, Cloning, Bill Gates and Babies), each of which a sparsity measure should have. The main contributions of this paper are the proofs and the associated summary table which classify commonly-used sparsity measures based on whether or not they satisfy these six propositions and the corresponding proofs. Only one of these measures satisfies all six: The Gini Index. measures based on whether or not they satisfy these six propositions and the corresponding proofs. Only one of these measures satisfies all six: The Gini Index.

  1. Comparing gains and losses.

    Science.gov (United States)

    McGraw, A Peter; Larsen, Jeff T; Kahneman, Daniel; Schkade, David

    2010-10-01

    Loss aversion in choice is commonly assumed to arise from the anticipation that losses have a greater effect on feelings than gains, but evidence for this assumption in research on judged feelings is mixed. We argue that loss aversion is present in judged feelings when people compare gains and losses and assess them on a common scale. But many situations in which people judge and express their feelings lack these features. When judging their feelings about an outcome, people naturally consider a context of similar outcomes for comparison (e.g., they consider losses against other losses). This process permits gains and losses to be normed separately and produces psychological scale units that may not be the same in size or meaning for gains and losses. Our experiments show loss aversion in judged feelings for tasks that encourage gain-loss comparisons, but not tasks that discourage them, particularly those using bipolar scales.

  2. Regeneration and reprogramming compared

    Directory of Open Access Journals (Sweden)

    Robles Vanesa

    2010-01-01

    Full Text Available Abstract Background Dedifferentiation occurs naturally in mature cell types during epimorphic regeneration in fish and some amphibians. Dedifferentiation also occurs in the induction of pluripotent stem cells when a set of transcription factors (Oct4, Sox2, Klf4 and c-Myc is over expressed in mature cell types. Results We hypothesised that there are parallels between dedifferentiation or reprogramming of somatic cells to induced pluripotent stem cells and the natural process of dedifferentiation during epimorphic regeneration. We analysed expression levels of the most commonly used pluripotency associated factors in regenerating and non-regenerating tissue and compared them with levels in a pluripotent reference cell. We found that some of the pluripotency associated factors (oct4/pou5f1, sox2, c-myc, klf4, tert, sall4, zic3, dppa2/4 and fut1, a homologue of ssea1 were expressed before and during regeneration and that at least two of these factors (oct4, sox2 were also required for normal fin regeneration in the zebrafish. However these factors were not upregulated during regeneration as would be expected if blastema cells acquired pluripotency. Conclusions By comparing cells from the regeneration blastema with embryonic pluripotent reference cells we found that induced pluripotent stem and blastema cells do not share pluripotency. However, during blastema formation some of the key reprogramming factors are both expressed and are also required for regeneration to take place. We therefore propose a link between partially reprogrammed induced pluripotent stem cells and the half way state of blastema cells and suggest that a common mechanism might be regulating these two processes.

  3. Operations dashboard: comparative study

    Science.gov (United States)

    Ramly, Noor Nashriq; Ismail, Ahmad Zuhairi; Aziz, Mohd Haris; Ahmad, Nurul Haszeli

    2011-10-01

    In this present days and age, there are increasing needs for companies to monitor application and infrastructure health. Apart from having proactive measures to secure their application and infrastructure, many see monitoring dashboards as crucial investment in disaster preparedness. As companies struggle to find the best solution to cater for their needs and interest for monitoring their application and infrastructure's health, this paper summarizes the studies made on several known off-the-shelf operations dashboard and in-house developed dashboard. A few criteria of good dashboard are collected from previous studies carried out by several researchers and rank them according to importance and business needs. The finalized criteria that will be discussed in later sections are data visualization, performance indicator, dashboard personalization, audit capability and alert/ notification. Comparative studies between several popular dashboards were then carried out to determine whether they met these criteria that we derived from the first exercise. The findings hopefully can be used to educate and provide an overview of selecting the best IT application and infrastructure operations dashboard that suit business needs, thus become the main contribution of this paper.

  4. Comparative literature in Mexico

    Directory of Open Access Journals (Sweden)

    Luz Aurora Pimentel

    2007-07-01

    Full Text Available A partir de quelques appréciations critiques, cet article propose un bref parcours de la littérature comparée au Mexique, allant des origines de la discipline à l’état actuel des études comparatistes. Il se concentre en particulier sur la façon dont la spécialité comparatiste a été intégrée aux études de troisième cycle de la Faculté de Philosophie et Lettres de l’UNAM, ainsi que sur la façon dont la discipline poursuit son évolution grâce à tout un groupe de collaborateurs.A partir de algunas apreciaciones criticas, este articulo propone un breve recorrido de la literatura comparada en México, que va de los origenes de la disciplina al estado actual de los estudios comparatistas. En él se detalla especialmente la manera en que la especialidad comparatista se integró en los estudios de postgrado de la Facultad de Filosofía y Letras de la UNAM, y cómo la disciplina prosigue su evolución gracias a todo un grupo de colaboradores.

  5. Comparative Supreme Justice

    Directory of Open Access Journals (Sweden)

    Ditlev Tamm

    2011-12-01

    Full Text Available This article deals with the great variety of Supreme Courts in the world today and presents some selected courts. Supreme Courts are found in most countries both as only apex courts or in a courts’ system where also supreme administrative courts or constitutional courts are found. The starting point is the variation of supreme justice in the Nordic countries where one apex court is the system of Denmark and Norway whereas administrative courts are found in Sweden and Finland. Constitutional courts stem from the European tradition and are most abundant in Europe and in countries with a civil law system but especially in Africa they are also found in common law countries. Mexico is mentioned as a specific example of a Supreme Court that has taken upon itself to be a main player in the endeavour to communicate the law to a general audience. The article is a presentation with samples of what is going to be a project on comparative supreme justice in which the position of supreme courts in the various states, the recruitment scheme and competence of the courts and other such factors will be analyzed on a global basis.

  6. Comparative waste forms study

    Energy Technology Data Exchange (ETDEWEB)

    Wald, J.W.; Lokken, R.O.; Shade, J.W.; Rusin, J.M.

    1980-12-01

    A number of alternative process and waste form options exist for the immobilization of nuclear wastes. Although data exists on the characterization of these alternative waste forms, a straightforward comparison of product properties is difficult, due to the lack of standardized testing procedures. The characterization study described in this report involved the application of the same volatility, mechanical strength and leach tests to ten alternative waste forms, to assess product durability. Bulk property, phase analysis and microstructural examination of the simulated products, whose waste loading varied from 5% to 100% was also conducted. The specific waste forms investigated were as follows: Cold Pressed and Sintered PW-9 Calcine; Hot Pressed PW-9 Calcine; Hot Isostatic Pressed PW-9 Calcine; Cold Pressed and Sintered SPC-5B Supercalcine; Hot Isostatic pressed SPC-5B Supercalcine; Sintered PW-9 and 50% Glass Frit; Glass 76-68; Celsian Glass Ceramic; Type II Portland Cement and 10% PW-9 Calcine; and Type II Portland Cement and 10% SPC-5B Supercalcine. Bulk property data were used to calculate and compare the relative quantities of waste form volume produced at a spent fuel processing rate of 5 metric ton uranium/day. This quantity ranged from 3173 L/day (5280 Kg/day) for 10% SPC-5B supercalcine in cement to 83 L/day (294 Kg/day) for 100% calcine. Mechanical strength, volatility, and leach resistance tests provide data related to waste form durability. Glass, glass-ceramic and supercalcine ranked high in waste form durability where as the 100% PW-9 calcine ranked low. All other materials ranked between these two groupings.

  7. Ebolavirus comparative genomics

    Science.gov (United States)

    Jun, Se-Ran; Leuze, Michael R.; Nookaew, Intawat; Uberbacher, Edward C.; Land, Miriam; Zhang, Qian; Wanchai, Visanu; Chai, Juanjuan; Nielsen, Morten; Trolle, Thomas; Lund, Ole; Buzard, Gregory S.; Pedersen, Thomas D.; Wassenaar, Trudy M.; Ussery, David W.

    2015-01-01

    The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). PMID:26175035

  8. Curative Effect Observation of Montelukast Sodium Joint Budesonide Nasal Spray in the Treatment of Allergic Rhinitis%孟鲁司特钠联合布地奈德鼻喷剂治疗变应性鼻炎的疗效观察

    Institute of Scientific and Technical Information of China (English)

    郑艳

    2015-01-01

    Objective To analysis the clinical curative effect of budesonide nasal spray joint meng LuSi sodium of treatment with allergic rhinitis. Methods Choose 80 patients with allergic rhinitis,(35) were randomly divided into control group and observation group (45), compared two groups of clinical curative effect. Results Observation group effective rate was 97.78%,the control group was 45.71%,the observation group is significantly higher than control group (P<0.05). Conclusion For allergic rhinitis take budesonide nasal spray joint meng LuSi sodium treatment,curative effect is obvious.%目的:分析布地奈德鼻喷剂联合孟鲁司特钠治疗变应性鼻炎临床疗效。方法选取80例变应性鼻炎患者,随机分为对照组(35)与观察组(45),对比两组临床疗效。结果观察组有效率为97.78%,对照组为45.71%,观察组明显高于对照组(P<0.05)。结论对变应性鼻炎采取布地奈德鼻喷剂联合孟鲁司特钠治疗,疗效明显。

  9. Comparative law as method and the method of comparative law

    NARCIS (Netherlands)

    Hage, J.C.; Adams, M.; Heirbaut, D.

    2014-01-01

    This article addresses both the justificatory role of comparative law within legal research (comparative law as method) and the method of comparative law itself. In this connection two questions will be answered: 1. Is comparative law a method, or a set of methods, for legal research? 2. Does compar

  10. Comparative Magma Oceanography

    Science.gov (United States)

    Jones, J. H.

