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577 results on '"Lamontagne, Francois"'

51. Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study

Author

Heyland, Daren K., Marquis, Francois, Lamontagne, Francois, Albert, Martin, Turgeon, Alexis F., Khwaja, Kosar A., Garland, Allan, Hall, Richard, Chapman, Martin G., Kutsiogannis, Demetrios J., Martin, Claudio, Sessler, Daniel I., and Day, Andrew G.

Published
2020
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52. Factors influencing decisions by critical care physicians to withdraw life-sustaining treatments in critically ill adult patients with severe traumatic brain injury

Author

Turgeon, Alexis F., Dorrance, Kristin, Archambault, Patrick, Lauzier, Francois, Lamontagne, Francois, Zarychanski, Ryan, Fowler, Robert, Moore, Lynne, Lacroix, Jacques, English, Shane, Boutin, Amelie, Muscedere, John, Burns, Karen E.A., Griesdale, Donald, McIntyre, Lauralyn A., Scales, Damon, Bernard, Francis, Yamada, Janet, and Squires, Janet E.

Subjects
Terminal care -- Surveys -- Practice, Physicians -- Surveys -- Practice, Critical care medicine -- Surveys -- Practice, Decision making -- Surveys, Brain injuries -- Surveys -- Care and treatment, Evidence-based medicine, Family, Brain research, Health
Abstract

BACKGROUND: Most deaths in critically ill patients with severe traumatic brain injury are associated with a decision to withdraw life-sustaining treatments. We aimed to identify the behavioural determinants that influence recommendations by critical care physicians to consider the withdrawal of life-sustaining treatments in this population. METHODS: We conducted a descriptive qualitative study based on the Theoretical Domains Framework of critical care physicians caring for patients with severe traumatic brain injury across Canada. We stratified critical care physicians by regions and used a purposive sampling strategy. We conducted semistructured phone interviews using a piloted and pre tested interview guide. We transcribed the interviews verbatim and verified the content for accuracy. We performed the analysis using a 3-step approach: coding, generation of specific beliefs and generation of specific themes. RESULTS: We recruited 20 critical care physicians across 4 geographic regions. After reaching saturation, we identified 7 core themes across 4 Theoretical Domains Framework domains for factors relevant to the decision to withdraw life-sustaining treatments. Four factors (i.e., clinical triggers, social triggers, interaction with families and intentions with medical decisions) were identified before the decision is made and 3 were identified during the decision-making process (i.e., considerations, priorities and knowledge needs). We identified multiple themes reflecting internal (n = 18, 8 Theoretical Domains Framework domains) and external (n = 15, 6 Theoretical Domains Framework domains) influences on the decision to withdraw life-sustaining treatments. INTERPRETATION: We identified several core themes and domains considered by critical care physicians in Canada in the decision to withdraw life-sustaining treatments in critically ill patients with severe traumatic brain injury. Future research should aim at identifying the factors influencing surrogate decisionmakers in the decision to withdraw life-sustaining treatments in these patients., Severe traumatic brain injury is a major public health issue, and the leading cause of death and disability among people under 45 years of age. (1) Mortality rates remain high, [...]

Published
2019
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53. Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial

Author

Garg, Amit X., Chan, Matthew T.V., Cuerden, Meaghan S., Devereaux, P.J., Abbasi, Seyed Hesameddin, Hildebrand, Ainslie, Lamontagne, Francois, Lamy, Andre, Noiseux, Nicolas, Parikh, Chirag R., Perkovic, Vlado, Quantz, Mackenzie, Rochon, Antoine, Royse, Alistair, Sessler, Daniel I., Shah, Pallav J., Sontrop, Jessica M., Tagarakis, Georgios I., Teoh, Kevin H., Vincent, Jessica, Walsh, Michael, Yared, Jean-Pierre, Yusuf, Salim, and Whitlock, Richard P.

Subjects
Acute kidney failure -- Care and treatment, Cardiac patients -- Health aspects, Heart surgery -- Complications and side effects -- Health aspects, Heart-lung machines -- Usage, Methylprednisolone -- Health aspects -- Usage -- Complications and side effects, Aprotinin, Death, Risk assessment, Corticosteroid drugs, Coronary artery bypass, Glucocorticoids, Central nervous system agents, Surgery, Kidney diseases, Steroids (Organic compounds), Caregivers, Chronic kidney failure, Health
Abstract

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater ([greater than or equal to] 26.5 [micro]mol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388, About 20% of the 4 million cardiopulmonary bypass surgeries performed worldwide each year are complicated by acute kidney injury, defined as a sudden reduction in kidney function. (1) Acute kidney [...]

Published
2019
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54. Permissive hypotension during shock resuscitation: equipoise in all patients?

Author

Lamontagne, Francois, Marshall, John C., and Adhikari, Neill K. J.

Subjects
Vasopressin -- Usage, Resuscitation -- Methods -- Complications and side effects, Shock -- Complications and side effects -- Care and treatment, Hypotension -- Risk factors -- Care and treatment, Health care industry
Abstract

Author(s): Francois Lamontagne [sup.1] , John C. Marshall [sup.2] , Neill K. J. Adhikari [sup.3] Author Affiliations: (1) 0000 0000 9064 6198, grid.86715.3d, Centre de recherche du CHU de Sherbrooke [...]

Published
2018
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57. Implementation of Recommendations on the Use of Corticosteroids in Severe COVID-19

Author

Camirand-Lemyre, Felix, Merson, Laura, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Burrell, Aidan J. C., Citarella, Barbara Wanjiru, Domingue, Marie-Pier, Levesque, Simon, Usuf, Effua, Wils, Evert-Jan, Ohshimo, Shinichiro, Martin-Loeches, Ignacio, Sandulescu, Oana, Laake, Jon Henrik, Lamontagne, Francois, Camirand-Lemyre, Felix, Merson, Laura, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Burrell, Aidan J. C., Citarella, Barbara Wanjiru, Domingue, Marie-Pier, Levesque, Simon, Usuf, Effua, Wils, Evert-Jan, Ohshimo, Shinichiro, Martin-Loeches, Ignacio, Sandulescu, Oana, Laake, Jon Henrik, and Lamontagne, Francois

Abstract

IMPORTANCE Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. OBJECTIVES To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). EXPOSURE Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. MAIN OUTCOMES AND MEASURES Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. RESULTS Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timin

Published
2023

58. Intravenous vitamin C therapy in adult patients with sepsis:A rapid practice guideline

Author

Reintam Blaser, Annika, Alhazzani, Waleed, Belley-Cote, Emilie, Møller, Morten Hylander, Adhikari, Neill K. J., Burry, Lisa, Coopersmith, Craig M., Al Duhailib, Zainab, Fujii, Tomoko, Granholm, Anders, Gunst, Jan, Hammond, Naomi, Ke, Lu, Lamontagne, Francois, Loudet, Cecilia, Morgan, Matt, Ostermann, Marlies, Reinikainen, Matti, Rosenfeld, Ricardo, Spies, Claudia, Oczkowski, Simon, Reintam Blaser, Annika, Alhazzani, Waleed, Belley-Cote, Emilie, Møller, Morten Hylander, Adhikari, Neill K. J., Burry, Lisa, Coopersmith, Craig M., Al Duhailib, Zainab, Fujii, Tomoko, Granholm, Anders, Gunst, Jan, Hammond, Naomi, Ke, Lu, Lamontagne, Francois, Loudet, Cecilia, Morgan, Matt, Ostermann, Marlies, Reinikainen, Matti, Rosenfeld, Ricardo, Spies, Claudia, and Oczkowski, Simon

Abstract

Background: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy?. Methods: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. Results: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI −2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD −18.9 h, 95% CI −26.5 to −11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD −0.69, 95% CI −1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a

Published
2023

59. An analysis of protocols and publications suggested that most discontinuations of clinical trials were not based on preplanned interim analyses or stopping rules

Author

Stegert, Mihaela, Kasenda, Benjamin, Elm, Erik von, You, John J., Blümle, Anette, Tomonaga, Yuki, Saccilotto, Ramon, Amstutz, Alain, Bengough, Theresa, Meerpohl, Joerg J., Tikkinen, Kari A.O., Neumann, Ignacio, Carrasco-Labra, Alonso, Faulhaber, Markus, Mulla, Sohail, Mertz, Dominik, Akl, Elie A., Bassler, Dirk, Busse, Jason W., Ferreira-González, Ignacio, Lamontagne, Francois, Nordmann, Alain, Gloy, Viktoria, Olu, Kelechi Kalu, Raatz, Heike, Moja, Lorenzo, Rosenthal, Rachel, Ebrahim, Shanil, Schandelmaier, Stefan, Sun, Xin, Vandvik, Per O., Johnston, Bradley C., Walter, Martin A., Burnand, Bernard, Schwenkglenks, Matthias, Hemkens, Lars G., Bucher, Heiner C., Guyatt, Gordon H., Briel, Matthias, and von Elm, Erik

Published
2016
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60. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial

Author

Writing Committee for the REMAP-CAP Investigators, Lawler, Patrick R, Derde, Lennie PG, van de Veerdonk, Frank L, McVerry, Bryan J, Huang, David T, Berry, Lindsay R, Lorenzi, Elizabeth, van Kimmenade, Roland, Gommans, Frank, Vaduganathan, Muthiah, Leaf, David E, Baron, Rebecca M, Kim, Edy Y, Frankfurter, Claudia, Epelman, Slava, Kwan, Yvonne, Grieve, Richard, O'Neill, Stephen, Sadique, Zia, Puskarich, Michael, Marshall, John C, Higgins, Alisa M, Mouncey, Paul R, Rowan, Kathryn M, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Au, Carly, Beane, Abi, van Bentum-Puijk, Wilma, Bonten, Marc JM, Bradbury, Charlotte A, Brunkhorst, Frank M, Burrell, Aidan, Buzgau, Adrian, Buxton, Meredith, Cecconi, Maurizio, Cheng, Allen C, Cove, Matthew, Detry, Michelle A, Estcourt, Lise J, Ezekowitz, Justin, Fitzgerald, Mark, Gattas, David, Godoy, Lucas C, Goossens, Herman, Haniffa, Rashan, Harrison, David A, Hills, Thomas, Horvat, Christopher M, Ichihara, Nao, Lamontagne, Francois, Linstrum, Kelsey M, McAuley, Daniel F, McGlothlin, Anna, McGuinness, Shay P, McQuilten, Zoe, Murthy, Srinivas, Nichol, Alistair D, Owen, David RJ, Parke, Rachael L, Parker, Jane C, Pollock, Katrina M, Reyes, Luis Felipe, Saito, Hiroki, Santos, Marlene S, Saunders, Christina T, Seymour, Christopher W, Shankar-Hari, Manu, Singh, Vanessa, Turgeon, Alexis F, Turner, Anne M, Zarychanski, Ryan, Green, Cameron, Lewis, Roger J, Angus, Derek C, Berry, Scott, Gordon, Anthony C, McArthur, Colin J, Webb, Steve A, and Apollo - University of Cambridge Repository

Subjects
Male, Renin-Angiotensin System, Hospitalization, Angiotensin Receptor Antagonists, Critical Illness, Humans, COVID-19, Female, Angiotensin-Converting Enzyme Inhibitors, Bayes Theorem, Receptors, Chemokine, Middle Aged, COVID-19 Drug Treatment
Abstract

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: NCT02735707.

