Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study
Identifieur interne : 000403 ( Main/Exploration ); précédent : 000402; suivant : 000404Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study
Auteurs : Yaseen M. Arabi [Arabie saoudite] ; Sarah Shalhoub [Canada] ; Yasser Mandourah ; Fahad Al-Hameed ; Awad Al-Omari ; Eman Al Qasim [Arabie saoudite] ; Jesna Jose [Arabie saoudite] ; Basem Alraddadi ; Abdullah Almotairi ; Kasim Al Khatib ; Ahmed Abdulmomen ; Ismael Qushmaq ; Anees A. Sindi ; Ahmed Mady [Arabie saoudite, Égypte] ; Othman Solaiman ; Rajaa Al-Raddadi ; Khalid Maghrabi ; Ahmed Ragab ; Ghaleb A. Al Mekhlafi ; Hanan H. Balkhy ; Abdulrahman Al Harthy [Arabie saoudite] ; Ayman Kharaba ; Jawaher A. Gramish ; Abdulsalam M. Al-Aithan [Arabie saoudite] ; Abdulaziz Al-Dawood [Arabie saoudite] ; Laura Merson [Royaume-Uni] ; Frederick G. Hayden [Royaume-Uni] ; Robert Fowler [Canada]Source :
- Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America [ 1058-4838 ] ; 2019.
Abstract
The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.
This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.
Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%];
In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.
Url:
DOI: 10.1093/cid/ciz544
PubMed: 31925415
PubMed Central: 7108209
Affiliations:
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Arabi</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shalhoub, Sarah" sort="Shalhoub, Sarah" uniqKey="Shalhoub S" first="Sarah" last="Shalhoub">Sarah Shalhoub</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario</institution>, London,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff 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country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jose, Jesna" sort="Jose, Jesna" uniqKey="Jose J" first="Jesna" last="Jose">Jesna Jose</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alraddadi, Basem" sort="Alraddadi, Basem" uniqKey="Alraddadi B" first="Basem" last="Alraddadi">Basem Alraddadi</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0008"><institution>Department of Medicine, University of Jeddah</institution></nlm:aff></affiliation></author><author><name sortKey="Almotairi, Abdullah" sort="Almotairi, Abdullah" uniqKey="Almotairi A" first="Abdullah" last="Almotairi">Abdullah Almotairi</name><affiliation><nlm:aff id="AF0009"><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Khatib, Kasim" sort="Al Khatib, Kasim" uniqKey="Al Khatib K" first="Kasim" last="Al Khatib">Kasim Al Khatib</name><affiliation><nlm:aff id="AF0010"><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</nlm:aff><wicri:noCountry code="subfield">Makkah</wicri:noCountry></affiliation></author><author><name sortKey="Abdulmomen, Ahmed" sort="Abdulmomen, Ahmed" uniqKey="Abdulmomen A" first="Ahmed" last="Abdulmomen">Ahmed Abdulmomen</name><affiliation><nlm:aff id="AF0011"><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Qushmaq, Ismael" sort="Qushmaq, Ismael" uniqKey="Qushmaq I" first="Ismael" last="Qushmaq">Ismael Qushmaq</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sindi, Anees A" sort="Sindi, Anees A" uniqKey="Sindi A" first="Anees A" last="Sindi">Anees A. Sindi</name><affiliation><nlm:aff id="AF0012"><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0014"><institution>Tanta University Hospitals</institution>,<country country="EG">Egypt</country></nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solaiman, Othman" sort="Solaiman, Othman" uniqKey="Solaiman O" first="Othman" last="Solaiman">Othman Solaiman</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Raddadi, Rajaa" sort="Al Raddadi, Rajaa" uniqKey="Al Raddadi R" first="Rajaa" last="Al-Raddadi">Rajaa Al-Raddadi</name><affiliation><nlm:aff id="AF0016"><institution>Department of Community Medicine, Faculty of Medicine, King Abdulaziz University</institution></nlm:aff></affiliation></author><author><name