    1999-01-01

    The question of whether the Earth ever passed through a magma ocean stage is of considerable interest. Geochemical evidence strongly suggests that the Moon had a magma ocean and the evidence is mounting that the same was true for Mars. Analyses of martian (SNC) meteorites have yielded insights into the differentiation history of Mars, and consequently, it is interesting to compare that planet to the Earth. Three primary features of Mars contrast strongly to those of the Earth: (i) the extremely ancient ages of the martian core, mantle, and crust (about 4.55 b.y.); (ii) the highly depleted nature of the martian mantle; and (iii) the extreme ranges of Nd isotopic compositions that arise within the crust and depleted mantle. The easiest way to explain the ages and diverse isotopic compositions of martian basalts is to postulate that Mars had an early magma ocean. Cumulates of this magma ocean were later remelted to form the SNC meteorite suite and some of these melts assimilated crustal materials enriched in incompatible elements. The REE pattern of the crust assimilated by these SNC magmas was LREE enriched. If this pattern is typical of the crust as a whole, the martian crust is probably similar in composition to melts generated by small degrees of partial melting (about 5%) of a primitive source. Higher degrees of partial melting would cause the crustal LREE pattern to be essentially flat. In the context of a magma ocean model, where large degrees of partial melting presumably prevailed, the crust would have to be dominated by late-stage, LREE-enriched residual liquids. Regardless of the exact physical setting, Nd and W isotopic evidence indicates that martian geochemical reservoirs must have formed early and that they have not been efficiently remixed since. The important point is that in both the Moon and Mars we see evidence of a magma ocean phase and that we recognize it as such. Several lines of theoretical inference point to an early Earth that was also hot

  11. Site compare scripts and output

    Data.gov (United States)

    U.S. Environmental Protection Agency — Monthly site compare scripts and output used to generate the model/ob plots and statistics in the manuscript. The AQS hourly site compare output files are not...

  12. Optical comparator uses holographic subtraction

    Science.gov (United States)

    Vahey, D. W.; Verber, C. M.

    1980-01-01

    Integrated optical comparator compares reference and signal voltages by their effects on coherent light beam. If both voltages are same, beam is essentially unperturbed. If voltages differ, light is deflected by previously recorded hologram to detector.

  13. Comparators in nanometer CMOS technology

    CERN Document Server

    Goll, Bernhard

    2015-01-01

    This book covers the complete spectrum of the fundamentals of clocked, regenerative comparators, their state-of-the-art, advanced CMOS technologies, innovative comparators inclusive circuit aspects, their characterization and properties. Starting from the basics of comparators and the transistor characteristics in nanometer CMOS, seven high-performance comparators developed by the authors in 120nm and 65nm CMOS are described extensively. Methods and measurement circuits for the characterization of advanced comparators are introduced. A synthesis of the largely differing aspects of demands on modern comparators and the properties of devices being available in nanometer CMOS, which are posed by the so-called nanometer hell of physics, is accomplished. The book summarizes the state of the art in integrated comparators. Advanced measurement circuits for characterization will be introduced as well as the method of characterization by bit-error analysis usually being used for characterization of optical receivers. ...

  14. All-optical analog comparator

    OpenAIRE

    Pu Li; Xiaogang Yi; Xianglian Liu; Dongliang Zhao; Yongpeng Zhao; Yuncai Wang

    2016-01-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical device...

  15. Dynamics of Chinese comparative advantage

    NARCIS (Netherlands)

    J. Hinloopen (Jeroen); J.G.M. van Marrewijk (Charles)

    2004-01-01

    textabstractWe analyze the dynamics of Chinese comparative advantage as measured by export shares and the Balassa index using 3-digit and 4-digit sectors for the period 1970 – 1997. We use novel tools to identify periods of rapid structural change and the persistence of comparative advantage, such a

  16. Dynamics of Chinese comparative advantage

    NARCIS (Netherlands)

    J. Hinloopen; C. van Marrewijk

    2004-01-01

    We analyze the dynamics of Chinese comparative advantage as measured by export shares and the Balassa index using 3-digit and 4-digit sectors for the period 1970 ¿ 1997. We use novel tools to identify periods of rapid structural change and the persistence of comparative advantage, such as Galtonian

  17. Dynamics of Chinese Comparative Advantage

    NARCIS (Netherlands)

    J. Hinloopen (Jeroen); J.G.M. van Marrewijk (Charles)

    2004-01-01

    textabstractWe analyze the dynamics of Chinese comparative advantage as measured by export shares and the Balassa index using 3-digit and 4-digit sectors for the period 1970 – 1997. We use novel tools to identify periods of rapid structural change and the persistence of comparative advantage, such a

  18. What Comparative Psychology Is About.

    Science.gov (United States)

    Dewsbury, Donald A.

    1992-01-01

    Urges the inclusion of comparative psychology in the undergraduate curriculum. Defines zoological or comparative psychology as a field that explores the behavior patterns and minds of many animal species and the genesis, control, and consequences of a range of behavioral patterns. Traces the history and development of the discipline. Discusses…

  19. Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis.

    Science.gov (United States)

    Prosperini, Luca; Saccà, Francesco; Cordioli, Cinzia; Cortese, Antonio; Buttari, Fabio; Pontecorvo, Simona; Bianco, Assunta; Ruggieri, Serena; Haggiag, Shalom; Brescia Morra, Vincenzo; Capra, Ruggero; Centonze, Diego; Di Battista, Giancarlo; Ferraro, Elisabetta; Francia, Ada; Galgani, Simonetta; Gasperini, Claudio; Millefiorini, Enrico; Mirabella, Massimiliano; Pozzilli, Carlo

    2017-02-01

    In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i.e. switching from IFNB to GA or viceversa (in the case of non-responders) or starting high-dose IFNB (in the case of highly active treatment-naïves). Propensity score matching in a 1:1:1 ratio was used to select only patients with similar baseline characteristics, retaining 330 and 120 patients in dataset A and B, respectively. In dataset A, the 24-month proportion with NEDA-3 was greater in both NTZ group (67%) and FNG group (42%) than in INJ group (35%) (p ≤ 0.016); however, NTZ was superior to FNG in promoting the attainment of NEDA-3 status (p = 0.034). In dataset B, the 24-month proportion with NEDA-3 was greater in NTZ group (75%) and FNG group (67%) than in INJ group (40%), but the small cohort sizes most likely prevented the detection of any statistically significant difference. Our study provides real-world evidence that NTZ was more effective than both FNG and INJ in non-responders, while it could seem that, in highly active treatment-naïves, NTZ was as effective as FNG and both were superior to INJ.

  20. All-optical analog comparator

    Science.gov (United States)

    Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

    2016-08-01

    An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

  1. Physician Compare National Downloadable File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Physician Compare National Downloadable File is organized at the individual eligible professional level; each line is unique at the professional/enrollment...

  2. Comparative Ellipsis and Variable Binding

    CERN Document Server

    Lerner, J; Lerner, Jan; Pinkal, Manfred

    1995-01-01

    In this paper, we discuss the question whether phrasal comparatives should be given a direct interpretation, or require an analysis as elliptic constructions, and answer it with Yes and No. The most adequate analysis of wide reading attributive (WRA) comparatives seems to be as cases of ellipsis, while a direct (but asymmetric) analysis fits the data for narrow scope attributive comparatives. The question whether it is a syntactic or a semantic process which provides the missing linguistic material in the complement of WRA comparatives is also given a complex answer: Linguistic context is accessed by combining a reconstruction operation and a mechanism of anaphoric reference. The analysis makes only few and straightforward syntactic assumptions. In part, this is made possible because the use of Generalized Functional Application as a semantic operation allows us to model semantic composition in a flexible way.

  3. Comparing Osteoporosis Drugs: The Bisphosphonates

    Science.gov (United States)

    Drugs to Treat Low Bone Density Comparing Osteoporosis Drugs: The Bisphosphonates What is osteoporosis (low bone density)? Osteoporosis is a condition in which the body does not build enough new bone. ...

  4. Teaching Comparative Politics: Beyond Preliminaries

    Science.gov (United States)

    Starrels, John

    1978-01-01

    Recommends that college teachers of comparative European politics attempt to broaden the geographic scope of the subject matter, integrate fact and theory, and make the course interesting and relevant to undergraduate students. (Author/DB)

  5. Biofuel: a comparative case study

    OpenAIRE

    Siddiqui, Aamir; Kading, Christopher; Carter, Kasey

    2013-01-01

    Approved for public release; distribution is unlimited This project analyzes the governments role in the commercialization of biofuel by comparing biofuel commercialization efforts to those of nuclear power and nanotechnology commercialization. The PESTEL framework is applied to nuclear power and nanotechnology to identify key factors relevant to successful commercialization. These success factors are compared to current government biofuel policies to infer the likelihood of successful bio...

  6. Comparative Methodology and Postmodern Relativism

    Science.gov (United States)

    Young, Robert

    1997-09-01

    The author addresses the problems of conducting comparative studies in education if one adopts a viewpoint of postmodern relativism. While acknowledging the value of postmodernist thought in opening up a new understanding of the educational process, he finds that postmodernism raises difficulties when one attempts to deal with the differences and interactions between cultures. He rejects the extremes of both relativism and universalism and argues that comparative studies should be based on a balance between the two.

  7. Corporate Finance and Comparative Advantage

    OpenAIRE

    Keuschnigg, Christian; Egger, Peter

    2009-01-01

    Since innovative firms are often financially constrained, access to external funds is important for the expansion of innovative industries. This paper reports four important results. First, comparative advantage is shaped by factor endowments as well as fundamental determinants of corporate finance. In particular, a larger equity ratio of firms and tough governance standards relax finance constraints and create a comparative advantage in innovative industries. Second, factor price equalizatio...

  8. Non-Comparative versus Comparative Advertising of Quality

    OpenAIRE

    Emons, Winand; Fluet, Claude

    2011-01-01

    Two firms produce a good with a horizontal and a vertical character- istic called quality. The difference in the unobservable quality levels determines how the firms share the market. We consider two scenar- ios: In the first one, firms disclose quality; in the second one, they send costly signals thereof. Under non-comparative advertising a firm advertises its own quality, under comparative advertising a firm adver- tises the quality differential. In either scenario, under comparat...

  9. Cloud computing for comparative genomics.

    Science.gov (United States)

    Wall, Dennis P; Kudtarkar, Parul; Fusaro, Vincent A; Pivovarov, Rimma; Patil, Prasad; Tonellato, Peter J

    2010-05-18

    Large comparative genomics studies and tools are becoming increasingly more compute-expensive as the number of available genome sequences continues to rise. The capacity and cost of local computing infrastructures are likely to become prohibitive with the increase, especially as the breadth of questions continues to rise. Alternative computing architectures, in particular cloud computing environments, may help alleviate this increasing pressure and enable fast, large-scale, and cost-effective comparative genomics strategies going forward. To test this, we redesigned a typical comparative genomics algorithm, the reciprocal smallest distance algorithm (RSD), to run within Amazon's Elastic Computing Cloud (EC2). We then employed the RSD-cloud for ortholog calculations across a wide selection of fully sequenced genomes. We ran more than 300,000 RSD-cloud processes within the EC2. These jobs were farmed simultaneously to 100 high capacity compute nodes using the Amazon Web Service Elastic Map Reduce and included a wide mix of large and small genomes. The total computation time took just under 70 hours and cost a total of $6,302 USD. The effort to transform existing comparative genomics algorithms from local compute infrastructures is not trivial. However, the speed and flexibility of cloud computing environments provides a substantial boost with manageable cost. The procedure designed to transform the RSD algorithm into a cloud-ready application is readily adaptable to similar comparative genomics problems.

