Search

Background: Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19., Methods: This pragmatic, multicentre, open-label, randomised, controlled, platform trial was conducted across 63 sites in the USA, Spain, Brazil, Italy, and Mexico. Patients aged at least 18 years hospitalised for COVID-19 (moderate or severe illness) were randomly assigned (1:1), via an interactive voice system or web-response system, to receive locally available SGLT2 inhibitor (administered orally, once daily) plus standard-of-care or standard-of-care for 30 days. The primary outcome was organ support-free days evaluated through 21 days, assessed using intention-to-treat approach. This trial is registered on ClinicalTrials.gov, NCT04505774., Findings: The first patient was randomly assigned to the SGLT2 inhibitor domain on Dec 3, 2021. On March 31, 2023, at the recommendation of the data and safety monitoring board, enrolment in the SGLT2 inhibitor domain for both moderately and severely ill hospitalised patients was stopped prematurely for futility due to a low likelihood of finding a treatment benefit. The final randomised population consisted of 575 patients (mean age 72 years [SD 13], 242 (42%) female and 154 (27%) Hispanic; 504 in the moderate illness group and 71 in the severe illness group). 573 patients had a known 21-day outcome; 215 (75%) of 285 patients in the SGLT2 inhibitor plus standard-of-care group did not require respiratory or cardiovascular organ support versus 231 (80%) of 288 patients in the standard-of-care group. The adjusted odds ratio (OR) for an SGLT2 inhibitor effect on organ support-free days was 0·74 (95% Credible Interval [CrI] 0·48-1·13; where OR higher than 1 indicated treatment benefit, yielding a posterior probability of futility P(OR <1·2) of 99% and a posterior probability of inferiority P(OR<1·0) of 91%). There were 37 deaths (13%) in the SGLT2 inhibitor plus standard-of-care group and 42 deaths (15%) in the standard-of-care group at 90 days (hazard ratio 0·91 [95% CrI 0·58-1·43], probability of hazard ratio <1 of 66%). No safety concerns were observed with SGLT2 inhibitors, including no cases of ketoacidosis., Interpretation: SGLT2 inhibitors did not significantly increase days free of organ support or reduce mortality in patients hospitalised with COVID-19. SGLT2 inhibitors were well tolerated with no observed safety concerns. Overall, these findings do not support the use of SGLT2 inhibitors as standard care in patients hospitalised with COVID-19., Funding: National Institutes of Health., Competing Interests: Declaration of interests MNK has received research grant support from University of Pittsburgh, AstraZeneca, Boehringer Ingelheim, and Pfizer; has served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Regeneron, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received other research support from AstraZeneca and Vifor Pharma; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. He holds stock options from Artera Health and Saghmos Therapeutics. OV has received institutional research support from AstraZeneca, Bayer, and Cardurion, and has served as a consultant or advisory board member for AstraZeneca, Cardior, Cytokinetics, and Sanofi. JSB reports research grants from National Institutes of Health and American Heart Association and has consulted for Janssen. HRR reports receiving grants from the National Heart, Lung, and Blood Institute during the conduct of the study, as well as nonfinancial support from Abbott Vascular, SHL Telemedicine, Siemens, and Phillips outside the submitted work. ADA is an employee of Medtronic. SDS has received research grants from Alexion, Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI, and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boeringer-Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. ASB has received research grant support to his institution from National Institutes of Health/National Heart, Lung, and Blood Institute, National Institutes of Health/National Institute on Aging, American College of Cardiology Foundation, and the Centers for Disease Control and Prevention. AP reports a research grant from the German Research Foundation. MNG reports receiving grants from National Institutes of Health, Agency for Healthcare Research and Quality, and the US Centers for Disease Control and Prevention and receiving personal fees from Regeneron for serving on the data safety monitoring board for monoclonal antibody trials in COVID-19. LZK reports receiving personal fees from Cerus Corp, University of Maryland, Coagulant Therapeutics, Haemonetics, and Gamma Diagnostics. PK receives grant funding as a principal investigator from NIH and Cerenovus; consulting fees as a scientific advisor to Basking Biosciences, Bayer, Lumosa, and Shionogi; and royalties for online publication from UpToDate. KSK reports grants from National Institutes of Health during the conduct of the study, funding from Eisai outside the submitted work, and personal fees from National Institutes of Health for committee service indirectly related to the research. LBK reports that her institution received funding from National Institutes of Health to perform the study. AJ reports receiving funding from AstraZeneca to study mechanisms of action of dapagliflozin. LW reports funding from the National Institutes of Health for ACTIV-4A and ACTIV-4C. JLSM reports receiving honoraria from Roche la Hoffman and Novartis. MQH reports receiving research funding from National Institutes of Health and NIAID. JLS reports research grants or contracts from Amgen, BMS, GSK, Medtronic, Pfizer, Sanofi-Aventis; funding for educational activities or lectures from Pfizer, BMS, Novo Nordisk, AstraZeneca, and funding for consulting from Bayer, Boehringer Ingelheim, BMS, Novo Nordisk, and AstraZeneca. RDL has received grants from Amgen, BMS, and GSK; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, and NovoNordisk; and Honoraria from AstraZeneca, Daiichi Sankyo, NovoNordisk and Pfizer. JLC reports direct support for this project from National Institutes of Health/National Heart, Lung, and Blood Institute; grants from National Institutes of Health/National Heart, Lung, and Blood Institute, National Institutes of Health/NIAID, the Department of Defense, the Department of Veterans Affairs, and the COPD Foundation, outside of this project; and support paid to his institution outside this project from CDL Behring, LLC, AstraZeneca, and Novartis, GBMH. B-AK (through SOCAR Research) received grants from National Institutes of Health. MWG reports funding in part by the National Institutes of Health Agreement 1OT2HL156812 through the National Heart, Lung, and Blood Institute CONNECTS programme. MDN serves as chief medical officer for Haima Therapeutics and has received grants from the National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Department of Defense, Haemonetics, and Instrumentation Laboratories. He has received personal fees from Haemonetics, Takeda, CSL Behring, and Janssen Pharmaceuticals. JSH is the study chair for ACTIV-4a under a National Heart, Lung, and Blood Institute–University of Pittsburgh grant subaward. SLW, SB, JFL, ESL, ALK, MC, CC, and AA declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research., (© 2023. The Author(s).)

Background: Open-label platform trials and a prospective meta-analysis suggest efficacy of anti-interleukin (IL)-6R therapies in hospitalized patients with coronavirus disease 2019 (COVID-19) receiving corticosteroids. This study evaluated the efficacy and safety of sarilumab, an anti-IL-6R monoclonal antibody, in the treatment of hospitalized patients with COVID-19., Methods: In this adaptive, phase 2/3, randomized, double-blind, placebo-controlled trial, adults hospitalized with COVID-19 received intravenous sarilumab 400 mg or placebo. The phase 3 primary analysis population included patients with critical COVID-19 receiving mechanical ventilation (MV). The primary outcome was proportion of patients with ≥1-point improvement in clinical status from baseline to day 22., Results: There were 457 and 1365 patients randomized and treated in phases 2 and 3, respectively. In phase 3, patients with critical COVID-19 receiving MV (n = 298; 28.2% on corticosteroids), the proportion with ≥1-point improvement in clinical status (alive, not receiving MV) at day 22 was 43.2% for sarilumab and 35.5% for placebo (risk difference, +7.5%; 95% confidence interval [CI], -7.4 to 21.3; P =.3261), a relative risk improvement of 21.7%. In post hoc analyses pooling phase 2 and 3 critical patients receiving MV, the hazard ratio for death for sarilumab vs placebo was 0.76 (95% CI, .51 to 1.13) overall and 0.49 (95% CI, .25 to .94) in patients receiving corticosteroids at baseline., Conclusions: This study did not establish the efficacy of sarilumab in hospitalized patients with severe/critical COVID-19. Post hoc analyses were consistent with other studies that found a benefit of sarilumab in patients receiving corticosteroids., Clinical Trials Registration: NCT04315298., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Unique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting., Competing Interests: Declaration of interests SMB reports personal fees from Hamilton for chairing a data safety and monitoring board (DSMB). EG reports grants and research contracts from Philips and Radiometer, consulting fees from Baxter, and speaker's fees from Edwards. MNG reports fees from Regeneron for DSMB participation; she has received support to attend board meetings for the American Thoracic Society. MOH reports fees from Elsevier for statistical peer review, from Berkeley Research Group, Pura Vida Investments, and Guidepoint Advisers for statistical consulting, and from the American Thoracic Society for contributions as a statistical editor of the Annals of the American Thoracic Society. SJ reports fees from Drager, Fisher-Paykel, Baxter, Medtronic, and Fresenius-Xenios for lectures and training courses for physicians and nurses. JCM reports consulting fees from Gilead, and travel support from the Bill and Melinda Gates Foundation. MAM reports research funding from Roche-Genentec; he has received fees from Novartis, Johnson & Johnson, and Citius for DSMB participation. TWR reports personal fees from Sanofi for DSMB participation, and consulting fees and stock options from Cumberland Pharmaceuticals for contributions on a consultancy basis as Director of Medical Affairs. LBW has received research contracts from Boehringer Ingelheim, Genentech, and CSL Behring; she reports consulting fees from Boehringer Ingelheim, Merck, Quark, Citius, and Foresee; she has served on a data monitoring committee for the SIGNET trial and on DSMBs for the INVENT COVID and CounterCovid trials. WHS has received research funding from Endpoint Health and Merck; he reports personal consulting fees from Aerpio Pharmaceuticals, Merck, and Baxter; he