Nevertheless, even if the esti- mates of bacteremia from routine daily activities are off by a factor of 1000, it is likely that the frequency and cumulative duration of exposure to bacteremia from routine daily events over 1 year are much higher than those that result from dental procedures. Results of Clinical Studies of IE Prophylaxis for Dental Procedures No prospective, randomized, placebo-controlled studies exist on the efficacy of antibiotic prophylaxis to prevent IE in patients who undergo a dental procedure. Data from pub- lished retrospective or prospective case-control studies are limited by the following factors: (1) the low incidence of IE, which requires a large number of patients per cohort for statistical significance; (2) the wide variation in the types and severity of underlying cardiac conditions, which would re- quire a large number of patients with specific matched control subjects for each cardiac condition; and (3) the large variety of invasive dental procedures and dental disease states, which would be difficult to standardize for control groups. These and other limitations complicate the interpretation of the results of published studies of the efficacy of IE prophylaxis in patients who undergo dental procedures. Although some retrospective studies suggested that there was a benefit from prophylaxis, these studies were small in size and reported insufficient clinical data. Furthermore, in a number of cases, the incubation period between the dental procedure and the onset of symptoms of IE was van der Meer and colleagues85 published a study of dental procedures in the Netherlands and the efficacy of antibiotic prophylaxis to prevent IE in patients with native or prosthetic cardiac valves. 