  10. Sociological analysis and comparative education

    Science.gov (United States)

    Woock, Roger R.

    1981-12-01

    It is argued that comparative education is essentially a derivative field of study, in that it borrows theories and methods from academic disciplines. After a brief humanistic phase, in which history and philosophy were central for comparative education, sociology became an important source. In the mid-50's and 60's, sociology in the United States was characterised by Structural Functionalism as a theory, and Social Survey as a dominant methodology. Both were incorporated into the development of comparative education. Increasingly in the 70's, and certainly today, the new developments in sociology are characterised by an attack on Positivism, which is seen as the philosophical position underlying both functionalism and survey methods. New or re-discovered theories with their attendant methodologies included Marxism, Phenomenological Sociology, Critical Theory, and Historical Social Science. The current relationship between comparative education and social science is one of uncertainty, but since social science is seen to be returning to its European roots, the hope is held out for the development of an integrated social theory and method which will provide a much stronger basis for developments in comparative education.

  11. Taking Causality Seriously in Comparative Constitutional Law: Insights from Comparative Politics and Comparative Political Economy

    OpenAIRE

    Whytock, CA

    2015-01-01

    By highlighting the many ways that constitutions vary, comparative constitutional law raises interesting and important causal questions: What explains cross-national constitutional variation, and what are the real-world consequences of different constitutional arrangements? But comparative constitutional law scholarship so far has done relatively little to address these issues of constitutional causes and consequences in a rigorous manner. In this paper, I argue that scholars have much to gai...

  12. Airline Safety: A Comparative Analysis.

    Science.gov (United States)

    1987-01-01

    Argentinas Olympic AUA (Austria) PIA (Pakistan) Avianca (Colombia) Pan American British Airways PAL (Philippines) East African Qantas Egyptair Sabena El...S.TP OFR O T PEIDCV E Airline Safety: A Comparative Analysis TRlES IS1j0’~fJ 6. PERFORMING 01G. REPORT NUMBER AU TNOR( ) Sign . CONTRACT OR GRANT NUMBER...OF I NOVa IS 1 OBSOLETE SECURITY CLASSIFICATION OF THIS PAGE j",.n Des. Enterod) 87 jO 1 4 Xb AIRLINE SAFETY: A COMPARATIVE ANALYSIS by Mary Katherine

  13. BOOK REVIEW: The Current Comparator

    Science.gov (United States)

    Petersons, Oskars

    1989-01-01

    This 120-page book is a concise, yet comprehensive, clearly-written and well-illustrated monograph that covers the subject matter from basic principles through design, construction and calibration details to the principal applications. The book will be useful, as a primer, to the uninitiated and, as a reference book to the practitioner involved with transformer-type ratio devices. The length of the book and the style of presentation will not overburden any informed reader. The described techniques and the cited references are primarily from the work at the National Research Council, Canada (NRC). Any omissions, however, are not serious with respect to coverage of the subject matter, since most of the development work has been done at NRC. The role of transformers and transformer-like devices for establishing accurate voltage and current ratios has been recognized for over half a century. Transformer techniques were much explored and developed in the fifties and sixties for accuracy levels suitable for standards laboratories. Three-winding voltage transformers were developed for scaling of impedances in connection with the calculable Thompson Lampard capacitor; three-winding current transformers or current comparators were initially explored for the calibration of current transformers and later for specialized impedance measurements. Extensive development of the current comparator and its applications has been and is still being conducted at the NRC by a team that was started and, until his retirement, led by N L Kusters. The team is now led by W J M Moore. He and P N Miljanic, the authors of this book, have had the principal roles in the development of the current comparator. It is fortunate for the field of metrology that considerabe resources and a talented group of researchers were available to do this development along with mechanisms that were available to transfer this technology to a private sector instrument manufacturer and, thus, disseminate it world wide

  14. Comparative genomics of Dothideomycete fungi

    NARCIS (Netherlands)

    Burgt, van der A.

    2014-01-01

    Fungi are a diverse group of eukaryotic micro-organisms particularly suited for comparative genomics analyses. Fungi are important to industry, fundamental science and many of them are notorious pathogens of crops, thereby endangering global food supply. Dozens of fungi have been sequenced in the la

  15. Acquisition of English comparative adjectives.

    Science.gov (United States)

    Graziano-King, Janine; Cairns, Helen Smith

    2005-05-01

    Two experiments investigated the acquisition of English comparative adjective forms, Adj + er and more Adj. In Experiment 1, 72 children, four- and seven-years-old, indicated their preferences for the synthetic or periphrastic comparative form for 16 adjectives in a forced-choice judgement task; their responses were compared to those of a group of adults (Graziano-King, 2003). In Experiment 2, a group of 29 children, ranging in age from 5;1 to 10;9, and a group of 11 adults performed a forced-choice judgement task, similar to that of Experiment 1, and an elicited production task, responding to the same 32 adjectives for both tasks. The two studies together support an acquisition trajectory of three stages. In the first stage, children show no preference for either form of the comparative; in the second, they adopt a suffixation rule; and in the third, they abandon the general rule and become conservative learners, eventually reaching the adult target.

  16. Job Satisfaction in Fisheries Compared

    Science.gov (United States)

    Pollnac, Richard; Bavinck, Maarten; Monnereau, Iris

    2012-01-01

    This article draws comparative lessons from seven job satisfaction studies on marine capture fishing that were recently carried out in nine countries and three geographical regions--Asia, Africa, and the Caribbean. The seven studies made use of an identical job satisfaction assessment tool and present information on a selection of metiers mainly…

  17. Comparative genomic hybridization: practical guidelines.

    NARCIS (Netherlands)

    Jeuken, J.W.M.; Sprenger, S.H.; Wesseling, P.

    2002-01-01

    Comparative genomic hybridization (CGH) is a technique used to identify copy number changes throughout a genome. Until now, hundreds of CGH studies have been published reporting chromosomal imbalances in a large variety of human neoplasms. Additionally, technical improvements of specific steps in a

  18. Higher holonomies: comparing two constructions

    DEFF Research Database (Denmark)

    Schaetz, Florian; Arias Abad, Camilo

    2015-01-01

    We compare two different constructions of higher-dimensional parallel transport. On the one hand, there is the two-dimensional parallel transport associated with 2-connections on 2-bundles studied by Baez–Schreiber [2], Faria Martins–Picken [11] and Schreiber–Waldorf [12]. On the other hand, ther...

  19. An Experiment in Comparative Advantage.

    Science.gov (United States)

    Haupert, Michael J.

    1996-01-01

    Describes an undergraduate economics course experiment designed to teach the concepts of comparative advantage and opportunity costs. Students have a limited number of labor hours and can chose to produce either wheat or steel. As the project progresses, the students trade commodities in an attempt to maximize use of their labor hours. (MJP)

  20. Comparative Education: Phoenix or Dodo?

    Science.gov (United States)

    Sheehan, Barry A.

    The current crisis in the field of comparative education is one of methodology: the quasi-scientific approach, which is widely used and expensively funded, necessarily jettisons a whole range of variables which are not measurable and which may well have more explanatory power. The quantitative studies have not been shown to yield anything which is…

  1. Comparative Perspectives on Literacy Research.

    Science.gov (United States)

    Street, Brian V.

    Three possible directions for literacy research in the United Kingdom (UK), in terms of three comparative perspectives are (1) cross-cultural, (2) academic/practitioner, and (3) adult/school. Walter Ong's argument that with the advent of writing human consciousness and ways of thinking were altered fundamentally, underlies many of the claims for…

  2. ETHIOPIAN WITNESS PROTECTION SYSTEM: COMPARATIVE ...

    African Journals Online (AJOL)

    ANALYSIS WITH UNHCHR AND GOOD PRACTICES OF. WITNESS ... Oromia Justice Sector Professionals Training and Legal Research Institute; he can be reached at ... affect its implementation by comparing it with good practices of witness .... witness protection were a matter for individual police forces and approaches.

  3. Understanding Comparability of Examination Standards

    Science.gov (United States)

    Coe, Robert

    2010-01-01

    Much of the argument about comparability of examination standards is at cross-purposes; contradictory positions are in fact often both defensible, but they are using the same words to mean different things. To clarify this, two broad conceptualisations of standards can be identified. One sees the standard in the observed phenomena of performance…

  4. Comparing Candidate Hospital Report Cards

    Energy Technology Data Exchange (ETDEWEB)

    Burr, T.L.; Rivenburgh, R.D.; Scovel, J.C.; White, J.M.

    1997-12-31

    We present graphical and analytical methods that focus on multivariate outlier detection applied to the hospital report cards data. No two methods agree which hospitals are unusually good or bad, so we also present ways to compare the agreement between two methods. We identify factors that have a significant impact on the scoring.

  5. Comparability of happiness across nations

    NARCIS (Netherlands)

    R. Veenhoven (Ruut)

    2009-01-01

    textabstractCross-national research on happiness is soaring, but doubts about the comparability of happiness remain. One source of doubt is the possibility of cultural measurement bias. Another source of doubt is the theory that happiness depends on standards of the good life that differ widely acro

  6. Job satisfaction in fisheries compared

    NARCIS (Netherlands)

    Pollnac, R.; Bavinck, M.; Monnereau, I.