Published
2023

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

Author

Bradbury, Charlotte A., Lawler, Patrick R., Stanworth, Simon J., McVerry, Bryan J., McQuilten, Zoe, Higgins, Alisa M., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Berry, Lindsay R., Lorenzi, Elizabeth, Zarychanski, Ryan, Arabi, Yaseen M., Annane, Djillali, Beane, Abi, Van Bentum-Puijk, Wilma, Bhimani, Zahra, Bihari, Shailesh, Bonten, Marc J. M., Brunkhorst, Frank M., Buzgau, Adrian, Buxton, Meredith, Carrier, Marc, Cheng, Allen C., Cove, Matthew, Detry, Michelle A., Estcourt, Lise J., Fitzgerald, Mark, Girard, Timothy D., Goligher, Ewan C., Goossens, Herman, Haniffa, Rashan, Hills, Thomas, Huang, David T., Horvat, Christopher M., Hunt, Beverley J., Ichihara, Nao, Lamontagne, Francois, Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Marshall, John C., McAuley, Daniel F., McGlothlin, Anna, McGuinness, Shay P., Middeldorp, Saskia, Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Neal, Matthew D., Nichol, Alistair D., Parke, Rachael L., Parker, Jane C., Reyes, Luis, Saito, Hiroki, Santos, Marlene S., Saunders, Christina T., Serpa-Neto, Ary, Seymour, Christopher W., Shankar-Hari, Manu, Singh, Vanessa, Tolppa, Timo, Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Derde, Lennie P. G., Webb, Steve A., Gordon, Anthony C., Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Vermassen, Joris, REMAP-CAP Investigators, University of Bristol [Bristol], University Health Network, University of Toronto, University of Oxford, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Monash University [Melbourne], Imperial College London, University of Manitoba [Winnipeg], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University Medical Center [Utrecht], St. Michael's Hospital, 215522, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH, U.S. Department of Defense, DOD, National Institute of General Medical Sciences, NIGMS, National Institute of Neurological Disorders and Stroke, NINDS, Gordon and Betty Moore Foundation, GBMF, Medtronic, Baxter International, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Wellcome Trust, WT, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, LAM Therapeutics, Canadian Institutes of Health Research, IRSC: 158584, Medical Research Council, MRC, National Institute for Health and Care Research, NIHR, European Commission, EC, National Heart and Lung Institute, NHLI, Queen's University Belfast, QUB: US8962032, National Health and Medical Research Council, NHMRC: APP1101719, National Medical Research Council, NMRC, Health Research Council of New Zealand, HRC: 16/631, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Innovate UK, Horizon 2020, Pharmaceuticals Bayer, Swedish Orphan Biovitrum, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support: This study was funded by the following: the Platform for European Preparedness Against (Re-)Emerging Epidemics (PREPARE) consortium of the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Rapid European COVID-19 Emergency Research Response (RECOVER) consortium of the European Union’s Horizon 2020 Research and Innovation Programme (grant 101003589), the Australian National Health and Medical Research Council (grant APP1101719), the Health Research Council of New Zealand (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the NIHR and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the University of Pittsburgh Medical Center (UPMC) Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (grant PHRC-20-0147), the Minderoo Foundation, and the Wellcome Trust Innovations Project (grant 215522). Dr Shankar-Hari is funded by an NIHR clinician scientist fellowship (grant CS-2016-16-011) and Dr Gordon is funded by an NIHR research professorship (grant RP-2015-06-18)., The REMAP-CAP platform is supported by the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Canadian Critical Care Clinical Trials Group, the Irish Critical Care Clinical Trials Network, the UK Critical Care Research Group and the International Forum of Acute Care Trialists., REMAP-CAP was supported in the Netherlands by the Research Collaboration Critical Care the Netherlands, reported receipt of personal fees from Lilly, BMS-Pfizer, Bayer, Amgen, Novartis, Janssen, Portola, Ablynx, and Grifols. Dr Lawler reported receipt of personal fees from Novartis, CorEvitas, and Brigham and Women’s Hospital and royalties from McGraw-Hill Publishing. Dr McVerry reported receipt of grants from the National Heart, Lung, and Blood Institute and Bayer Pharmaceuticals and personal fees from Boehringer Ingelheim. Dr L. Berry reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Lorenzi reported being an employee of Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Zarychanski reported receipt of grants from the Canadian Institutes of Health Research, LifeArc, Research Manitoba, the CancerCare Manitoba Foundation, Peter Munk Cardiac Centre, and the Thistledown Foundation and research operating support as the Lyonel G. Israels Research Chair in Hematology. Dr Bonten reported membership in international study steering committees, advisory boards, and independent data safety and monitoring committees funded by Janssen Vaccines, Merck Sharp & Dohme, AstraZeneca, Pfizer, and Sanofi Pasteur (all reimbursements to UMC Utrecht). Dr Brunkhorst reported receipt of grants from Jena University Hospital. Dr Buxton reported receipt of a gift from the Breast Cancer Research Foundation and contracts with Amgen and Eisai. Dr Carrier reported receipt of grants from BMS-Pfizer and personal fees from Bayer, Sanofi, Servier, Leo Phama, and BMS-Pfizer to his institution. Dr Cove reported receipt of grants from the National Medical Research Council and personal fees from Baxter and Medtronic. Dr Estcourt reported receipt of grants from the UK National Institute for Health Research (NIHR) and the European Union Horizon 2020 Research and Innovation Programme. Dr Haniffa reported receipt of grants from the UK Research and Innovation/Medical Research Council African Critical Care Registry Network. Dr Horvat reported receipt of grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke. Dr Ichihara reported being affiliated with the Department of Healthcare Quality Assessment, University of Tokyo, which is a social collaboration supported by the National Clinical Database, Johnson & Johnson, and Nipro Corporation. Dr Marshall reported receipt of personal fees from AM Pharma and Critical Care Medicine. Dr McAuley reported receipt of personal fees from Bayer, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Lilly, Vir Biotechnology, Faron Pharmaceutical, and SOBI and grants from the NIHR, the Wellcome Trust, Innovate UK, the UK Medical Research Council, and the Northern Ireland Health and Social Care Research and Development Division, in addition, Dr McAuley had a Queen’s University Belfast patent for novel treatment for inflammatory disease (US8962032), was co-director of research at the Intensive Care Society until June 2021, and was director of the Efficacy and Mechanisms Evaluation Program for the UK Medical Research Council/NIHR. Dr Middeldorp reported receipt of personal fees from Daiichi Sankyo, Bayer, Pfizer, Boehringer Ingelheim, Portola/Alexion, AbbVie, BMS-Pfizer, Sanofi, and Viatris, all paid to his institution, and grants from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim. Dr Neal reported equity in Haima Therapeutics, receipt of personal fees from Janssen Pharma and Haemonetics, and receipt of grants from Instrumentation Laboratory, the National Institutes of Health, and the Department of Defense. Dr Nichol reported receipt of personal fees from AM Pharma, paid to his university, and grants from Baxter. Dr Parke reported receipt of grants from Fisher and Paykel Healthcare NZ. Dr Serpa-Neto reported receipt of personal fees from Drager and Endpoint Health. Dr Seymour reported receipt of grants from the Gordon and Betty Moore Foundation and the National Institutes of Health/National Institute of General Medical Sciences. Dr Lewis reported being senior medical scientist at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr S. Berry reported being an employee with an ownership role at Berry Consultants, Berry Consultants receives payments for the statistical analysis and design of REMAP-CAP. Dr Derde reported being a coordinating committee member for the European Clinical Research Alliance on Infectious Diseases, a member of the Dutch Intensivists Task Force on Acute Infectious Threats, a member of the International Scientific Advisory Board for Sepsis Canada, and a member of the Dutch Academy of Sciences’ Pandemic Preparedness Plan committee. Dr Gordon reported receipt of personal fees from 30 Respiratory, paid to his institution. No other disclosures were reported., European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Investigators, REMAP-CAP Writing Committee for the REMAP-CAP, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, and Intensive Care Medicine

Subjects
Adult, Male, Platelet Aggregation Inhibitors/adverse effects, Critical Illness, [SDV]Life Sciences [q-bio], Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Hemorrhage, Aspirin/adverse effects, Hemorrhage/chemically induced, INFECTION, Humans, COAGULOPATHY, Aspirin, Anticoagulants, COVID-19, Bayes Theorem, Venous Thromboembolism, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Critical Illness/mortality, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Purinergic P2Y Receptor Antagonists/adverse effects, Purinergic P2Y Receptor Antagonists, COVID-19/complications, Female, Human medicine, Anticoagulants/adverse effects, Platelet Aggregation Inhibitors, Venous Thromboembolism/drug therapy
Abstract

Contains fulltext : 248713.pdf (Publisher’s version ) (Closed access) IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). CONCLUSIONS AND RELEVANCE: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02735707.

Published
2022

63. Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.

Author

Reintam Blaser, Annika, Alhazzani, Waleed, Belley‐Cote, Emilie, Møller, Morten Hylander, Adhikari, Neill K. J., Burry, Lisa, Coopersmith, Craig M., Al Duhailib, Zainab, Fujii, Tomoko, Granholm, Anders, Gunst, Jan, Hammond, Naomi, Ke, Lu, Lamontagne, Francois, Loudet, Cecilia, Morgan, Matt, Ostermann, Marlies, Reinikainen, Matti, Rosenfeld, Ricardo, and Spies, Claudia

Subjects
VITAMIN C, SEPSIS, SEPTIC shock, ACUTE kidney failure, INTENSIVE care units
Abstract

Background: This Rapid Practice Guideline provides an evidence‐based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? Methods: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence‐to‐decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. Results: At longest follow‐up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI −2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD −18.9 h, 95% CI −26.5 to −11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD −0.69, 95% CI −1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. Conclusions: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged. [ABSTRACT FROM AUTHOR]

Published
2023
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64. Outcomes and characteristics of patients hospitalized for COVID-19 in British Columbia, Ontario and Quebec during the Omicron wave.

Author

Lee, Terry, Cheng, Matthew P., Vinh, Donald C., Lee, Todd C., Tran, Karen C., Winston, Brent W., Sweet, David, Boyd, John H., Walley, Keith R., Haljan, Greg, McGeer, Allison, Lamontagne, Francois, Fowler, Robert, Maslove, David M., Singer, Joel, Patrick, David M., Marshall, John C., Burns, Kevin D., Murthy, Srinivas, and Mann, Puneet K.

Subjects
COVID-19, SARS-CoV-2 Omicron variant, SARS-CoV-2, ADULT respiratory distress syndrome, COVID-19 pandemic
Abstract

Background: Omicron is the current predominant variant of concern of SARS-CoV-2. We hypothesized that vaccination alters outcomes of patients hospitalized with COVID-19 during the Omicron wave and that these patients have different characteristics and outcomes than in previous waves. Methods: This is a substudy of the Host Response Mediators in Coronavirus (COVID-19) Infection (ARBs CORONA I) trial, which included adults admitted to hospital with acute COVID-19 up to July 2022 from 9 hospitals in British Columbia, Ontario and Quebec. We excluded emergency department visits without hospital admission, readmissions and admissions for another reason. Using adjusted regression analysis, we compared mortality and organ dysfunction between vaccinated (≥ 2 doses) and unvaccinated patients during the Omicron wave, as well as between all patients in the Omicron and first 3 waves of the COVID-19 pandemic. Results: During the Omicron wave, 28-day mortality was significantly lower in vaccinated (n = 19/237) than unvaccinated hospitalized patients (n = 12/127) (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15--0.89); vaccinated patients had lower risk of admission to the intensive care unit, invasive ventilation and acute respiratory distress syndrome and shorter hospital length of stay. Patients hospitalized during the Omicron wave had more comorbidities than in previous waves, and lower 28-day mortality than in waves 1 and 2 (adjusted OR 0.38, 95% CI 0.24--0.59; and 0.42, 95% CI 0.26--0.65) but not wave 3 (adjusted OR 0.81, 95% CI 0.43--1.51) and had less organ dysfunction than in the first 2 waves. Interpretation: Patients who were at least double vaccinated had lower mortality than unvaccinated patients hospitalized during the Omicron wave. Patients hospitalized during the Omicron wave had more chronic disease and lower mortality than in the first 2 waves, but not wave 3. Changes in vaccination, treatments and predominant SARS-CoV-2 variant may have decreased mortality in patients hospitalized during the Omicron wave. [ABSTRACT FROM AUTHOR]

Published
2023
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65. A multi-center prospective cohort study of patient transfers from the intensive care unit to the hospital ward

Author

Stelfox, Henry T., Leigh, Jeanna Parsons, Dodek, Peter M., Turgeon, Alexis F., Forster, Alan J., Lamontagne, Francois, and Fowler, Rob A.

Subjects
Medical research -- Analysis -- Surveys, Medicine, Experimental -- Analysis -- Surveys, Medical records -- Analysis -- Surveys, Nurses -- Surveys, Health care industry
Abstract

Purpose To provide a 360-degree description of ICU-to-ward transfers. Methods Prospective cohort study of 451 adults transferred from a medical-surgical ICU to a hospital ward in 10 Canadian hospitals July 2014-January 2016. Transfer processes documented in the medical record. Patient (or delegate) and provider (ICU/ward physician/nurse) perspectives solicited by survey 24-72 h after transfer. Results Medical records (100%) and survey responses (ICU physicians-80%, ICU nurses-80%, ward physicians-46%, ward nurses-64%, patients-74%) were available for most transfers. The median time from initiation to completion of transfer was 25 h (IQR 6-52). ICU physicians and nurses reported communicating with counterparts via telephone (78 and 75%) when transfer was requested (82 and 24%) or accepted (31 and 59%) and providing more elements of clinical information than ward physicians (mean 4.7 vs. 3.9, p < 0.001) and nurses (5.0 vs. 4.4, p < 0.001) reported receiving. Patients were more likely to report satisfaction with the transfer when they received more information (OR 1.32, 95% CI 1.18-1.48), had their questions addressed (OR 3.96, 95% CI 1.33-11.84), met the ward physician prior to transfer (OR 4.61, 95% CI 2.90-7.33), and were assessed by a nurse within 1 h of ward arrival (OR 4.70, 95% CI 2.29-9.66). Recommendations for improvement included having a documented care plan travel with the patient (all stakeholders), standardized face-to-face handover (physicians), avoiding transfers at shift change (nurses) and informing patients about pending transfers in advance (patients). Conclusions ICU-to-ward transfers are characterized by failures of patient flow and communication; experienced differently by patients, ICU/ward physicians and nurses, with distinct suggestions for improvement., Author(s): Henry T. Stelfox [sup.1], Jeanna Parsons Leigh [sup.2], Peter M. Dodek [sup.3], Alexis F. Turgeon [sup.4], Alan J. Forster [sup.5], Francois Lamontagne [sup.6], Rob A. Fowler [sup.7], Andrea Soo [...]

Published
2017
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66. The intensive care medicine research agenda on septic shock

Author

Perner, Anders, Gordon, Anthony C., Angus, Derek C., Lamontagne, Francois, Machado, Flavia, Russell, James A., and Timsit, Jean-Francois

Subjects
Ferring Pharmaceuticals, Medical research -- Health aspects, Medicine, Experimental -- Health aspects, Mortality -- United Kingdom, Medical colleges -- Health aspects, Septic shock -- Health aspects, Health care industry
Abstract

Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field., Author(s): Anders Perner [sup.1], Anthony C. Gordon [sup.2], Derek C. Angus [sup.3], Francois Lamontagne [sup.4], Flavia Machado [sup.5], James A. Russell [sup.6], Jean-Francois Timsit [sup.7], John C. Marshall [sup.8], John [...]

Published
2017
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68. Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis*

Author

Richards-Belle, Alvin, primary, Hylands, Mathieu, additional, Muttalib, Fiona, additional, Taran, Shaurya, additional, Rochwerg, Bram, additional, Day, Andrew, additional, Mouncey, Paul R., additional, Radermacher, Peter, additional, Couban, Rachel, additional, Asfar, Pierre, additional, Adhikari, Neill K. J., additional, and Lamontagne, Francois, additional

Published
2022
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69. Haemoglobin transfusion threshold in traumatic brain injury optimisation (HEMOTION): a multicentre, randomised, clinical trial protocol

Author

Turgeon, Alexis F, primary, Fergusson, Dean A, additional, Clayton, Lucy, additional, Patton, Marie-Pier, additional, Zarychanski, Ryan, additional, English, Shane, additional, Docherty, Annemarie, additional, Walsh, Timothy, additional, Griesdale, Donald, additional, Kramer, Andreas H, additional, Scales, Damon, additional, Burns, Karen E. A., additional, Boyd, John Gordon, additional, Marshall, John C, additional, Kutsogiannis, Demetrios J, additional, Ball, Ian, additional, Hébert, Paul C, additional, Lamontagne, Francois, additional, Costerousse, Olivier, additional, St-Onge, Maude, additional, Lessard Bonaventure, Paule, additional, Moore, Lynne, additional, Neveu, Xavier, additional, Rigamonti, Andrea, additional, Khwaja, Kosar, additional, Green, Robert S, additional, Laroche, Vincent, additional, Fox-Robichaud, Alison, additional, and Lauzier, Francois, additional

Published
2022
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71. Subgroup analyses in randomised controlled trials : cohort study on trial protocols and journal publications

Author

Kasenda, Benjamin, Schandelmaier, Stefan, Sun, Xin, von Elm, Erik, You, John, Blümle, Anette, Tomonaga, Yuki, Saccilotto, Ramon, Amstutz, Alain, Bengough, Theresa, Meerpohl, Joerg J, Stegert, Mihaela, Olu, Kelechi K, Tikkinen, Kari A O, Neumann, Ignacio, Carrasco-Labra, Alonso, Faulhaber, Markus, Mulla, Sohail M, Mertz, Dominik, Akl, Elie A, Bassler, Dirk, Busse, Jason W, Ferreira-González, Ignacio, Lamontagne, Francois, Nordmann, Alain, Gloy, Viktoria, Raatz, Heike, Moja, Lorenzo, Rosenthal, Rachel, Ebrahim, Shanil, Vandvik, Per O, Johnston, Bradley C, Walter, Martin A, Burnand, Bernard, Schwenkglenks, Matthias, Hemkens, Lars G, Bucher, Heiner C, Guyatt, Gordon H, and Briel, Matthias

Published
2014

73. Management of Acute Respiratory Distress Syndrome and Refractory Hypoxemia. A Multicenter Observational Study

Author

Duan, Erick H., Adhikari, Neill K. J., DʼAragon, Frederick, Cook, Deborah J., Mehta, Sangeeta, Alhazzani, Waleed, Goligher, Ewan, Charbonney, Emmanuel, Arabi, Yaseen M., Karachi, Tim, Turgeon, Alexis F., Hand, Lori, Zhou, Qi, Austin, Peggy, Friedrich, Jan, Lamontagne, Francois, Lauzier, François, Patel, Rakesh, Muscedere, John, Hall, Richard, Aslanian, Pierre, Piraino, Thomas, Albert, Martin, Bagshaw, Sean M., Jacka, Mike, Wood, Gordon, Henderson, William, Dorscheid, Delbert, Ferguson, Niall D., and Meade, Maureen O.

Published
2017
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75. 7 versus 14 days of antibiotic treatment for critically ill patients with bloodstream infection: a pilot randomized clinical trial

Author

Daneman, Nick, Rishu, Asgar H., Pinto, Ruxandra, Aslanian, Pierre, Bagshaw, Sean M., Carignan, Alex, Charbonney, Emmanuel, Coburn, Bryan, Cook, Deborah J., Detsky, Michael E., Dodek, Peter, Hall, Richard, Kumar, Anand, Lamontagne, Francois, Lauzier, Francois, Marshall, John C., Martin, Claudio M., McIntyre, Lauralyn, Muscedere, John, Reynolds, Steven, Sligl, Wendy, Stelfox, Henry T., Wilcox, M. Elizabeth, Fowler, Robert A., and on behalf of the Canadian Critical Care Trials Group

Published
2018
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78. Health-related quality-of-life and health-utility reporting in critical care

Author

Lau, Vincent Issac, primary, Johnson, Jeffrey A, additional, Bagshaw, Sean M, additional, Rewa, Oleksa G, additional, Basmaji, John, additional, Lewis, Kimberley A, additional, Wilcox, M Elizabeth, additional, Barrett, Kali, additional, Lamontagne, Francois, additional, Lauzier, Francois, additional, Ferguson, Niall D, additional, Oczkowski, Simon J W, additional, Fiest, Kirsten M, additional, Niven, Daniel J, additional, Stelfox, Henry T, additional, Alhazzani, Waleed, additional, Herridge, Margaret, additional, Fowler, Robert, additional, Cook, Deborah J, additional, Rochwerg, Bram, additional, and Xie, Feng, additional

Published
2022
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82. Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis

Author

Zeraatkar, Dena, primary, Cusano, Ellen, additional, Martínez, Juan Pablo Díaz, additional, Qasim, Anila, additional, Mangala, Sophia, additional, Kum, Elena, additional, Bartoszko, Jessica Julia, additional, Devji, Tahira, additional, Agoritsas, Thomas, additional, Guyatt, Gordon, additional, Izcovich, Ariel, additional, Khamis, Assem M, additional, Lamontagne, Francois, additional, Rochwerg, Bram, additional, Vandvik, Per, additional, Brignardello-Petersen, Romina, additional, and Siemieniuk, Reed Alexander Cunningham, additional

Published
2022
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83. sj-docx-1-mdm-10.1177_0272989X221100717 – Supplemental material for A Machine-Learning Approach for Estimating Subgroup- and Individual-Level Treatment Effects: An Illustration Using the 65 Trial

Author

Sadique, Zia, Grieve, Richard, Diaz-Ordaz, Karla, Mouncey, Paul, Lamontagne, Francois, and O’Neill, Stephen

Subjects
111708 Health and Community Services, 111799 Public Health and Health Services not elsewhere classified, 160807 Sociological Methodology and Research Methods, FOS: Health sciences, FOS: Sociology
Abstract

Supplemental material, sj-docx-1-mdm-10.1177_0272989X221100717 for A Machine-Learning Approach for Estimating Subgroup- and Individual-Level Treatment Effects: An Illustration Using the 65 Trial by Zia Sadique, Richard Grieve, Karla Diaz-Ordaz, Paul Mouncey, Francois Lamontagne and Stephen O’Neill in Medical Decision Making

Published
2022
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85. COVID-19 symptoms at hospital admission vary with age and sex

Author

Abdukahil, Sheryl Ann, Abe, Ryuzo, Abel, Laurent, Absil, Lara, Acker, Andrew, Adachi, Shingo, Adam, Elisabeth, Adriao, Diana, Ainscough, Kate, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Al-Dabbous, Tala, Al-Fares, Abdulrahman, Al Qasim, Eman, Alalqam, Razi, Alex, Beatrice, Alexandre, Kevin, Alfoudri, Huda, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Allavena, Clotilde, Allou, Nathalie, Alves, Joao, Alves, Rita, Amaral, Maria, Ammerlaan, Heidi, Ampaw, Phoebe, Andini, Roberto, Andrejak, Claire, Angheben, Andrea, Angoulvant, Francois, Ansart, Severine, Antonelli, Massimo, De Brito, Carlos Alexandre Antunes, Arabi, Yaseen, Aragao, Irene, Arcadipane, Antonio, Arenz, Lukas, Arlet, Jean-Benoit, Arnold-Day, Christel, Arora, Lovkesh, Artaud-Macari, Elise, Asensio, Angel, Assie, Jean Baptiste, Atique, Anika, Auchabie, Johann, Aumaitre, Hugues, Azemar, Laurene, Azoulay, Cecile, Bach, Benjamin, Bachelet, Delphine, Baillie, J. Kenneth, Bak, Erica, Bakakos, Agamemnon, Banisadr, Firouze, Barbalho, Renata, Barclay, Wendy S., Barnikel, Michaela, Barrelet, Audrey, Barrigoto, Cleide, Basmaci, Romain, Rincon, Diego Fernando Bautista, Bedossa, Alexandra, Behilill, Sylvie, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bennett, Suzanne, Bento, Luis, Berdal, Jan-Erik, Bergeaud, Delphine, Bertolino, Lorenzo, Bessis, Simon, Bevilcaqua, Sybille, Bhavsar, Krishna, Bin Humaid, Felwa, Bissuel, Francois, Biston, Patrick, Bitker, Laurent, Blanco-Schweizer, Pablo, Blot, Mathieu, Boccia, Filomena, Bogaert, Debby, Bompart, Francois, Booth, Gareth, Borges, Diogo, Borie, Raphael, Bos, Jeanet, Bosse, Hans Martin, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kevin, Bouillet, Laurence, Bouisse, Camille, Boureau, Anne-Sophie, Bouscambert, Maude, Bouziotis, Jason, Boxma, Bianca, Boyer-Besseyre, Marielle, Boylan, Maria, Braga, Cynthia, Brandenburger, Timo, Brazzi, Luca, Breen, Dorothy, Breen, Patrick, Brickell, Kathy, Brozzi, Nicolas, Buchtele, Nina, Buesaquillo, Christian, Bugaeva, Polina, Buisson, Marielle, Burhan, Erlina, Bustos, Ingrid G., Butnaru, Denis, Carcel, Sheila, Cabie, Andre, Cabral, Susana, Caceres, Eder, Callahan, Mia, Calligy, Kate, Calvache, Jose Andres, Camoes, Joao, Campana, Valentine, Campbell, Paul, Canepa, Cecilia, Cantero, Mireia, Caraux-Paz, Pauline, Cardoso, Filipa, Cardoso, Filipe, Cardoso, Sofia, Carelli, Simone, Carlier, Nicolas, Carney, Gayle, Carpenter, Chloe, Carret, Marie-Christine, Carrier, Francois Martin, Carson, Gail, Casanova, Maire-Laure, Cascao, Mariana, Casimiro, Jose, Cassandra, Bailey, Castaneda, Silvia, Castanheira, Nidyanara, Castor-Alexandre, Guylaine, Castrillon, Henry, Castro, Ivo, Catarino, Ana, Catherine, Francois-Xavier, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Chas, Julie, Chassin, Camille, Chen, Anjellica, Chen, Yih-Sharng, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chirouze, Catherine, Chiumello, Davide, Cho, Hwa Jin, Cho, Sung Min, Cholley, Bernard, Cidade, Jose Pedro, Herreros, Jose Miguel Cisneros, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Clohisey, Sara, Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Colin, Gwenhael, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connelly, J. P., Connor, Marie, Conrad, Anne, Contreras, Sofia, Cooke, Graham S., Copland, Mary, Cordel, Hugues, Corley, Amanda, Cormican, Sarah, Cornelis, Sabine, Corpuz, Arianne Joy, Corvaisier, Gregory, Couffignal, Camille, Couffin-Cadiergues, Sandrine, Courtois, Roxane, D'Orleans, Charles Crepy, Croonen, Sabine, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Csete, Marc, Cucino, Alberto, Cullen, Caroline, Cummings, Matthew, Curley, Gerard, Curlier, Elodie, Custodio, Paula, D'Aragon, Frederick, Filipe, Ana Da Silva, Da Silveira, Charlene, D'Ortenzio, Eric, Dabaliz, Al-Awwab, Dagens, Andrew B., Dalton, Heidi, Dalton, Jo, Daneman, Nick, Dankwa, Emmanuelle A., Dantas, Jorge, De Castro, Nathalie, De Mendoza, Diego, Franca, Rafael Freitas De Oliveira, De Rosa, Rosanna, De Silva, Thushan, De Vries, Peter, Dean, David, Debray, Marie-Pierre, Dechert, William, Deconninck, Lauren, Decours, Romain, Delacroix, Isabelle, Delavigne, Karen, Deligiannis, Ionna, Dell'amore, Andrea, Delobel, Pierre, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Desai, Mehul, Descamps, Diane, Desvallee, Mathilde, Dewayanti, Santi Rahayu, Diallo, Alpha, Diamantis, Sylvain, Dias, Andre, Diaz, Juan Jose Diaz, Diaz, Rodrigo, Didier, Kevin, Diehl, Jean-Luc, Dieperink, Wim, Dimet, Jerome, Dinot, Vincent, Diouf, Alphonsine, Dishon, Yael, Djossou, Felix, Docherty, Annemarie B., Dong, Andy, Donnelly, Christl A., Donnelly, Maria, Donohue, Chloe, Dorival, Celine, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downer, Triona, Downing, Mark, Drake, Tom, Dubee, Vincent, Dubos, Francois, Ducancelle, Alexandra, Dudman, Susanne, Dunning, Jake, Mangoni, Emanuele Durante, Duranti, Silvia, Durham, Lucian, III, Dussol, Bertrand, Duval, Xavier, Dyrhol-Riise, Anne Margarita, Eira, Carla, Vidal, Jose Ernesto, El Sanharawi, Mohammed, Elapavaluru, Subbarao, Elharrar, Brigitte, Elkheir, Natalie, Ellerbroek, Jacobien, Ellis, Rachael, Eloy, Philippine, Elshazly, Tarek, Enderle, Isabelle, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Esperatti, Mariano, Esperou, Helene, Esposito-Farese, Marina, Estevao, Joao, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Isabelle, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron J., Faria, Pedro, Farshait, Nataly, Fatoni, Arie Zainul, Faure, Karine, Fayed, Mohamed, Feely, Niamh, Fernandes, Jorge, Fernandes, Marilia, Fernandes, Susana, Ferrao, Joana, Devouge, Eglantine Ferrand, Ferraz, Mario, Ferreira, Benigno, Ferrer-Roca, Ricard, Figueiredo-Mello, Claudia, Flateau, Clara, Fletcher, Tom, Florio, Letizia Lucia, Foley, Claire, Fomin, Victor, Fonseca, Claudio Duarte, Fonseca, Tatiana, Fontela, Patricia, Forsyth, Simon, Foti, Giuseppe, Fourn, Erwan, Fowler, Rob, Franch-Llasat, Diego, Fraser, Christophe, Fraser, John, Freire, Marcela Vieira, Ribeiro, Ana Freitas, Friedrich, Caren, Fry, Stephane, Fuentes, Nora, Fukuda, Masahiro, Gomez-Junyent, Joan, Gaborieau, Valerie, Gachet, Benoit, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean-Charles, Gagneux-Brunon, Amandine, Gaiao, Sergio, Gallagher, Phil, Curto, Elena Gallego, Gamble, Carrol, Garan, Arthur, Garcia-Gallo, Esteban, Garcia, Rebekha, Garot, Denis, Garrait, Valerie, Gault, Nathalie, Gavin, Aisling, Gaymard, Alexandre, Gebauer, Johannes, Morlaes, Louis Gerbaud, Germano, Nuno, Ghosn, Jade, Giani, Marco, Giaquinto, Carlo, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Giordano, Guillermo, Girvan, Michelle, Gissot, Valerie, Giwangkancana, Gezy, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, Francois, Goepel, Siri, Goffard, Jean-Christophe, Golob, Jonathan, Gorenne, Isabelle, Goujard, Cecile, Goulenok, Tiphaine, Grable, Margarite, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Green, Christopher A., Greenhalf, William, Greffe, Segolene, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Lordemann, Anja Grosse, Gruner, Heidi, Gu, Yusing, Guedj, Jeremie, Guellec, Dewi, Guerguerian, Anne-Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, Guimard, Thomas, Haber, Daniel, Hakak, Sheeba, Hall, Matthew, Halpin, Sophie, Hamer, Ansley, Hamidfar, Rebecca, Hammond, Terese, Hardwick, Hayley, Harley, Kristen, Harrison, Ewen M., Harrison, Janet, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez-Trujillo, Aquiles, Hentzien, Maxime, Hernandez-Montfort, Jaime, Hidayah, Astarini, Higgins, Dawn, Higgins, Eibhilin, Hinton, Samuel, Hipolito-Reis, Ana, Hiraiwa, Hiroaki, Hiscox, Julian A., Ho, Antonia Ying Wai, Hoctin, Alexandre, Hoffmann, Isabelle, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Hoshino, Kota, Hough, Catherine L., Hsu, Jimmy Ming-Yang, Hulot, Jean-Sebastien, Ijaz, Samreen, Illes, Hajnal-Gabriela, Inacio, Hugo, Dominguez, Carmen Infante, Iosifidis, Elias, Irvine, Lacey, Isgett, Sarah, Isidoro, Tiago, Isnard, Margaux, Itai, Junji, Ivulich, Daniel, Jaafoura, Salma, Jabot, Julien, Jackson, Clare, Jamieson, Nina, Jaureguiberry, Stephane, Javidfar, Jeffrey, Jean-Benoit, Zabbe, Jego, Florence, Jenum, Synne, Sotomayor, Ruth Jimbo, Garcia, Ruth Noemi Jorge, Joseph, Cedric, Joseph, Mark, Jouvet, Philippe, Jung, Hanna, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabina, Kalomoiri, Smaragdi, Kandamby, Darshana Hewa, Kandel, Chris, Kant, Ravi, Kartsonaki, Christiana, Kasugai, Daisuke, Katz, Kevin, Johal, Simreen Kaur, Keating, Sean, Kelly, Andrea, Kelly, Sadie, Kennedy, Lisa, Kennon, Kalynn, Kerroumi, Younes, Kestelyn, Evelyne, Khalid, Imrana, Khalil, Antoine, Khan, Coralie, Khan, Irfan, Kho, Michelle E., Khoo, Saye, Kida, Yuri, Kiiza, Peter, Kildal, Anders Benjamin, Kimmoun, Antoine, Kindgen-Milles, Detlef, Kitamura, Nobuya, Klenerman, Paul, Bekken, Gry Kloumann, Knight, Stephen, Kobbe, Robin, Vasconcelos, Malte Kohns, Korten, Volkan, Kosgei, Caroline, Krawczyk, Karolina, Vecham, Pavan Kumar, Kumar, Deepali, Kurtzman, Ethan, Kutsogiannis, Demetrios, Kyriakoulis, Konstantinos, L'her, Erwan, Lachatre, Marie, Lacoste, Marie, Laffey, John G., Lagrange, Marie, Laine, Fabrice, Lambert, Marc, Lamontagne, Francois, Langelot-Richard, Marie, Lantang, Eka Yudha, Lanza, Marina, Laouenan, Cedric, Laribi, Samira, Lariviere, Delphine, Launay, Odile, Lavie-Badie, Yoan, Law, Andrew, Le Bihan, Clement, Le Bris, Cyril, Le Coustumier, Eve, Le Falher, Georges, Le Gac, Sylvie, Le Hingrat, Quentin, Le Marechal, Marion, Le Mestre, Soizic, Le Moing, Vincent, Le Nagard, Herve, Le Turnier, Paul, Leon, Rafael, Le, Minh, Santos, Marta Leal, Leal, Ema, Lee, James, Lee, Su Hwan, Lee, Todd, Leeming, Gary, Lefebvre, Benedicte, Lefebvre, Laurent, Lefevre, Benjamin, Lellouche, Francois, Lemaignen, Adrien, Lemee, Veronique, Lemmink, Gretchen, Leone, Michela, Lepiller, Quentin, Lescure, Francois-Xavier, Lesens, Olivier, Lesouhaitier, Mathieu, Levy-Marchal, Claire, Levy, Bruno, Levy, Yves, Bassi, Gianluigi Li, Liang, Janet, Lim, Wei Shen, Lina, Bruno, Lind, Andreas, Lingas, Guillaume, Lion-Daolio, Sylvie, Liu, Keibun, Loforte, Antonio, Lolong, Navy, Lopes, Diogo, Lopez-Colon, Dalia, Loubet, Paul, Lucet, Jean Christophe, Luna, Carlos M., Lungu, Olguta, Luong, Liem, Luton, Dominique, Lyons, Ruth, Mueller, Fredrik, Mueller, Karl Erik, Maasikas, Olavi, Macdonald, Sarah, Machado, Moise, Macheda, Gabrielle, Sanchez, Juan Macias, Madhok, Jai, Mahieu, Rafael, Mahy, Sophie, Maier, Lars Siegfrid, Maillet, Mylene, Maitre, Thomas, Malfertheiner, Maximilian, Malik, Nadia, Maltez, Fernando, Malvy, Denis, Mambert, Marina, Manda, Victoria, Mandei, Jose M., Manning, Edmund, Manuel, Aldric, Malaque, Ceila Maria Sant Ana, Marino, Flavio, Mariz, Carolline De Araujo, Eid, Charbel Maroun, Marques, Ana, Marquis, Catherine, Marsh, Brian, Marsh, Laura, Marshall, John, Martelli, Celina Turchi, Martin-Blondel, Guillaume, Martin-Loeches, Ignacio, Martin-Quiros, Alejandro, Martin, Dori-Ann, Martin, Emily, Martinot, Martin, Rego, Caroline Martins, Martins, Ana, Martins, Joao, Martucci, Gennaro, Marwali, Eva Miranda, Jimenez, Juan Fernado Masa, Maslove, David, Mason, Sabina, Matan, Moshe, Mathieu, Daniel, Mattei, Mathieu, Matulevics, Romans, Maulin, Laurence, Mc Evoy, Natalie, McCarthy, Aine, McCarthy, Anne, McCloskey, Colin, McConnochie, Rachael, McDermott, Sherry, McDonald, Sarah, McElwee, Samuel, McEvoy, Natalie, McGeer, Allison, McGuinness, Niki, McLean, Kenneth A., McNicholas, Bairbre, Meaney, Edel, Mear-Passard, Cecile, Mechlin, Maggie, Mele, Ferruccio, Menon, Kusum, Mentre, France, Mentzer, Alexander J., Mercier, Noemie, Merckx, Antoine, Mergler, Blake, Merson, Laura, Mesquita, Antonio, Meybeck, Agnes, Meynert, Alison M., Meyssonnier, Vanina, Meziane, Amina, Mezidi, Medhi, Michelanglei, Celine, Mihnovits, Vladislav, Maldonado, Hugo Miranda, Mone, Mary, Moin, Asma, Molina, David, Molinos, Elena, Monteiro, Agostinho, Montes, Claudia, Montrucchio, Giorgia, Moore, Sarah, Moore, Shona C., Morales-Cely, Lina, Moro, Lucia, Tutillo, Diego Rolando Morocho, Motos, Ana, Mouquet, Hugo, Perrot, Clara Mouton, Moyet, Julien, Mullaert, Jimmy, Munblit, Daniel, Murphy, Derek, Murris, Marlene, Myrodia, Dimitra Melia, N'guyen, Yohan, Neant, Nadege, Neb, Holger, Nekliudov, Nikita A., Neto, Raul, Neumann, Emily, Neves, Bernardo, Ng, Pauline Yeung, Ng, Wing Yiu, Choileain, Orna Ni, Nichol, Alistair, Nonas, Stephanie, Noret, Marion, Norman, Lisa, Notari, Alessandra, Noursadeghi, Mahdad, Nowicka, Karolina, Nseir, Saad, Nunez, Jose I., Nyamankolly, Elsa, O'Donnell, Max, O'Hearn, Katie, O'Neil, Conar, Occhipinti, Giovanna, Ogston, Tawnya, Ogura, Takayuki, Oh, Tak-Hyuk, Ohshimo, Shinichiro, Oinam, Budha Charan Singh, Oliveira, Ana Pinho, Oliveira, Joao, Olliaro, Piero, Ong, David S. Y., Oosthuyzen, Wilna, Openshaw, Peter J. M., Orozco-Chamorro, Claudia Milena, Orquera, Andres, Osatnik, Javier, Ouamara, Nadia, Ouissa, Rachida, Owyang, Clark, Oziol, Eric, Povoas, Diana, Pagadoy, Maider, Pages, Justine, Palacios, Mario, Palmarini, Massimo, Panarello, Giovanna, Panda, Prasan Kumar, Panigada, Mauro, Pansu, Nathalie, Papadopoulos, Aurelie, Parra, Briseida, Pasquier, Jeremie, Patauner, Fabian, Patrao, Luis, Paul, Christelle, Paul, Mical, Paulos, Jorge, Paxton, William A., Payen, Jean-Francois, Pearse, India, Peek, Giles J., Peelman, Florent, Peiffer-Smadja, Nathan, Peigne, Vincent, Pejkovska, Mare, Peltan, Ithan D., Pereira, Rui, Perez, Daniel, Perpoint, Thomas, Pesenti, Antonio, Petrousova, Lenka, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pharand, Scott, Piagnerelli, Michael, Picard, Walter, Picone, Olivier, Piel-Julian, Marie, Pierobon, Carola, Pimentel, Carlos, Piroth, Lionel, Pius, Riinu, Piva, Simone, Plantier, Laurent, Plotkin, Daniel, Poissy, Julien, Pokorska-Spiewak, Maria, Poli, Sergio, Pollakis, Georgios, Popielska, Jolanta, Postma, Douwe F., Povoa, Pedro, Powis, Jeff, Prapa, Sofia, Prebensen, Christian, Preiser, Jean-Charles, Prestre, Vincent, Price, Nicholas, Prinssen, Anton, Pritchard, Mark G., Proenca, Lucia, Puechal, Oriane, Purcell, Gregory, Quesada, Luisa, Quist-Paulsen, Else, Quraishi, Mohammed, Ratsep, Indrek, Rossler, Bernhard, Rabaud, Christian, Rafiq, Marie, Ragazzo, Gabrielle, Rainieri, Fernando, Ramakrishnan, Nagarajan, Ramanathan, Kollengode, Rammaert, Blandine, Rapp, Christophe, Rasmin, Menaldi, Rau, Cornelius, Rebaudet, Stanislas, Redl, Sarah, Reeve, Brenda, Reid, Liadain, Reis, Renato, Remppis, Jonathan, Remy, Martine, Renk, Hanna, Resende, Liliana, Resseguier, Anne-Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Richardson, David, Richardson, Denise, Richier, Laurent, Riera, Jordi, Rios, Ana Lucia, Rishu, Asgar, Rispal, Patrick, Risso, Karine, Nunez, Maria Angelica Rivera, Rizer, Nicholas, Roberto, Andre, Roberts, Stephanie, Robertson, David L., Robineau, Olivier, Roche-Campo, Ferran, Rodari, Paola, Rodeia, Simao, Abreu, Julia Rodriguez, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon-Albuquerque, Roberto, Jr., Roriz, Melanie, Rosa-Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Rossanese, Andrea, Rossignol, Benedicte, Rossignol, Patrick, Roy, Carine, Roze, Benoit, Russell, Clark D., Ryckaert, Steffi, Holten, Aleksander Rygh, Choez, Xavier Sanchez, Saba, Isabela, Sadat, Musharaf, Saidani, Nadia, Salazar, Leonardo, Sales, Gabriele, Sallaberry, Stephane, Salvator, Helene, Sanchez-Miralles, Angel, Sanchez, Olivier, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandulescu, Oana, Santos, Marlene, Sarfo-Mensah, Shirley, Sarton, Benjamine, Saviciute, Egle, Savvidou, Parthena, Scarsbrook, Joshua, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Scott-Brown, James, Scott, Janet T., Sedillot, Nicholas, Seitz, Tamara, Semaille, Caroline, Semple, Malcolm G., Senneville, Eric, Sequeira, Filipa, Sequeira, Tania, Shadowitz, Ellen, Shamsah, Mohammad, Sharma, Pratima, Shaw, Catherine A., Shaw, Victoria, Shiban, Nisreen, Shime, Nobuaki, Shimizu, Hiroaki, Shimizu, Keiki, Shrapnel, Sally, Shum, Hoi Ping, Mohammed, Nassima Si, Sigfrid, Louise, Silva, Catarina, Silva, Maria Joao, Sin, Wai Ching, Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Solis, Monserrat, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnes, Song, Myung Jin, Song, Rima, Song, Tae, Sonntagbauer, Michael, Soum, Edouard, Uva, Maria Sousa, Sousa, Marta, Souza-Dantas, Vicente, Sperry, Alexandra, Sriskandan, Shiranee, Staudinger, Thomas, Stecher, Stephanie-Susanne, Stienstra, Ymkje, Stiksrud, Birgitte, Streinu-Cercel, Adrian, Streinu-Cercel, Anca, Strudwick, Samantha, Stuart, Ami, Stuart, David, Sultana, Asfia, Summers, Charlotte, Surovcova, Magdalena, Svistunov, Andrey A., Syrigos, Konstantinos, Sztajnbok, Jaques, Szuldrzynski, Konstanty, Teoule, Francois, Tabrizi, Shirin, Tagherset, Lysa, Talarek, Ewa, Taleb, Sara, Talsma, Jelmer, Van Tan, Le, Tanaka, Hiroyuki, Tanaka, Taku, Taniguchi, Hayato, Tardivon, Coralie, Tattevin, Pierre, Taufik, M. Azhari, Tedder, Richard S., Teixeira, Joao, Tellier, Marie-Capucine, Terpstra, Pleun, Terrier, Olivier, Terzi, Nicolas, Tessier-Grenier, Hubert, Thibault, Vincent, Thiberville, Simon-Djamel, Thill, Benoit, Thompson, A. A. Roger, Thompson, Shaun, Thomson, David, Thomson, Emma C., Thuy, Duong Bich, Thwaites, Ryan S., Timashev, Peter S., Timsit, Jean-Francois, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Toki, Maria, Tonby, Kristian, Santos-Olmo, Rosario Maria Torres, Torres, Antoni, Torres, Margarida, Trioux, Theo, Trieu, Huynh Trung, Tromeur, Cecile, Trontzas, Ioannis, Troost, Jonathan, Trouillon, Tiffany, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turtle, Lance C. W., Twardowski, Pawel, Uchiyama, Makoto, Ullrich, Roman, Uribe, Alberto, Usman, Asad, Val-Flores, Luis, Van de Velde, Stijn, Van den Berge, Marcel, Van der Feltz, Machteld, Van der Vekens, Nicky, Van der Voort, Peter, Van der Werf, Sylvie, Van Dyk, Marlice, Van Gulik, Laura, Van Hattem, Jarne, Van Lelyveld, Steven, Van Netten, Carolien, Vanel, Noemie, Vanoverschelde, Henk, Vauchy, Charline, Veislinger, Aurelie, Velazco, Jorge, Ventura, Sara, Verbon, Annelies, Vieira, Cesar, Villanueva, Joy Ann, Villar, Judit, Villeneuve, Pierre-Marc, Villoldo, Andrea, Chau, Nguyen Van Vinh, Visseaux, Benoit, Visser, Hannah, Vuorinen, Aapeli, Vuotto, Fanny, Wang, Chih-Hsien, Wei, Jia, Weil, Katharina, Wesselius, Sanne, Wham, Murray, Whelan, Bryan, White, Nicole, Wiedemann, Aurelie, Wille, Keith, Wils, Evert-Jan, Xynogalas, Ioannis, Suen, Jacky Y., Yacoub, Sophie, Yamazaki, Masaki, Yazdanpanah, Yazdan, Yelnik, Cecile, Yerkovich, Stephanie, Yokoyama, Toshiki, Yonis, Hodane, Young, Paul, Yuliarto, Saptadi, Zabbe, Marion, Zacharowski, Kai, Zahran, Maram, Zambon, Maria, Zanella, Alberto, Zawadka, Konrad, Zayyad, Hiba, Zoufaly, Alexander, Zucman, David, and NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

