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1: Am J Respir Crit Care Med. 2008 Sep 1;178(5):527-33. Epub 2008 Jun 12.
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Mortality reduction with influenza vaccine in patients with pneumonia outside "flu" season: pleiotropic benefits or residual confounding?

Eurich DT, Marrie TJ, Johnstone J, Majumdar SR.

Department of Public Health Sciences, School of Public Health, University of Alberta, 13-103 Clinical Sciences Bldg., Edmonton, AB, T6G 2G3 Canada. deurich@ualberta.ca

RATIONALE: Observational studies suggest a 50% mortality reduction for older patients receiving influenza vaccination; some deem this magnitude of benefit implausible and invoke confounding by the "healthy user effect" as an alternate explanation. OBJECTIVES: To evaluate unrecognized confounding by hypothesizing the presence of a 50% mortality reduction with vaccination for patients with pneumonia outside of influenza season. METHODS: Clinical, laboratory, and functional data were prospectively collected on 1,813 adults with community-acquired pneumonia admitted to six hospitals outside of influenza season in the Capital Health region (AB, Canada). Vaccination status was ascertained by interview and chart review. Outcome was in-hospital mortality. Influenza-vaccinated patients were matched to a nonvaccinated control using propensity scores, and then multivariable regression was used to determine the independent association between vaccination and mortality. MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 352 vaccine recipients and 352 matched control subjects. Most (85%) patients were 65 years or older, 29% had severe pneumonia, and 12% died. Influenza vaccination was associated with a 51% mortality reduction (28 of 352 [8%] died vs. 53 of 352 [15%] control subjects; unadjusted odds ratio [OR], 0.49; 95% confidence interval [CI], 0.30-0.79; P = 0.004) outside influenza season. Adjustment for age, sex, and comorbidities did not alter these findings (adjusted OR, 0.45; 95% CI, 0.27-0.76). More complete adjustment for confounding (e.g., functional and socioeconomic status) markedly attenuated these benefits and their statistical significance (adjusted OR, 0.81; 95% CI, 0.35-1.85; P = 0.61). CONCLUSIONS: The 51% reduction in mortality with vaccination initially observed in patients with pneumonia who did not have influenza was most likely a result of confounding. Previous observational studies may have overestimated mortality benefits of influenza vaccination.

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PMID: 18556629 [PubMed - indexed for MEDLINE]