sortKey="Maghrabi, Khalid" sort="Maghrabi, Khalid" uniqKey="Maghrabi K" first="Khalid" last="Maghrabi">Khalid Maghrabi</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Ragab, Ahmed" sort="Ragab, Ahmed" uniqKey="Ragab A" first="Ahmed" last="Ragab">Ahmed Ragab</name><affiliation><nlm:aff id="AF0017"><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Mekhlafi, Ghaleb A" sort="Al Mekhlafi, Ghaleb A" uniqKey="Al Mekhlafi G" first="Ghaleb A" last="Al Mekhlafi">Ghaleb A. Al Mekhlafi</name><affiliation><nlm:aff id="AF0018"><institution>Department of Intensive Care Services, Prince Sultan Military Medical City</institution></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan H" sort="Balkhy, Hanan H" uniqKey="Balkhy H" first="Hanan H" last="Balkhy">Hanan H. Balkhy</name><affiliation><nlm:aff id="AF0019"><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Harthy, Abdulrahman" sort="Al Harthy, Abdulrahman" uniqKey="Al Harthy A" first="Abdulrahman" last="Al Harthy">Abdulrahman Al Harthy</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kharaba, Ayman" sort="Kharaba, Ayman" uniqKey="Kharaba A" first="Ayman" last="Kharaba">Ayman Kharaba</name><affiliation><nlm:aff id="AF0020"><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</nlm:aff><wicri:noCountry code="subfield">Al-Madinah</wicri:noCountry></affiliation></author><author><name sortKey="Gramish, Jawaher A" sort="Gramish, Jawaher A" uniqKey="Gramish J" first="Jawaher A" last="Gramish">Jawaher A. Gramish</name><affiliation><nlm:aff id="AF0021"><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Aithan, Abdulsalam M" sort="Al Aithan, Abdulsalam M" uniqKey="Al Aithan A" first="Abdulsalam M" last="Al-Aithan">Abdulsalam M. Al-Aithan</name><affiliation wicri:level="1"><nlm:aff id="AF0022"><institution>Department of Medicine, Critical Care Division, King Abdulaziz Hospital</institution>, Al Ahsa,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Al Dawood, Abdulaziz" sort="Al Dawood, Abdulaziz" uniqKey="Al Dawood A" first="Abdulaziz" last="Al-Dawood">Abdulaziz Al-Dawood</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G" last="Hayden">Frederick G. 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Arabi</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shalhoub, Sarah" sort="Shalhoub, Sarah" uniqKey="Shalhoub S" first="Sarah" last="Shalhoub">Sarah Shalhoub</name><affiliation wicri:level="1"><nlm:aff id="AF0002"><institution>Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario</institution>, London,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0003"><institution>King Fahad Armed Forces Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mandourah, Yasser" sort="Mandourah, Yasser" uniqKey="Mandourah Y" first="Yasser" last="Mandourah">Yasser Mandourah</name><affiliation><nlm:aff id="AF0004"><institution>Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Hameed, Fahad" sort="Al Hameed, Fahad" uniqKey="Al Hameed F" first="Fahad" last="Al-Hameed">Fahad Al-Hameed</name><affiliation><nlm:aff id="AF0005"><institution>Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Omari, Awad" sort="Al Omari, Awad" uniqKey="Al Omari A" first="Awad" last="Al-Omari">Awad Al-Omari</name><affiliation><nlm:aff id="AF0006"><institution>Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Qasim, Eman" sort="Al Qasim, Eman" uniqKey="Al Qasim E" first="Eman" last="Al Qasim">Eman Al Qasim</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Jose, Jesna" sort="Jose, Jesna" uniqKey="Jose J" first="Jesna" last="Jose">Jesna Jose</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alraddadi, Basem" sort="Alraddadi, Basem" uniqKey="Alraddadi B" first="Basem" last="Alraddadi">Basem Alraddadi</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation><affiliation><nlm:aff id="AF0008"><institution>Department of Medicine, University of Jeddah</institution></nlm:aff></affiliation></author><author><name