Antiepileptic hypersensitivity syndrome in children.

OBJECTIVE: To assess clinical features and outcomes of childhood antiepileptic hypersensitivity syndrome (AHS). AHS is an idiosyncratic reaction to aromatic anticonvulsants that can result in severe multiorgan dysfunction and death. METHODS: Children with suspected AHS (fever, rash, lymphadenopathy, liver dysfunction) were identified by an in-house computerized adverse drug event reporting system. The medical charts of children with suspected AHS were reviewed. A MEDLINE search (from 1966 to October 1999) was performed using the term antiepileptic hypersensitivity syndrome. RESULTS: Fourteen of 36 children who experienced a rash, urticaria, pruritus, fever, or hepatotoxicity associated with aromatic anticonvulsants met the criteria for AHS (mean age 10.4 +/- 6.5 y; males to females 8:6, white to African-American to biracial 10:3:1). Eight patients were receiving phenytoin, six carbamazepine, and four phenobarbital alone or in combination. The mean time from exposure to development of symptoms was 23.0 +/- 14.8 days. In addition to rash and fever (present in all patients by definition), other common features of AHS were lymphocytosis (71.4%), elevated erythrocyte sedimentation rate (64.3%), elevated aminotransferases (64.3%), lymphadenopathy (57.1%), eosinophilia (42.8%, coagulopathy (42.8%), leukocytosis (35.7%), leukopenia (35.7%), hyperbilirubinemia (35.7%), and nephritis (7.1%). All children recovered except one, who died from complications of liver failure. Clinical outcome was simimlar between children who received systemic steroid therapy (n=5) and those who did not. Antiepileptics producing AHS were discontinued in all patients. CONCLUSIONS: AHS can be fatal in children if not promptly recognized. Fever, rash, and hepatotoxicity should serve as presumptive evidence for AHS, which requires immediate discontinuation of an offending anticonvulsant.

Bismuth subgallate-epinephrine paste in adenotonsillectomies.

OBJECTIVE: To evaluate the role of bismuth subgallate-epinephrine (BSE) paste as a hemostatic in adenotonsillectomies. DATA SOURCES: MEDLINE (January 1966-October 1999) and Current Contents (January 1997-October 1999) were searched, using bismuth subgallate, adenoidectomy, tonsillectomy, and adenotonsillectomy as search terms. A citation search was performed using Science Citation Index (January 1977-October 1999). DATA SYNTHESIS: Adenotonsillectomies are common procedures; although there are few complications, hemorrhage is a concern. Bismuth subgallate has historically been used as an astringent and hemostatic. An evaluation of studies of bismuth subgallate and BSE paste was conducted. CONCLUSIONS: There is minimal evidence to support this practice, but data suggest that epinephrine may be the active ingredient in BSE paste. BSE paste is inexpensive, poses little risk, and may decrease postoperative bleeding; therefore, it may be a reasonable hemostatic agent.

Creatine: a review of efficacy and safety.

OBJECTIVE: To provide an overview of the data on the efficacy and safety of the nutritional supplement creatine. DATA SOURCES: Human studies in English in MEDLINE, Current Contents, BIOSIS, Science Citation Index, and the popular media (including a LEXIS-NEXIS search and information from the World Wide Web and lay media) for 1966 to July 1999 using the search terms creatine, creatine supplement#, creatine monophosphate, and creatine NOT kinase. DATA SYNTHESIS: Creatine use is common among professional athletes. Its use has spread to college athletes, recreational athletes, and even children. Most creatine supplement regimens include a loading dose of 20 to 30 grams divided in 4 equal doses for 5 to 7 days, followed by a 2 gram per day maintenance dose. The increased creatine in the muscle may allow larger stores of phosphocreatine to build, and provide extra energy in the form of adenosine triphosphate. Despite the many clinical trials, high-quality research is lacking. Laboratory investigations of endurance isotonic exercises, strength and endurance during isotonic exercises, isokinetic torque, isometric force, and ergometer performance have yielded roughly an equal number of published studies showing a positive effect or lack of effect. Field studies (i.e., on subjects participating in sports activities) are less impressive than laboratory studies. Performance was more often improved for short-duration, high-intensity activities. Reports have linked creatine to weight gain, cramping, dehydration, diarrhea, and dizziness. Creatine may decrease renal function, but only two case reports of this effect have been published. Creatine appears to be well tolerated in short-term trials. CONCLUSION: While creatine may enhance the performance of high-intensity, short-duration exercise, it is not useful in endurance sports. Because commercially marketed creatine products do not meet the same quality control standards of pharmaceuticals, there is always a concern of impurities or doses higher or lower than those on the labeling. Consumers should balance the quality of information supporting the use of creatine with the known and theoretical risks of using the product, including possible renal dysfunction.

Discontinuation rates of Helicobacter pylori treatment regimens: a meta-analysis.

We conducted a meta-analysis to determine what factors in treatment regimens for Helicobacter pylori are associated with increased discontinuation rates. Studies were selected from the 1990-1996 MEDLINE data base, and references in published articles and reviews were obtained. Each article was uniformally abstracted for factors that could potentially affect dropout rates. Drug regimens with high numbers of doses per day had highest dropout rates (p=0.0001). The total dropout rate was lowest for regimens containing a proton pump inhibitor (OR = 0.75, CI 0.57, 0.98). The rate was high in regimens containing a bismuth compound due to side effects (OR = 2.79, CI 1.78, 4.36). The main finding was that drug regimens for eradication of H. pylori that have a high number of doses per day result in higher discontinuation rates than regimens with fewer doses per day.

Removal of iron dextran by hemodialysis: an in vitro study.

