Banner‐Goodspeed, Valerie

Objectives To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). Design Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. Hypothesis We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. Setting Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. Patients Previously independently living adult ICU survivors of COVID-19. Interventions None. Measurements and Main Results The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). Conclusions More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

AbstractIntroductionCoronavirus disease 2019 (COVID‐19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID‐19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID‐19 as well as describe the differences in outcomes between patients with and without pre‐existing hypothyroidism using an observational, multinational registry.MethodsIn an observational cohort study we enrolled patients 18 years or older, with laboratory‐confirmed severe acute respiratory syndrome coronavirus‐2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID‐19 hospitalization, (2) in‐hospital mortality and (3) hospital‐free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality.ResultsAmong the 20,366 adult patients included in the study, pre‐existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59–80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre‐existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in‐hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital‐free days (estimated difference 0.01 days; 95% CI: −0.45, 0.47; p = .97). Pre‐existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis.ConclusionsIn an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID‐19. Pre‐existing hypothyroidism in hospitalized patients with COVID‐19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID‐19 on the thyroid gland and its function is needed in the future.

IMPORTANCE: At the start of the coronavirus disease 2019 pandemic, medications repurposed for management of coronavirus disease 2019 were used in the absence of clinical trial evidence. OBJECTIVES: To describe the variation and evolution in use of repurposed medications for coronavirus disease 2019. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study of adults hospitalized with coronavirus disease 2019 between February 15, 2020, and April 12, 2021, across 76 United States and international hospitals within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness Universal Study coronavirus disease 2019 registry. MAIN OUTCOMES AND MEASURES: Hospital variation was quantified using multivariable adjusted random effects logistic regression models and unsupervised clustering. Repurposed medications included antivirals, corticosteroids, hydroxychloroquine, immunomodulators, and therapeutic dose anticoagulants. RESULTS: Among 7,069 adults hospitalized with coronavirus disease 2019, 1,979 (28%) received antivirals, 2,876 (41%) received corticosteroids, 1,779 (25%) received hydroxychloroquine, 620 (9%) received immunomodulators, and 2,154 (31%) received therapeutic dose anticoagulants. Contribution of hospital site to risk-adjusted variation was 46% for antivirals, 30% for corticosteroids, 48% for hydroxychloroquine, 46% for immunomodulators, and 52% for therapeutic dose anticoagulants. Compared with the early pandemic, the later pandemic practice phenotypes converged with increased use of antivirals (odds ratio, 3.14; 95% CI, 2.40–4.10) and corticosteroids (odds ratio, 5.43; 95% CI, 4.23–6.97), with decreased use of hydroxychloroquine (odds ratio, 0.02; 95% CI, 0.01–0.04) and immunomodulators (odds ratio, 0.49; 95% CI, 0.34–0.70). There was no clinically significant change in the use of therapeutic dose anticoagulants (odds ratio, 1.01; 95% CI, 1.01–1.02). There were no differences in risk-adjusted mortality between hospitals with high rates of repurposed medication use compared with hospitals with low rates of use. CONCLUSIONS AND RELEVANCE: Hospital variation in the use of repurposed medications varied widely across hospitals early in the pandemic and later converged with the emergence of randomized clinical trials. Platforms developed for rapid activation and enrollment in clinical trials of repurposed medications are needed prior to the next pandemic to expedite effective, evidence-based practice.

Abstract Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID‐19) patient outcomes from the international VIRUS registry ( https://clinicaltrials.gov/ct2/show/NCT04323787 ). We find that COVID‐19 patients administered unfractionated heparin but not enoxaparin have a higher mortality‐rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e−52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e−8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e−5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow‐up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID‐19 patients.

OBJECTIVES: To describe the outcomes of hospitalized patients in a multicenter, international coronavirus disease 2019 registry. DESIGN: Cross-sectional observational study including coronavirus disease 2019 patients hospitalized with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between February 15, 2020, and November 30, 2020, according to age and type of organ support therapies. SETTING: About 168 hospitals in 16 countries within the Society of Critical Care Medicine’s Discovery Viral Infection and Respiratory Illness University Study coronavirus disease 2019 registry. PATIENTS: Adult hospitalized coronavirus disease 2019 patients who did and did not require various types and combinations of organ support (mechanical ventilation, renal replacement therapy, vasopressors, and extracorporeal membrane oxygenation). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was hospital mortality. Secondary outcomes were discharge home with or without assistance and hospital length of stay. Risk-adjusted variation in hospital mortality for patients receiving invasive mechanical ventilation was assessed by using multilevel models with hospitals as a random effect, adjusted for age, race/ethnicity, sex, and comorbidities. Among 20,608 patients with coronavirus disease 2019, the mean (± sd ) age was 60.5 (±17), 11,1887 (54.3%) were men, 8,745 (42.4%) were admitted to the ICU, and 3,906 (19%) died in the hospital. Hospital mortality was 8.2% for patients receiving no organ support ( n = 15,001). The most common organ support therapy was invasive mechanical ventilation ( n = 5,005; 24.3%), with a hospital mortality of 49.8%. Mortality ranged from 40.8% among patients receiving only invasive mechanical ventilation ( n =1,749) to 71.6% for patients receiving invasive mechanical ventilation, vasoactive drugs, and new renal replacement therapy ( n = 655). Mortality was 39% for patients receiving extracorporeal membrane oxygenation ( n = 389). Rates of discharge home ranged from 73.5% for patients who did not require organ support therapies to 29.8% for patients who only received invasive mechanical ventilation, and 8.8% for invasive mechanical ventilation, vasoactive drugs, and renal replacement; 10.8% of patients older than 74 years who received invasive mechanical ventilation were discharged home. Median hospital length of stay for patients on mechanical ventilation was 17.1 days (9.7-28 d). Adjusted interhospital variation in mortality among patients receiving invasive mechanical ventilation was large (median odds ratio 1.69). CONCLUSIONS: Coronavirus disease 2019 prognosis varies by age and level of organ support. Interhospital variation in mortality of mechanically ventilated patients was not explained by patient characteristics and requires further evaluation.

Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance. Design: Double-blind, randomized clinical trial (ClinicalTrials.gov: NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the F io 2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days. Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group ( p = 0.02) and independent of shock ( p = 0.04). Categorical change in S/F improved ( p = 0.01) but not after adjustment for shock ( p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%). Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.

Introduction Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.