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      Antivirals for Treatment of Influenza : A Systematic Review and Meta-analysis of Observational Studies

      research-article

      , BHSc, , MLIS, RD, , MD, MPH, , MD, , MSc, , MD, MHSc, , BHSc, , MD, , MD, MPH, MSc, , MD, PhD, , MSc, PhD, , BHSc, , MSc, , MD, MPH, MPP, , MD, MPH, PhD, , MD, PhD, , MB, ChB, MSc, , MD, MSc, PhD

      Annals of internal medicine

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          Abstract

          Background:

          Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza.

          Purpose:

          To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.

          Data Sources:

          MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists.

          Study Selection:

          Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness.

          Data Extraction:

          Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

          Data Synthesis:

          74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low–quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine.

          Limitations:

          Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias.

          Conclusion:

          Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low.

          Primary Funding Sources:

          World Health Organization and Mc-Master University.

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          Author and article information

          Journal
          0372351
          596
          Ann Intern Med
          Ann. Intern. Med.
          Annals of internal medicine
          0003-4819
          1539-3704
          29 July 2019
          27 February 2012
          03 April 2012
          03 August 2019
          : 156
          : 7
          : 512-524
          Affiliations
          McMaster University, Hamilton, Ontario, Canada; Evidence Based Medicine Center, Lanzhou University, Gansu, China; Niagara Region Public Health, Thorold, Ontario, Canada; Norwegian Knowledge Center for the Health Services, Oslo, Norway; University of Bergen, Bergen, Norway; Centers for Disease Control and Prevention, At-lanta, Georgia; State University of New York, Buffalo, New York; and Iberoamerican Cochrane Centre, CIBERESP-IIB Sant Pau, Barcelona, Spain.
          Author notes

          Mr. Hsu and Ms. Santesso contributed equally to this work.

          Current author addresses and author contributions are available at www.annals.org.

          Current Author Addresses: Mr. Hsu; Ms. Santesso; Drs. Mustafa, Brozek, Hopkins, Hovhannisyan, Ivanova, and Schünemann; Ms. Cheung; and Mr. Wong: Department of Clinical Epidemiology and Biostatistics, McMaster University Health Sciences Center, Area 2C, 1280 Main Street West, Hamilton, Ontario L8N 4K1, Canada.

          Ms. Chen and Ms. Tian: Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Gansu, Number 199, Donggang West Road, Chengguan District, Lanzhou, Gansu 730000, China.

          Dr. Flottorp: Department of Public Health and Primary Health Care, University of Bergen, Box 7800, 5020 Bergen, Norway.

          Dr. Sæterdal: Norwegian Knowledge Center for the Health Services, Nasjonalt kunnskapssenter for helsetjenesten, Box 7004, St. Olavs plass, N-0130 Oslo, Norway.

          Dr. Uyeki: Centers for Disease Control and Prevention, Influenza Division, Mailstop A32, 1600 Clifton Road Northeast, Atlanta, GA 30333. Dr. Akl: State University of New York at Buffalo, Department of Medicine, ECMC-DK Miller Building, 462 Grider Street, Buffalo, NY 14215.

          Dr. Alonso-Coello: Centro Cochrane Iberoamericano, Hospital de la Santa Creu i Sant Pau, 171 Carrer Sant Antoni Maria Claret, 08041 Barcelona, Spain.

          Dr. Smaill: McMaster University Health Sciences Centre, Department of Pathology and Molecular Medicine, 1280 Main Street West, Hamilton, Ontario L8N 4K1, Canada.

          Author Contributions:

          Conception and design: J. Hsu, N. Santesso, R. Mustafa, J. Brozek, J.P. Hopkins, A. Cheung, L. Ivanova, S.A. Flottorp,I. Sæterdal, A.D. Wong, T.M. Uyeki, H.J. Schünemann.

          Analysis and interpretation of the data: J. Hsu, N. Santesso, R. Mustafa, Y.L. Chen, J.P. Hopkins, I. Sæterdal, T.M. Uyeki, H.J. Schünemann.

          Drafting of the article: J. Hsu, N. Santesso, J.P. Hopkins, H.J. Schünemann.

          Critical revision of the article for important intellectual content: J. Hsu,N. Santesso, R. Mustafa, J.P. Hopkins, G. Hovhannisyan, L. Ivanova, A.D. Wong, T.M. Uyeki, E.A. Akl, P. Alonso-Coello, F. Smaill, H.J. Schünemann.

          Final approval of the article: N. Santesso, R. Mustafa, J. Brozek, Y.L. Chen, J.P. Hopkins, G. Hovhannisyan, I. Sæterdal, A.D. Wong, T.M. Uyeki, E.A. Akl, P. Alonso-Coello, F. Smaill, H.J. Schünemann. Provision of study materials or patients: R. Mustafa.

          Statistical expertise: H.J. Schünemann.

          Obtaining of funding: H.J. Schünemann.

          Administrative, technical, or logistic support: J. Hsu, H.J. Schünemann. Collection and assembly of data: J. Hsu, N. Santesso, R. Mustafa, J. Brozek, Y.L. Chen, J.P. Hopkins, A.Cheung, G. Hovhannisyan, L. Ivanova, S.A. Flottorp, I. Sæterdal, A.D. Wong, J. Tian, E.A. Akl, P. Alonso-Coello, F. Smaill, H.J. Schünemann.

          Requests for Single Reprints: Holger J. Schünemann, MD, PhD, Department of Clinical Epidemiology and Biostatistics, WHO Collaborating Center for Evidence-informed Policy Making, McMaster University Health Sciences Center, Room 2C16, 1280 Main Street West, Hamilton, Ontario L8N 4K1, Canada; schuneh@ 123456mcmaster.ca .
          Article
          PMC6679687 PMC6679687 6679687 hhspa1040855
          10.7326/0003-4819-156-7-201204030-00411
          6679687
          22371849
          Categories
          Article

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