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

Yawning

Gift of Dr. Mary Jane Esplen.B Flat [key]Temp di Valse [tempo]Piano vocal ukulele [instrumentation]Popular song [form/genre]I've suffered alot in my time [first line]Yawning, yawning, I'm always [first line of chorus]Publisher's advertisement on inside front, and back cover [note]Black cover with a big 7 [illustration

Persistent crying in infants and children as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation

Jan Bonhoeffer, Patricia Vermeer, Scott Halperin, Anne Kempe, Stanley Music, Judy Shindman, Wikke Walop, The Brighton Collaboration Persistent Crying Working Grou

Cultural meaning for women composers: Charlotte (“Minna”) Brandes and the Beautiful Dead in the German Enlightenment

This article explores the cultural meanings of female musical authorship in the late German Enlightenment through a case study of Charlotte ("Minna") Brandes, a composer, keyboardist, and opera singer. With Minna's death in 1788 at the age of twenty-three, her father, the playwright Johann Christian Brandes, and her close friend and teacher Johann Friedrich Hönicke prepared two memorials to her memory, a biography and a collection of her music, the latter titled Musikalische Nachlass von Minna Brandes (Hamburg, 1788). These memorials situated her authorship in the contexts of pedagogy and education, the composition of occasional works for the home, and the solace offered by music amidst bereavement and illness. The principal discourse was of death itself. Minna's memorialization shared with the novels of Goethe a topos of the beautiful female dead in which the female corpse (or its representation) was exhibited as a beautiful artifact. Death turned Minna from composer into a passive, aestheticized object of male authorship. These discursive contexts contained Minna's activities as a composer within a framework of bourgeois femininity. Both Minna's father and her teacher were at pains to stress that she sought neither fame nor fortune from her compositions. However, such representations of Minna were misleading. Her collected works suggest she was working toward a published collection of strophic German songs and toward the composition of operatic music for her own performance. The idealizing tropes of the memorials are also challenged by Johann Christian's later memoirs in which his daughter's turn to composition is situated in what he described as her multiple breaches of deferential daughterly conduct. Minna's reported profligacy during her final illness may have stimulated the posthumous publication of her music, which was possibly a form of fund raising for her multiply bereaved father, a corrective to his emotional and financial loss. The healthy list of 518 subscribers indicates that youthful female death was marketable as a topos occasioning the pleasures of melancholy