SummaryBackgroundAlthough HDL cholesterol concentrations are strongly and inversely associated with risk of coronary heart disease, interventions that raise HDL cholesterol do not reduce risk of coronary heart disease. HDL cholesterol efflux capacity—a prototypical measure of HDL function—has been associated with coronary heart disease after adjusting for HDL cholesterol, but its effect on incident coronary heart disease risk is uncertain.MethodsWe measured cholesterol efflux capacity and assessed its relation with vascular risk factors and incident coronary heart disease events in a nested case-control sample from the prospective EPIC-Norfolk study of 25 639 individuals aged 40–79 years, assessed in 1993–97 and followed up to 2009. We quantified cholesterol efflux capacity in 1745 patients with incident coronary heart disease and 1749 control participants free of any cardiovascular disorders by use of a validated ex-vivo radiotracer assay that involved incubation of cholesterol-labelled J774 macrophages with apoB-depleted serum from study participants.FindingsCholesterol efflux capacity was positively correlated with HDL cholesterol concentration (r=0·40; p<0·0001) and apoA-I concentration (r=0·22; p<0·0001). It was also inversely correlated with type 2 diabetes (r=–0·18; p<0·0001) and positively correlated with alcohol consumption (r=0·12; p<0·0001). In analyses comparing the top and bottom tertiles, cholesterol efflux capacity was significantly and inversely associated with incident coronary heart disease events, independent of age, sex, diabetes, hypertension, smoking and alcohol use, waist:hip ratio, BMI, LDL cholesterol concentration, log-triglycerides, and HDL cholesterol or apoA-I concentrations (odds ratio 0·64, 95% CI 0·51–0·80). After a similar multivariable adjustment the risk of incident coronary heart disease was 0·80 (95% CI 0·70–0·90) for a per-SD change in cholesterol efflux capacity.InterpretationHDL cholesterol efflux capacity might provide an alternative mechanism for therapeutic modulation of the HDL pathway beyond HDL cholesterol concentration to help reduce risk of coronary heart disease.FundingUS National Institutes of Health, UK Medical Research Council, Cancer Research UK.

Improving patient safety is at the forefront of policy and practice. While considerable progress has been made in understanding the frequency, causes and consequences of error in hospitals, less is known about the safety of primary care.We investigated how often patient safety incidents occur in primary care and how often these were associated with patient harm.We searched 18 databases and contacted international experts to identify published and unpublished studies available between 1 January 1980 and 31 July 2014. Patient safety incidents of any type were eligible. Eligible studies were critically appraised using validated instruments and data were descriptively and narratively synthesised.Nine systematic reviews and 100 primary studies were included. Studies reported between <1 and 24 patient safety incidents per 100 consultations. The median from population-based record review studies was 2-3 incidents for every 100 consultations/records reviewed. It was estimated that around 4% of these incidents may be associated with severe harm, defined as significantly impacting on a patients well-being, including long-term physical or psychological issues or death (range <1% to 44% of incidents). Incidents relating to diagnosis and prescribing were most likely to result in severe harm.Millions of people throughout the world use primary care services on any given day. This review suggests that safety incidents are relatively common, but most do not result in serious harm that reaches the patient. Diagnostic and prescribing incidents are the most likely to result in avoidable harm.This systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO CRD42012002304)

Background: Anaphylaxis is an acute, potentially fatal, multi-organ system, allergic reaction caused by the release of chemical mediators from mast cells and basophils. Uncertainty exists around epidemiological measures of incidence and prevalence, risk factors, risk of recurrence, and death due to anaphylaxis. This systematic review aimed to (1) understand and describe the epidemiology of anaphylaxis and (2) describe how these characteristics vary by person, place, and time. Methods: Using a highly sensitive search strategy, we identified systematic reviews of epidemiological studies, descriptive and analytical epidemiological investigations, and studies involving analysis of routine data. Results: Our searches identified a total of 5 843 potentially eligible studies, of which 49 satisfied our inclusion criteria. Of these, three were suitable for pooled estimates of prevalence. The incidence rates for all-cause anaphylaxis ranged from 1.5 to 7.9 per 100 000 person-years. These data indicated that an estimated 0.3% (95% CI 0.1-0.5) of the population experience anaphylaxis at some point in their lives. Food, drugs, stinging insects, and latex were the most commonly identified triggers. Conclusions: Anaphylaxis is a common problem, affecting an estimated 1 in 300 of the European population at some time in their lives. Future research needs to