Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Impact of teamwork and communication training interventions on safety culture and patient safety in emergency departments: a systematic review

© 2020 Lippincott Williams & Wilkins, Inc. This is a non-final version of an article published in final form in Journal of Patient Safety, available at: https://dx.doi.org/10.1097/PTS.0000000000000782.Objectives: To narratively summaries literature reporting on the effect of teamwork and communication training interventions on culture and patient safety in emergency department (ED) settings. Methods: We searched PubMed, EMBASE, Psych Info CINAHL, Cochrane, Science Citation Inc, Web of Science, and Educational Resources Information Centre for peer-reviewed journal articles published from January 1, 1988, until June 8, 2018 that assessed teamwork and communication interventions focusing on how they influence patient safety in the ED were selected. One additional search update was performed in July 2019. Results: Sixteen studies were included from 8,700 screened publications. The studies’ design, interventions, and evaluation methods varied widely. The most impactful ED training interventions were End-of-Course Critique, TeamSTEPPS, and crisis resource management (CRM)-based training. CRM and TeamSTEPPS CRM-based training curriculum were used in most of the studies. Multiple tools, including the Kirkpatrick (KP) evaluation model, Agency for Healthcare Research and Quality Hospital Survey on Patient Safety Culture, TeamSTEPPS Teamwork Attitudes Questionnaire, the Safety Attitudes Questionnaire, and the Communication and Teamwork Skills Assessment were used to assess the impact of such interventions. Improvements in one of the domains of safety culture and related domains were found in all studies. Four empirical studies established improvements in patient health outcomes that occurred following simulation CRM training (KP4), but there was no effect on mortality. Conclusion: Overall, teamwork and communication training interventions improve the safety culture in ED settings and may positively affect patient outcome. The implementation of safety culture programs may be considered to reduce incidence of medical errors and adverse events.Peer reviewe