Supporting Sustainable e-learning: A UK National Forum

This article outlines the progress of a national Supporting Sustainable eLearning Forum, funded by the UK Learning and Teaching Support Network Generic Centre. The aim of the forum was to move e-learning on from project innovation to embedded practice, and address questions around the scaleable nature of e-learning. Assimilated views of a wide range of support staff are presented. These include ideas on how to devise strategies for supporting Higher Education lecturers in the design, development and implementation of online courses; disseminate good practice in supporting sustainable approaches to eLearning; and contribute to the ongoing debate in the sharing and reuse of e-learning resources

Statistical methods for automated drug susceptibility testing: Bayesian minimum inhibitory concentration prediction from growth curves

Determination of the minimum inhibitory concentration (MIC) of a drug that prevents microbial growth is an important step for managing patients with infections. In this paper we present a novel probabilistic approach that accurately estimates MICs based on a panel of multiple curves reflecting features of bacterial growth. We develop a probabilistic model for determining whether a given dilution of an antimicrobial agent is the MIC given features of the growth curves over time. Because of the potentially large collection of features, we utilize Bayesian model selection to narrow the collection of predictors to the most important variables. In addition to point estimates of MICs, we are able to provide posterior probabilities that each dilution is the MIC based on the observed growth curves. The methods are easily automated and have been incorporated into the Becton--Dickinson PHOENIX automated susceptibility system that rapidly and accurately classifies the resistance of a large number of microorganisms in clinical samples. Over seventy-five studies to date have shown this new method provides improved estimation of MICs over existing approaches.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS217 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

DeLLITE Depression in late life: an intervention trial of exercise. Design and recruitment of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Physical activity shows potential in combating the poor outcomes associated with depression in older people. Meta-analyses show gaps in the research with poor trial design compromising certainty in conclusions and few programmes showing sustained effects.</p> <p>Methods/design</p> <p>The Depression in Late Life: an Intervention Trial of Exercise (DeLLITE) is a 12 month randomised controlled trial of a physical activity intervention to increase functional status in people aged 75 years and older with depressive symptoms. The intervention involves an individualised activity programme based on goal setting and progression of difficulty of activities delivered by a trained nurse during 8 home visits over 6 months. The control group received time matched home visits to discuss social contacts and networks. Baseline, 6 and 12 months measures were assessed in face to face visits with the primary outcome being functional status (SPPB, NEADL). Secondary outcomes include depressive symptoms (Geriatric Depression Scale), quality of life (SF-36), physical activity (AHS Physical Activity Questionnaire) and falls (self report).</p> <p>Discussion</p> <p>Due to report in 2008 the DeLLITE study has recruited 70% of those eligible and tests the efficacy of a home based, goal setting physical activity programme in improving function, mood and quality of life in older people with depressive symptomatology. If successful in improving function and mood this trial could prove for the first time that there are long term health benefit of physical activity, independent of social activity, in this high risk group who consume excess health related costs.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Register ACTRN12605000475640</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

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Constructing accessible CBA: minor works or major renovations?

Constructing accessible CBA: minor works or major renovations

Patient and public involvement to support liver disease research

Patient and public involvement (PPI) has become increasingly important to ensure the needs of patients are fully considered when they participate in clinical trials. Most funders now require a plan for PPI in grant applications. When fully embraced and correctly implemented, PPI adds an important dimension to clinical trials, and its continuing development is critical if we are to maintain the public's support for clinical research. The development of a PPI panel for the National Institute for Health Research Birmingham Liver Biomedical Research Unit (NIHR BRU) has helped to: promote research locally and nationally; improve recruitment to and participation in trials; promote public engagement and education activities; and improve the quality and relevance of consent forms and information sheets for participants. The NIHR BRU has the support of a PPI panel which constantly champions the research being undertaken to the wider community. This paper describes how the panel was established and why it is so effective. </jats:p