title: Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors.
abstract: BACKGROUND
  Functional status limitations may be associated with both an increased risk of death and a decreased likelihood of influenza vaccination, and so may confound the association of influenza vaccination and risk of all cause mortality in seniors.
  
  
  METHODS
  We conducted a nested case-control study of persons >or=65 years of age that included 252 cases who died during an influenza season and 576 age-matched controls. We identified functional limitations by medical record review, and compared the effect of adjustment for those factors with that of adjustment for disease covariates defined by diagnosis codes, using methods reported by previous influenza vaccine effectiveness studies, on the association of influenza vaccination and risk of death.
  
  
  RESULTS
  Functional limitations, such as requiring assistance for bathing, were highly prevalent in cases, even in the subgroup defined as free of comorbidity by diagnosis code criteria, and were associated with a decreased likelihood of vaccination among controls. Adjustment for functional limitations resulted in an estimate of the relative risk of death in vaccinated persons compared with unvaccinated persons that was closer to the null [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.47-1.06] than the unadjusted estimate (OR, 0.59; 95% CI, 0.41-0.83). In contrast, adjustment for diagnosis code covariates moved the estimate further from the null (OR, 0.45; 95% CI, 0.30-0.68).
  
  
  CONCLUSIONS
  Functional limitations appear to be important confounders of the association of vaccination and risk of death, while adjustment for diagnosis code covariates did not control for a healthy vaccinee bias. Further research is needed on methods to reduce the influence of bias in observational studies of influenza vaccine effectiveness.
authors.affiliation: Center for Health Studies, Group Health Cooperative, Seattle, WA 98101, USA. jackson.l@ghc.rog
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Nelson
authors.forename: Patti
authors.initials: P
authors.lastname: Benson
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Reid
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D015982:Bias; D015986:Confounding Factors, Epidemiologic; D004185:Disability Evaluation; D004812:Epidemiologic Methods; D005260:Female; D015577:Geriatric Assessment; D006304:Health Status; D006801:Humans; D007252:Influenza Vaccines; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D012621:Seasons; D016896:Treatment Outcome; D014861:Washington / Q000453:epidemiology
chemical_list: D007252:Influenza Vaccines