Abstract

Funding This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z]; the Bill and Melinda Gates Foundation [OPP1209135]. Country-specifc support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359]; the Health Research Board Ireland [CTN Award 2014-012]; National Institute for Health Research (NIHR) [award CO-CIN-01]; the Medical Research Council (MRC) [grant MC_PC_19059]; the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907]; NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927]; Liverpool Experimental Cancer Medicine Centre [grant reference C18616/ A25153]; NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013]; EU Platform for European Preparedness Against (Re-)-)emerging Epidemics (PREPARE) [FP7 project 602525]; National Institutes of Health (NIH) [UL1TR002240]; and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above. publishersversion published

Published
2021

86. One-Year Outcomes in Caregivers of Critically Ill Patients

Author

Cameron, Jill I., Chu, Leslie M., Matte, Andrea, Tomlinson, George, Chan, Linda, Thomas, Claire, Friedrich, Jan O., Mehta, Sangeeta, Lamontagne, Francois, Levasseur, Melanie, Ferguson, Niall D., Adhikari, Neill K.J., Rudkowski, Jill C., Meggison, Hilary, Skrobik, Yoanna, Flannery, John, Bayley, Mark, Batt, Jane, dos Santos, Claudia, Abbey, Susan E., Tan, Adrienne, Lo, Vincent, Mathur, Sunita, Parotto, Matteo, Morris, Denise, Flockhart, Linda, Fan, Eddy, Lee, Christie M., Wilcox, M. Elizabeth, Ayas, Najib, Choong, Karen, Fowler, Robert, Scales, Damon C., Sinuff, Tasnim, Cuthbertson, Brian H., Rose, Louise, Robles, Priscila, Burns, Stacey, Cypel, Marcelo, Singer, Lianne, Chaparro, Cecilia, Chow, Chung-Wai, Keshavjee, Shaf, Brochard, Laurent, Hébert, Paul, Slutsky, Arthur S., Marshall, John C., Cook, Deborah, and Herridge, Margaret S.

Published
2016
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89. Heparin-induced thrombocytopenia in the critically ill: Interpreting the 4Ts test in a randomized trial

Author

Crowther, Mark, Cook, Deborah, Guyatt, Gordon, Zytaruk, Nicole, McDonald, Ellen, Williamson, David, Albert, Martin, Dodek, Peter, Finfer, Simon, Vallance, Shirley, Heels-Ansdell, Diane, McIntyre, Lauralyn, Mehta, Sangeeta, Lamontagne, Francois, Muscedere, John, Jacka, Michael, Lesur, Olivier, Kutsiogiannis, Jim, Friedrich, Jan, Klinger, James R., Qushmaq, Ismael, Burry, Lisa, Khwaja, Kosar, Sheppard, Jo-Ann, and Warkentin, Theodore E.