sortKey="Almotairi, Abdullah" sort="Almotairi, Abdullah" uniqKey="Almotairi A" first="Abdullah" last="Almotairi">Abdullah Almotairi</name><affiliation><nlm:aff id="AF0009"><institution>Department of Critical Care Medicine, King Fahad Medical City</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Khatib, Kasim" sort="Al Khatib, Kasim" uniqKey="Al Khatib K" first="Kasim" last="Al Khatib">Kasim Al Khatib</name><affiliation><nlm:aff id="AF0010"><institution>Intensive Care Department, Al-Noor Specialist Hospital</institution>, Makkah</nlm:aff><wicri:noCountry code="subfield">Makkah</wicri:noCountry></affiliation></author><author><name sortKey="Abdulmomen, Ahmed" sort="Abdulmomen, Ahmed" uniqKey="Abdulmomen A" first="Ahmed" last="Abdulmomen">Ahmed Abdulmomen</name><affiliation><nlm:aff id="AF0011"><institution>Department of Critical Care Medicine, King Saud University</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Qushmaq, Ismael" sort="Qushmaq, Ismael" uniqKey="Qushmaq I" first="Ismael" last="Qushmaq">Ismael Qushmaq</name><affiliation><nlm:aff id="AF0007"><institution>Department of Medicine, King Faisal Specialist Hospital and Research Center</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Sindi, Anees A" sort="Sindi, Anees A" uniqKey="Sindi A" first="Anees A" last="Sindi">Anees A. Sindi</name><affiliation><nlm:aff id="AF0012"><institution>Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="AF0014"><institution>Tanta University Hospitals</institution>,<country country="EG">Egypt</country></nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Solaiman, Othman" sort="Solaiman, Othman" uniqKey="Solaiman O" first="Othman" last="Solaiman">Othman Solaiman</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Raddadi, Rajaa" sort="Al Raddadi, Rajaa" uniqKey="Al Raddadi R" first="Rajaa" last="Al-Raddadi">Rajaa Al-Raddadi</name><affiliation><nlm:aff id="AF0016"><institution>Department of Community Medicine, Faculty of Medicine, King Abdulaziz University</institution></nlm:aff></affiliation></author><author><name sortKey="Maghrabi, Khalid" sort="Maghrabi, Khalid" uniqKey="Maghrabi K" first="Khalid" last="Maghrabi">Khalid Maghrabi</name><affiliation><nlm:aff id="AF0015"><institution>Intensive Care Department, King Faisal Specialist Hospital and Research Center</institution>, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Ragab, Ahmed" sort="Ragab, Ahmed" uniqKey="Ragab A" first="Ahmed" last="Ragab">Ahmed Ragab</name><affiliation><nlm:aff id="AF0017"><institution>Intensive Care Department, King Fahd Hospital</institution>, Jeddah</nlm:aff><wicri:noCountry code="subfield">Jeddah</wicri:noCountry></affiliation></author><author><name sortKey="Al Mekhlafi, Ghaleb A" sort="Al Mekhlafi, Ghaleb A" uniqKey="Al Mekhlafi G" first="Ghaleb A" last="Al Mekhlafi">Ghaleb A. Al Mekhlafi</name><affiliation><nlm:aff id="AF0018"><institution>Department of Intensive Care Services, Prince Sultan Military Medical City</institution></nlm:aff></affiliation></author><author><name sortKey="Balkhy, Hanan H" sort="Balkhy, Hanan H" uniqKey="Balkhy H" first="Hanan H" last="Balkhy">Hanan H. Balkhy</name><affiliation><nlm:aff id="AF0019"><institution>Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Harthy, Abdulrahman" sort="Al Harthy, Abdulrahman" uniqKey="Al Harthy A" first="Abdulrahman" last="Al Harthy">Abdulrahman Al Harthy</name><affiliation wicri:level="1"><nlm:aff id="AF0013"><institution>Intensive Care Department, King Saud Medical City</institution>, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kharaba, Ayman" sort="Kharaba, Ayman" uniqKey="Kharaba A" first="Ayman" last="Kharaba">Ayman Kharaba</name><affiliation><nlm:aff id="AF0020"><institution>Department of Critical Care, King Fahad Hospital, Ohoud Hospital</institution>, Al-Madinah</nlm:aff><wicri:noCountry code="subfield">Al-Madinah</wicri:noCountry></affiliation></author><author><name