Asthma and gastro-oesophageal reflux disease (GORD) are common medical conditions that frequently co-exist. GORD has been postulated as a trigger for asthma; however, evidence remains conflicting. Proposed mechanisms by which GORD causes asthma include direct airway irritation from micro-aspiration and vagally mediated oesophagobronchial reflux. Furthermore, asthma might precipitate GORD. Thus a temporal association between the two does not establish that GORD triggers asthma. To evaluate the effectiveness of GORD treatment in adults and children with asthma, in terms of its benefits for asthma. The Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, Embase, reference lists of articles, and online clinical trial databases were searched. The most recent search was conducted on 23 June 2020. We included randomised controlled trials comparing treatment of GORD in adults and children with a diagnosis of both asthma and GORD versus no treatment or placebo. A combination of two independent revi number of secondary outcomes related to asthma management. This review determined with moderate certainty that with treatment, lung function measures improved slightly, and use of rescue medications for asthma control was reduced. Further, evidence is insufficient to assess results in children, or to compare surgery versus medical therapy.This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BIA 10-2474, a fatty acid amide hydrolase (FAAH) inhibitor, after first administration to healthy male and female participants. Participants (n = 116) were recruited into this phase I, double-blind, randomized, placebo-controlled, single ascending dose and multiple ascending dose (10-day) study. The primary outcome was the safety and tolerability of BIA 10-2474. Secondary outcomes were pharmacokinetics of BIA 10-2474 and pharmacodynamics, considering plasma concentrations of anandamide and three other fatty acid amides (FAAs) and leukocyte FAAH activity. Single oral doses of 0.25-100 mg and repeated oral doses of 2.5-50 mg were evaluated. BIA 10-2474 was well tolerated up to 100 mg as a single dose and up to 20 mg once daily for 10 days. In the cohort receiving repeated administrations of 50 mg, there were central nervous system adverse events in five of six participants, one with fatal outcome, which led to early termination of the study. BIA 10-2474 showed a linear relationship between dose and area under plasma concentration-time curve (AUC) across the entire dose range and reached steady state within 5-6 days of administration, with an accumulation ratio, based on AUC0-24h , of less then 2 on Day 10. BIA 10-2474 was rapidly absorbed with a mean terminal elimination half-life of 8-10 hours (Day 10). BIA 10-2474 caused reversible, dose-related increases in plasma FAAs. In conclusion, we propose that these data, as well as the additional data generated since the clinical trial was stopped, do not provide a complete mechanistic explanation for the tragic fatality.Interindividual differences in drug response are a common concern in both drug development and across layers of care. While genetics clearly influences drug response and toxicity of many drugs, a substantial fraction of the heritable pharmacological and toxicological variability remains unexplained by known genetic polymorphisms. read more In recent years, population-scale sequencing projects have unveiled tens of thousands of coding and noncoding pharmacogenetic variants with unclear functional effects that might explain at least part of this missing heritability. However, translating these personalized variant signatures into drug response predictions and actionable advice remains challenging and constitutes one of the most important frontiers of contemporary pharmacogenomics. Conventional prediction methods are primarily based on evolutionary conservation, which drastically reduces their predictive accuracy when applied to poorly conserved pharmacogenes. Here, we review the current state-of-the-art of computational variant effect predictors across variant classes and critically discuss their utility for pharmacogenomics. Besides missense variants, we discuss recent progress in the evaluation of synonymous, splice, and noncoding variations. Furthermore, we discuss emerging possibilities to assess haplotypes and structural variations. We advocate for the development of algorithms trained on pharmacogenomic instead of pathogenic data sets to improve the predictive accuracy in order to facilitate the utilization of next-generation sequencing data for personalized clinical decision support and precision pharmacogenomics. Hidradenitis suppurativa (HS) is a chronic inflammatory condition related to multiple systemic diseases and infections. This retrospective cross-sectional study from 1999 to 2015 used the database of Clalit Health Services, the largest managed care organization in Israel, to explore the association between HS and hepatitis B and C. Sociodemographic and clinical information was compared using χ tests for sex and socioeconomic status and t-tests for age. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to compare the odds of hepatitis B and C in those with and without HS. In multivariate analysis controlling for sex, age as a continuous variable, Arab ancestry, and history of drug abuse, HS was associated with a 1.87-fold increased odds (95% CI 1.11-3.17, P=0.019) of hepatitis B (HBV). HS was also associated with HCV in multivariate analysis controlling for sex, age per year, Arab ancestry, alcohol use, and drug use, with a 1.74-fold increased odds (95% CI 1.05-2.89, P=0.032) of hepatitis C (HCV) among those with HS as compared to controls. This study demonstrated an association between HS and both hepatitis B and hepatitis C.This study demonstrated an association between HS and both hepatitis B and hepatitis C. Postoperative pain is common and may be severe. Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, may reduce the incidence and severity of opioid-induced adverse events (AEs). To assess the analgesic efficacy and adverse effects of single-dose intravenous ketorolac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. We searched the following databases without language restrictions CENTRAL, MEDLINE, Embase and LILACS on 20 April 2020. We checked clinical trials registers and reference lists of retrieved articles for additional studies. Randomized double-blind trials that compared a single postoperative dose of intravenous ketorolac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. We used standard methodological procedures expected by Cochrane. Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.