title: Effectiveness of inactivated influenza vaccines in preventing influenza-associated deaths and hospitalizations among Ontario residents aged ≥ 65 years: estimates with generalized linear models accounting for healthy vaccinee effects.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Influenza Division, United States Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America ; Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, South Bend, Indiana, United States of America.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ridenhour
authors.forename: Michael A
authors.initials: MA
authors.lastname: Campitelli
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Kwong
authors.forename: Laura C
authors.initials: LC
authors.lastname: Rosella
authors.forename: Ben G
authors.initials: BG
authors.lastname: Armstrong
authors.forename: Punam
authors.initials: P
authors.lastname: Mangtani
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Calzavara
authors.forename: David K
authors.initials: DK
authors.lastname: Shay
mesh_terms: D000368:Aged; D016001:Confidence Intervals; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000401:mortality* / Q000517:prevention & control*; D016014:Linear Models; D009864:Ontario / Q000453:epidemiology; D011159:Population Surveillance; D012621:Seasons; D016896:Treatment Outcome; D014611:Vaccination / Q000706:statistics & numerical data*; D015164:Vaccines, Inactivated / Q000276:immunology*
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated