Staff training to improve participant recruitment into surgical randomised controlled trials : A feasibility study within a trial (SWAT) across four host trials simultaneously

The PROMoting THE Use of SWATs (PROMETHEUS) programme was funded by the Medical Research Council (MRC) [grant number MR/R013748/1]. The DISC host trial is funded by the Health Technology Assessment Programme (Grant Ref: 15/102/04). IntAct is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (Grant Ref: 14/150/62). The EME Programme is funded by the MRC and NIHR, with contributions from the CSO in Scotland and Health and Care Research Wales and the HSC R&D Division, Public Health Agency in Northern Ireland. PROFHER-2 is funded by the Health Technology Assessment Programme (Grant Ref: 16/73/03). START: REACTS is funded by the NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 16/61/18. The development of the training intervention was funded by the MRC Network of Hubs for Trials Methodology Research (MR/L004933/1- R53) and supported by the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomized controlled Trials In Invasive procedures - MR/K025643/1). The online version of the training intervention was funded by the NIHR and is hosted on the NIHR Learn platform (https://learn.nihr.ac.uk/course/view.php?id=385). It is based on the face-to face GRANULE training course funded by the Bowel Disease Research Foundation in collaboration with the University of Birmingham, University of Bristol and former MRC ConDuCT-II Hub. This work was part-funded by the Wellcome Trust [ref: 204829] through the Centre for Future Health (CFH) at the University of York. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the MRC or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.Peer reviewedPublisher PD

Appraisal of literature reviews on end-of-life care for minority ethnic groups in the UK and a critical comparison with policy recommendations from the UK end-of-life care strategy

<p>Abstract</p> <p>Background</p> <p>Evidence of low end-of-life (EoL) care service use by minority ethnic groups in the UK has given rise to a body of research and a number of reviews of the literature. This article aims to review and evaluate literature reviews on minority ethnic groups and EoL care in the UK and assess their suitability as an evidence base for policy.</p> <p>Methods</p> <p>Systematic review. Searches were carried out in thirteen electronic databases, eight journals, reference lists, and grey literature. Reviews were included if they concerned minority ethnic groups and EoL care in the UK. Reviews were graded for quality and key themes identified.</p> <p>Results</p> <p>Thirteen reviews (2001-2009) met inclusion criteria. Seven took a systematic approach, of which four scored highly for methodological quality (a mean score of six, median seven). The majority of systematic reviews were therefore of a reasonable methodological quality. Most reviews were restricted by ethnic group, aspect of EoL care, or were broader reviews which reported relevant findings. Six key themes were identified.</p> <p>Conclusions</p> <p>A number of reviews were systematic and scored highly for methodological quality. These reviews provide a good reflection of the primary evidence and could be used to inform policy. The complexity and inter-relatedness of factors leading to low service use was recognised and reflected in reviews' recommendations for service improvement. Recommendations made in the UK End-of-Life Care Strategy were limited in comparison, and the Strategy's evidence base concerning minority ethnic groups was found to be narrow. Future policy should be embedded strongly in the evidence base to reflect the current literature and minimise bias.</p

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Staff training to improve participant recruitment into surgical randomised controlled trials : a feasibility Study Within A Trial (SWAT) across four host randomised controlled trials simultaneously

Objective To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection. Study design and setting Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later. Results Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre and post training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002) – there was no effect on recruitment rate. Conclusion It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations. Trial registration ISRCTN registry: DISC (ISRCTN18254597), registered on 4th April 2017; PROFHER 2 (ISRCTN76296703), registered on 5th April 2018; IntAct (ISRCTN13334746), registered on 10th April 2017; and START:REACTS (ISRCTN17825590), registered on 5th March 2018. The training SWAT has been submitted to the MRC SWAT repository (SWAT111) Keywords: Randomised controlled trial (RCT), Study Within A Trial (SWAT), recruitment, staff training, professional education, feasibility study, surgical trial

The Impact of Brand Quality on Shareholder Wealth

This study examines the impact of brand quality on three components of shareholder wealth: stock returns, systematic risk, and idiosyncratic risk. The study finds that brand quality enhances shareholder wealth insofar as unanticipated changes in brand quality are positively associated with stock returns and negatively related to changes in idiosyncratic risk. However, unanticipated changes in brand quality can also erode shareholder wealth because they have a positive association with changes in systematic risk. The study introduces a contingency theory view to the marketing-finance interface by analyzing the moderating role of two factors that are widely followed by investors. The results show an unanticipated increase (decrease) in current-period earnings enhances (depletes) the positive impact of unanticipated changes in brand quality on stock returns and mitigates (enhances) their deleterious effects on changes in systematic risk. Similarly, brand quality is more valuable for firms facing increasing competition (i.e., unanticipated decreases in industry concentration). The results are robust to endogeneity concerns and across alternative models. The authors conclude by discussing the nuanced implications of their findings for shareholder wealth, reporting brand quality to investors, and its use in employee evaluation