sortKey="Gramish, Jawaher A" sort="Gramish, Jawaher A" uniqKey="Gramish J" first="Jawaher A" last="Gramish">Jawaher A. Gramish</name><affiliation><nlm:aff id="AF0021"><institution>Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh</nlm:aff><wicri:noCountry code="subfield">Riyadh</wicri:noCountry></affiliation></author><author><name sortKey="Al Aithan, Abdulsalam M" sort="Al Aithan, Abdulsalam M" uniqKey="Al Aithan A" first="Abdulsalam M" last="Al-Aithan">Abdulsalam M. Al-Aithan</name><affiliation wicri:level="1"><nlm:aff id="AF0022"><institution>Department of Medicine, Critical Care Division, King Abdulaziz Hospital</institution>, Al Ahsa,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Al Dawood, Abdulaziz" sort="Al Dawood, Abdulaziz" uniqKey="Al Dawood A" first="Abdulaziz" last="Al-Dawood">Abdulaziz Al-Dawood</name><affiliation wicri:level="1"><nlm:aff id="AF0001"><institution>Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center</institution>, King Abdulaziz Medical City, Riyadh,<country country="SA">Saudi Arabia</country></nlm:aff><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G" last="Hayden">Frederick G. Hayden</name><affiliation wicri:level="1"><nlm:aff id="AF0023"><institution>International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University</institution>,<country country="GB">United Kingdom</country></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation><nlm:aff id="AF0024"><institution>Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine</institution>, Charlottesville</nlm:aff><wicri:noCountry code="subfield">Charlottesville</wicri:noCountry></affiliation></author><author><name sortKey="Fowler, Robert" sort="Fowler, Robert" uniqKey="Fowler R" first="Robert" last="Fowler">Robert Fowler</name><affiliation wicri:level="1"><nlm:aff id="AF0025"><institution>Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital</institution>, Ontario,<country country="CA">Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America</title><idno type="ISSN">1058-4838</idno><idno type="eISSN">1537-6591</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Abstract</title><sec id="s0100"><title>Background</title><p>The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.</p></sec><sec id="s0101"><title>Methods</title><p>This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.</p></sec><sec id="s0102"><title>Results</title><p>Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; <italic>P</italic> = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; <italic>P</italic> = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; <italic>P</italic> = .29).</p></sec><sec id="s0103"><title>Conclusions</title><p>In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author><author><name sortKey="Hayden, Fg" uniqKey="Hayden F">FG Hayden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C Martellaro</name></author><author><name sortKey="Callison, J" uniqKey="Callison J">J Callison</name></author><author><name sortKey="Munster, Vj" uniqKey="Munster V">VJ Munster</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D Falzarano</name></author><author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name></author><author><name sortKey="Rasmussen, Al" uniqKey="Rasmussen A">AL Rasmussen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Momattin, H" uniqKey="Momattin H">H Momattin</name></author><author><name sortKey="Mohammed, K" uniqKey="Mohammed K">K Mohammed</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hart, Bj" uniqKey="Hart B">BJ Hart</name></author><author><name sortKey="Dyall, J" uniqKey="Dyall J">J Dyall</name></author><author><name sortKey="Postnikova, E" uniqKey="Postnikova E">E Postnikova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalid, M" uniqKey="Khalid M">M Khalid</name></author><author><name sortKey="Al Rabiah, F" uniqKey="Al Rabiah F">F Al Rabiah</name></author><author><name