The incidence of asthma has been positively associated with obesity. Asthma comprises diverse ''phenotypes'' reflecting heterogeneity in a number of characteristics, including response to therapy. The present authors examined whether body mass index (BMI) influenced the response to placebo, as well as to two asthma controller medications.A post hoc analysis was performed, pooling data from four double-blind, placebo-controlled studies randomising 3,073 moderate asthmatic adults to montelukast (n51,439), beclomethasone (n5894) or placebo (n5740). The primary end point was asthma control days; other end points were forced expiratory volume in one second, b-agonist use and nocturnal awakening. Analyses were conducted using BMI classification into normal (,25.0 kg?m ; 16%) categories, as well as BMI as a continuous variable.The treatment groups were balanced for BMI, demographic characteristics and parameters of asthma control. The placebo response for all end points was generally lower with increasing BMI. Similarly, the response to the inhaled corticosteroid decreased, whereas the response to the leukotriene antagonist remained stable.In conclusion, post hoc data from the present study suggested that body mass index may influence the natural history of asthma control (as reflected by response to placebo) and may differentially influence response to the two active agents, warranting explicit testing in future prospective studies.

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Objective To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia.Design Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology).Setting Healthcare claims data from the IMS Lifelink database in the United States.Participants Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011after a minimum of six months' enrolment. Main outcomes measures Hypotension requiring admission to hospital.Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted.Results Among 383 567 new users of study drugs (tamsulosin 297 596; 5ARI 85 971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10 000 person years) than for 5ARIs (31.3 events per 10 000 person years) or all accrued person time (29.1 events per 10 000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis. ConclusionsWe observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.

Purpose To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births. Methods We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation. Conclusions We observed a marked increase in ondansetron use by study year, prescribed to nearly one-quarter of insured pregnant women in 2014, occurring in conjunction with decreased use of promethazine and metoclopramide. Given the widespread use of ondansetron in pregnancy, data establishing product efficacy and methodologically rigorous evaluation of post-marketing safety are needed. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6-week, randomised, placebocontrolled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days).A total of 730 adult patients with asthma, age 15-65 yrs, with a forced expiratory volume in one second (FEV1) at baseline of 50-85% of predicted and o15% improvement in FEV1 after inhaled b-agonist were enrolled. After a 2-week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 mg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions.The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV1. The mean (¡SD) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0 ¡ 35.8, montelukast 50.7 ¡ 37.1, beclomethasone 57.9 ¡ 36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (¡SD) from baseline in FEV1 was 12.1¡18.7 and 13.9¡20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4¡20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences.A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6-week treatment period. Eur Respir J 2003; 21: 123-128

No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

F luoroquinolones are commonly prescribed broad-spectrum antibiotics. 1 Although highly effective, they are known to cause cardiac arrhythmia, hypersensitivity reactions and central nervous system effects including agitation and insomnia. 2,3 Recent reports of tendon rupture 4 and retinal detachment 5 suggest that these drugs may damage collagen and connective tissue. Case reports of acute kidney injury with the use of fluoroquinolones have been published, 6 and the product label includes renal failure in a list of potential, but uncommon, adverse reactions. 2 In clinical practice, when oral fluoroquinolones are prescribed, the potential for acute kidney injury is generally not a clinical consideration. We aimed to quantify the risk of acute kidney injury with the use of oral fluoroquinolones among men. This study population was limited to men because the cohort we studied was formed to investigate health issues that affect older men. Case reports indicate that the use of fluoroquinolones may lead to acute kidney injury. We studied the association between the use of oral fluoroquinolones and acute kidney injury, and we examined interaction with renin-angiotensin-system blockers. Methods Data source

Improvements in monitoring have occurred over the last 5 yr, but observations of neurological function are not routine in all units, and are not continued after removal of the epidural catheter in the majority. The authors suggest that acute pain services should be responsible for protocols for the investigation and treatment of epidural haematomas.