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

Inferences of Cause-and-Effect from Correlational Data

Color poster with text, graphs, and tables.History is filled with examples of humans' inherent tendency to infer cause-and-effect from a mere association. In the abstract, the implication is that when researchers state that "Variable X" and "Variable Y" are correlated, people may mistakenly infer that "Variable X" causes "Variable Y." This study hypothesized that the conflation of correlation with causation is common and that the order in which variables are presented has an influence on which variable is assumed to be the cause and which the effect; and that the influence of variable order is most robust when correlations are presented both visually and in text.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Building Blocks of Scientific Psychology : Understanding of Probabilistic Trends and Correlation-Versus-Causation

Color poster with text, images, and charts.Two related deficits occur in the design and interpretation of scientific research on human behavior. Understanding the distinction between causal and non-causal associations (and evidence required for each), and understanding the probabilistic nature of associations between variables (i.e., probabilistic reasoning). Training in psychological science, particularly in research methods classes, often centers on addressing these deficits in rational thinking. To determine the magnitude of these deficits, this study investigated the inferences that people draw from causal and non-causal research scenarios.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Causal Inference from Descriptions of Experimental and Non-experimental Research : Public Understanding of Correlation-Versus-Causation

Color poster with text and tables.The distinction between correlation and causation is emphasized in various college courses. However, previous research suggests that college students frequently incorrectly infer cause and effect relationships from correlational data. These incorrect inferences are made more often when the direction of the causal relationship seems intuitive, a bias that may be perpetuated by incorrect media and scholarly representation of correlational findings. The purpose of this study was to investigate the inferences general community members draw from hypothetical descriptions of experimental and non-experimental research on human behavior.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

JROTC, but with Scientists

The Junior Reserve Officer Training Corps (JROTC) attempts to recruit military officers from High Schools by having them interact with military officers. Ed Morrison from Barrow County Schools, and Warren Matthews from Georgia Tech will talk to us about using a Race to the Top Grant to use scientists and engineers to recruit students into the Science Technology Engineering and Mathematics (STEM) fields. The main difference as that this program uses more interactive video conferences with scientists and fewer pushups. Georgia Tech Biomedial Engineering student Katelyn Roberts also explains how this Direct to Discovery program in Barrow county motivated her current educational path

Improving the Approach to Defining, Classifying, Reporting and Monitoring Adverse Events in Seriously Ill Older Adults: Recommendations from a Multi-stakeholder Convening.

BACKGROUND: Clinical trials are needed to study topics relevant to older adults with serious illness. Investigators conducting clinical trials with this population are challenged by how to appropriately define, classify, report, and monitor serious and non-serious adverse events (SAEs/AEs), given that some traditionally reported AEs (pressure ulcers, delirium) and SAEs (death, hospitalization) are common in persons with serious illness, and may be consistent with their goals of care. OBJECTIVES: A multi-stakeholder group convened to establish greater clarity on and new approaches to address this critical issue. PARTICIPANTS: Thirty-two study investigators, members of regulatory and sponsor agencies, and patient stakeholders took part. APPROACH: The group met virtually four times and, using a collaborative approach, conducted a survey, select interviews, and reviewed regulatory guidance to collectively define the problem and identify a new approach. RESULTS: SAE/AE challenges fell into two areas: (1) definitions and classifications, including (a) implausible relationships, (b) misalignment with patient-centered care goals, and (c) well-known associations, and (2) reporting and monitoring, including (a) limited guidance, (b) inconsistent standards across regulators, and (c) Data Safety Monitoring Board (DSMB) member knowledge gaps. Problems largely reflected practice norms rather than regulatory requirements that already support context-specific and aggregate reporting. Approaches can be improved by adopting principles that better align strategies for addressing adverse events with the type of intervention being tested, favoring routine and aggregate over expedited reporting, and prioritizing how SAE/AEs relate to patient-centered care goals. Reporting plans and decisions should follow an algorithm underpinned by these principles. CONCLUSIONS: Adoption of the proposed approach-and supporting it with education and better alignment with regulatory guidance and procedures-could improve the quality and efficiency of clinical trials safety involving older adults with serious illness and other vulnerable populations

Characterization of an L-Ascorbate Catabolic Pathway with Unprecedented Enzymatic Transformations

L-Ascorbate (vitamin C) is ubiquitous in both our diet and the environment. Ralstonia eutropha H16 (Cupriavidus necator ATCC 17699) uses L-ascorbate as sole carbon source but lacks the genes encoding the known catabolic pathways. RNAseq identified eight candidate catabolic genes. Sequence similarity networks and genome neighborhood networks guided predictions for function of the encoded proteins; the predictions were confirmed by in vitro assays and in vivo growth phenotypes of gene deletion mutants. L-Ascorbate, a lactone, is oxidized and ring-opened by enzymes in the cytochrome b561 and gluconolactonase families, respectively, to form 2,3-diketo-L-gulonate. A protein predicted to have a WD40-like fold catalyzes an unprecedented benzilic acid rearrangement involving migration of a carboxylate group to form 2-carboxy-L-lyxonolactone; the lactone is hydrolyzed by a member of the amidohydrolase superfamily to yield 2-carboxy-L-lyxonate. A member of the PdxA family of oxidative decarboxylases catalyzes a novel decarboxylation that uses NAD+ catalytically. The product, L-lyxonate, is catabolized to alpha-ketoglutarate by a previously characterized pathway.</p