sortKey="Khan, B" uniqKey="Khan B">B Khan</name></author><author><name sortKey="Al Mobeireek, A" uniqKey="Al Mobeireek A">A Al Mobeireek</name></author><author><name sortKey="Butt, Ts" uniqKey="Butt T">TS Butt</name></author><author><name sortKey="Al Mutairy, E" uniqKey="Al Mutairy E">E Al Mutairy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Momattin, H" uniqKey="Momattin H">H Momattin</name></author><author><name sortKey="Dib, J" uniqKey="Dib J">J Dib</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S Shalhoub</name></author><author><name sortKey="Farahat, F" uniqKey="Farahat F">F Farahat</name></author><author><name sortKey="Al Jiffri, A" uniqKey="Al Jiffri A">A Al-Jiffri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name></author><author><name sortKey="Saad, Mm" uniqKey="Saad M">MM Saad</name></author><author><name sortKey="Baig, K" uniqKey="Baig K">K Baig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Ghamdi, M" uniqKey="Al Ghamdi M">M Al Ghamdi</name></author><author><name sortKey="Alghamdi, Km" uniqKey="Alghamdi K">KM Alghamdi</name></author><author><name sortKey="Ghandoora, Y" uniqKey="Ghandoora Y">Y Ghandoora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suissa, S" uniqKey="Suissa S">S Suissa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Suissa, S" uniqKey="Suissa S">S Suissa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Shalhoub, S" uniqKey="Shalhoub S">S Shalhoub</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A Al Omari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Al Omari, A" uniqKey="Al Omari A">A Al-Omari</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author><author><name sortKey="Costabel, U" uniqKey="Costabel U">U Costabel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Alothman, A" uniqKey="Alothman A">A Alothman</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Vincent, Jl" uniqKey="Vincent J">JL Vincent</name></author><author><name sortKey="De Mendonca, A" uniqKey="De Mendonca A">A de Mendonça</name></author><author><name sortKey="Cantraine, F" uniqKey="Cantraine F">F Cantraine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author><author><name sortKey="Al Hameed, F" uniqKey="Al Hameed F">F Al-Hameed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delaney, Jw" uniqKey="Delaney J">JW Delaney</name></author><author><name sortKey="Pinto, R" uniqKey="Pinto R">R Pinto</name></author><author><name sortKey="Long, J" uniqKey="Long J">J Long</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hernan, Ma" uniqKey="Hernan M">MA Hernán</name></author><author><name sortKey="Brumback, B" uniqKey="Brumback B">B Brumback</name></author><author><name sortKey="Robins, Jm" uniqKey="Robins J">JM Robins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Faries, De" uniqKey="Faries D">DE Faries</name></author><author><name sortKey="Kadziola, Za" uniqKey="Kadziola Z">ZA Kadziola</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Robins, Jm" uniqKey="Robins J">JM Robins</name></author><author><name sortKey="Hernan, Ma" uniqKey="Hernan M">MA Hernán</name></author><author><name sortKey="Brumback, B" uniqKey="Brumback B">B Brumback</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name></author><author><name sortKey="Kao, Ry" uniqKey="Kao R">RY Kao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, Tp" uniqKey="Sheahan T">TP Sheahan</name></author><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beigel, Jh" uniqKey="Beigel J">JH Beigel</name></author><author><name sortKey="Voell, J" uniqKey="Voell J">J Voell</name></author><author><name sortKey="Kumar, P" uniqKey="Kumar P">P Kumar</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Arabie saoudite</li><li>Canada</li><li>Royaume-Uni</li><li>Égypte</li></country></list><tree><noCountry><name sortKey="Abdulmomen, Ahmed" sort="Abdulmomen, Ahmed" uniqKey="Abdulmomen A" first="Ahmed" last="Abdulmomen">Ahmed Abdulmomen</name><name