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Association Between Salicylates and Reye's Syndrome-Reply

Thomas J. Halpin, MD, MPH; Francis J. Holtzhauer, MS; Robert J. Campbell, MS; Lois J. Hall; Adolfo Correa-Villaseñor, MD, MPH; Richard Lanese, PhD; Janet Rice, PhD; Eugene S. Hurwitz, MD
JAMA. 1983;249(7):884. doi:10.1001/jama.1983.03330310019014.
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In Reply.—  Soller and Stander, on the basis of an unpublished analysis of our data, raise the issue of two potential biases: protopathic and product confusion bias. The existence of protopathic bias, or bias caused by the disease preceding the risk factor, depends on how the onset of RS is defined. We defined the onset of RS as the first day of severe vomiting. In the second year of our study, aspirin was classified as a positive exposure for cases only if ingested before the first day of severe vomiting. Thus, this bias regarding the temporal association of aspirin and RS should not be a problem if the onset of vomiting properly identifies the onset of RS. Even if clinical RS can precede severe vomiting, a retrospective determination of the exact onset on the basis of a complex of nonspecific symptoms, eg, headache, fever, or sore throat, symptoms all compatible


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