CRITICAL APPRAISAL OF ARTICLE ON HARM

Among patients with acute rheumatic fever, will discontinuation of penicillin have adverse effects? Clinical question patients with rheumatic fever taking penicillin Population: discontinuance of penicillin Intervention: Harm, complications Outcome: Discontinuing Rheumatic Fever Prophylaxis in Selected Adolescents and Young Adults: A Prospective Study Ximena BerriosXimena Berrios, MD; Emilo del Campo, MD; Beatriz Guzman, RN; and Alan L. Bisno, MDEmilo del CampoBeatriz GuzmanAlan L. Bisno Search terms: penicillin, rheumatic fever, safety, discontinuance

Relevance Yes. The objective of the study is to assess the safety of discontinuing prophylaxis with antimicrobial agents in patients judged to be at relatively low risk for recurrence of acute rheumatic fever. (page 1,Abstract,2 nd paragraph) Is the objective of the article similar to your dilemma? Validity Yes. The investigator only included patients ranging in age at study entry from 15 to 44 years (mean, 24.5 years). Patients were entered in the Control and Prevention Program because of an attack of acute rheumatic fever (observed and documented by the Program physicians) that fulfilled the modified Jones criteria or because they were referred from ambulatory clinics with rheumatic valvular heart disease. The latter was confirmed by Program cardiologists who did clinical examinations as well as reviewed electrocardiograms and chest roentgenograms. (page 3, Methods: Patients, 2 nd paragraph) Were there clearly identified comparison groups?

Validity The patients were categorized as those those with aortic valvular involvement, mitral stenosis, or polyvalvular disease who receive prophylaxis for life In patients and those who discontinued prophylaxis. Patients who did not have carditis during their previous attack(s), prophylaxis was discontinued after 5 years or at age 18, whichever was longer. In those with only mild mitral regurgitation or healed carditis, prophylaxis was stopped after 10 years or at age 25. The same regimen was used for patients whose sole cardiac sequela was mild mitral regurgitation. (page 3, Methods: Criteria for cessation of prophlaxis,3 rd paragraph) ) Were there clearly identified comparison groups? Yes. The exposures and outcomes were measured in the same way in the groups compared. The outcomes of all groups were determined through endoscopic examination of bleeding ulcers in all groups. (page 30, Materials and Methods, 4 th paragraph) Were the exposures and outcomes measured in the same way in the groups compared?

Yes the follow up was sufficiently long to detect the outcome. Follow up was done every 3 months. The study began in July 1982 and terminated in September (page 4, Results: Follow up, 1st paragraph ) Was follow-up sufficiently long and complete?

During this period, 59 postprophylactic patients (approximately 80% of whom entered the study during the first 6 months) were followed prospectively for a total of 1032 scheduled visits and 3346 patient-months (mean months of follow-up per patient, 56.7 months; median, 67.5 months; range, 10 to 75 months). Twelve patients entered in the off-prophylaxis protocol did not complete the study. They therefore have a 80 % follow up. (page 4, Results:Follow-up,1 st paragraph) (page 5, Results: Follow-up, 3rd paragraph) Was follow-up sufficiently long and complete?

The discontinuation of prophylaxis was done before any outcome was observed. There were two recurrences of rheumatic fever during the 3346 patient-months (278.8 patient-years) of follow-up between 1982 and 1986, yielding a recurrence rate of 0.72 (CI, 0.2 to 2.6) per 100 patient- years of prospective surveillance (page 5, Results: last t paragraph) Is the temporal relationship between the exposure and outcome correct and dose response gradient present? Since almost all the answers for the validity guides are valid, the study can be considered valid. Overall, is the study valid?

Results Among 59 patients, 48 had completed their period of prophylaxis There were two recurrences of rheumatic fever during the 3346 patient-months (278.8 patient-years) of follow-up Recurrence rate: 0.72 (CI, 0.2 to 2.6) per 100 patient-years of prospective surveillance. Ninety-five percent confidence intervals were determined using the Poisson probability function generator (SAS version 6.03, SAS Institute Inc., 1988). (page 5, Results & page 4, Statistical Analysis) Among 59 patients, 48 had completed their period of prophylaxis There were two recurrences of rheumatic fever during the 3346 patient-months (278.8 patient-years) of follow-up Recurrence rate: 0.72 (CI, 0.2 to 2.6) per 100 patient-years of prospective surveillance. Ninety-five percent confidence intervals were determined using the Poisson probability function generator (SAS version 6.03, SAS Institute Inc., 1988). (page 5, Results & page 4, Statistical Analysis) What is the magnitude of the association between exposure and outcome? Was the estimate of the risk precise?

Clinical Applicability Yes. (page 1, Abstract: Patients & page 3, Methods: Patients) 28 year-old female cardiovascular problem ARF 40 females (+ 19 males) mean age : years old ARF Are the study patients similar to my own? What is our patient’s risk of benefit and harm from the exposure? Is our patient so different from those in the study that its results cannot apply? No, our patient is the same with the patients included in the study. Therefore, this study can be applied to our patient. prone to develop recurrent attacks if they have immunologically significant group A streptococcal throat infections antibacterial prophylaxis with penicillin has an over-all benefit possibility of recurrence despite completion of therapy affected by exposure to the pathogens, reliability in reporting promptly to the physician any episodes of pharyngitis, and the incidence of rheumatic fever in the community. risk for development of or exacerbation of rheumatic heart disease and carditis (page 2, Conclusion & page 8, Discussion)

Based on the appraisal, the patient will be advised that prophylactic treatment of Penicillin for her acute rheumatic fever may be discontinued after 5 years given that there was no carditis during the attack. Otherwise, it will have to take 10 years. Individuals who have reached their early twenties, had their most recent attack more than 5 years ago, and are free of rheumatic heart disease can be taken off prophylaxis with relative safety. What alternative treatments are available? There was no mention in the article of alternative medications.