sortKey="Al Hameed, Fahad" sort="Al Hameed, Fahad" uniqKey="Al Hameed F" first="Fahad" last="Al-Hameed">Fahad Al-Hameed</name><name sortKey="Al Khatib, Kasim" sort="Al Khatib, Kasim" uniqKey="Al Khatib K" first="Kasim" last="Al Khatib">Kasim Al Khatib</name><name sortKey="Al Mekhlafi, Ghaleb A" sort="Al Mekhlafi, Ghaleb A" uniqKey="Al Mekhlafi G" first="Ghaleb A" last="Al Mekhlafi">Ghaleb A. Al Mekhlafi</name><name sortKey="Al Omari, Awad" sort="Al Omari, Awad" uniqKey="Al Omari A" first="Awad" last="Al-Omari">Awad Al-Omari</name><name sortKey="Al Raddadi, Rajaa" sort="Al Raddadi, Rajaa" uniqKey="Al Raddadi R" first="Rajaa" last="Al-Raddadi">Rajaa Al-Raddadi</name><name sortKey="Almotairi, Abdullah" sort="Almotairi, Abdullah" uniqKey="Almotairi A" first="Abdullah" last="Almotairi">Abdullah Almotairi</name><name sortKey="Alraddadi, Basem" sort="Alraddadi, Basem" uniqKey="Alraddadi B" first="Basem" last="Alraddadi">Basem Alraddadi</name><name sortKey="Balkhy, Hanan H" sort="Balkhy, Hanan H" uniqKey="Balkhy H" first="Hanan H" last="Balkhy">Hanan H. Balkhy</name><name sortKey="Gramish, Jawaher A" sort="Gramish, Jawaher A" uniqKey="Gramish J" first="Jawaher A" last="Gramish">Jawaher A. Gramish</name><name sortKey="Kharaba, Ayman" sort="Kharaba, Ayman" uniqKey="Kharaba A" first="Ayman" last="Kharaba">Ayman Kharaba</name><name sortKey="Maghrabi, Khalid" sort="Maghrabi, Khalid" uniqKey="Maghrabi K" first="Khalid" last="Maghrabi">Khalid Maghrabi</name><name sortKey="Mandourah, Yasser" sort="Mandourah, Yasser" uniqKey="Mandourah Y" first="Yasser" last="Mandourah">Yasser Mandourah</name><name sortKey="Qushmaq, Ismael" sort="Qushmaq, Ismael" uniqKey="Qushmaq I" first="Ismael" last="Qushmaq">Ismael Qushmaq</name><name sortKey="Ragab, Ahmed" sort="Ragab, Ahmed" uniqKey="Ragab A" first="Ahmed" last="Ragab">Ahmed Ragab</name><name sortKey="Sindi, Anees A" sort="Sindi, Anees A" uniqKey="Sindi A" first="Anees A" last="Sindi">Anees A. Sindi</name><name sortKey="Solaiman, Othman" sort="Solaiman, Othman" uniqKey="Solaiman O" first="Othman" last="Solaiman">Othman Solaiman</name></noCountry><country name="Arabie saoudite"><noRegion><name sortKey="Arabi, Yaseen M" sort="Arabi, Yaseen M" uniqKey="Arabi Y" first="Yaseen M" last="Arabi">Yaseen M. Arabi</name></noRegion><name sortKey="Al Aithan, Abdulsalam M" sort="Al Aithan, Abdulsalam M" uniqKey="Al Aithan A" first="Abdulsalam M" last="Al-Aithan">Abdulsalam M. Al-Aithan</name><name sortKey="Al Dawood, Abdulaziz" sort="Al Dawood, Abdulaziz" uniqKey="Al Dawood A" first="Abdulaziz" last="Al-Dawood">Abdulaziz Al-Dawood</name><name sortKey="Al Harthy, Abdulrahman" sort="Al Harthy, Abdulrahman" uniqKey="Al Harthy A" first="Abdulrahman" last="Al Harthy">Abdulrahman Al Harthy</name><name sortKey="Al Qasim, Eman" sort="Al Qasim, Eman" uniqKey="Al Qasim E" first="Eman" last="Al Qasim">Eman Al Qasim</name><name sortKey="Jose, Jesna" sort="Jose, Jesna" uniqKey="Jose J" first="Jesna" last="Jose">Jesna Jose</name><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name></country><country name="Canada"><noRegion><name sortKey="Shalhoub, Sarah" sort="Shalhoub, Sarah" uniqKey="Shalhoub S" first="Sarah" last="Shalhoub">Sarah Shalhoub</name></noRegion><name sortKey="Fowler, Robert" sort="Fowler, Robert" uniqKey="Fowler R" first="Robert" last="Fowler">Robert Fowler</name></country><country name="Égypte"><noRegion><name sortKey="Mady, Ahmed" sort="Mady, Ahmed" uniqKey="Mady A" first="Ahmed" last="Mady">Ahmed Mady</name></noRegion></country><country name="Royaume-Uni"><noRegion><name sortKey="Merson, Laura" sort="Merson, Laura" uniqKey="Merson L" first="Laura" last="Merson">Laura Merson</name></noRegion><name sortKey="Hayden, Frederick G" sort="Hayden, Frederick G" uniqKey="Hayden F" first="Frederick G" last="Hayden">Frederick G. Hayden</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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