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

Educational Objective
To understand the effects of hydrocortisone on mortality and organ support in patients with severe COVID-19
1 Credit CME
Key Points

Question  Does intravenous hydrocortisone, administered either as a 7-day fixed-dose course or restricted to when shock is clinically evident, improve 21-day organ support–free days (a composite end point of in-hospital mortality and the duration of intensive care unit–based respiratory or cardiovascular support) in patients with severe coronavirus disease 2019 (COVID-19)?

Findings  In this bayesian randomized clinical trial that included 403 patients and was stopped early after results from another trial were released, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority, respectively, with regard to the odds of improvement in organ support–free days within 21 days.

Meaning  Although suggestive of benefit for hydrocortisone in patients with severe COVID-19, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Abstract

Importance  Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective  To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, and Participants  An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.

Interventions  The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).

Main Outcomes and Measures  The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).

Results  After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.

Conclusions and Relevance  Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.

Trial Registration  ClinicalTrials.gov Identifier: NCT02735707

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Article Information

Accepted for Publication: August 21, 2020.

Corresponding Author: Derek C. Angus, MD, MPH, Department of Critical Care Medicine, University of Pittsburgh, 3550 Terrace St, 614 Scaife Hall, Pittsburgh, PA 15261 (angusdc@upmc.edu).

Published Online: September 2, 2020. doi:10.1001/jama.2020.17022

Authors/Writing Committee for REMAP-CAP: Derek C. Angus, MD, MPH; Lennie Derde, MD; Farah Al-Beidh, PhD; Djillali Annane, MD, PhD; Yaseen Arabi, MD; Abigail Beane, MSc; Wilma van Bentum-Puijk, MS; Lindsay Berry, PhD; Zahra Bhimani, MPH, PMP; Marc Bonten, MD; Charlotte Bradbury, MD, PhD; Frank Brunkhorst, MD; Meredith Buxton, PhD; Adrian Buzgau, MSc; Allen C. Cheng, MD; Menno de Jong, MD; Michelle Detry, PhD; Lise Estcourt, MD; Mark Fitzgerald, PhD; Herman Goossens, MD; Cameron Green, MSc; Rashan Haniffa, MD; Alisa M. Higgins, PhD; Christopher Horvat, MD, MHA; Sebastiaan J. Hullegie, MD; Peter Kruger, MD; Francois Lamontagne, MD; Patrick R. Lawler, MD; Kelsey Linstrum, MS; Edward Litton, MD; Elizabeth Lorenzi, PhD; John Marshall, MD; Daniel McAuley, MD; Anna McGlothin, PhD; Shay McGuinness, MD; Bryan McVerry, MD; Stephanie Montgomery, MS; Paul Mouncey, MSc; Srinivas Murthy, MD; Alistair Nichol, MD; Rachael Parke, RN, PhD; Jane Parker, RN; Kathryn Rowan, PhD; Ashish Sanil, PhD; Marlene Santos, MSc; Christina Saunders, PhD; Christopher Seymour, MD, MSc; Anne Turner, RN, MPH; Frank van de Veerdonk, MD; Balasubramanian Venkatesh, MD; Ryan Zarychanski, MD; Scott Berry, PhD; Roger J. Lewis, MD, PhD; Colin McArthur, MD; Steven A. Webb, MD, PhD; Anthony C. Gordon, MD.

Affiliations of Authors/Writing Committee for REMAP-CAP: The Clinical Research Investigation and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Angus, Horvat, Linstrum, Montgomery, Seymour); The UPMC Health System Office of Healthcare Innovation, Pittsburgh, Pennsylvania (Angus, Horvat, Montgomery, Seymour); Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands (Derde, van Bentum-Puijk, Bonten, Hullegie); Intensive Care Center, University Medical Center Utrecht, Utrecht, the Netherlands (Derde); Division of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom (Al-Beidh, Gordon); Intensive Care Unit, Raymond Poincaré Hospital (AP-HP), Paris, France (Annane); Simone Veil School of Medicine, University of Versailles, Versailles, France (Annane); University Paris Saclay, Garches, France (Annane); Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia (Arabi); Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom (Beane); Berry Consultants LLC, Austin, Texas (L. Berry, Detry, Fitzgerald, Lorenzi, McGlothin, Sanil, Saunders, S. Berry, Lewis); Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada (Bhimani, Marshall, Santos); Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands (Bonten); Bristol Royal Informatory, Bristol, United Kingdom (Bradbury); University of Bristol, Bristol, United Kingdom (Bradbury); Center for Clinical Studies and Center for Sepsis Control and Care (CSCC), Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany (Brunkhorst); Global Coalition for Adaptive Research, San Francisco, California (Buxton); Helix, Monash University, Melbourne, Victoria, Australia (Buzgau); Infection Prevention and Healthcare Epidemiology Unit, Alfred Health, Melbourne, Victoria, Australia (Cheng); Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia (Cheng, Green, Higgins, McGuinness, Nichol, Parker, Webb); Department of Medical Microbiology, Amsterdam University Medical Center, University of Amsterdam, the Netherlands (de Jong); Department of Microbiology, Antwerp University Hospital, Antwerp, Belgium (Goossens); NHS Blood and Transplant, Bristol, United Kingdom (Estcourt); Transfusion Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom (Estcourt); Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka (Haniffa); Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand (Haniffa); Intensive Care Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia (Kruger); Université de Sherbrooke, Sherbrooke, Quebec, Canada (Lamontagne); Cardiac Intensive Care Unit, Peter Munk Cardiac Centre, University Health Network, Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada (Lawler); School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia, Australia (Litton, Webb); Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada (Marshall); Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, United Kingdom (McAuley); Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand (McGuinness, Parke); The Health Research Council of New Zealand, Wellington, New Zealand (McGuinness, Parke); Medical Research Institute of New Zealand, Wellington, New Zealand (McGuinness, Parke, Turner, McArthur); Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (McVerry); Clinical Trials Unit, Intensive Care National Audit & Research Centre (ICNARC), London, United Kingdom (Mouncey, Rowan); University of British Columbia School of Medicine, Vancouver, Canada (Murthy); Department of Anesthesia and Intensive Care, St Vincent’s University Hospital, Dublin, Ireland (Nichol); School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland (Nichol); Department of Intensive Care, Alfred Health, Melbourne, Victoria, Australia (Nichol); School of Nursing, University of Auckland, Auckland, New Zealand (Parke); Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (van de Veerdonk); Southside Clinical Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia (Venkatesh); The George Institute for Global Health, Sydney, Australia (Venkatesh); Department of Medicine, Critical Care and Hematology/Medical Oncology, University of Manitoba, Winnipeg, Manitoba, Canada (Zarychanski); Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, California (Lewis); Department of Emergency Medicine, David Geffen School of Medicine at University of California, Los Angeles (Lewis); Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand (McArthur); St John of God Hospital, Subiaco, Western Australia, Australia (Webb).

Author Contributions: Dr Angus had full access to all corticosteroid domain data and all baseline data in the study; Dr Lewis had full access to all data required for the primary analyses. Together, Drs Angus and Lewis take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Angus, S. Berry, Bonten, Cheng, de Jong, Derde, Fitzgerald, Goossens, Gordon, Green, Horvat, Kruger, Lawler, Lewis, Litton, Marshall, McArthur, McGuinness, Montgomery, Murthy, Nichol, Parke, Parker, Rowan, Seymour, Venkatesh, Webb.

Acquisition, analysis, or interpretation of data: Angus, Al-Beidh, Annane, Arabi, Bentum-Puijk, Beane, L. Berry, S. Berry, Mouncey, Bhimani, Bonten, Bradbury, Brunkhorst, Buxton, Buzgau, Cheng, Derde, Detry, Estcourt, Fitzgerald, Gordon, Green, Haniffa, Higgins, Horvat, Hullegie, Kruger, Lamontagne, Lewis, Linstrum, Lorenzi, Marshall, McArthur, McAuley, McGlothlin, McGuinness, McVerry, Murthy, Nichol, Parker, Rowan, Sanil, Santos, Saunders, Seymour, Turner, van de Veerdonk, Webb, Zarychanski.

Drafting of the manuscript: Angus, S. Berry, Gordon, Horvat, Marshall, McArthur, Murthy, Santos.

Critical revision of the manuscript for important intellectual content: Angus, Al-Beidh, Annane, Arabi, Bentum-Puijk, Beane, L. Berry, S. Berry, Mouncey, Bhimani, Bonten, Bradbury, Brunkhorst, Buxton, Buzgau, Cheng, de Jong, Derde, Detry, Estcourt, Fitzgerald, Goossens, Gordon, Green, Haniffa, Higgins, Horvat, Hullegie, Kruger, Lamontagne, Lawler, Lewis, Linstrum, Litton, Lorenzi, Marshall, McArthur, McAuley, McGlothlin, McGuinness, McVerry, Montgomery, Nichol, Parke, Parker, Rowan, Sanil, Saunders, Seymour, Turner, van de Veerdonk, Venkatesh, Webb, Zarychanski.

Statistical analysis: Angus, L. Berry, S. Berry, Detry, Fitzgerald, Higgins, Lewis, Lorenzi, McGlothlin, Sanil, Saunders, Seymour, Webb.

Obtained funding: Annane, Bonten, Buxton, Cheng, de Jong, Derde, Estcourt, Goossens, Gordon, Higgins, Kruger, Litton, Marshall, McArthur, Montgomery, Murthy, Nichol, Rowan, Turner, Webb.

Administrative, technical, or material support: Angus, Al-Beidh, Arabi, Bentum-Puijk, Mouncey, Bhimani, Brunkhorst, Buxton, Buzgau, Cheng, Derde, Gordon, Green, Higgins, Horvat, Hullegie, Kruger, Lewis, Linstrum, Marshall, McArthur, McGuinness, Montgomery, Nichol, Parker, Rowan, Santos, Seymour, Turner, Webb.

Supervision: Angus, Arabi, Mouncey, Bonten, Buxton, Kruger, Lewis, McArthur, McGuinness, Montgomery, Murthy, Nichol, Parke, Rowan, Seymour.

Conflict of Interest Disclosures: Dr Angus reported receiving personal fees from Ferring Pharmaceuticals Inc, Bristol-Myers Squibb, Bayer AG, and ALung Technologies Inc outside the submitted work; in addition, Dr Angus had a patent to selepressin—compounds, compositions, and methods for treating sepsis pending and a patent to proteomic biomarkers of sepsis in elderly patients pending. Dr Annane reported receiving grants from French Ministry of Health during the conduct of the study. Dr Bentum-Puijk reported receiving European Union FP7-Health-2013-INNOVATION-1 grant No. 602525 and H2020 RECOVER grant agreement No. 101003589 during the conduct of the study. Dr L. Berry reported receiving grants for PREPARE Network from the European Commission; Australia funding grants for OPTIMISE-CAP; and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr S. Berry reported receiving grants for PREPARE Network from the European Commission, Australia funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr Mouncey reported receiving grants from European Commission FP7 and the National Institute for Health Research (NIHR) during the conduct of the study. Dr Bhimani reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr Bradbury reported receiving personal fees from Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Novartis, Portola, Bayer, and Ablynx outside the submitted work. Dr Brunkhorst reported receiving grants from the European Union during the conduct of the study. Dr Buxton reported receiving grants from the Breast Cancer Research Foundation during the conduct of the study and grants from Bayer, Amgen, Eli Lilly and Company, Janssen, Kazia Therapeutics, DelMar Pharma, Eisai, the National Brain Tumor Society, the National Foundation for Cancer Research, and the Asian Foundation for Cancer Research; gifts from the Yousefzadeh Family Foundation and Jeffrey Tarrant; and personal fees from Berry Consultants LLC outside the submitted work. Dr Cheng reported receiving grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. Dr de Jong reported receiving personal fees from Roche, Janssen, Vertex, and Visterra outside the submitted work. Dr Derde reported receiving European Union FP7-HEALTH-2013-INNOVATION-1 grant 602525 and H2020 RECOVER grant agreement No. 101003589 during the conduct of the study and being a member of the COVID-19 guideline committee for the Society of Critical Care Medicine/European Society of Intensive Care Medicine (ESICM)/Surviving Sepsis Campaign, member of the ESICM COVID-19 taskforce, and chair of the Dutch intensivists (NVIC) taskforce on infectious threats. Dr Detry reported receiving grants for the PREPARE Network from the European Commission, Australia funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr Estcourt reported receiving grants from the NIHR during the conduct of the study. Dr Fitzgerald reported receiving grants for PREPARE Network from the European Commission, Australian funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr Gordon reported receiving grants from the NIHR and the NIHR Research Professorship; nonfinancial support from the NIHR Clinical Research Network and the NIHR Imperial Biomedical Research Centre during the conduct of the study; and personal fees from GlaxoSmithKline and Bristol-Myers Squibb outside the submitted work. Dr Haniffa reported the Critical Care Asia project, where he is co-coordinator, is supported by the Wellcome Trust through the University of Oxford. Dr Higgins reported receiving grants from the NHMRC, the Health Research Council of New Zealand, and the Minderoo Foundation during the conduct of the study. Dr Horvat reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study. Dr Hullegie reported receiving grants from the European Commission during the conduct of the study. Dr Kruger reported receiving personal fees from Smiths Medical outside the submitted work. Dr Lamontagne reported serving as methodological chair (nonvoting) for the World Health Organization (WHO) guideline on corticosteroids for COVID-19. The WHO guideline was initiated before any data from REMAP-CAP was made available. The first guideline panel meeting only reviewed data from the RECOVERY trial and the GLUCOCOVID trial. At a subsequent guideline panel meeting, the panel reviewed a meta-analysis commissioned by the WHO that included data from REMAP-CAP. Both the WHO-led meta-analysis and the guideline document are under review at the time of writing. Dr Lewis reported being the senior medical scientist at Berry Consultants LLC during the conduct of the study. Dr Lorenzi reported receiving grants from the European Commission for the PREPARE Network, Australia funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr Marshall reported receiving personal fees from AM Pharma outside the submitted work and being a member of the international trial steering committee for REMAP-CAP; Canadian principal investigator for REMAP-CAP; chair of the International Forum for Acute Care Trialists; and co-chair of the WHO Working Group on Clinical Characterization and Management. Dr McArthur reported receiving grants from the Health Research Council of New Zealand during the conduct of the study. Dr McAuley reported receiving personal fees from GlaxoSmithKline, Boehringer Ingelheim, and Bayer for consultancy outside the submitted work; in addition, Dr McAuley reported a patent for a novel treatment for acute respiratory distress syndrome issued to his institution. Dr McGlothlin reported receiving grants from the European Commission for the PREPARE Network, Australian funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr McVerry reported receiving salary support from UPMC Learning While Doing Program and the Translational Breast Cancer Research Foundation during the conduct of the study and grants from Bayer Pharmaceuticals Inc and the NIH/National Heart, Lung, and Blood Institute outside the submitted work. Dr Murthy reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr Nichol reported receiving grants from the Health Research Board of Ireland during the conduct of the study. Dr Parke reported that research in the CVICU Auckland City Hospital is supported in part by an unrestricted grant from Fisher and Paykel Healthcare Limited, New Zealand. Dr Sanil reported receiving grants from the European Commission for PREPARE Network, Australia funding grants for OPTIMISE-CAP, and New Zealand funding grants for REMAP-CAP during the conduct of the study. Dr Saunders reported receiving grants from the European Commission for PREPARE Network, Australia funding grants for OPTIMISE-CAP, and New Zealand funding grants from REMAP-CAP during the conduct of the study. Dr Seymour reported receiving grants from the NIH’s National Institute of General Medical Sciences and personal fees from Beckman Coulter Inc and Edwards Lifesciences Inc outside the submitted work. Dr Turner reported receiving grants from the Health Research Council of New Zealand during the conduct of the study. Dr Venkatesh reported receiving institutional research support from Baxter outside the submitted work. Dr Webb reported receiving grants from the NHMRC and the Minderoo Foundation during the conduct of the study. Dr Zarychanski reported receiving research operating support from the Canadian Institutes of Health Research and the Lyonel G. Professorship of Hematology at the University of Manitoba. No other disclosures were reported.

Funding/Support: This study was supported by the Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (grant 602525), the Australian National Health and Medical Research Council (grant APP1101719), the New Zealand Health Research Council (grant 16/631), the Canadian Institute of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program (grant 158584), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (grant CTN 2014-012), the UPMC Learning While Doing Program, the Breast Cancer Research Foundation, the French Ministry of Health (grant PHRC-20-0147), and the Minderoo Foundation.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The study has 4 regional nonprofit sponsors (Monash University, Melbourne, Australia [Australasian sponsor]; Utrecht Medical Center, Utrecht, the Netherlands [European sponsor]; St Michael’s Hospital, Canada [Canadian sponsor], and GCAR, San Francisco, California [US sponsor]). Several authors are employees of these organizations. However, beyond the declared author contributions, the sponsors had no additional role.

The REMAP-CAP Investigators: See eAppendix 5 in Supplement 2 for a list of all REMAP-CAP Investigators.

Disclaimer: Dr Angus is Senior Editor at JAMA, but he was not involved in any of the decisions regarding review of the manuscript or its acceptance.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We are grateful to the NIHR Clinical Research Network (UK), UPMC Health System Health Services Division (US), and the Direction de la Recherche Clinique et de l’Innovation de l’AP-HP (France) for their support of participant recruitment. Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18).

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With a personal account, you can:
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  • Customize your interests
  • Fully personalize your learning experience
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With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close