Intravenous iron dextran is frequently prescribed for iron-deficient hemodialysis patients, a practice that has increased during the erythropoietin era. Whether iron dextran is removed by hemodialysis has been a concern, especially for high permeability membranes. The purpose of this in vitro study was to measure iron dextran clearance by nine different hemodialyzers (Fresenius F3, F8, and F80B; Baxter CF25, CA150, CA210, and CT190; Toray BK2.1P; and Hospal Filtral 16) representing six types of membranes (polysulfone, cuprophane, cellulose acetate, cellulose triacetate, polymethylmethacrylate, and polyacrylonitrile) and including membranes considered high efficiency and high flux. Clearances were assessed using a closed-loop, fixed-volume reservoir model. Absolute drug removal also was determined over the 30-minute experiments. Iron dextran clearance did not exceed 25 mL/min, and clearances also were minimal after a single automated reuse with glutaraldehyde sterilant. A maximum of 8% of iron dextran was removed during the experiment. We conclude that iron dextran clearance by the nine hemodialyzers studied was small or too low to be detected in this sensitive in vitro dialysis system and that adjusting dosing schedules is not needed.

Physicians' perceptions and knowledge of drug costs: results of a survey.

The objective of this survey was to determine physicians' opinions of the importance of drug costs, sources of drug cost information used, preferences for mechanisms to lower drug costs, and to assess knowledge of the relative cost of common drugs. A questionnaire containing opinion statements and five categories of drugs to be ranked from least to most expensive was sent to 598 physicians at our tertiary-care, university-affiliated teaching hospital. In all, 398 (66.6%) surveys were completed. Survey results indicate that physicians are interested in lowering the cost of drug therapy, and that they are knowledgeable of relative drug costs but would like more cost information to make more informed prescribing decisions. Most believe that a readily available drug cost index is the most beneficial mechanism to decrease drug expenditures.

Use of nifedipine in the hypertensive diseases of pregnancy.

OBJECTIVE: To review the available data about the use of nifedipine to treat hypertension in pregnancy. DATA SOURCES: All English language cases and studies published after 1984 and indexed in MEDLINE, Excerpta Medica, and BIOSIS PREVIEWS under the headings nifedipine, hypertension in pregnancy, uteroplacental blood flow, maternal/fetal hemodynamics, preeclampsia, and pregnancy outcome. MAIN OUTCOME MEASURES: The primary outcome indicators included the safety and antihypertensive efficacy of nifedipine in pregnancy; the effects of nifedipine on maternal/fetal hemodynamics; and the effect, if any, of nifedipine on perinatal outcome. CONCLUSIONS: Tradiational drug therapy choices for hypertension in pregnancy continue to be hydralazine for acute reduction of blood pressure and methyldopa for the management of chronic hypertension. Current data indicate that nifedipine is an appropriate second-line antihypertensive medication in pregnancy, but more clinical trials are needed before it can be considered an appropriate choice for initial therapy. As do other antihypertensive agents, nifedipine provides maternal benefit by lowering blood pressure and reducing the risk of cerebral hemorrhage and end-organ damage. However, perinatal benefit of nifedipine remains to be established.

Criteria-based adverse drug reaction reporting and the use of a relational database.

The criteria-based ADR reporting program at Shands Hospital has been successful. When the Joint Commission reviewed this program in January 1991, they were satisfied that it met their standards. Efforts are now focusing on improving the capture of ADRs, which will make the information available from the database even more valuable. Data from Shands Hospital will contribute to postmarketing surveillance, patient care, and staff education, and these data will influence drug usage evaluations and the formulary. Observations will be used to recommend alternate therapies to prevent ADRs as well as methods to manage reactions should they occur. The listing of criteria has facilitated the reporting of ADRs at Shands Hospital, and communication of the information has been greatly enhanced by the ADR database. Efficiency has been improved as a result.

Drug-food interaction counseling programs in teaching hospitals.

The results of a survey to characterize drug-food interaction counseling programs in teaching hospitals and solicit opinions on these programs from pharmacists and dietitians are reported. A questionnaire was mailed to the pharmacy director and the director of dietary services at teaching hospitals nationwide. The questionnaire contained 33 questions relating to hospital characteristics, drug-food interaction counseling programs, and the standard calling for such programs issued by the Joint Commission on Accreditation of Healthcare Organizations. Of 792 questionnaires mailed, 425 were returned (response rate, 53.7). A majority of the pharmacists and dietitians (51.2%) did not consider their drug-food interaction counseling program to be formal; some had no program. The pharmacy department was involved more in program development than in the daily operation of such programs. The most frequent methods of identifying patients for counseling were using lists of patients' drugs and using physicians' orders. A mean of only five drugs were targeted per program. Slightly over half the respondents rated the Joint Commission standard less effective than other standards in its ability to improve patient care. A majority of teaching hospitals did not have formal drug-food interaction counseling programs. Pharmacists and dietitians did not view these programs as greatly beneficial and did not believe that the Joint Commission has clearly delineated the requirements for meeting its standard.

Organization and operation of P & T Committees in the state of Florida: a survey.

To determine the structure and function of P & T Committees in Florida, a survey was initiated. Questionnaires were mailed to all 289 hospitals in the state. Topics addressed included hospital demographics (type of service provided, institution ownership, hospital size), P & T Committee structure (size of the committee, membership breakdown by specialty, chairman specialty, number of meetings per year), formulary additions (personnel authorized to request drug additions, process for adding drugs to the formulary, monitoring new drug use), and formulary systems (prevalence of therapeutic interchange programs, methods of communicating formulary changes). Overall survey response rate was 71.5%. In general, P & T Committees in Florida appear to be functioning at a relatively high level. Since there is little current information about the composition and operation of P & T Committees in hospitals around the country, it is hoped that this survey will be useful to P & T Committees that wish to upgrade or expand their activities.