Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Message Journal, Issue 5: COVID-19 SPECIAL ISSUE Capturing visual insights, thoughts and reflections on 2020/21 and beyond...

If there is a theme running through the Message Covid-19 special issue, it is one of caring. Of our own and others’ resilience and wellbeing, of friendship and community, of students, practitioners and their futures, of social justice, equality and of doing the right thing. The veins of designing with care run through the edition, wide and deep. It captures, not designers as heroes, but those with humble views, exposing the need to understand a diversity of perspectives when trying to comprehend the complexity that Covid-19 continues to generate. As graphic designers, illustrators and visual communicators, contributors have created, documented, written, visualised, reflected, shared, connected and co-created, designed for good causes and re-defined what it is to be a student, an academic and a designer during the pandemic. This poignant period in time has driven us, through isolation, towards new rules of living, and new ways of working; to see and map the world in a different light. A light that is uncertain, disjointed, and constantly being redefined. This Message issue captures responses from the graphic communication design community in their raw state, to allow contributors to communicate their experiences through both their written and visual voice. Thus, the reader can discern as much from the words as the design and visualisations. Through this issue a substantial number of contributions have focused on personal reflection, isolation, fear, anxiety and wellbeing, as well as reaching out to community, making connections and collaborating. This was not surprising in a world in which connection with others has often been remote, and where ‘normal’ social structures of support and care have been broken down. We also gain insight into those who are using graphic communication design to inspire and capture new ways of teaching and learning, developing themselves as designers, educators, and activists, responding to social justice and to do good; gaining greater insight into society, government actions and conspiracy. Introduction: Victoria Squire - Coping with Covid: Community, connection and collaboration: James Alexander & Carole Evans, Meg Davies, Matthew Frame, Chae Ho Lee, Alma Hoffmann, Holly K. Kaufman-Hill, Joshua Korenblat, Warren Lehrer, Christine Lhowe, Sara Nesteruk, Cat Normoyle & Jessica Teague, Kyuha Shim. - Coping with Covid: Isolation, wellbeing and hope: Sadia Abdisalam, Tom Ayling, Jessica Barness, Megan Culliford, Stephanie Cunningham, Sofija Gvozdeva, Hedzlynn Kamaruzzaman, Merle Karp, Erica V. P. Lewis, Kelly Salchow Macarthur, Steven McCarthy, Shelly Mayers, Elizabeth Shefrin, Angelica Sibrian, David Smart, Ane Thon Knutsen, Isobel Thomas, Darryl Westley. - Coping with Covid: Pedagogy, teaching and learning: Bernard J Canniffe, Subir Dey, Aaron Ganci, Elizabeth Herrmann, John Kilburn, Paul Nini, Emily Osborne, Gianni Sinni & Irene Sgarro, Dave Wood, Helena Gregory, Colin Raeburn & Jackie Malcolm. - Coping with Covid: Social justice, activism and doing good: Class Action Collective, Xinyi Li, Matt Soar, Junie Tang, Lisa Winstanley. - Coping with Covid: Society, control and conspiracy: Diana Bîrhală, Maria Borțoi, Patti Capaldi, Tânia A. Cardoso, Peter Gibbons, Bianca Milea, Rebecca Tegtmeyer, Danne Wo

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

Hollywood goes hypercommercial

This program examines the rise of product placements, tie-ins with fast food chains, and toy merchandising in feature films. Argues that mainstream movies have become vehicles for advertising and marketing various products

The incidence of cardiac arrest in the intensive care unit:A systematic review and meta-analysis

The incidence of cardiac arrest in the intensive care unit (ICU-CA) has not been widely reported. We undertook a systematic review and meta-analysis of studies reporting the incidence of cardiac arrest in adult, general intensive care units. The review was prospectively registered with PROSPERO (CRD42017079717). The search identified 7550 records, which included 20 relevant studies for qualitative analysis and 16 of these were included for quantitative analyses. The reported incidence of ICU-CA was 22.7 per 1000 admissions (95% CI: 17.4–29.6) with survival to hospital discharge of 17% (95% CI: 9.5–28.5%). We estimate that at least 5446 patients in the UK have a cardiac arrest after ICU admission. There are limited data and significant variation in the incidence of ICU-CA and efforts to synthesise these are limited by inconsistent reporting. Further prospective studies with standardised process and incidence measures are required to define this important patient group. </jats:p