Influenza vaccination and all-cause mortality in community-dwelling elderly in Ontario, Canada, a cohort study
ABSTRACT 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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ABSTRACT: Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications. We conducted a retrospective cohort study among Ontario residents aged ≥65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations. During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥65 years was 22% (95% confidence interval [CI], -6%-42%) for all influenza-associated deaths, 25% (95% CI, 13%-37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%-31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively. By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ∼4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.PLoS ONE 10/2013; 8(10):e76318. DOI:10.1371/journal.pone.0076318 · 3.53 Impact Factor
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ABSTRACT: Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness.American journal of epidemiology 08/2013; 178(8). DOI:10.1093/aje/kwt124 · 4.98 Impact Factor
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ABSTRACT: As pregnant women are considered a high-risk group for severe influenza illness, current recommendations advise vaccination of all pregnant women with inactivated influenza vaccine. Nevertheless, rates of maternal influenza vaccination have historically been low, possibly reflecting ongoing concerns about vaccine safety. Until recently, the majority of evidence concerning safety of influenza vaccination during pregnancy was limited to post-marketing pharmacovigilance studies; however, in the past 5 years, one randomized clinical trial and a number of observational studies reflecting seasonal trivalent inactivated influenza vaccines and monovalent H1N1 influenza vaccines have been published. This review summarizes the evidence pertaining to fetal and neonatal outcomes following influenza vaccination during pregnancy for comparative analytic studies published between 2008 and August 2013. Since the majority of these studies are observational in nature, issues related to study quality are also addressed.Expert Review of Vaccines 12/2013; 12(12):1417-30. DOI:10.1586/14760584.2013.851607 · 4.22 Impact Factor