Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

2016 United Kingdom national guideline on the sexual health care of men who have sex with men.

This guideline is intended for use in UK Genitourinary medicine clinics and sexual health services but is likely to be of relevance in all sexual health settings, including general practice and Contraception and Sexual Health (CASH) services, where men who have sex with men (MSM) seek sexual health care or where addressing the sexual health needs of MSM may have public health benefits. For the purposes of this document, MSM includes all gay, bisexual and all other males who have sex with other males and both cis and trans men. This document does not provide guidance on the treatment of particular conditions where this is covered in other British Association for Sexual Health and HIV (BASHH) Guidelines but outlines best practice in multiple aspects of the sexual health care of MSM. Where prevention of sexually transmitted infections including HIV can be addressed as an integral part of clinical care, this is consistent with the concept of combination prevention and is included. The document is designed primarily to provide guidance on the direct clinical care of MSM but also makes reference to the design and delivery of services with the aim of supporting clinicians and commissioners in providing effective services. Methodology This document was produced in accordance with the guidance set out in the BASHH CEG's document 'Framework for guideline development and assessment' published in 2010 at http://www.bashh.org/guidelines and with reference to the Agree II instrument. Following the production of the updated framework in April 2015, the GRADE system for assessing evidence was adopted and the draft recommendations were regraded. Search strategy (see also Appendix 1) Ovid Medline 1946 to December 2014, Medline daily update, Embase 1974 to December 2014, Pubmed NeLH Guidelines Database, Cochrane library from 2000 to December 2014. Search language English only. The search for Section 3 was conducted on PubMed to December 2014. Priority was given to peer-reviewed papers published in scientific journals, although for many issues evidence includes conference abstracts listed on the Embase database. In addition, for 'Identification of problematic recreational drug and alcohol use' section and 'Sexual problems and dysfunctions in MSM' section, searches included PsycINFO. Methods Article titles and abstracts were reviewed and if relevant the full text article was obtained. Priority was given to randomised controlled trial and systematic review evidence, and recommendations made and graded on the basis of best available evidence. Piloting and feedback The first draft of the guideline was circulated to the writing group and to a small group of relevant experts, third sector partners and patient representatives who were invited to comment on the whole document and specifically on particular sections. The revised draft was reviewed by the CEG and then reviewed by the BASHH patient/public panel and posted on the BASHH website for public consultation. The final draft was piloted before publication. Guideline update The guidelines will be reviewed and revised in five years' time, 2022

Refugees or ravenous predators: detecting predation on new recruits to tropical estuarine nurseries

Many of the most abundant small and juvenile fishes within shallow water estuarine nursery habitats consume other fish to some degree but have rarely been considered as potentially important predators in the functioning of these systems because of the low (<50%) average occurrence of fish in their diets. Predation by abundant minor piscivores on new recruits when they first enter the nursery may make a significant contribution to the predation mortality of this critical life-history stage. To determine the potential importance of minor piscivores as predators on new recruits, temporal patterns in the diets of 15 common species of minor piscivores were examined and related to the abundance of new recruits (≤20 mm FL) in biweekly seine samples over 13 months in shallow (<1.5 m) sandy habitats in the Ross River estuary in north-eastern Queensland, Australia. The high spatial patchiness of new recruits made it difficult to correlate their abundance with their consumption by minor piscivores, and there was no relationship detected between the abundance of new recruits and the occurrence of fish in the diets of minor piscivores. To gain broader insight into spatio-temporal patterns in the consumption of fish prey by minor piscivores, we utilised a collection of fishes sampled during various studies over 6 years from 17 estuaries in the region to examine the diets of >3500 individuals from 20 spp. of minor piscivores. Patterns in the consumption of fish prey by these minor piscivores, especially the highly abundant sparids, sillaginids and ambassids, revealed that the low average occurrence of fish in their diet greatly underestimated the predation pressure imposed by these on fish prey at particular locations and times. For most sampling occasions and locations few minor piscivores consumed fish prey (consumed by 0% of individuals examined), while occasionally a large proportion of individuals within a taxon did so (50–100% of individuals consumed fish prey). Often at such times/locations multiple species of minor piscivores simultaneously preyed heavily on fish. When minor piscivores consumed fish, they preyed mainly on small new recruits. Because many of these minor piscivores are relatively recent recruits, many of the small and juvenile fishes believed to gain refuge in shallow estuarine nurseries may themselves be important predators on fish subsequently recruiting to these habitats, and so potentially play a significant role in structuring estuarine fish faunas and the functioning of shallow water nurseries