Steroid therapy and outcome of parapneumonic pleural effusions (STOPPE): Study protocol for a multicenter, double-blinded, placebo-controlled randomized clinical trial

BACKGROUND: Community-acquired pneumonia (CAP) is a major global disease. Parapneumonic effusions often complicate CAP and range from uninfected (simple) to infected (complicated) parapneumonic effusions and empyema (pus). CAP patients who have a pleural effusion at presentation are more likely to require hospitalization, have a longer length of stay and higher mortality than those without an effusion. Conventional management of pleural infection, with antibiotics and chest tube drainage, fails in about 30% of cases. Several randomized controlled trials (RCT) have evaluated the use of corticosteroids in CAP and demonstrated some potential benefits. Importantly, steroid use in pneumonia has an acceptable safety profile with no adverse impact on mortality. A RCT focused on pediatric patients with pneumonia and a parapneumonic effusion demonstrated shorter time to recovery. The effects of corticosteroid use on clinical outcomes in adults with parapneumonic effusions have not been tested. We hypothesize that parapneumonic effusions develop from an exaggerated pleural inflammatory response. Treatment with systemic steroids may dampen the inflammation and lead to improved clinical outcomes. The steroid therapy and outcome of parapneumonic pleural effusions (STOPPE) trial will assess the efficacy and safety of systemic corticosteroid as an adjunct therapy in adult patients with CAP and pleural effusions. METHODS: STOPPE is a pilot multicenter, double-blinded, placebo-controlled RCT that will randomize 80 patients with parapneumonic effusions (2:1) to intravenous dexamethasone or placebo, administered twice daily for 48 hours. This exploratory study will capture a wide range of clinically relevant endpoints which have been used in clinical trials of pneumonia and/or pleural infection; including, but not limited to: time to clinical stability, inflammatory markers, quality of life, length of hospital stay, proportion of patients requiring escalation of care (thoracostomy or thoracoscopy), and mortality. Safety will be assessed by monitoring for the incidence of adverse events during the study. DISCUSSION: STOPPE is the first trial to assess the efficacy and safety profile of systemic corticosteroids in adults with CAP and pleural effusions. This will inform future studies on feasibility and appropriate trial endpoints. TRIAL REGISTRATION: ACTRN1261800094720

Information transfer: what do decision makers want and need from researchers?

<p>Abstract</p> <p>Purpose</p> <p>The purpose of this study was to undertake a systematic assessment of the need for research-based information by decision-makers working in community-based organizations. It is part of a more comprehensive knowledge transfer and exchange strategy that seeks to understand both the content required and the format/methods by which such information should be presented.</p> <p>Methods</p> <p>This was a cross-sectional telephone survey. Questions covered current practices, research use, and demographic information, as well as preferences for receiving research information. Three types of organizations participated: Children's Treatment Centres of Ontario (CTCs); Ontario Community Care Access Centres (CCACs); and District Health Councils (DHCs). The analysis used descriptive statistics and analyses of variance (ANOVA) to describe and explore variations across organizations.</p> <p>Results</p> <p>The participation rate was 70%. The highest perception of barriers to the use of research information was reported by the CCAC respondents, followed by CTCs and DHCs. The CTCs and DHCs reported greater use of research evidence in planning decisions as compared to the CCACs. Four sources of information transfer were consistently identified. These were websites, health-related research journals, electronic mail, and conferences and workshops. Preferred formats for receiving information were executive summaries, abstracts, and original articles.</p> <p>Conclusion</p> <p>There were a number of similarities across organization type with respect to perceived barriers to research transfer, as well as the types of activities the organizations engaged in to promote research use in decision-making. These findings support the importance of developing interactive, collaborative knowledge transfer strategies, as well as the need to foster relationships with health care decision-makers, practitioners and policymakers.</p

Individual differences in eyewitness accuracy across multiple lineups of faces

Theories of face recognition in cognitive psychology stipulate that the hallmark of accurate identification is the ability to recognize a person consistently, across different encounters. In this study, we apply this reasoning to eyewitness identification by assessing the recognition of the same target person repeatedly, over six successive lineups. Such repeat identifications are challenging and can be performed only by a proportion of individuals, both when a target exhibits limited and more substantial variability in appearance across lineups (Experiments 1 and 2). The ability to do so correlates with individual differences in identification accuracy on two established tests of unfamiliar face recognition (Experiment 3). This indicates that most observers have limited facial representations of target persons in eyewitness scenarios, which do not allow for robust identification in most individuals, partly due to limitations in their ability to recognize unfamiliar faces. In turn, these findings suggest that consistency of responses across multiple lineups of faces could be applied to assess which individuals are accurate eyewitnesses

Feature instructions improve face-matching accuracy

Identity comparisons of photographs of unfamiliar faces are prone to error but important for applied settings, such as person identification at passport control. Finding techniques to improve face-matching accuracy is therefore an important contemporary research topic. This study investigated whether matching accuracy can be improved by instruction to attend to specific facial features. Experiment 1 showed that instruction to attend to the eyebrows enhanced matching accuracy for optimized same-day same-race face pairs but not for other-race faces. By contrast, accuracy was unaffected by instruction to attend to the eyes, and declined with instruction to attend to ears. Experiment 2 replicated the eyebrow-instruc- tion improvement with a different set of same-race faces, comprising both optimized same- day and more challenging different-day face pairs. These findings suggest that instruction to attend to specific features can enhance face-matching accuracy, but feature selection is cru- cial and generalization across face sets may be limited

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