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

Yaxchilan The Design of a Maya Ceremonial City

A comprehensive catalog and analysis of all the city\u27s extant buildings and sculptures

Yaxchilan The Design of a Maya Ceremonial City

A comprehensive catalog and analysis of all the city\u27s extant buildings and sculptures

Landscape and a Visual Narrative of Creation and Origin at the Olmec Ceremonial Center of La Venta

Includes case studies of specific geographic areas to provide a comprehensive overview of the wider Mesoamerican region. Condenses and explains evidence from found objects, rock carvings, historical accounts, and sacred texts. Interdisciplinary scope relevant to archaeology, anthropology, art history, sociology, landscape and cultural studie

Making “Meaning”: Pre-Columbian Archaeology, Art History, and the Legacy of Terence Grieder

This book examines the scholarly work of Terence Grieder, an early pre-Columbian art historian of wide-ranging interests and often provocative stances. Through a series of topical essays focused a variety of Pre-Columbian art historical topics, former students, professional colleagues, and other intellectual descendants discuss his major ideas through examples drawn from their own work. The work of those he mentored and interacted with is, in the end, the most important testament to his continuing influence in the field. (Note: A web-based version of this book is available at https://uhlibraries.pressbooks.pub/makingmeaningterencegrieder or doi.org/10.52713/VJQB6067.

The p.Arg86Gln change in GARP2 (glutamic acid-rich protein-2) is a common West African-related polymorphism

The aim of the present study is to probe the potential association between previously-reported GARP2 mutations and retinitis pigmentosa (RP) using Scottish RP patients and controls. Exons 4, 5 and 8 in DNA from blood or buccal samples (130 autosomal recessive and simplex RP patients, 31controls) were amplified and analysed for single-strand conformational polymorphism by capillary electrophoresis (CE-SSCP) and confirmed by sequencing. The p.Arg86Gln mutation in exon 4 was found in just one patient (out of 130), and in 10 of the 31 unaffected subjects. All of these occurrences were in people of West African origin (patient and controls). Two polymorphisms in exon 5, p.His100Arg and p.Gly109Gly, and a c.534+20A>G change in the intronic region flanking the 3' end of exon 8 were also found not to be associated with RP. The Scottish population examined here had no mutations in the GARP2 exons surveyed that could be associated with RP. The p.Arg86Gln mutation actually appears to be a polymorphism common in ethnic West Africans and not associated with RP. This change may provide a useful marker for West African ancestry