has received personal fees for DSMB participation from BioAegis. SPC reports consulting fees from Vir Biotechnology. The other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The first Covid-19 patient was admitted to Montefiore Medical Center (MMC) on March 10, 2020. Soon thereafter there was a rapid and exponential surge of Covid-19 admissions to MMC that could have resulted in catastrophic consequences if MMC had been overwhelmed, as happened in Europe. To adjust to this crisis our institution, under the inspiring leadership of Dr. Philip Ozuah, President and CEO of Montefiore Medicine, adopted an "all hands on deck" approach, mobilizing our entire workforce to expand our units to accommodate the growing number of patients being admitted. Given that the internal medicine (IM) and ICU units are part of the department of medicine (DOM), the DOM was at the center of this mobilization. The DOM is the largest department at MMC and mobilizing it required careful planning, seamless teamwork, and strong leadership. To achieve that goal, we applied a framework that we designate the " 3C framework ," denoting C oordination, C ommunication, and C ollaboration. In this report we describe the many initiatives the Montefiore Einstein DOM implemented during the Covid-19 pandemic using the 3C framework. These included establishing the Medicine Covid-19 Taskforce to lead our efforts, starting a daily newsletter for up-to-date communications, rapidly expanding the ICU and IM units, converting most specialty inpatient consults to eConsults, coordinating research studies, and more. The goal of this report is to serve as a guide on how the 3C framework helped us organize, mobilize, and energize the department of medicine effectively and efficiently during this unprecedented crisis., Competing Interests: YT was previously (1/2015 – 6/2017) the PI on a basic research project jointly funded by the Juvenile Diabetes Research Foundation and Pfizer that is unrelated to the current manuscript. YT has two patent applications. (PCT/US2016/067775 & US provisional No: 61/883,062) that are not related to the current manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tomer, Ng Gong, Keller, Southern, Kitsis, Kajita, Shapiro, Jariwala and Epstein.)

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU., Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility., Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning., Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available., Competing Interests: Dr. Evans has disclosed that she is a PI on a multi-center observational cohort study of hospitalized patients with severe acute respiratory infection, funded by the CDC Foundation. Drs. Prescott, Chertow, and Mammen disclosed government work. Dr. Fan received funding from Lung Technologies, MC3 Cardiopulmonary, and Fresenius Medical Care. Dr. Derde’s institution received funding from ZonMw (Den Haag, Europe) grant number 10150062010003, the Canadian Institutes of Health Research (CIHR), and from Rapid European COVID-19 Emergency Research response (RECOVER) (Europe, H2020) grant agreement No 101003589, and her institution has agreements with Faron (interferon), SOBI (anakinra), and Abbvie (lopinavir/r) to supply drugs for the above-funded studies. Dr. Du’s institution received funding from the Ministry of Science and Technology for a COVID-19–related study (NCT04244591). Dr. Crowther received funding from Servier Canada, Asahi Kasei, Precision Biologicals, Hemostasis Reference Laboratory, Pfizer, CSL Behring, Diagnostica Stago, and he disclosed that he undertakes significant amounts of both medical malpractice and product work in the general areas of hematology and thromboembolism. Dr. Belley-Cote received funding from CIHR, Roche, and Bayer as a principal investigator for the ACT trial that evaluates hydroxychloroquine, interferon beta, colchicine, aspirin, and rivaroxaban in patients with COVID-19. Dr. Zarychanski received operating grants from CIHR, LifeArc Foundation, Thistledown Foundation, and Research Manitoba for grants related to anticoagulation in COVID-19. Dr. McGreer’s institution received funding from Appili Therapeutics. Dr. Hayden disclosed he is a nonpaid consultant for multiple companies involved in developing COVID-19 countermeasures (Arcturus, Cidara, Gilead, GSK, resTORbio, Regeneron, SAB Biotherapeutics, Takeda, Vir), and he is a DSMB member for CytoDyn. Dr. Martin received funding from serving on a clinical trial data monitoring board. Dr. Antonelli received funding from consulting for Intersurgical and ESTOR. Dr. Waleed Alhazzani is the principal investigator on awake proning trial in COVID-19 COVI-PRONE. Dr. Yaseen Arabi is the principal investigator on a clinical trial for lopinavir/ritonavir and interferon in Middle East respiratory syndrome (MERS) and he was a nonpaid consultant on antiviral active for MERS-coronavirus (CoV) for Gilead Sciences and SAB Biotherapeutics. He is an investigator on REMAP-CAP trial and is a Board Members of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). He is a co-investigator on the REMAP-CAP trial and on an awake proning trial in COVID-19 (COVI-PRONE). Dr. Maurizio Cecconi declared consultancy work with Edwards Lifesciences, Directed Systems, and Cheetah Medical: Dr. Lennie Derde is an investigator on REMAP-CAP trial, the NVIC (Dutch National ICU society) chair of Taskforce Infectious Diseases (standing committee), member of ESICM Coronavirus Taskforce (started with this outbreak), and chair of the ESICM Clinical Training Committee; all are unpaid positions. Dr. Laura Evans is the team leader for the critical care section of the NIH COVID-19 management guideline. Dr. Eddy Fan declared receiving consultancy fees from ALung Technologies and MC3 Cardiopulmonary. Dr. Frederick Hayden is a noncompensated consultant to Gilead Sciences, Regeneron, Cidara, Fujifilm, Ridgeback, Merck, Roche/Genentech, GSK, Vir, resTORbio, and SAB Biotherapeutics, and he is a DSMB member for CytoDyn therapeutic clinical trial: Dr. Manoj J. Mammen is an investigator for the U.S. NIH PASSive Immunity Trial for Our Nation (PassItOn) trial: Dr. Greg Martin is a member of the NIH COVID-19 treatment guidelines, principal investigator for COVID-19 diagnostic testing (U.S. NIH RADx program) and has served as a research consultant to Genentech, Grifols, Regeneron and Siemens. Dr. Massimo Antonelli declared consultancy with Toray/Estor and Fisher and Pykel and research grant from GE. Dr. Flavia Machado is member of the executive committee for the CODEX study. Dr. Sheila Nainan Myatra is on the steering committee of the COVID Steroid 2 Trial (ClinicalTrials.gov Identifier: NCT04509973) and the HydrOxychloroquine Prophylaxis Evaluation (HOPE) Trial (CTRI registration No.CTRI/2020/05/025067). Dr Naomi Hammond is on the steering committee of the COVID Steroid 2 Trial (ClinicalTrials.gov Identifier: NCT04509973) and the HydrOxychloroquine Prophylaxis Evaluation (HOPE) Trial (CTRI registration No.CTRI/2020/05/025067). Dr. Emilie Belley-Cote reports grants from Bayer, grants from Roche outside the submitted work. She is a principal investigator for the ACT trial: The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed., Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19., Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients., Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237)., Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality., Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09])., Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults., Trial Registration: ClinicalTrials.gov: NCT04332991.

Background: The recent pandemic highlights the essential nature of optimizing the use of invasive mechanical ventilation (IMV) in complex critical care settings. This review of reviews maps evidence-based practices (EBPs) that are associated with better outcomes among adult patients with acute respiratory failure or ARDS on the continuum of care, from intubation to liberation., Research Question: What EPBs are recommended to reduce the duration of IMV and mortality rate among patients with acute respiratory failure/ARDS?, Study Design and Methods: We identified an initial set of reports that links EBPs to mortality rates and/or duration of IMV. We conducted a review of reviews, focusing on preappraised guidelines, meta-analyses, and systematic reviews. We searched Scopus, CINAHL, and PubMed from January 2016 to January 2019 for additional evidence that has not yet been incorporated into current guidelines., Results: Our initial search produced 61 publications that contained 42 EBPs. We excluded 42 manuscripts during the data extraction process, primarily because they were not associated with improved patient outcomes. The remaining 19 preappraised guidelines, meta-analyses, and systematic reviews met our full inclusion criteria and spanned the continuum of IMV care from intubation to liberation. These contained 20 EBPs, a majority of which were supported with moderate levels of evidence. Of these, six EBPs focused on intubation and escalation of care, such as ventilator management and synchrony; ten EBPs reduced complications associated with IMV, which included spontaneous awakening and breathing trials and early mobility protocols; and four EBPs promoted timely extubation and postextubation recovery., Interpretation: This review describes EBPs that are associated with fewer ventilator days and/or lower mortality rates among patients who received IMV for acute respiratory failure/ARDS. Many of these EBPs are connected across the care continuum, which indicates the need to promote and assess effective implementation jointly, rather than individually., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The preponderance of studies on frailty assessment in critically ill adults have used the Clinical Frailty Scale (CFS) to quantify frailty and previous research suggests that surrogates were more likely to be optimistic than physicians in their CFS scores. Whether discordance between surrogates and physicians was relevant to prognosis has been underexplored. Therefore, in a prospective observational cohort of 298 critically ill older adults, we aimed 1) to describe factors related to discordance and 2) to estimate the relationship between such discordance and hospital mortality and other short-term outcomes. Discordance between surrogates and physician was present in 89/298 (29.9%) and independently associated with a higher risk of hospital mortality. Discordance was not associated with markers of intensity of treatment such as intubation, blood transfusion, incident dialysis for acute renal failure and prolonged hospital length of stay. Understanding factors relevant to discordance between physicians and surrogates may lend further insights into short-term prognosis for older adults with critical illness., Competing Interests: None declared by authors