    2012-01-01

    This article draws comparative lessons from seven job satisfaction studies on marine capture fishing that were recently carried out in nine countries and three geographical regions—Asia, Africa, and the Caribbean. The seven studies made use of an identical job satisfaction assessment tool and presen

  7. Comparative Psychology: An Epigenetic Approach.

    Science.gov (United States)

    Greenberg, Gary

    1987-01-01

    A comparative psychology course oriented around the themes of phylogeny and ontogeny is described. The course emphasizes the evolution and development of behavioral processes and includes a discussion of the concept of integrative levels and Schneirla's approach/withdrawal theory. The course evaluates genetic determinism and stresses the principle…

  8. An evaluation of prophylactic treatments to prevent post traumatic joint stiffness.

    Science.gov (United States)

    Efird, Will; Kellam, Patrick; Yeazell, Shawn; Weinhold, Paul; Dahners, Laurence E

    2014-11-01

    Arthrofibrosis is a major obstacle to restoring joint function after trauma. The objective of this study was to evaluate montelukast, forskolin, and triamcinolone as possible means of prophylaxis against the formation of arthrofibrosis. Forty-eight rats underwent surgical knee trauma with post-operative immobilization in full flexion. The treatment groups were: control (CTL), oral montelukast (3.75 mg/kg/day) (MLK), intra-articular forskolin injections (0.6 mg/kg) (FSK), and intra-articular triamcinolone injections (0.68 mg/kg) (STR). Rats were sacrificed after 14 days and femorotibial contracture angles were measured with the posterior capsule intact and with the posterior capsule cut. A 0.015Nm extension moment was applied to the knee. All treatment groups had significant reductions in contracture angle compared to the control. Mean contractures with the posterior capsule intact were 32°(CTL), 20° (MLK), 22° (FSK), and 7° (STR). Contractures with the posterior capsule cut were 28° (CTL), 19° (MLK), 20° (FSK), and 5° (STR). The STR group was significantly better than FSK and MLK. Triamcinolone injections provided dramatic reductions in stiffness. Both forskolin and montelukast provided significant, though lesser, reductions in stiffness. While the triamcinolone contracture angles were significantly better, the novel treatments of forskolin and montelukast provided encouraging results and should be studied further.

  9. COGNATE: comparative gene annotation characterizer.

    Science.gov (United States)

    Wilbrandt, Jeanne; Misof, Bernhard; Niehuis, Oliver

    2017-07-17

    The comparison of gene and genome structures across species has the potential to reveal major trends of genome evolution. However, such a comparative approach is currently hampered by a lack of standardization (e.g., Elliott TA, Gregory TR, Philos Trans Royal Soc B: Biol Sci 370:20140331, 2015). For example, testing the hypothesis that the total amount of coding sequences is a reliable measure of potential proteome diversity (Wang M, Kurland CG, Caetano-Anollés G, PNAS 108:11954, 2011) requires the application of standardized definitions of coding sequence and genes to create both comparable and comprehensive data sets and corresponding summary statistics. However, such standard definitions either do not exist or are not consistently applied. These circumstances call for a standard at the descriptive level using a minimum of parameters as well as an undeviating use of standardized terms, and for software that infers the required data under these strict definitions. The acquisition of a comprehensive, descriptive, and standardized set of parameters and summary statistics for genome publications and further analyses can thus greatly benefit from the availability of an easy to use standard tool. We developed a new open-source command-line tool, COGNATE (Comparative Gene Annotation Characterizer), which uses a given genome assembly and its annotation of protein-coding genes for a detailed description of the respective gene and genome structure parameters. Additionally, we revised the standard definitions of gene and genome structures and provide the definitions used by COGNATE as a working draft suggestion for further reference. Complete parameter lists and summary statistics are inferred using this set of definitions to allow down-stream analyses and to provide an overview of the genome and gene repertoire characteristics. COGNATE is written in Perl and freely available at the ZFMK homepage ( https://www.zfmk.de/en/COGNATE ) and on github ( https

  10. 中日药品数据保护制度的比较研究%Comparative Study on Pharmaceutical Data Protection System of China and Japan

    Institute of Scientific and Technical Information of China (English)

    庞晓丛; 康德; 刘艾林; 杜冠华

    2016-01-01

    After joining World Trade Organization( WTO) , the Chinese government carried out pharmaceutical data protection under the TRIPS agreement, but there are still some deficiencies in the pharmaceutical data protection system of China.The rapid progress in the pharmaceutical industry of Japan was tightly related to the implement of pharmaceutical industry related polices, the re-investigation policy of post-marketing drugs in Japan not only played an important role in stimulating the initiatives of drug research companies, but also effec-tively weakened the side effects of the data protection system.By comparative study on pharmaceutical data protection system of China and Japan, this paper aims to find out the shortcomings existing in the process of the pharmaceutical data protection in China and provide some feasible suggestion for the further improvement of Chinese pharmaceutical data protection system.%中国正式加入世界贸易组织( WTO)之后,依照TRIPS协议相关规定实行药品数据保护,但是目前我国在药品数据保护制度方面还有许多不完善之处。日本医药产业的迅速崛起,与该国医药产业相关政策的实施密不可分,尤其是日本的药品再审查政策不仅在鼓励企业创新方面发挥作用,同时有效地减轻了数据保护的负面效应。本文通过中日药品数据保护制度的比较研究,发现我国在药品数据保护过程中的不足之处,为我国进一步完善数据保护制度提供借鉴和参考。

  11. Introduction to SamplerCompare

    Directory of Open Access Journals (Sweden)

    Madeleine B. Thompson

    2011-08-01

    Full Text Available SamplerCompare is an R package for comparing the performance of Markov chain Monte Carlo (MCMC samplers. It samples from a collection of distributions with a collection of MCMC methods over a range of tuning parameters. Then, using log density evaluations per uncorrelated observation as a figure of merit, it generates a grid of plots showing the results of the simulation. It comes with a collection of predefined distributions and samplers and provides R and C interfaces for defining additional ones. It also provides the means to import simulation data generated by external systems. This document provides background on the package and demonstrates the basics of running simulations, visualizing results, and defining distributions and samplers in R.

  12. Enhancer Identification through Comparative Genomics

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Bristow, James; Pennacchio, Len A.

    2006-10-01

    With the availability of genomic sequence from numerousvertebrates, a paradigm shift has occurred in the identification ofdistant-acting gene regulatory elements. In contrast to traditionalgene-centric studies in which investigators randomly scanned genomicfragments that flank genes of interest in functional assays, the modernapproach begins electronically with publicly available comparativesequence datasets that provide investigators with prioritized lists ofputative functional sequences based on their evolutionary conservation.However, although a large number of tools and resources are nowavailable, application of comparative genomic approaches remains far fromtrivial. In particular, it requires users to dynamically consider thespecies and methods for comparison depending on the specific biologicalquestion under investigation. While there is currently no single generalrule to this end, it is clear that when applied appropriately,comparative genomic approaches exponentially increase our power ingenerating biological hypotheses for subsequent experimentaltesting.

  13. Comparative Habitability of Transiting Exoplanets

    CERN Document Server

    Barnes, Rory; Evans, Nicole

    2015-01-01

    Exoplanet habitability is traditionally assessed by comparing a planet's semi-major axis to the location of its host star's "habitable zone," the shell around a star for which Earth-like planets can possess liquid surface water. The Kepler space telescope has discovered numerous planet candidates near the habitable zone, and many more are expected from missions such as K2, TESS and PLATO. These candidates often require significant follow-up observations for validation, so prioritizing planets for habitability from transit data has become an important aspect of the search for life in the universe. We propose a method to compare transiting planets for their potential to support life based on transit data, stellar properties and previously reported limits on planetary emitted flux. For a planet in radiative equilibrium, the emitted flux increases with eccentricity, but decreases with albedo. As these parameters are often unconstrained, there is an "eccentricity-albedo degeneracy" for the habitability of transiti...

  14. BANK RATING. A COMPARATIVE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Batrancea Ioan

    2015-07-01

    Full Text Available Banks in Romania offers its customers a wide range of products but which involves both risk taking. Therefore researchers seek to build rating models to help managers of banks to risk of non-recovery of loans and interest. In the following we highlight rating Raiffeisen Bank, BCR-ERSTE Bank and Transilvania Bank, based on the models CAAMPL and Stickney making a comparative analysis of the two rating models.

  15. Comparative Politics and Public Finance

    OpenAIRE

    Persson, Torsten; Roland, Gerard; Tabellini, Guido

    2000-01-01

    This paper presents a model of electoral accountability to compare the public finance outcomes under a presidential-congressional and a parliamentary system. In a presidential-congressional system, contrary to a parliamentary system, there are no endogenous incentives for legislative cohesion, but this allows for a clearer separation of powers. These features lead to clear differences in the public finance performance of the two systems. A parliamentary system has redistribution towards a maj...

  16. ECONOMIC COMPARABILITY OF INFORMATION SYSTEMS.

    Science.gov (United States)

    not only on the probability distributions of channel in and outputs (events and messages) characterizing the information systems . This remains true when... information systems are interpreted as statistical experiments used to test hypotheses. Some pairs of information systems are, however, comparable...in the sense that one is preferable to another irrespective of the payoff function. There exists thus a partial ordering of information systems according

  17. Detecting selection needs comparative data

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Hubisz, Melissa J.

    2005-01-01

    Positive selection at the molecular level is usually indicated by an increase in the ratio of non-synonymous to synonymous substitutions (dN/dS) in comparative data. However, Plotkin et al. 1 describe a new method for detecting positive selection based on a single nucleotide sequence. We show here...... that this method is particularly sensitive to assumptions regarding the underlying mutational processes and does not provide a reliable way to identify positive selection....

  18. Comparative Microbial Genomics and Forensics.

    Science.gov (United States)

    Massey, Steven E

    2016-08-01

    Forensic science concerns the application of scientific techniques to questions of a legal nature and may also be used to address questions of historical importance. Forensic techniques are often used in legal cases that involve crimes against persons or property, and they increasingly may involve cases of bioterrorism, crimes against nature, medical negligence, or tracing the origin of food- and crop-borne disease. Given the rapid advance of genome sequencing and comparative genomics techniques, we ask how these might be used to address cases of a forensic nature, focusing on the use of microbial genome sequence analysis. Such analyses rely on the increasingly large numbers of microbial genomes present in public databases, the ability of individual investigators to rapidly sequence whole microbial genomes, and an increasing depth of understanding of their evolution and function. Suggestions are made as to how comparative microbial genomics might be applied forensically and may represent possibilities for the future development of forensic techniques. A particular emphasis is on the nascent field of genomic epidemiology, which utilizes rapid whole-genome sequencing to identify the source and spread of infectious outbreaks. Also discussed is the application of comparative microbial genomics to the study of historical epidemics and deaths and how the approaches developed may also be applicable to more recent and actionable cases.

