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

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 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.


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 McMaster University.

Annals of Internal Medicine current issue

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