Published
2014
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90. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author

REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, Ewan C, Bradbury, Charlotte A, McVerry, Bryan J, Lawler, Patrick R, Berger, Jeffrey S, Gong, Michelle N, Carrier, Marc, Reynolds, Harmony R, Kumar, Anand, Turgeon, Alexis F, Kornblith, Lucy Z, Kahn, Susan R, Marshall, John C, Kim, Keri S, Houston, Brett L, Derde, Lennie PG, Cushman, Mary, Tritschler, Tobias, Angus, Derek C, Godoy, Lucas C, McQuilten, Zoe, Kirwan, Bridget-Anne, Farkouh, Michael E, Brooks, Maria M, Lewis, Roger J, Berry, Lindsay R, Lorenzi, Elizabeth, Gordon, Anthony C, Ahuja, Tania, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Baumann Kreuziger, Lisa, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadze, Tamta, Coiffard, Benjamin, Contreras, Aira, Costantini, Todd W, de Brouwer, Sophie, Detry, Michelle A, Duggal, Abhijit, Džavík, Vladimír, Effron, Mark B, Eng, Heather F, Escobedo, Jorge, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Froess, Joshua D, Fu, Zhuxuan, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Girard, Timothy D, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Haniffa, Rashan, Hegde, Sheila M, Hendrickson, Carolyn M, Higgins, Alisa M, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Huang, David T, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei, King, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Grégoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Gallego Lima, Felipe, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Lother, Sylvain A, Marten, Nicole, Saud Marinez, Andréa, Martinez, Mary, Mateos Garcia, Eduardo, Mavromichalis, Stavroula, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nicolau, Jose C, Nunez-Garcia, Brenda, Park, John J, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Pompilio, Mauricio, Quigley, John G, Rosenson, Robert S, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler O, Satterwhite, Lewis, Saunders, Christina T, Schreiber, Jake, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Silva, Delcio G, Singhal, Aneesh B, Slutsky, Arthur S, Solvason, Dayna, Stanworth, Simon J, Turner, Anne M, van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zhong, Yongqi, Berry, Scott M, McArthur, Colin J, Neal, Matthew D, Hochman, Judith S, Webb, Steven A, Zarychanski, Ryan, Bradbury, Charlotte A [0000-0001-5248-8165], McVerry, Bryan J [0000-0002-1175-4874], Lawler, Patrick R [0000-0001-5155-5071], Carrier, Marc [0000-0001-8296-2972], Kim, Keri S [0000-0002-8480-4801], Houston, Brett L [0000-0002-8776-4083], Cushman, Mary [0000-0002-7871-6143], Tritschler, Tobias [0000-0002-8775-0511], Godoy, Lucas C [0000-0001-6171-1269], Gordon, Anthony C [0000-0002-0419-547X], Ahuja, Tania [0000-0003-1833-4124], Aryal, Diptesh [0000-0002-1431-8293], Baumann Kreuziger, Lisa [0000-0002-1171-0548], Beane, Abi [0000-0001-7046-1580], Coiffard, Benjamin [0000-0002-8896-5346], Detry, Michelle A [0000-0002-2794-1439], Escobedo, Jorge [0000-0003-1942-7402], Estcourt, Lise J [0000-0003-4309-9162], Everett, Brendan M [0000-0002-6331-5224], Fu, Zhuxuan [0000-0002-9190-195X], Galen, Benjamin T [0000-0001-8172-258X], Girard, Timothy D [0000-0002-9833-4871], Greenstein, Yonatan Y [0000-0002-5718-4408], Haniffa, Rashan [0000-0002-8288-449X], Hegde, Sheila M [0000-0001-8157-8899], Hendrickson, Carolyn M [0000-0003-4662-2385], Higgins, Alisa M [0000-0001-8295-7559], Hindenburg, Alexander A [0000-0002-1232-2168], Horvat, Christopher M [0000-0002-1593-2252], Huang, David T [0000-0001-7649-1633], Jacobson, Jeffrey R [0000-0001-8929-994X], Kim, Yuri [0000-0001-5978-5779], King, Andrew J [0000-0002-9809-0563], Kutcher, Matthew E [0000-0003-4566-5359], Leifer, Eric S [0000-0001-6888-8307], Litton, Edward [0000-0002-5125-6829], Mateos Garcia, Eduardo [0000-0002-0904-4056], Mouncey, Paul R [0000-0002-8510-8517], Nunez-Garcia, Brenda [0000-0002-0355-4557], Parnia, Sam [0000-0002-6158-4404], Quigley, John G [0000-0003-3116-4545], Saunders, Christina T [0000-0003-4325-9568], Yuriditsky, Eugene [0000-0003-2263-9297], Zhong, Yongqi [0000-0002-4042-7450], Neal, Matthew D [0000-0001-8931-6236], and Apollo - University of Cambridge Repository

Subjects
Male, Heparin, Critical Illness, Anticoagulants, COVID-19, Hemorrhage, Thrombosis, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Logistic Models, Odds Ratio, Humans, Female, Hospital Mortality, Treatment Failure, Aged
Abstract

BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio

Published
2021

91. Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

Author

Siemieniuk, Reed AC, primary, Bartoszko, Jessica J, additional, Díaz Martinez, Juan Pablo, additional, Kum, Elena, additional, Qasim, Anila, additional, Zeraatkar, Dena, additional, Izcovich, Ariel, additional, Mangala, Sophia, additional, Ge, Long, additional, Han, Mi Ah, additional, Agoritsas, Thomas, additional, Arnold, Donald, additional, Ávila, Camila, additional, Chu, Derek K, additional, Couban, Rachel, additional, Cusano, Ellen, additional, Darzi, Andrea J, additional, Devji, Tahira, additional, Foroutan, Farid, additional, Ghadimi, Maryam, additional, Khamis, Assem, additional, Lamontagne, Francois, additional, Loeb, Mark, additional, Miroshnychenko, Anna, additional, Motaghi, Sharhzad, additional, Murthy, Srinivas, additional, Mustafa, Reem A, additional, Rada, Gabriel, additional, Rochwerg, Bram, additional, Switzer, Charlotte, additional, Vandvik, Per O, additional, Vernooij, Robin WM, additional, Wang, Ying, additional, Yao, Liang, additional, Guyatt, Gordon H, additional, and Brignardello-Petersen, Romina, additional

Published
2021
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92. Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial

Author

Stoppe, Christian, McDonald, Bernard, Meybohm, Patrick, Christopher, Kenneth B., Fremes, Stephen, Whitlock, Richard, Mohammadi, Siamak, Kalavrouziotis, Dimitri, Elke, Gunnar, Rossaint, Rolf, Helmer, Philipp, Zacharowski, Kai, Günther, Ulf, Parotto, Matteo, Niemann, Bernd, Böning, Andreas, Mazer, C. David, Jones, Philip M., Ferner, Marion, Lamarche, Yoan, Lamontagne, Francois, Liakopoulos, Oliver J., Cameron, Matthew, Müller, Matthias, Zarbock, Alexander, Wittmann, Maria, Goetzenich, Andreas, Kilger, Erich, Schomburg, Lutz, Day, Andrew G., and Heyland, Daren K.

Abstract

IMPORTANCE: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. OBJECTIVE: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score–predicted mortality of 5% or more or planned combined surgical procedures were randomized. INTERVENTIONS: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 μg/L of sodium selenite prior to cardiopulmonary bypass, 2000 μg/L immediately postoperatively, and 1000 μg/L each day in intensive care for a maximum of 10 days or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. RESULTS: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction–free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. CONCLUSIONS AND RELEVANCE: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02002247

Published
2023
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93. What really matters in end-of-life discussions? Perspectives of patients in hospital with serious illness and their families

Author

You, John J., Dodek, Peter, Lamontagne, Francois, Downar, James, Sinuff, Tasnim, Jiang, Xuran, Day, Andrew G., and Heyland, Daren K.

Subjects
Terminally ill persons -- Beliefs, opinions and attitudes -- Family -- Care and treatment, Terminal care -- Social aspects, Health
Abstract

Background: The guideline-recommended elements to include in discussions about goals of care with patients with serious illness are mostly based on expert opinion. We sought to identify which elements are most important to patients and their families. Methods: We used a cross-sectional study design involving patients from 9 Canadian hospitals. We asked older adult patients with serious illness and their family members about the occurrence and importance of 11 guideline-recommended elements of goals-of-care discussions. In addition, we assessed concordance between prescribed goals of care and patient preferences, and we measured patient satisfaction with goals-of-care discussions using the Canadian Health Care Evaluation Project (CANHELP) questionnaire. Results: Our study participants included 233 patients (mean age 81.2 yr) and 205 family members (mean age 60.2 yr). Participants reported that clinical teams had addressed individual elements of goals-of-care discussions infrequently (range 1.4%-31.7%). Patients and family members identified the same 5 elements as being the most important to address: preferences for care in the event of life-threatening illness, values, prognosis, fears or concerns, and questions about goals of care. Addressing more elements was associated with both greater concordance between patients' preferences and prescribed goals of care, and greater patient satisfaction. Interpretation: We identified elements of goals-of-care discussions that are most important to older adult patients in hospital with serious illness and their family members. We found that guideline- recommended elements of goals-of-care discussions are not often addressed by health care providers. Our results can inform interventions to improve the determination of goals of care in the hospital setting., In Canada, dying is often an in-hospital, technology-laden experience. (1-4) Rates of cardiopulmonary resuscitation (CPR) before death continue to increase among older adult patients in hospital, (5) and one-fifth of [...]

Published
2014
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94. Clinical Presentation of Patients with Ebola Virus Disease in Conakry, Guinea

Author

Bah, Elhadj Ibrahima, Lamah, Marie-Claire, Fletcher, Tom, Jacob, Shevin T., Brett-Major, David M., Sall, Amadou Alpha, Shindo, Nahoko, Fischer, William A., Lamontagne, Francois, Saliou, Sow Mamadou, Bausch, Daniel G., Moumié, Barry, Jagatic, Tim, Sprecher, Armand, Lawler, James V., Mayet, Thierry, Jacquerioz, Frederique A., Méndez Baggi, María F., Vallenas, Constanza, Clement, Christophe, Mardel, Simon, Faye, Ousmane, Faye, Oumar, Soropogui, Baré, Magassouba, Nfaly, Koivogui, Lamine, Pinto, Ruxandra, and Fowler, Robert A.

Published
2015
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95. Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19.

Author

Rocheleau, Genevieve L. Y., Lee, Terry, Mohammed, Yassene, Goodlett, David, Burns, Kevin, Cheng, Matthew P., Tran, Karen, Sweet, David, Marshall, John, Slutsky, Arthur S., Murthy, Srinivas, Singer, Joel, Patrick, David M., Du, Bin, Peng, Zhiyong, Lee, Todd C., Boyd, John H., Walley, Keith R., Lamontagne, Francois, and Fowler, Robert

Published
2022
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96. Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

Author

Zeraatkar, Dena, primary, Cusano, Ellen, additional, Martinez, Juan Pablo Díaz, additional, Qasim, Anila, additional, Mangala, Sophia O., additional, Kum, Elena, additional, Bartoszko, Jessica J., additional, Devji, Tahira, additional, Agoritsas, Thomas, additional, Lamontagne, Francois, additional, Rochwerg, Bram, additional, Vandvik, Per O, additional, Brignardello-Petersen, Romina, additional, and Siemieniuk, Reed, additional

Published
2021
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97. Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19: Meta-analysis/Meta-regression Adjusted for Confounding Factors

Author

Lee, Terry, primary, Cau, Alessandro, additional, Cheng, Matthew Pellan, additional, Levin, Adeera, additional, Lee, Todd C., additional, Vinh, Donald C., additional, Lamontagne, Francois, additional, Singer, Joel, additional, Walley, Keith R., additional, Murthy, Srinivas, additional, Patrick, David, additional, Rewa, Oleksa G., additional, Winston, Brent W., additional, Marshall, John, additional, Boyd, John, additional, Tran, Karen, additional, Kalil, Andre C., additional, Mcculoh, Russell, additional, Fowler, Robert, additional, Luther, James M., additional, and Russell, James A., additional

Published
2021
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98. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19 – Preliminary report

Author

Gordon, Anthony C., Mouncey, Paul R., Al-Beidh, Farah, Rowan, Kathryn M., Nichol, Alistair D., Arabi, Yaseen M., Annane, Djillali, Beane, Abi, van Bentum-Puijk, Wilma, Berry, Lindsay R., Bhimani, Zahra, Bonten, Marc J.M., Bradbury, Charlotte A., Brunkhorst, Frank M., Buzgau, Adrian, Cheng, Allen C., Detry, Michelle A., Duffy, Eamon J., Estcourt, Lise J., Fitzgerald, Mark, Goossens, Herman, Haniffa, Rashan, Higgins, Alisa M., Hills, Thomas E., Horvat, Christopher M., Lamontagne, Francois, Lawler, Patrick R., Leavis, Helen L., Linstrum, Kelsey M., Litton, Edward, Lorenzi, Elizabeth, Marshall, John C., Mayr, Florian B., McAuley, Danny, McGlothlin, Anna, McGuinness, Shay P, McVerry, Bryan J., Montgomery, Stephanie K., Morpeth, Susan C., Murthy, Srinivas, Orr, Katrina, Parke, Rachael L., Parker, Jane C., Patanwala, Asad E., Pettilä, Ville, Rademaker, Emma, Santos, Marlene S., Saunders, Christina T., Seymour, Christopher W., Shankar-Hari, Manu, Sligl, Wendy I., Turgeon, Alexis F., Turner, Anne M., van de Veerdonk, Frank L., Zarychanski, Ryan, Green, Cameron, Lewis, Roger J., Angus, Derek C., McArthur, Colin J., Berry, Scott, Webb, Steve A., and Derde, Lennie P.G.

