Enacting corporate governance of health care safety and quality: a dramaturgy of hospital boards in England

The governance of patient safety is a challenging concern for all health systems. Yet, while the role of executive Boards receives increased scrutiny, the area remains theoretically and methodologically underdeveloped. Specifically, we lack a detailed understanding of the performative aspects at play: what Board members say and do to discharge their accountabilities for patient safety. This article draws on qualitative data from overt non-participant observation of four NHS hospital Foundation Trust Boards in England. Applying a dramaturgical framework to explore scripting, setting, staging and performance, we found important differences between case study sites in the performative dimensions of processing and interpretation of infection control data. We detail the practices associated with these differences - the legitimation of current performance, the querying of data classification, and the naming and shaming of executives – to consider their implications

Effective board governance of safe care: a (theoretically underpinned) cross-sectioned examination of the breadth and depth of relationships through national quantitative surveys and in-depth qualitative case studies

Background: Recent high-profile reports into serious failings in the quality of hospital care in the NHS raise concerns over the ability of trust boards to discharge their duties effectively. Objectives: Our study aimed to generate theoretically grounded empirical evidence on the associations between board governance, patient safety processes and patient-centred outcomes. The specific aims were as follows: (1) to identify the types of governance activities undertaken by hospital trust boards in the English NHS with regard to ensuring safe care in their organisation; (2) in foundation trusts, to explore the role of boards and boards of governors with regards to the oversight of patient safety in their organisation; (3) to assess the association between particular hospital trust board oversight activities and patient safety processes and clinical outcomes; (4) to identify the facilitators and barriers to developing effective hospital trust board governance of safe care; and (5) to assess the impact of external commissioning arrangements and incentives on hospital trust board oversight of patient safety. Methods: The study comprised three distinct but interlocking strands: (1) a narrative systematic review in order to describe, interpret and synthesise key findings and debates concerning board oversight of patient safety; (2) in-depth mixed-methods case studies in four organisations to assess the impact of hospital board governance and external incentives on patient safety processes and outcomes; and (3) two national surveys exploring board management in NHS acute and specialist hospital trusts in England, and relating board characteristics to whole-organisation outcomes. Results: A very high proportion of trust boards reported the kinds of desirable characteristics and board-related processes that research says may be associated with higher performance. Our analysis of the symbolic aspects of board activities highlights the role and differences in local processes of organising the governance of patient safety. Most boards do allocate considerable amount of time to discussing patient safety and quality-related issues and were using a wide range of hard performance metrics and soft intelligence to monitor its organisation with regard to patient safety. Although the board of governors is generally perceived to be well-meaning, they were also considered to be being largely ineffective in helping to promote and deliver safer care for their organisations. We did not find any statistically significant relationship between board attributes (self-reported) and processes and any patient safety outcome measures. However, we did find a significant relationship between two dimensions of the Board Self-Assessment Questionnaire and two specific-and-related national staff survey organisational ‘process’ measures: (1) staff feeling safe to raise concerns about errors, near-misses and incidents and (2) staff feeling confident that their organisation would address their concerns, if raised. We also found that contracting and external financial incentives appeared to play only a relatively minor role in incentivising quality and safety improvement. Conclusions: Our research is the first large-scale mixed-methods study of hospital board activity and behaviour related to the oversight of patient safety in the English NHS and the key findings should be used to influence the design of future governance arrangements as well as the training and support of board. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Plagioclase preferred orientation in layered mylonites : evaluation of flow laws for the lower crust

Submitted in partial fulfillment of the requirements for the degree of Master of Science at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2008We evaluate the applicability of plagioclase and gabbro flow laws by comparing predicted and observed deformation mechanisms in gabbroic shear zones. Gabbros and layered gabbro mylonites were collected from the Southwest Indian Ridge (SWIR), ODP Hole 735B. Deformation temperatures are constrained by two-pyroxene thermometry, stress is estimated from grain size, and deformation mechanisms are analyzed by microstructure and the presence or absence of a lattice preferred orientation (LPO). Our analyses indicate that mylonite layers deformed at a strain rate in the range of 10-12 to 10- 11 s-1, while coarse-grained gabbro deformed at a strain rate of approximately 10-14 to 10- 13 s-1. Plagioclase in pure plagioclase mylonite layers exhibit strong LPOs indicating they deform by dislocation creep. Plagioclase grain size in mixed plagioclase-pyroxene mylonite layers is finer than in pure plagioclase layers, and depends on the size and proportion of pyroxenes. Progressive mixing of pyroxene and plagioclase within gabbro mylonite layers is accompanied by weakening of the LPO indicating that phase mixing promotes a transition to diffusion creep processes that involve grain boundary sliding. Our results indicate that experimental flow laws are accurate at geologic strain rates, although the strain rate for diffusion creep of fine-grained gabbro may be underestimated. At the conditions estimated for the SWIR crust, our calculations suggest that strain localization leads to a factor of two to four decrease in lower crustal viscosity. Even so, the viscosity of lower gabbroic crust is predicted to be similar to that of dry upper mantle

NGS technologies for analyzing germplasm diversity in genebanks*

More than 70 years after the first ex situ genebanks have been established, major efforts in this field are still concerned with issues related to further completion of individual collections and securing of their storage. Attempts regarding valorization of ex situ collections for plant breeders have been hampered by the limited availability of phenotypic and genotypic information. With the advent of molecular marker technologies first efforts were made to fingerprint genebank accessions, albeit on a very small scale and mostly based on inadequate DNA marker systems. Advances in DNA sequencing technology and the development of high-throughput systems for multiparallel interrogation of thousands of single nucleotide polymorphisms (SNPs) now provide a suite of technological platforms facilitating the analysis of several hundred of Gigabases per day using state-of-the-art sequencing technology or, at the same time, of thousands of SNPs. The present review summarizes recent developments regarding the deployment of these technologies for the analysis of plant genetic resources, in order to identify patterns of genetic diversity, map quantitative traits and mine novel alleles from the vast amount of genetic resources maintained in genebanks around the world. It also refers to the various shortcomings and bottlenecks that need to be overcome to leverage the full potential of high-throughput DNA analysis for the targeted utilization of plant genetic resources

Strategies for identifying familial hypercholesterolaemia in non-specialist clinical settings

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: The purpose of this review is to assess the effectiveness of interventions to systematically improve identification of FH in non-specialist settings compared to usual care (incidental approaches to identify FH in non-specialist settings)

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file 32: Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.Peer reviewedPublisher PD

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk