You measure what you value: how a Middle Eastern Polytechnic developed a sustainable review and improvement framework

Bahrain Polytechnic (BP) was established in 2008 to fill a gap in the Kingdom’s labour market for work ready graduates. Around that time newspaper reports highlighted a lack of quality and consistency in some private universities in Bahrain. Bahrain’s Qualifications and Quality Assurance Authority was in development so, in the absence of national guidelines, BP developed its own Quality Assurance Model to gain stakeholder confidence in the quality of its education. This comprised a Quality Management System with policies and procedures, and a self-review loop. The government was quick to redress quality concerns threatening the reputation of Higher Education in the Kingdom and today there are many external auditing agencies, each with their own paradigms and criteria. However, evidence that accountability audits produce quality improvement where it matters most - in the classroom - is lacking. An essential element in this failure is the dissolution of trust. This case-study tells of BP’s journey towards a more efficient and effective Self-Review model that shifts the focus from accountability and control to improvement and sustainability by taking into account Bahrain’s cultural context and the Polytechnic’s unique curricula and building on existing relationships to engender trust and commitment

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

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

Tenecteplase-tissue-type plasminogen activator evaluation for minor ischemic stroke with proven occlusion

Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK-tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. TNK-Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK-tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ≤5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0-1). Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01-20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0-1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0-1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09-2.5; P=0.026). Administration of TNK-tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. http://www.clinicaltrials.gov. Unique identifier: NCT01654445

Building communities of educational enquiry

This article aims to outline key factors to be considered in the development of communities of enquiry in an educational context and to establish a conceptual and theoretical framework within which much needed empirical work can be carried out. The literature surveyed considers both different types of community and different theoretical positions on how communities develop. Seven factors emerge. 1) A community depends on its members' opportunities to engage in dialogue and other modes of participation. 2) Participation in a community is sustained through the quality of relationships. 3) Perspectives and assumptions underpin the relationships of a community and may offer insights into the dynamics and operation of the community. 4) How a community operates is governed by its structure and context, including the extent to which its structure is imposed or constrained either internally or externally. 5) As a community develops, a climate for its operation also emerges - involving aspects such as tone, environment and potential conflict. 6) The purpose of an enquiry will influence this climate and there may be a need to accommodate or harmonise a multiplicity of purposes arising from the complex interrelationships, perspectives and assumptions involved. 7) A key issue for all communities is control, in relation to who has access to the community, to resources, constraints and power within it. The authors conclude by highlighting a number of tensions or dualities arising from these themes and potential implications for empirical investigations in this field and for those who may seek to build a community of educational enquiry

Randomized assessment of rapid endovascular treatment of ischemic stroke.

BACKGROUND: Among patients with a proximal vessel occlusion in the anterior circulation, 60 to 80% of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment. We evaluated rapid endovascular treatment in addition to standard care in patients with acute ischemic stroke with a small infarct core, a proximal intracranial arterial occlusion, and moderate-to-good collateral circulation. METHODS: We randomly assigned participants to receive standard care (control group) or standard care plus endovascular treatment with the use of available thrombectomy devices (intervention group). Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset. Patients with a large infarct core or poor collateral circulation on computed tomography (CT) and CT angiography were excluded. Workflow times were measured against predetermined targets. The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care (shift analysis). RESULTS: The trial was stopped early because of efficacy. At 22 centers worldwide, 316 participants were enrolled, of whom 238 received intravenous alteplase (120 in the intervention group and 118 in the control group). In the intervention group, the median time from study CT of the head to first reperfusion was 84 minutes. The rate of functional independence (90-day modified Rankin score of 0 to 2) was increased with the intervention (53.0%, vs. 29.3% in the control group; P CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality. (Funded by Covidien and others; ESCAPE ClinicalTrials.gov number, NCT01778335.)