title: Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies.
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.
  
  
  OBJECTIVE
  To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 to 0.89]; 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 to 1.18]) 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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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 McMaster University.
authors.affiliation: McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hsu
authors.forename: Nancy
authors.initials: N
authors.lastname: Santesso
authors.forename: Reem
authors.initials: R
authors.lastname: Mustafa
authors.forename: Jan
authors.initials: J
authors.lastname: Brozek
authors.forename: Yao Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Hopkins
authors.forename: Adrienne
authors.initials: A
authors.lastname: Cheung
authors.forename: Gayane
authors.initials: G
authors.lastname: Hovhannisyan
authors.forename: Liudmila
authors.initials: L
authors.lastname: Ivanova
authors.forename: Signe A
authors.initials: SA
authors.lastname: Flottorp
authors.forename: Ingvil
authors.initials: I
authors.lastname: Saeterdal
authors.forename: Arthur D
authors.initials: AD
authors.lastname: Wong
authors.forename: Jinhui
authors.initials: J
authors.lastname: Tian
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Uyeki
authors.forename: Elie A
authors.initials: EA
authors.lastname: Akl
authors.forename: Pablo
authors.initials: P
authors.lastname: Alonso-Coello
authors.forename: Fiona
authors.initials: F
authors.lastname: Smaill
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schünemann
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D006760:Hospitalization; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000401:mortality; D053139:Oseltamivir / Q000009:adverse effects / Q000627:therapeutic use; D012299:Rimantadine / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D053243:Zanamivir / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D012299:Rimantadine; D053139:Oseltamivir; D000547:Amantadine; D053243:Zanamivir