  19. Comparative optimism about healthy eating.

    Science.gov (United States)

    Sproesser, Gudrun; Klusmann, Verena; Schupp, Harald T; Renner, Britta

    2015-07-01

    The present study investigated people's perception of their own as compared to their peers' healthy eating and related these perceptions to actual healthy eating, BMI, and subsequent healthy eating behavior. Data were collected within the framework of the longitudinal cohort study Konstanz Life Study (T1: N = 770; T2: N = 510). Our results demonstrated an optimistic bias on the group level. Specifically, people rated their own eating behavior as healthier on average than that of their average peers. This comparative optimism occurred even when actual healthy eating was unfavorable and BMI was high. However, it increased with actual healthy eating behavior. Importantly, optimistic perceptions were positively related to the intention to eat healthily and healthy eating six months later. Hence, the results suggest that an optimistic comparative view of one's own healthy eating is grounded in reality and boosts rather than deters subsequent health behavior. This implies that there might not be a need to reduce optimistic perceptions of healthy eating behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Comparative genomics of Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Quan-Jiang Dong; Qing Wang; Ying-Nin Xin; Ni Li; Shi-Ying Xuan

    2009-01-01

    Genomic sequences have been determined for a number of strains of Helicobacter pylori (H pylori) and related bacteria.With the development of microarray analysis and the wide use of subtractive hybridization techniques,comparative studies have been carried out with respect to the interstrain differences between H pylori and inter-species differences in the genome of related bacteria.It was found that the core genome of H pylori constitutes 1111 genes that are determinants of the species properties.A great pool of auxillary genes are mainly from the categories of cag pathogenicity islands,outer membrane proteins,restriction-modification system and hypothetical proteins of unknown function.Persistence of H pylori in the human stomach leads to the diversification of the genome.Comparative genomics suggest that a host jump has occurs from humans to felines.Candidate genes specific for the development of the gastric diseases were identified.With the aid of proteomics,population genetics and other molecular methods,future comparative genomic studies would dramatically promote our understanding of the evolution,pathogenesis and microbiology of H pylori.

  1. Postcoital Sperm Assessment Comparative Study.

    Science.gov (United States)

    Pelekanos, Michael J

    2015-11-01

    This postcoital sperm assessment study was performed over a 10 month time period (November 2014-August 2015). Fifteen couples enrolled in the study. The study was a non-blinded, non-randomized, single-center comparison study comparing The Stork® OTC (Rinovum Women's Health, Monroeville, PA) to natural intercourse (NI), using the subjects as their own control/baseline. This was an efficacy study designed to compare the number of sperm in the cervical mucus following the use of The Stork OTC conception aid with the number of sperm in the cervical mucus following natural intercourse. Subjects used both The Stork OTC conception system and the natural intercourse method to evaluate concentrations of sperm in the cervical mucus. Post-coital test (PCT) data was collected demonstrating higher concentrations of sperm within the cervical mucus with The Stork OTC conception system versus natural intercourse for 85% of test subjects in this study. Of the 15 couples enrolled in the study, 2 were lost to follow-up. Mean age for male subjects was 31.7 +/ 5.4 years of age and mean age for female subjects was 29.7+/- 5.4. The average sperm score value of the 85% of test subjects with higher sperm concentrations from The Stork OTC was 3.23 times the score value of sperm concentration compared to natural intercourse. The remaining 15% of test subjects showed no change in sperm score value between The Stork OTC and natural intercourse.

  2. Low Cost Reversible Signed Comparator

    Directory of Open Access Journals (Sweden)

    Farah Sharmin

    2013-10-01

    Full Text Available Nowadays exponential advancement in reversible comp utation has lead to better fabrication and integration process. It has become very popular ove r the last few years since reversible logic circuit s dramatically reduce energy loss. It consumes less p ower by recovering bit loss from its unique input-o utput mapping. This paper presents two new gates called RC-I and RC-II to design an n-bit signed binary comparator where simulation results show that the p roposed circuit works correctly and gives significa ntly better performance than the existing counterparts. An algorithm has been presented in this paper for constructing an optimized reversible n-bit signed c omparator circuit. Moreover some lower bounds have been proposed on the quantum cost, the numbers of g ates used and the number of garbage outputs generated for designing a low cost reversible sign ed comparator. The comparative study shows that the proposed design exhibits superior performance consi dering all the efficiency parameters of reversible logic design which includes number of gates used, quantum cost, garbage output and constant inputs. This proposed design has certainly outperformed all the other existing approaches.

  3. Comparing techniques for pterygium surgery

    Directory of Open Access Journals (Sweden)

    Atilla Alpay

    2008-09-01

    Full Text Available Atilla Alpay, Suat Hayri Ugurbas, Berktug ErdoganDepartment of Ophthalmology, Faculty of Medicine, Zonguldak, Karaelmas University, Zonguldak, TurkeyPurpose: To compare various techniques of pterygium surgery including bare sclera, intraoperative mitomycin C application, conjunctival flap reconstruction, and conjunctival autografting technique.Methods: This study is designed to compare 4 currently used techniques in order to determine the complication and recurrence rates after pterygium exision. Included in the study were 77 eyes from 60 patients. Bare sclera technique was used to treat 21 primary pterygia; mitomycin C was used to treat 20 (16 primary, 4 recurrent pterygia; 18 (17 primary, 1 recurrent pterygia were treated by conjuntival flap reconstruction; and 18 (9 primary, 9 recurrent pterygia were treated by conjunctival autografting technique. All patients who underwent surgery were followed up for between 6 months and 2 years.Results: Eight recurrences (38.09% were observed in the bare sclera group whereas there were 5 (25% recurrences in the mitomycin C group. In the conjunctival flap reconstruction group, 6 (33.33% recurrences were detected. In the conjunctival autografting group, 3 recurrences were  observed. There were no major complications threatening visual ability in the surgical patients.Conclusion: A comparison of the groups demonstrated that the recurrence rate was highest in the bare sclera group, and lowest in conjunctival autografting and mitomycin C treatment groups respectively. Although the conjunctival autografting technique is a more difficult and time consuming technique than the others, cosmetic and surgical results were found to be superior. We advise conjunctival autografting for the treatment of pterygium in view of the high recurrence rates of other techniques, and the possible complications of mitomycin C treatment for benign disease.Keywords: pterygium, comparing, techniques, mitomycin C

  4. Phytozome Comparative Plant Genomics Portal

    Energy Technology Data Exchange (ETDEWEB)

    Goodstein, David; Batra, Sajeev; Carlson, Joseph; Hayes, Richard; Phillips, Jeremy; Shu, Shengqiang; Schmutz, Jeremy; Rokhsar, Daniel

    2014-09-09

    The Dept. of Energy Joint Genome Institute is a genomics user facility supporting DOE mission science in the areas of Bioenergy, Carbon Cycling, and Biogeochemistry. The Plant Program at the JGI applies genomic, analytical, computational and informatics platforms and methods to: 1. Understand and accelerate the improvement (domestication) of bioenergy crops 2. Characterize and moderate plant response to climate change 3. Use comparative genomics to identify constrained elements and infer gene function 4. Build high quality genomic resource platforms of JGI Plant Flagship genomes for functional and experimental work 5. Expand functional genomic resources for Plant Flagship genomes

  5. Comparing toxic air pollutant programs

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, S.C. [ECKENFELDER Inc., Greenville, SC (United States)

    1997-05-01

    This article compares state and federal toxic air pollutant programs. The Clean Air Act Ammendments created a program for the control of Hazardous Air Pollutants based on the establishment of control technology standards. State toxic programs can be classified into two categories: control technology-based and ambient concentration-based. Many states have opened to implement the MACT standards while enforcing their own state air toxics programs. Specific topics discussed include the following: the Federal air toxics program; existing state regulations; New Jersey Air Toxic Program; New York Toxics program.

  6. Building and using comparable corpora

    CERN Document Server

    Sharoff, Serge; Zweigenbaum, Pierre; Fung, Pascale

    2013-01-01

    The 1990s saw a paradigm change in the use of corpus-driven methods in NLP. In the field of multilingual NLP (such as machine translation and terminology mining) this implied the use of parallel corpora. However, parallel resources are relatively scarce: many more texts are produced daily by native speakers of any given language than translated. This situation resulted in a natural drive towards the use of comparable corpora, i.e. non-parallel texts in the same domain or genre. Nevertheless, this research direction has not produced a single authoritative source suitable for researchers and stu

  7. Comparing India and the West

    Directory of Open Access Journals (Sweden)

    S.N. Balagangadhara

    2008-10-01

    Full Text Available During the last two decades, I have been pursuing an unorthodox way of studying cultural differences, focusing mainly on the Indian and the western cultures. Because I believe that one can answer questions about the circumscription of the words ‘Indian’ and ‘western’ cultures satisfactorily (Balangangadhara, 1994, I will assume their intelligibility in what follows. In this paper, I want to raise a rather intriguing problem about comparing these two cultures. I shall do that without looking at other approaches to the issue and in the form of an argument. In order to come to the point quickly, let me make use of Said’s 'Orientalism.'

  8. Comparative stereology of mouse atria.

    Science.gov (United States)

    Bossen, E H; Sommer, J R; Waugh, R A

    1981-01-01

    The left and right atria of the mouse were compared to each other and to the mouse left ventricle using stereologic techniques. The volume fraction (Vv) and surface area per unit cell volume (Sv) of the interior junctional sarcoplasmic reticulum (IJSR), total JSR and extended JSR were greater in the left atrium than in right. The Vv and Sv of the free SR, transverse tubules, and mitochondria were similar in the two atria. It is suggested that the differences in junctional sarcoplasmic reticulum between the atria can be accounted for by a difference in distribution of two types of cells whose anatomy is analogous to working and conducting fibers in the ventricle. The Sv and Vv of the transverse tubules, mitochondria, and all the components of the sarcoplasmic reticulum except for the free SR were greater in the left ventricle than in either atrium. The greater calcium content and sensitivity to extracellular calcium of the atria may explain the greater volume of free SR in the atria as compared to the left ventricle. The Sv of the plasmalemma of the atria and of the Sv of the plasmalemma of the transverse tubules of the left ventricles supports the suggestion of others that there is a constant ratio of surface area to cell volume in cardiac cells.

  9. Comparative effectiveness in esophagogastric cancer.

    Science.gov (United States)

    Knab, Lawrence M; Belotte, Jim; Munshi, Hidayatullah G; Bentrem, David J

    2015-01-01

    Cancer of the esophagus and the gastroesophageal junction (GEJ) continues to have a dismal prognosis, with the incidence of esophageal cancer increasing in the United States. Although radical resection was initially the primary treatment for this disease process, systemic chemotherapy and radiation have been shown to play a role in prolonging survival in most patient populations. This chapter explores the evidence that guides treatment for esophageal and GEJ cancer today. Chemotherapy and radiation therapy were introduced as treatment modalities for esophageal and GEJ cancers when it became evident that surgical therapy alone provided poor long-term survival rates. A variety of treatment strategies have been explored including preoperative (neoadjuvant) and postoperative (adjuvant) chemotherapy, with and without radiation. The evidence suggests that neoadjuvant chemotherapy or chemoradiotherapy provides better outcomes compared to surgery alone for esophageal, GEJ, and gastric cancers. Studies indicate a trend towards improved survival when neoadjuvant chemoradiotherapy is compared to chemotherapy alone. When patients have undergone resection with node-positive disease without receiving neoadjuvant therapy, some form of adjuvant treatment is recommended. This chapter also explores the surgical management of esophageal, GEJ, and gastric cancers including the extent of the gastric lymph node dissection. It also includes a discussion about adherence to national guidelines in terms of gastric cancer treatment and esophageal and gastric lymph node examinations.

  10. [Drug registries: post-marketing evaluation of the benefit-risk profile and promotion of appropriateness. The regional point of view].

    Science.gov (United States)

    Martelli, Luisa; Venegoni, Mauro

    2013-06-01

    Italian Regions and the Italian regulatory agency share a common interest in promoting the appropriateness of drug use, containing drug expenditure and acquiring additional evidence on the effectiveness and safety of drugs. Drug registries can help attaining these objectives. Specifically, the registries implemented in Italy were able to cover the first two objectives, whereas some critical issues were raised on the third one. For instance, the data recorded in the registries are not available at regional level to conduct safety and effectiveness investigations. This is a paradox, when considering that drugs included in the registries have a risk-benefit profile that is only partially defined at the moment of marketing. Currently, researchers and regions can conduct epidemiological research (cohort and case control studies), on the basis of record-linkage procedures, on all drugs prescribed in general practice (which are older drugs with a better defined risk-benefit profile). The expected outcomes of registries should be more clearly defined: when the main aim is to promote appropriateness, the recording of only a very limited amount of data should be required (to avoid a bureaucratic burden on clinicians).The Italian centers of the ENCePP network might play an important role in planning and conducting drug registries: through the presence in the steering committees of the registries, and in conducting epidemiological studies that make the most of this powerful instrument.

  11. [Clinical safety studies based on 30 026 post-marketing cases of Shenqi Fuzheng injection by intensive hospital monitoring nested NCCS].

    Science.gov (United States)

    Wang, Lian-xin; Xie, Yan-ming; Ai, Qing-hua; Xu, Wen-fu

    2015-12-01

    This study adopted a large sample, multicenter, registered hospital centralized monitoring nested prospective case-control study design. From the real world clinical application of Shenqi Fuzheng injection, monitored 30 026 cases of patients with the use of Shenqi Fuzheng injection. A total of 51 adverse drug reaction (ADR) cases was monitored, including 1 case of severe adverse reactions. ADR incidence rate was 1.7 per 1,000. Blood samples were collected from patients with allergic reactions and their matched controls. Related biological indicators of allergic reactions were unified detected and analysed in order to explore the mechanism of allergic reaction and promote the clinical safety.

  12. Application of Natural Language Processing and Network Analysis Techniques to Post-market Reports for the Evaluation of Dose-related Anti-Thymocyte Globulin Safety Patterns.

    Science.gov (United States)

    Botsis, Taxiarchis; Foster, Matthew; Arya, Nina; Kreimeyer, Kory; Pandey, Abhishek; Arya, Deepa

    2017-04-26

    To evaluate the feasibility of automated dose and adverse event information retrieval in supporting the identification of safety patterns. We extracted all rabbit Anti-Thymocyte Globulin (rATG) reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) from the product's initial licensure in April 16, 1984 through February 8, 2016. We processed the narratives using the Medication Extraction (MedEx) and the Event-based Text-mining of Health Electronic Records (ETHER) systems and retrieved the appropriate medication, clinical, and temporal information. When necessary, the extracted information was manually curated. This process resulted in a high quality dataset that was analyzed with the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA) to explore the association of rATG dosing with post-transplant lymphoproliferative disorder (PTLD). Although manual curation was necessary to improve the data quality, MedEx and ETHER supported the extraction of the appropriate information. We created a final dataset of 1,380 cases with complete information for rATG dosing and date of administration. Analysis in PANACEA found that PTLD was associated with cumulative doses of rATG >8 mg/kg, even in periods where most of the submissions to FAERS reported low doses of rATG. We demonstrated the feasibility of investigating a dose-related safety pattern for a particular product in FAERS using a set of automated tools.

  13. Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions.

    Science.gov (United States)

    Grosso, Anthony; Douglas, Ian; Hingorani, Aroon; MacAllister, Raymond; Smeeth, Liam

    2008-11-01

    Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs.

  14. Efficacy and tolerability of sequential intravenous/oral moxifloxacin therapy in pneumonia: results of the first post-marketing surveillance study with intravenous moxifloxacin in hospital practice.

    Science.gov (United States)

    Barth, J; Stauch, K; Landen, H

    2005-01-01

    This study aimed to investigate the efficacy, safety and tolerability of sequential intravenous (IV)/oral therapy with moxifloxacin in pneumonia under general hospital treatment conditions. Patients with pneumonia were documented in this non-interventional multicentre study. The patients were treated with IV moxifloxacin or moxifloxacin sequential therapy (IV and oral) in hospitals throughout Germany. Exclusion criteria were limited to the contraindications mentioned in the summary of product characteristics. The participating hospital-based physicians documented the patients' demography, anamnesis, antibiotic pretreatment, concomitant diseases and medications. Moxifloxacin therapy and symptom status were recorded daily up to the ninth day and on the last day of treatment. The physicians assessed the efficacy and tolerability of IV moxifloxacin therapy and reported all adverse events observed within the treatment period. The 1749 documented patients had a mean age of 66.2 (SD 15.5) years; 56.4% were males and 43.5% females. The majority (99.3%) were treated with moxifloxacin 400mg once daily. On average, moxifloxacin was given for 7.6 days (SD 3.2). In cases of sequential therapy (78.9% of patients), IV moxifloxacin was switched to oral moxifloxacin after a mean of 4.1 days (SD 1.8). Moxifloxacin produced a significant clinical improvement in 58.2% of patients by day 3 of therapy, in 84.2% by day 5 and in 89.4% by day 7. Recovery occurred in 27.0% of patients by day 5, in 54.0% by day 7 and in 87.0% by day 14. It took a mean of 3.4 days (SD 1.9) until improvement and 7.2 days (SD 3.0) until cure. Overall efficacy of IV moxifloxacin therapy was rated by the physicians as 'very good' or 'good' in 82.9% of patients. Tolerability was rated in 94.3% of patients as 'very good' or 'good'. Adverse events were recorded for 92 (5.3%) patients, but events were considered by the attending physician to be related to moxifloxacin therapy for only 45 patients (2.6%). IV moxifloxacin shows high efficacy in the treatment of pneumonia under routine clinical treatment conditions. IV moxifloxacin relieves pneumonia-associated symptoms rapidly and allows an early switch to oral administration. Because of its high efficacy and very good safety and tolerability profile, moxifloxacin delivers excellent benefits as first-line therapy for pneumonia.

  15. Re-evaluation of the Safety of Albendazole in Post-marketing%阿苯达唑上市后安全性再评价报告

    Institute of Scientific and Technical Information of China (English)

    郑荣远; 朱振国; 杨学志; 殷为勇; 王新施; 曹立亚; 吴晔; 任经天

    2008-01-01

    目的:评价阿苯达唑(ADZ)上市后用药的安全性,提出风险管理、合理用药的建议.方法:检索国内外医药文献数据库,收集1994~2005年间的与ADZ安全性评价相关的数据信息,用流行病学方法对ADZ不良反应的报告文献、病例资料进行调查,并作统计分析.结果:共收集ADZ临床治疗文献190篇,不良反应214例.儿童和老年患者多发,以神经系统和皮肤损害所占比例最高,如脑炎综合征、药疹等.结论:ADZ用药人群存在治疗风险,严重不良反应可致死、致残;应加强ADZ的风险管理,规范用药.保障用药安全.

  16. Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax in the Vaccine Adverse Event Reporting System (VAERS in the United States, 1990‒2015.

    Directory of Open Access Journals (Sweden)

    Pedro L Moro

    2016-07-01

    Full Text Available In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur, was licensed for use in the United States.To assess adverse events (AEs after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS, a spontaneous reporting surveillance system.We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990-July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness, and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS. Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB data mining was used to identify disproportional AE reporting after HDCV.VAERS received 1,611 reports after HDCV; 93 (5.8% were serious. Among all reports, the three most common AEs included pyrexia (18.2%, headache (17.9%, and nausea (16.5%. Among serious reports, four deaths appeared to be unrelated to vaccination.This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies.

  17. Pre-market approval and post-market direct-to-consumer advertising of medical devices in Australia: a case study of breast cancer screening and diagnostic devices.

    Science.gov (United States)

    Vreugdenburg, T D; Willis, C D; Mundy, L; Hiller, J E

    2013-01-01

    While research investigating direct-to-consumer advertising of therapeutic goods in Australia has historically focused on prescription medicines, recent action taken by regulators against companies promoting medical devices has placed the industry into the spotlight. Despite the need to effectively regulate direct-to-consumer advertising of medical devices due to its potential harms, inadequacies in the current regulatory system have been noted. Under the present system, devices with a questionable evidence base may enter the Australian marketplace without an evaluation of their effectiveness, and regulators are reliant on industry self-regulation and consumer complaints to draw attention to cases of advertising misconduct. Although some successes in the present system have been observed, we argue that the outlined inadequacies continue to enable the promotion of medical devices to consumers without thorough or sufficient examination of evidence. © 2011 The Authors; Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  18. Post-marketing safety evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir: A drug-use investigation in patients with high risk factors.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2016-10-01

    Peramivir, the only injectable anti-influenza neuraminidase inhibitor medically available in Japan at present, is considered first-line treatment in patients with high risk factors for influenza exacerbation. We conducted a drug-use investigation of peramivir in inpatients with high risk factors (old age, pregnancy, and underlying disease such as chronic respiratory disease) from January 2010 to March 2013. Data of 772 patients from 124 facilities across Japan were collected; peramivir's safety in 770 patients and effectiveness in 688 patients were examined. In total, 412 adverse events were observed in 219 patients (28.4%). Of these, 155 events were adverse drug reactions (ADRs) observed in 98 patients (12.7%). Major ADRs (≥2%) were increased aspartate aminotransferase (5.1%), increased alanine aminotransferase (3.8%) and decreased white blood cell count (2.5%). Fourteen serious ADRs were observed in 12 patients (1.6%). All serious ADRs were resolved or improved except for two events for which outcomes were unknown. Multivariate analyses revealed that ADR incidences were significantly associated with these four backgrounds of patients: medical history, no influenza vaccination, renal impairment and other infection(s). With regard to its effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration, which was the same as in other previous surveillance studies. This surveillance study indicated the safety of peramivir in the treatment of influenza inpatients with high risk factors under routine clinical settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance.