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, COVID-19, Odds ratio, Intensive care unit, law.invention, Coronavirus, Sarilumab, chemistry.chemical_compound, Tocilizumab, chemistry, Interquartile range, law, Intensive care, Internal medicine, Interleukin-6 receptor, Medicine, business
Abstract

BackgroundThe efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.MethodsWe evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours of commencing organ support in an intensive care unit, were randomized to receive either tocilizumab (8mg/kg) or sarilumab (400mg) or standard care (control). The primary outcome was an ordinal scale combining in-hospital mortality (assigned −1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with pre-defined triggers to declare superiority, efficacy, equivalence or futility.ResultsTocilizumab and sarilumab both met the pre-defined triggers for efficacy. At the time of full analysis 353 patients had been assigned to tocilizumab, 48 to sarilumab and 402 to control. Median organ support-free days were 10 (interquartile range [IQR] −1, 16), 11 (IQR 0, 16) and 0 (IQR −1, 15) for tocilizumab, sarilumab and control, respectively. Relative to control, median adjusted odds ratios were 1.64 (95% credible intervals [CrI] 1.25, 2.14) for tocilizumab and 1.76 (95%CrI 1.17, 2.91) for sarilumab, yielding >99.9% and 99.5% posterior probabilities of superiority compared with control. Hospital mortality was 28.0% (98/350) for tocilizumab, 22.2% (10/45) for sarilumab and 35.8% (142/397) for control. All secondary outcomes and analyses supported efficacy of these IL-6 receptor antagonists.ConclusionsIn critically ill patients with Covid-19 receiving organ support in intensive care, treatment with the IL-6 receptor antagonists, tocilizumab and sarilumab, improved outcome, including survival. (ClinicalTrials.govnumber:NCT02735707)

Published
2021

99. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author

Lawler, Patrick R, Golighe, Ewan C, Berge, Jeffrey S, Neal, Matthew D, McVerry, Bryan J, Nicolau, Jose C, Gong, Michelle N, Carrier, Marc, Rosenson, Robert S, Reynolds, Harmony R, Turgeon, Alexis F, Escobedo, Jorge, Huang, David T, Bradbury, Charlotte A, Houston, Brett L, Kornblith, Lucy Z, Kumar, Anand, Kah, Susan RN, Cushman, Mary, McQuilten, Zoe, Slutsky, Arthur S, Kim, Keri S, Gordon, Anthony C, Kirwan, Bridget-Anne, Brooks, Maria M, Higgins, Alisa M, Lewis, Roger J, Lorenzi, Elizabeth, Berry, Scott M, Berry, Lindsay R, Angus, Derek C, McArthur, Colin J, Webb, Steven A, Farkouh, Michael E, Hochman, Judith S, Zarychanski, Ryan, Aday, Aaron W, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen M, Aryal, Diptesh, Kreuziger, Lisa Baumann, Beane, Abi, Bhimani, Zahra, Bihari, Shailesh, Billett, Henny H, Bond, Lindsay, Bonten, Marc, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Castellucci, Lana A, Chekuri, Sweta, Chen, Jen-Ting, Cheng, Allen C, Chkhikvadzw, Tamta, Coiffard, Benjamin, Costantini, Todd W, de Brouwer, Sophie, Derde, Lennie PG, Detry, Michelle A, Duggal, Abhijit, Dzavik, Vladimir, Effron, Mark B, Estcourt, Lise J, Everett, Brendan M, Fergusson, Dean A, Fitzgerald, Mark, Fowler, Robert A, Galanaud, Jean P, Galen, Benjamin T, Gandotra, Sheetal, Garcia-Madrona, Sebastian, Girard, Timothy D, Godoy, Lucas C, Goodman, Andrew L, Goossens, Herman, Green, Cameron, Greenstein, Yonatan Y, Gross, Peter L, Hamburg, Naomi M, Haniffa, Rashan, Hanna, George, Hanna, Nicholas, Hegde, Sheila M, Hendrickson, Carolyn M, Hite, R Duncan, Hindenburg, Alexander A, Hope, Aluko A, Horowitz, James M, Horvat, Christopher M, Hudock, Kristin, Hunt, Beverley J, Husain, Mansoor, Hyzy, Robert C, Iyer, Vivek N, Jacobson, Jeffrey R, Jayakumar, Devachandran, Keller, Norma M, Khan, Akram, Kim, Yuri, Kindzelski, Andrei L, Kin, Andrew J, Knudson, M Margaret, Kornblith, Aaron E, Krishnan, Vidya, Kutcher, Matthew E, Laffan, Michael A, Lamontagne, Francois, Le Gal, Gregoire, Leeper, Christine M, Leifer, Eric S, Lim, George, Lima, Felipe Gallego, Linstrum, Kelsey, Litton, Edward, Lopez-Sendon, Jose, Moreno, Jose L Lopez-Sendon, Lother, Sylvain A, Malhotra, Saurabh, Marcos, Miguel, Marinez, Andrea Saud, Marshall, John C, Marten, Nicole, Matthay, Michael A, McAuley, Daniel F, McDonald, Emily G, McGlothlin, Anna, McGuinness, Shay P, Middeldorp, Saskia, Montgomery, Stephanie K, Moore, Steven C, Guerreor, Raquel Morillo, Mouncey, Paul R, Murthy, Srinivas, Nair, Girish B, Nair, Rahul, Nichol, Alistair D, Nunez-Garcia, Brenda, Pandey, Ambarish, Park, Pauline K, Parke, Rachael L, Parker, Jane C, Parnia, Sam, Paul, Jonathan D, Gonzalez, Yessica S Perez, Pompilio, Mauricio, Prekker, Matthew E, Quigley, John G, Rost, Natalia S, Rowan, Kathryn, Santos, Fernanda O, Santos, Marlene, Santos, Mayler Olombrada, Satterwhite, Lewis, Saunders, Christina T, Schutgens, Roger EG, Seymour, Christopher W, Siegal, Deborah M, Jr, Silva Delcio G, Shankar-Hari, Manu, Sheehan, John P, Singhal, Aneesh B, Solvaso, Dayna, Stanworth, Simon J, Tritschler, Tobias, Turner, Anne M, Van Bentum-Puijk, Wilma, van de Veerdonk, Frank L, van Diepen, Sean, Vazquez-Grande, Gloria, Wahid, Lana, Wareham, Vanessa, Wells, Bryan J, Widmer, R Jay, Wilson, Jennifer G, Yuriditsky, Eugene, Zampieri, Fernando G, Investigators, ATTACC, Investigators, ACTIV-4a, Investigators, REMAP-CAP, Investigators, ATTACC, Investigators, ACTIV-4a, Investigators, REMAP-CAP, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 215522, AR7-162822, CS-2016-16-011, RP-2015-06-18, National Institutes of Health, NIH: 1OT2HL156812-01, OTA-20-011, UL1TR001445, National Heart, Lung, and Blood Institute, NHLBI, Breast Cancer Research Foundation, BCRF, National Center for Advancing Translational Sciences, NCATS, New York University, NYU, Medical Center, University of Pittsburgh, CancerCare Manitoba Foundation, CCMF, University of Manitoba, UM, Health Research Board, HRB: CTN 2014-012, Canadian Institutes of Health Research, CIHR, National Institute for Health Research, NIHR, European Commission, EC: 602525, FP7-HEALTH-2013-INNOVATION, National Health and Medical Research Council, NHMRC: APP1101719, APP1116530, Health Research Council of New Zealand, HRC: 158584, 16/631, 447335, Canada Research Chairs, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Horizon 2020: 101003589, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, The ATTACC platform was supported by grants from the Canadian Institutes of Health Research, LifeArc Foundation, Thistledown Foundation, Research Manitoba, Ontario Ministry of Health, Peter Munk Cardiac Centre, CancerCare Manitoba Foundation, and Victoria General Hospital Foundation. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (grant numbers, OTA-20-011 and 1OT2HL156812-01). The pilot program (PROTECT) was funded in part by a grant (UL1TR001445) from the New York University Clinical and Translational Science Award program, supported by the National Center for Advancing Translational Sciences of the NIH. The REMAP-CAP platform was supported by the European Union through FP7-HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium (602525) and the Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium (101003589), by the Australian National Health and Medical Research Council (APP1101719 and APP1116530), the Health Research Council of New Zealand (16/631), the Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant [158584] and Covid-19 Rapid Research Operating Grant [447335]), the U.K. National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the Learning While Doing Program at the University of Pittsburgh Medical Center, the Breast Cancer Research Foundation, the French Ministry of Health (PHRC-20-0147), the Minderoo Foundation, Am-gen, Eisai, the Global Coalition for Adaptive Research, and the Wellcome Trust Innovations Project (215522). Dr. Goligher is the recipient of an Early Career Investigator award from the Canadian Institutes of Health Research (grant AR7-162822). Dr. Gordon is supported by an NIHR Research Professorship (RP-2015-06-18), Dr. Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011), and Dr. Turgeon by a Canada Research Chair (Tier 2). Dr. Zarychanski is the recipient of the Lyonel G. Israels Research Chair in Hematology (University of Manitoba)., Listed are data that were included in the analysis involving patients with moderate severity of coronavirus disease 2019 (Covid-19). The denominators of patients in the anticoagulation group and the thrombophylaxis group are un-equal owing to response-adaptive randomization. The baseline characteristics of the patients according to d-dimer level are provided in Table S2 in the Supplementary Appendix. To convert the values for creatinine to micromoles per liter, multiply by 88.4. ULN denotes upper limit of the normal range. † Race or ethnic group was reported by the patients. ‡ The body-mass index is the weight in kilograms divided by the square of the height in meters. § Severe cardiovascular disease was defined as a baseline history of heart failure, myocardial infarction, coronary artery disease, peripheral arterial disease, or cerebrovascular disease (stroke or transient ischemic attack) in the ATTACC (Antithrombotic Therapy to Ameliorate Complications of Covid-19) and ACTIV-4a (A Multicenter, Adaptive, Ran-domized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults with COVID-19) platforms and as a baseline history of New York Heart Association class IV symptoms in the REMAP-CAP platform (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia). ¶ Chronic respiratory disease was defined as a baseline history of asthma, chronic obstructive pulmonary disease, bron-chiectasis, interstitial lung disease, primary lung cancer, pulmonary hypertension, active tuberculosis, or the receipt of home oxygen therapy. ‖ Not listed are 74 patients who were coenrolled in the REMAP-CAP Antiplatelet Domain (39 in the anticoagulation group and 35 in the thromboprophylaxis group). ** In REMAP-CAP, levels of oxygen support (including no support) below the level of high-flow nasal cannula were not reported. †† The relative proportion of patients who were randomly assigned in each platform was imbalanced owing to imple-mentation of response-adaptive randomization in ATTACC on December 15, 2020. ‡‡ A total of 215 patients who were enrolled in the ATTACC platform were funded by the ACTIV4a platform by the National Heart, Lung, and Blood Institute. §§ Other participating countries were Mexico, Nepal, Australia, the Netherlands, and Spain., ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, Lawler, Patrick R [0000-0001-5155-5071], Neal, Matthew D [0000-0001-8931-6236], McVerry, Bryan J [0000-0002-1175-4874], Carrier, Marc [0000-0001-8296-2972], Escobedo, Jorge [0000-0003-1942-7402], Huang, David T [0000-0001-7649-1633], Bradbury, Charlotte A [0000-0001-5248-8165], Houston, Brett L [0000-0002-8776-4083], Kornblith, Lucy Z [0000-0002-1861-9691], Kim, Keri S [0000-0002-8480-4801], Gordon, Anthony C [0000-0002-0419-547X], Higgins, Alisa M [0000-0001-8295-7559], Aday, Aaron W [0000-0001-6243-3432], Aryal, Diptesh [0000-0002-1431-8293], Baumann Kreuziger, Lisa [0000-0002-1171-0548], Beane, Abi [0000-0001-7046-1580], Coiffard, Benjamin [0000-0002-8896-5346], Derde, Lennie PG [0000-0002-3577-5629], Detry, Michelle A [0000-0002-2794-1439], Estcourt, Lise J [0000-0003-4309-9162], Everett, Brendan M [0000-0002-6331-5224], Galen, Benjamin T [0000-0001-8172-258X], Girard, Timothy D [0000-0002-9833-4871], Godoy, Lucas C [0000-0001-6171-1269], Greenstein, Yonatan Y [0000-0002-5718-4408], Haniffa, Rashan [0000-0002-8288-449X], Hanna, George [0000-0001-8737-3843], Hegde, Sheila M [0000-0001-8157-8899], Hendrickson, Carolyn M [0000-0003-4662-2385], Hite, R Duncan [0000-0002-2625-8750], Hindenburg, Alexander A [0000-0002-1232-2168], Horvat, Christopher M [0000-0002-1593-2252], Jacobson, Jeffrey R [0000-0001-8929-994X], Kim, Yuri [0000-0001-5978-5779], King, Andrew J [0000-0002-9809-0563], Kutcher, Matthew E [0000-0003-4566-5359], Lima, Felipe Gallego [0000-0003-1204-5743], Lopez-Sendon Moreno, Jose L [0000-0001-9414-3990], Marcos, Miguel [0000-0003-1269-4487], McGlothlin, Anna [0000-0002-9079-6166], Mouncey, Paul R [0000-0002-8510-8517], Nunez-Garcia, Brenda [0000-0002-0355-4557], Parnia, Sam [0000-0002-6158-4404], Quigley, John G [0000-0003-3116-4545], Saunders, Christina T [0000-0003-4325-9568], Shankar-Hari, Manu [0000-0002-5338-2538], Sheehan, John P [0000-0002-4328-2613], Tritschler, Tobias [0000-0002-8775-0511], Yuriditsky, Eugene [0000-0003-2263-9297], Zampieri, Fernando G [0000-0001-9315-6386], Angus, Derek C [0000-0002-7026-5181], Apollo - University of Cambridge Repository, NIHR, and National Institute for Health Research

