Hypothesis: What causes appendicitis is not known; however, studies have suggested a relationship between viral diseases and appendicitis. Building on evidence of cyclic patterns of appendicitis with apparent outbreaks consistent with an infectious etiology, we hypothesized that there is a relationship between population rates of appendicitis and several infectious diseases. Design: Epidemiologic study. Setting: The National Hospital Discharge Survey Patients: Estimated US hospitalized population. Main Outcome Measures: International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis codes of the National Hospital Discharge Survey were queried from 1970 to 2006 to identify admissions for appendicitis, influenza, rotavirus, and enteric infections. Cointegration analysis of time series data was used to determine if the disease incidence trends for these various disease entities varied over time together. Results: Rates of influenza and nonperforating appendicitis declined progressively from the late 1970s to 1995 and rose thereafter, but influenza rates exhibited more distinct seasonal variation than appendicitis rates. Rotavirus infection showed no association with the incidence of nonperforating appendicitis. Perforating appendicitis showed a dissimilar trend to both nonperforating appendicitis and viral infection. Hospital admissions for enteric infections substantially increased over the years but were not related to appendicitis cases. Conclusions: Neither influenza nor rotavirus are likely proximate causes of appendicitis given the lack of a seasonal relationship between these disease entities. However, because of significant cointegration between the annual incidence rates of influenza and nonperforated appendicitis, it is possible that these diseases share common etiologic determinates, pathogenetic mechanisms, or environmental factors that similarly affect their incidence.
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