    Science.gov (United States)

    Yamazaki, Hiroyoshi; Kobayashi, Noriko; Taketsuna, Masanori; Tajima, Koyuki; Suzuki, Nahoko; Murakami, Masahiro

    2017-07-20

    To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.

  20. A novel supplemental approach to capturing post-marketing safety information on recombinant factor VIIa in acquired hemophilia: the Acquired Hemophilia Surveillance project

    Directory of Open Access Journals (Sweden)

    Lentz SR

    2014-01-01

    Full Text Available Steven R Lentz,1 Anand Tandra,2 Robert Z Gut,3 David L Cooper31Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 2Hematology, Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA; 3Clinical, Medical, and Regulatory Affairs, Novo Nordisk, Inc, Princeton, NJ, USAAcquired hemophilia (AH is a rare (incidence is 1 per 1.5 million but often severe bleeding disorder characterized by autoantibodies to coagulation factor VIII (FVIII. It is associated with life-threatening bleeding and ∼20% mortality.1,2 Recombinant factor VIIa (rFVIIa; NovoSeven® RT, Novo Nordisk A/S, Bagsværd, Denmark received an indication from the US Food and Drug Administration (FDA in October 2006 for the treatment of bleeding episodes and the prevention of bleeding in surgical interventions or invasive procedures in patients with AH.3View original paper by Collins and colleagues.

  1. Human papillomavirus vaccination catch-up campaign in 2009 for girls born 1993 to 1996 in the Netherlands in 2009 : Results of the post-marketing safety suveillance

    NARCIS (Netherlands)

    van ' t Klooster TM; Kemmeren JM; Vermeer-de Bondt PE; Oostvogels B; PHaff TAJ; de Melker HE; van der Maas NAT; EPI; cib

    2011-01-01

    In 2009 zijn over de humaan papillomavirus (HPV) vaccinatie inhaalcampagne geen ernstige verschijnselen na vaccinatie gemeld die door het vaccin zijn veroorzaakt. Het vaccin kan daardoor op de korte termijn als veilig worden beoordeeld. Dit blijkt uit onderzoek naar de mogelijke bijwerkingen van het

  2. Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study.

    Science.gov (United States)

    Watanabe, Junichiro; Ito, Yoshinori; Ohsumi, Shozo; Mizutani, Mitsuhiro; Tashiro, Hideya; Sakurai, Kenichi; Takahashi, Masato; Saito, Tsuyoshi; Tsurutani, Junji; Mukai, Hirofumi; Yoshinami, Tetsuhiro; Takao, Shintaro; Yamamoto, Yasuhisa; Matsuoka, Toshiyuki; Iwase, Hirotaka; Iwata, Hiroji; Nakamura, Seigo; Saeki, Toshiaki

    2017-06-29

    Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m(2)) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

  3. Post-marketing surveillance study of the long-term use of mizoribine for the treatment of lupus nephritis: 2-Year results.

    Science.gov (United States)

    Takeuchi, Tsutomu; Okada, Kenya; Yoshida, Hisao; Yagi, Nobuyuki

    2017-07-19

    To understand the status of mizoribine use in patients with lupus nephritis (LN) and to collect safety- and efficacy-related data on 2-year treatment with mizoribine. A continuous survey was conducted between March 2010 and July 2015. The analysis set included 559 patients (mean age 39.5 years, females 82.6%, mean duration of systemic lupus erythematosus (SLE) 8.4 years, mean duration of LN 5.9 years). Renal function was satisfactory for 6 months, but worsened from 12 months, with significant worsening at 24 months. By the ACR 2006 remission criteria (eGFR >60), at 24 months, 26.5% of patients achieved complete remission, and 63.3% achieved complete or partial remission. The urine protein to creatinine ratio decreased significantly. The SLE Disease Activity Index 2000 score decreased significantly at 12 and 24 months. Overall, 98 (17.5%) patients experienced 124 adverse drug reactions (ADRs); 3.6% experienced serious ADRs. Mizoribine was used with a steroid in 99.3% and an immunosuppressant in 51.2%; tacrolimus was used in 43.8%. The oral steroid dosage decreased from baseline to 24 months. The incidence of ADRs was not significantly different with concomitant tacrolimus use. The results suggest that long-term mizoribine is safe and effective, even when used with tacrolimus.

  4. Post-Marketing Surveillance of Human Rabies Diploid Cell Vaccine (Imovax) in the Vaccine Adverse Event Reporting System (VAERS) in the United States, 1990‒2015

    Science.gov (United States)

    Moro, Pedro L.; Woo, Emily Jane; Paul, Wendy; Lewis, Paige; Petersen, Brett W.; Cano, Maria

    2016-01-01

    Background In 1980, human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur), was licensed for use in the United States. Objective To assess adverse events (AEs) after HDCV reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. Methods We searched VAERS for US reports after HDCV among persons vaccinated from January 1, 1990–July 31, 2015. Medical records were requested for reports classified as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis and Guillain-Barré syndrome (GBS). Physicians reviewed available information and assigned a primary clinical category to each report using MedDRA system organ classes. Empirical Bayesian (EB) data mining was used to identify disproportional AE reporting after HDCV. Results VAERS received 1,611 reports after HDCV; 93 (5.8%) were serious. Among all reports, the three most common AEs included pyrexia (18.2%), headache (17.9%), and nausea (16.5%). Among serious reports, four deaths appeared to be unrelated to vaccination. Conclusions This 25-year review of VAERS did not identify new or unexpected AEs after HDCV. The vast majority of AEs were non-serious. Injection site reactions, hypersensitivity reactions, and non-specific constitutional symptoms were most frequently reported, similar to findings in pre-licensure studies. PMID:27410239

  5. Comparative transcriptomics in the Triticeae

    Directory of Open Access Journals (Sweden)

    Waugh Robbie

    2009-06-01

    Full Text Available Abstract Background Barley and particularly wheat are two grass species of immense agricultural importance. In spite of polyploidization events within the latter, studies have shown that genotypically and phenotypically these species are very closely related and, indeed, fertile hybrids can be created by interbreeding. The advent of two genome-scale Affymetrix GeneChips now allows studies of the comparison of their transcriptomes. Results We have used the Wheat GeneChip to create a "gene expression atlas" for the wheat transcriptome (cv. Chinese Spring. For this, we chose mRNA from a range of tissues and developmental stages closely mirroring a comparable study carried out for barley (cv. Morex using the Barley1 GeneChip. This, together with large-scale clustering of the probesets from the two GeneChips into "homologous groups", has allowed us to perform a genomic-scale comparative study of expression patterns in these two species. We explore the influence of the polyploidy of wheat on the results obtained with the Wheat GeneChip and quantify the correlation between conservation in gene sequence and gene expression in wheat and barley. In addition, we show how the conservation of expression patterns can be used to elucidate, probeset by probeset, the reliability of the Wheat GeneChip. Conclusion While there are many differences in expression on the level of individual genes and tissues, we demonstrate that the wheat and barley transcriptomes appear highly correlated. This finding is significant not only because given small evolutionary distance between the two species it is widely expected, but also because it demonstrates that it is possible to use the two GeneChips for comparative studies. This is the case even though their probeset composition reflects rather different design principles as well as, of course, the present incomplete knowledge of the gene content of the two species. We also show that, in general, the Wheat GeneChip is not able

  6. Challenges in Comparative Oral Epic

    Directory of Open Access Journals (Sweden)

    John Miles Foley

    2012-10-01

    Full Text Available Originally written in 2001 and subsequently published in China, this collaborative essay explores five questions central to comparative oral epic with regard to Mongolian, South Slavic, ancient Greek, and Old English traditions: “What is a poem in oral epic tradition?” “What is a typical scene or theme in oral epic tradition?” “What is a poetic line in oral epic tradition?” “What is a formula in an oral epic tradition?” “What is the register in oral epic poetry?” Now available for the first time in English, this essay reflects a foundational stage of what has become a productive and long-term collaboration between the Center for Studies in Oral Tradition and the Institute of Ethnic Literature of the Chinese Academy of Social Sciences.

  7. Comparative genomics of Listeria species.

    Science.gov (United States)

    Glaser, P; Frangeul, L; Buchrieser, C; Rusniok, C; Amend, A; Baquero, F; Berche, P; Bloecker, H; Brandt, P; Chakraborty, T; Charbit, A; Chetouani, F; Couvé, E; de Daruvar, A; Dehoux, P; Domann, E; Domínguez-Bernal, G; Duchaud, E; Durant, L; Dussurget, O; Entian, K D; Fsihi, H; García-del Portillo, F; Garrido, P; Gautier, L; Goebel, W; Gómez-López, N; Hain, T; Hauf, J; Jackson, D; Jones, L M; Kaerst, U; Kreft, J; Kuhn, M; Kunst, F; Kurapkat, G; Madueno, E; Maitournam, A; Vicente, J M; Ng, E; Nedjari, H; Nordsiek, G; Novella, S; de Pablos, B; Pérez-Diaz, J C; Purcell, R; Remmel, B; Rose, M; Schlueter, T; Simoes, N; Tierrez, A; Vázquez-Boland, J A; Voss, H; Wehland, J; Cossart, P

    2001-10-26

    Listeria monocytogenes is a food-borne pathogen with a high mortality rate that has also emerged as a paradigm for intracellular parasitism. We present and compare the genome sequences of L. monocytogenes (2,944,528 base pairs) and a nonpathogenic species, L. innocua (3,011,209 base pairs). We found a large number of predicted genes encoding surface and secreted proteins, transporters, and transcriptional regulators, consistent with the ability of both species to adapt to diverse environments. The presence of 270 L. monocytogenes and 149 L. innocua strain-specific genes (clustered in 100 and 63 islets, respectively) suggests that virulence in Listeria results from multiple gene acquisition and deletion events.

  8. Military Retention. A Comparative Outlook

    Directory of Open Access Journals (Sweden)

    Vasile Sminchise

    2016-06-01

    Full Text Available One of the main goals for human resources management structures and for armed forces leaders is to maintain all necessary personnel, both qualitatively and quantitatively for operational needs or for full required capabilities. The retention of military personnel is essential to keep morale and unit readiness and to reduce the costs for recruiting, training, replacement of manpower. Retention rates depend not only on money or other social measures. The goal for retention is to keep in use the most valuable resource that belongs to an organization: the human beings and their knowledge. The aim pf this paper is to provide a comparative analysis of retention measures in various countries based on Research and Technology Organisation report released in 2007 and, thus, provide more examples of retention measures as far as the Romanian military system is concerned.

  9. Comparing different dynamic stall models

    Energy Technology Data Exchange (ETDEWEB)

    Holierhoek, J.G. [Unit Wind Energy, Energy research Centre of the Netherlands, ZG, Petten (Netherlands); De Vaal, J.B.; Van Zuijlen, A.H.; Bijl, H. [Aerospace Engineering, Delft University of Technology, Delft (Netherlands)

    2012-07-16

    The dynamic stall phenomenon and its importance for load calculations and aeroelastic simulations is well known. Different models exist to model the effect of dynamic stall; however, a systematic comparison is still lacking. To investigate if one is performing better than another, three models are used to simulate the Ohio State University measurements and a set of data from the National Aeronautics and Space Administration Ames experimental study of dynamic stall and compare results. These measurements were at conditions and for aerofoils that are typical for wind turbines, and the results are publicly available. The three selected dynamic stall models are the ONERA model, the Beddoes-Leishman model and the Snel model. The simulations show that there are still significant differences between measurements and models and that none of the models is significantly better in all cases than the other models. Especially in the deep stall regime, the accuracy of each of the dynamic stall models is limited.

  10. Comparing Chains of Order Statistics

    CERN Document Server

    Hoffman, Charles

    2012-01-01

    Fix $0\\leq k\\leq m\\leq n$, and let $X_1,...,X_m,Y_1,...,Y_n$ be continuous, independent, and identically distributed random variables. We derive a probability distribution that compares the performance of a $k$-out-of-$m$ system to a $k$-out-of-$n$ system. By virtue of uniformity, we may recast our method of comparison to enumerating lattice paths of a certain exceedance, invoking the Chung-Feller Theorem and Ballot Numbers in our derivation. Another bijection shows that our probability distribution describes the proportion of the first $2k$ steps lying above $x=0$, for a $(m+n)$-step integer random walk, starting at $x=0$ and terminating at $x=m-n$.

  11. Comparing Simulations of AGN Feedback

    CERN Document Server

    Richardson, Mark L A; Devriendt, Julien; Slyz, Adrianne; Thacker, Robert J; Dubois, Yohan; Wurster, James; Silk, Joseph

    2016-01-01

    We perform adaptive mesh refinement (AMR) and smoothed particle hydrodynamics (SPH) cosmological zoom simulations of a region around a forming galaxy cluster, comparing the ability of the methods to handle successively more complex baryonic physics. In the simplest, non-radiative case, the two methods are in good agreement with each other, but the SPH simulations generate central cores with slightly lower entropies and virial shocks at slightly larger radii, consistent with what has been seen in previous studies. The inclusion of radiative cooling, star formation, and stellar feedback leads to much larger differences between the two methods. Most dramatically, at z=5, rapid cooling in the AMR case moves the accretion shock well within the virial radius, while this shock remains near the virial radius in the SPH case, due to excess heating, coupled with poorer capturing of the shock width. On the other hand, the addition of feedback from active galactic nuclei (AGN) to the simulations results in much better ag...

  12. Editorial: Journal of Comparative Psychology.

    Science.gov (United States)

    Burghardt, Gordon M

    2006-05-01

    Both continuity and change typically mark the changing of editors at a long-established journal with extended editorial terms. Change is inherent in any dynamic field and is independent of editorship, but editors have an influence that should be wielded in a fair, responsible, judicious, and scientifically rigorous manner, while inevitably reflecting their own perspectives and values. The Journal of Comparative Psychology will continue to publish exciting, fascinating, assessable, controversial, and well-written reports on research, be the topic traditional, interdisciplinary, applied, or one breaking risky new ground. Editorial standards must be high, but appropriate for various subfields, and as editor the author will try to make those judgments carefully. The author would also like to see more submissions of brief reports describing exciting developments as well as submissions on significant theoretical, conceptual, and methodological issues during his tenure as editor.

  13. Functional categories in comparative linguistics

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    ’, meaning-based categories. The use of meaning-based or semantic categories, however, does not necessarily result in the identification of cross-linguistically comparable data either, as was already shown by Greenberg (1966: 88) himself. Whereas formal categories are too narrow in that they do not cover all...... the structural variants attested across languages, semantic categories can be too wide, including too many structural variants to be useful for e.g. morphosyntactic typology. Furthermore, major typological word order studies after Greenberg (1966) have failed to keep formal and semantic categories apart......: language diversity and its importance for cognitive science. Behavioral and Brain Sciences 32-5, 429–92. Greenberg, Joseph H. 1963. Some universals of grammar with particular reference to the order of meaningful elements. In Joseph H. Greenberg (ed.), Universals of Language, 73-113. Cambridge: MIT. Keesing...

  14. [Comparative studies of face recognition].

    Science.gov (United States)

    Kawai, Nobuyuki

    2012-07-01

    Every human being is proficient in face recognition. However, the reason for and the manner in which humans have attained such an ability remain unknown. These questions can be best answered-through comparative studies of face recognition in non-human animals. Studies in both primates and non-primates show that not only primates, but also non-primates possess the ability to extract information from their conspecifics and from human experimenters. Neural specialization for face recognition is shared with mammals in distant taxa, suggesting that face recognition evolved earlier than the emergence of mammals. A recent study indicated that a social insect, the golden paper wasp, can distinguish their conspecific faces, whereas a closely related species, which has a less complex social lifestyle with just one queen ruling a nest of underlings, did not show strong face recognition for their conspecifics. Social complexity and the need to differentiate between one another likely led humans to evolve their face recognition abilities.

  15. Algorithms for Comparing Pedigree Graphs

    CERN Document Server

    Kirkpatrick, Bonnie; Finucane, Hilary; Jiang, Haitao; Zhu, Binhai; Karp, Richard M

    2010-01-01

    Pedigree graphs, which represent family relationships, are often constructed by collecting data from genealogical records to determine which pairs of people are parent and child. This process is expensive, and small mistakes in data collection--for example, one missing parent-child relationship--can cause large differences in the pedigree graphs created. In this paper, we introduce a simple pedigree definition based on a different type of data which is potentially easier to collect. This alternative characterization of a pedigree that describes a pedigree as a list of the descendants of each individual, rather than a list of parent-child relationships. We then introduce an algorithm that generates the pedigree graph from this list of descendants. We also consider the problem of comparing two pedigree graphs, which could be useful to evaluate the differences between pedigrees constructed via different methods. Specifically, this could be useful to evaluate pedigree reconstruction methods. We define the edit di...

  16. Comparative Habitability of Transiting Exoplanets

    Science.gov (United States)

    Barnes, Rory; Meadows, Victoria S.; Evans, Nicole

    2015-12-01

    Exoplanet habitability is traditionally assessed by comparing a planet’s semimajor axis to the location of its host star’s “habitable zone,” the shell around a star for which Earth-like planets can possess liquid surface water. The Kepler space telescope has discovered numerous planet candidates near the habitable zone, and many more are expected from missions such as K2, TESS, and PLATO. These candidates often require significant follow-up observations for validation, so prioritizing planets for habitability from transit data has become an important aspect of the search for life in the universe. We propose a method to compare transiting planets for their potential to support life based on transit data, stellar properties and previously reported limits on planetary emitted flux. For a planet in radiative equilibrium, the emitted flux increases with eccentricity, but decreases with albedo. As these parameters are often unconstrained, there is an “eccentricity-albedo degeneracy” for the habitability of transiting exoplanets. Our method mitigates this degeneracy, includes a penalty for large-radius planets, uses terrestrial mass-radius relationships, and, when available, constraints on eccentricity to compute a number we call the “habitability index for transiting exoplanets” that represents the relative probability that an exoplanet could support liquid surface water. We calculate it for Kepler objects of interest and find that planets that receive between 60% and 90% of the Earth’s incident radiation, assuming circular orbits, are most likely to be habitable. Finally, we make predictions for the upcoming TESS and James Webb Space Telescope missions.

  17. Digital Identifier Systems: Comparative Evaluation

    Directory of Open Access Journals (Sweden)

    Hamid Reza Khedmatgozar

    2015-02-01

    Full Text Available Identifier is one of the main elements in identifying an object in digital environment. Digital identifier systems were developed followed by a lot of problems such as violation of persistency and uniqueness of physical identifiers and URL in digital environment. These identifiers try to guarantee uniqueness and persistency of hostnames by using indirect names for Domain Name System (DNS. The main objective of this research is to identify qualified digital identifier system among other systems. To achieve the research objective, researchers have considered two major steps: first, identifying main criteria for distinguishing digital identifier based on literature review and focus group interview; and second, performing a comparative evaluation on common identifier systems in the world. Findings of first step demonstrated seven main criteria in three domains for distinguishing digital identifier systems: identifier uniqueness and persistency in the identifier features domain, digital identification, digital uniqueness, digital persistency and digital actionability in the digital coverage domain, and globality in the comprehensiveness of scope domain. In the second step, results of the comparative evaluation on common identifier systems indicated that six identifier systems, included, DOI, Handle, UCI, URN, ARK and PURL, are appropriate choices for using as a digital identifier system. Also, according to these results, three identification systems Including NBN, MARIAM and ISNI were identified as suitable choices for digital identification in certain specialized fields. According to many benefits of using these identifiers in important applied fields, such as, digital content chains and networks integration, digital right management, cross referencing, digital libraries and citation analysis, results of this study can help digital environment experts to diagnose digital identifier and their effective use in applied fields.

  18. COMPARATIVE HABITABILITY OF TRANSITING EXOPLANETS

    Energy Technology Data Exchange (ETDEWEB)

    Barnes, Rory; Meadows, Victoria S.; Evans, Nicole, E-mail: rory@astro.washington.edu [Astronomy Department, University of Washington, Box 951580, Seattle, WA 98195 (United States)

    2015-12-01

    Exoplanet habitability is traditionally assessed by comparing a planet’s semimajor axis to the location of its host star’s “habitable zon