To the Editor.—I welcomed the report by Steele et al dealing with oral antipyretic therapy (Amer J Dis Child 123:204-206, 1972). Their study reassures me that use of aspirin and acetaminophen in combination may be both safe and effective.
My experience with fever in children suggests that it may be more difficult to control in the evening than in the morning. How were the author's patients divided with respect to the time of day when they were treated? Was there any difference in the response of patients treated in the evening when compared with the morning hours? At what time of day were the salicylate levels drawn? The number of patients may be small for this kind of analysis, but the influence of circadian rhythms on the outcome of drug trials needs careful consideration. An awareness and understanding of these rhythms may provide clues to the mechanism(s) of antipyretic