Subjects
Male, covid-19, anticoagulation, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 030204 cardiovascular system & hematology, heparin, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Hemorrhage/chemically induced, 030212 general & internal medicine, Hospital Mortality, Heparin/administration & dosage, anticoagulation, 11 Medical and Health Sciences, Anticoagulants/administration & dosage, Thrombosis/prevention & control, low molecular weight heparin, General Medicine, Heparin, Middle Aged, Thrombosis, Patient Discharge, 3. Good health, Coagulation, Original Article, Female, ATTACC Investigators, medicine.symptom, Covid-19, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, medicine.drug_class, adaptive platform trial, Low molecular weight heparin, Inflammation, Hemorrhage, COVID-19/drug therapy, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, medicine, Humans, Intensive care medicine, Survival analysis, Aged, Science & Technology, business.industry, SARS-CoV-2, Anticoagulants, COVID-19, Odds ratio, Heparin, Low-Molecular-Weight, medicine.disease, Survival Analysis, COVID-19 Drug Treatment, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Heparin, Low-Molecular-Weight/therapeutic use, ACTIV-4a Investigators, Human medicine, REMAP-CAP Investigators, business
Abstract

BACKGROUNDThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODSIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTSThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.CONCLUSIONSIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589. opens in new tab, NCT04505774. opens in new tab, NCT02735707. opens in new tab, and NCT04359277. opens in new tab.)

Published
2021

100. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis

Author

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, [missing], Domingo, Pere, Mur, Isabel, Mateo, Gracia María, Gutierrez, Maria del Mar, Pomar, Virginia, de Benito, Natividad, Corbacho, Noemí, Herrera, Silvia, Millan, Lucia, Muñoz, Jessica, Malouf, Jorge, Molas, Maria Ema, Asensi, Victor, Horcajada, Juan Pablo, Estrada, Vicente, Gutierrez, Felix, Torres, Ferran, Perez-Molina, Jose A, Fortun, Jesús, Villar, Luisa M, Hohenthal, Ulla, Marttila, Harri, Vuorinen, Tytti, Nordberg, Marika, Valtonen, Mika, Frigault, Matthew J, Mansour, Michael K, Patel, Naomi J, Fernandes, Ana, Harvey, Liam, Foulkes, Andrea S, Healy, Brian C, Shah, Ruta, Bensaci, Ana Maria, Woolley, Ann E., Nikiforow, Sarah, Lin, Nina, Sagar, Manish, Shrager, Harry, Huckins, David S., Axelrod, Matthew, Pincus, Michael D, Fleisher, Jorge, Lampa, Jon, Nowak, Piotr, Vesterbacka, Jan C., Rasmuson, Johan, Skorup, Paul, Janols, Helena, Niward, Katarina F, Chatzidionysiou, Katerina, Asgeirsson, Hilmir, Parke, Åsa, Blennow, Ola, Svensson, Anna-Karin, Aleman, Soo, Sönnerborg, Anders, Henter, Jan-Inge, Horne, Anna Carin, Al-Beidh, Farah, Angus, Derek, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, Berry, Scott, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Cheng, Allen, Cove, Matt, De Jong, Menno, Derde, Lennie, Estcourt, Lise, Goossens, Herman, Gordon, Anthony, Green, Cameron, Haniffa, Rashan, Ichihara, Nao, Lamontagne, Francois, Lawler, Patrick, Litton, Ed, Marshall, John, McArthur, Colin, McAuley, Daniel, McGuinness, Shay, McVerry, Bryan, Montgommery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Reyes, Felipe, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Seymour, Chris, Shankar-Hari, Manu, Turgeon, Alexis, Turner, Anne, van Bentum-Puijk, Wilma, van de Veerdonk, Frank, Webb, Steve, Zarychanski, Ryan, Baillie, J Kenneth, Beasley, Richard, Cooper, Nichola, Fowler, Robert, Galea, James, Hills, Thomas, King, Andrew, Morpeth, Susan, Netea, Mihai, Ogungbenro, Kayode, Pettila, Ville, Tong, Steve, Uyeki, Tim, Youngstein, Taryn, Higgins, Alisa, Lorenzi, Elizabeth, Berry, Lindsay, Salama, Carlos, Rosas, Ivan O., Ruiz-Antorán, Belén, Muñez Rubio, Elena, Ramos Martínez, Antonio, Campos Esteban, José, Avendaño Solá, Cristina, Pizov, Reuven, Sanz Sanz, Jesus, Abad-Santos, Francisco, Bautista-Hernández, Azucena, García-Fraile, Lucio, Barrios, Ana, Gutiérrez Liarte, Ángela, Alonso Pérez, Tamara, Rodríguez-García, Sebastian C, Mejía-Abril, Gina, Prieto, Jose Carlos, Leon, Rafael, VEIGA, VIVIANE C., SCHEINBERG, PHILLIP, FARIAS, DANIELLE L.C., PRATS, JOÃO G., CAVALCANTI, ALEXANDRE B., MACHADO, FLAVIA R., ROSA, REGIS G., BERWANGER, OTÁVIO, AZEVEDO, LUCIANO C.P., LOPES, RENATO D., DOURADO, LETICIA K., CASTRO, CLAUDIO G., ZAMPIERI, FERNANDO G., AVEZUM, ALVARO, LISBOA, THIAGO C., ROJAS, SALOMÓN S.O., COELHO, JULIANA C., LEITE, RODRIGO T., CARVALHO, JULIO CESAR, ANDRADE, LUIS E.C., SANDES, ALEX R., PINTÃO, MARIA CAROLINA T., SANTOS, SUELI V., ALMEIDA, THIAGO M.L., COSTA, ANDRÉ N., GEBARA, OTAVIO C.E., FREITAS, FLAVIO G.R., PACHECO, EDUARDO S., MACHADO, DAVID J.B., MARTIN, JOSIANE, CONCEIÇÃO, FABIO G., SIQUEIRA, SUELLEN R.R., DAMIANI, LUCAS P., ISHIHARA, LUCIANA M., SCHNEIDER, DANIEL, DE SOUZA, DENISE, Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre Louis, Resche Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Tibi, Annick, Yazdanpanah, Yazdan, Dougados, Maxime, Bureau, Serge, Horby, Peter W, Landray, Martin J, Baillie, Kenneth J, Buch, Maya H, Chappell, Lucy C, Day, Jeremy N, Faust, Saul N, Haynes, Richard, Jaki, Thomas, Jeffery, Katie, Juszczak, Edmund, Lim, Wei Shen, Mafham, Marion, Montgomery, Alan, Mumford, Andrew, Thwaites, Guy, Kamarulzaman, Adeeba, Syed Omar, Sharifah Faridah, Ponnampalavanar, Sasheela, Raja Azwa, Raja Iskandar Syah, Wong, Pui Li, Kukreja, Anjanna, Ong, Hang Cheng, Sulaiman, Helmi, Basri, Sazali, Ng, Rong Xiang, Megat Johari, Bushra, Rajasuriar, Reena, Chong, Meng Li, Neelamegam, Malinee, Syed Mansor, Syed Mukhtar, Zulhaimi, Nurul Syuhada, Lee, Cheng Siang, Altice, Frederick, Price, Christina, Malinis, Maricar, Hasan, Mohd Shahnaz, Wong, Chee Kuan, Chidambaram, Suresh, Misnan, Nor Arisah, Mohd Thabit, Alif Adlan, Sim, Benedict, Bidin, Farah Nadiah, Mohd Abd Rahim, Mohd Abd Hafiz, Saravanamuttu, Sujana, Tuang, Wei Xuan, Mohamed Gani, Yasmin, Thangavelu, Suvintheran, Tay, Kim Heng, Ibrahim, Nur Munirah, Halid, Luqman Alhakim, Tan, Kok Tong, Mukri, Mohd Noor Azreet, Arip, Masita, Koh, Hui Moon, Syed Badaruddin, Syarifah Nurul Ain, Raja Sureja, Letchumi, Chun, Geok Ying, TORRE-CISNEROS, JULIAN, MERCHANTE, NICOLAS, LEON, RAFAEL, CARCEL, SHEILA, GARRIDO, JOSE CARLOS, Galun, Eitan, Soriano, Alex, Martínez, José Antonio, Castán, Clara, Paredes, Roger, Dalmau, David, Carbonell, Cristina, Espinosa, Gerard, Castro, Pedro, Muñóz, José, Almuedo, Alex, Prieto, Sergio, Pacheco, Iván, Ratain, Mark, Pisano, Jennifer, Strek, Mary, Adegunsoye, Ayodeji, Karrison, Theodore, Declercq, Jozefien, Van Damme, Karel, De Leeuw, Elisabeth, Bosteels, Cedric, Maes, Bastiaan, Vale, Claire L., Godolphin, Peter J., Fisher, David, Higgins, Julian P. T., Spiga, Francesca, Savovic, Jelena, Tierney, Jayne, Baron, Gabriel, Benbenishty, Julie S., Berry, Lindsay R., Broman, Niklas, Cavalcanti, Alexandre Biasi, Colman, Roos, De Buyser, Stefanie, Derde, Lennie P. G., Omar, Sharifah Faridah, Fernandez-Cruz, Ana, Feuth, Thijs, Garcia, Felipe, Garcia-Vicuna, Rosario, Gonzalez-Alvaro, Isidoro, Gordon, Anthony C., Horby, Peter W., Horick, Nora K., Kumar, Kuldeep, Lambrecht, Bart, Landray, Martin J., Leal, Lorna, Lederer, David J., Merchante, Nicolas, Mohan, Shalini V., Nivens, Michael C., Oksi, Jarmo, Perez-Molina, Jose A., Postma, Simone, Ramanan, Athimalaipet V., Reid, Pankti D., Rutgers, Abraham, Sancho-Lopez, Aranzazu, Seto, Todd B., Sivapalasingam, Sumathi, Soin, Arvinder Singh, Staplin, Natalie, Stone, John H., Strohbehn, Garth W., Sunden-Cullberg, Jonas, Torre-Cisneros, Julian, Tsai, Larry W., van Hoogstraten, Hubert, van Meerten, Tom, Veiga, Viviane Cordeiro, Westerweel, Peter E., Diaz, Janet V., Marshall, John C., Sterne, Jonathan A. C., Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), World Health Organization, and Group, WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working

Subjects
Male, medicine.medical_specialty, Randomization, Secondary infection, Placebo, Antibodies, Monoclonal, Humanized, Internal medicine, Cause of Death, Medicine and Health Sciences, Medicine, Humans, Prospective Studies, Prospective cohort study, Glucocorticoids, METAANALYSIS, Cause of death, Aged, Randomized Controlled Trials as Topic, business.industry, Coinfection, Interleukin-6, COVID-19, Odds ratio, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Hospitalization, Meta-analysis, Disease Progression, Drug Therapy, Combination, Female, business
Abstract

[Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.

Published
2021

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