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

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

Evaluation of fraternal versus identical twin approaches for observation impact assessments: An EnKF-based ocean assimilation application for the Gulf of Mexico

Abstract. Assessments of ocean data assimilation (DA) systems and observing system design experiments typically rely on identical or fraternal twin experiments. The identical twin approach has been recognized as yielding biased impact assessments in atmospheric predictions but these shortcomings are not sufficiently appreciated for oceanic DA applications. Here we present the first direct comparison of the fraternal and identical twin approach in an ocean DA application. We assess the assimilation impact for both approaches in a DA system for the Gulf of Mexico that uses the Ensemble Kalman Filter. Our comparisons show that, despite a reasonable error growth rate in both approaches, the identical twin produces a biased skill assessment overestimating the improvement from assimilating sea surface height and sea surface temperature observations while underestimating the value of assimilating temperature and salinity profiles. Such biases can lead to an undervaluation of some observing assets (in this case profilers) and thus misguided distribution of observing system investments

SEA-COOS: A Model for a Multi-State, Multi-Institutional Regional Observation System

The SouthEast Atlantic Coastal Ocean Observing System (SEA-COOS, www.seacoos.org) is a regional partnership that has initiated an integrated coastal ocean observing system for a four-state (North Carolina, South Carolina, Georgia, and Florida) region of the southeast coastal United States. The long-term intent of SEA-COOS is to establish a regional coastal ocean observing system that will be part of the coastal component of the national Integrated Ocean Observing System (IOOS) envisioned by Ocean.US. SEA-COOS was initiated in September, 2002 with funding from the Office of Naval Research (ONR) as a coordinating and enhancing effort between several existing subregional-scale efforts in the southeast, the Sea Grant Offices from the four states, and a number of federal agencies. This article briefly describes the essential elements of an observing system, the region-wide observations, overlapping circulation models, data management capabilities, and outreach and education activities of SEA-COOS, at present and planned for the coming year. Development of a governance system has also been pursued, and an initial structure is in place for SEA-COOS

Recent advancements in aircraft and in situ observations of tropical cyclones

Observations of tropical cyclones (TC) from aircraft and in situ platforms provide critical and unique information for analyzing and forecasting TC intensity, structure, track, and their associated hazards. This report, prepared for the tenth International Workshop on Tropical Cyclones (IWTC-10), discusses the data collected around the world in TCs over the past four years since the IWTC-9, improvements to observing techniques, new instruments designed to achieve sustained and targeted atmospheric and oceanic observations, and select research results related to these observations.In the Atlantic and Eastern and Central Pacific basins, changes to operational aircraft reconnaissance are discussed along with several of the research field campaigns that have taken place recently. The changes in the use and impact of these aircraft observations in numerical weather prediction models are also provided along with updates on some of the experimental aircraft instrumentation. Highlights from three field campaigns in the Western Pacific basin are also discussed. Examples of in-situ data collected within recent TCs such as Hurricane Ian (2022), also demonstrate that new, emerging technologies and observation strategies reviewed in this report, definitely have the potential to further improve ocean-atmosphere coupled intensity forecasts

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc