The objective of this study was to evaluate the effectiveness of influenza vaccines in reducing all-cause mortality among community-dwelling elderly. We included 25,922 Ontario residents over age 65 who responded to population health surveys. After full adjustment, influenza vaccination was associated with a statistically significant reduction in all-cause mortality during influenza seasons (hazard ratio (HR)=0.61; 95% CI 0.47-0.79). Contrary to expectations, statistically significant associations between influenza vaccination and mortality were also observed during periods preceding (HR=0.55; 95% CI 0.40-0.75) and following (HR=0.74; 95% CI 0.59-0.94) influenza seasons, indicating the presence of residual confounding. Adjustment for functional status indicators, excluding individuals with high one-year predicted mortality at baseline, and moving the start date of follow-up failed to eliminate the refractory confounding. Since observational studies are prone to bias, future efforts to estimate vaccine effectiveness in the elderly should strive to minimize bias through improved data quality, novel data sources, and/or new analytical techniques.
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