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

'Maenads dancing before the Martyrs' memorial': Oxford women writers and the classical tradition

For prominent Victorian women writers such as Elizabeth Barrett Browning and George Eliot some degree of classical education was closely associated with successful literary ambitions, but the schools and universities where the classics were taught remained closed to them. Women achieved full membership of Oxford university after the First World War, around the same time as the compulsory Greek element of the Oxford degree was abolished. Before this, many women students had to pursue intensive courses of Greek even when their main subject of study was English or history. Aspiring writers such as Vera Brittain and Dorothy L. Sayers rushed through classical texts like theIliad and theAeneid in the original languages, later producing imaginative and often challenging reworkings of classical texts which reflect the experiences of the modern, educated woman. The adaptation of epic themes to modern forms such as the First World War memoir and the detective story is an important similarity in Sayers’ and Brittain’s literary responses to classical literature

A Surfeit of Socks? The Impact of the First World War on Women Correspondents to Daily Newspapers

This article is based on such material and shows how the predominant subject matter for ladies’ letters during the war years was that of voluntary fundraising for the many charities and associations connected with the war. Such charities were often suggested to the women through personal or local ties - family members at the front; local regiments or Scottish connections. As we shall see, these women perceived their war work in localised or provincialised terms, and were led by the local elite, in both the city and the surrounding countryside. Whilst this approach did eventually lead to inequalities in provision for the men at the front, the hospitals and the prisoners of war, this voluntary approach was at first the only one which existed - and such an approach was part of the government’s own approach to the war until late 1915. After this time, and with the growing power of Lloyd George, the government and local authorities began to impose a more centralised and less personalised approach to the voluntary organisations. While this approach was at first resented by many of the charitable ladies affected, as can be seen in their letters to the newspapers, it was necessary in order to provide a more uniform approach to the provision of comforts and necessary medical items to the ever-increasing number of men and women in need