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Context: Cisapride, a gastrointestinal tract promotility agent, can cause life-threatening cardiac arrhythmias in patients susceptible either because of concurrent use of medications that interfere with cisapride metabolism or prolong the QT interval or because of the presence of other diseases that predispose to such arrhythmias. In June 1998, the US Food and Drug Administration (FDA) determined that use of cisapride was contraindicated in such patients and informed practitioners through additions to the boxed warning in the label and a "Dear Health Care Professional" letter sent by the drug's manufacturer.Objective: To evaluate the impact of the FDA's 1998 regulatory action regarding contraindicated use of cisapride.Design and Setting: Analysis of data for the 1-year periods before (July 1997-June 1998) and after (July 1998-June 1999) the regulatory action from the population-based, pharmacoepidemiology research databases of 2 managed care organizations (sites A and B) and a state Medicaid program (site C).Participants: Patients with at least 180 days of prior enrollment in 1 of the 3 sites who were prescribed cisapride at least once in the period before (n = 24 840) or after (n = 22 459) regulatory action. Patients could be included in both cohorts.Main Outcome Measures: Proportion of cisapride users in each period for whom cisapride use was contraindicated by the product label, based on computerized patient medical encounter records.Results: In the year prior to regulatory action, cisapride use was contraindicated for 26%, 30%, and 60% of users in study sites A, B, and C, respectively. In the year after regulatory action, use was contraindicated for 24%, 28%, and 58% of users, a reduction in contraindicated use of approximately 2 per 100 cisapride users at each site. When the analysis was restricted to new users of cisapride after regulatory action, only minor reductions in contraindicated use were found.Conclusion: The FDA's 1998 regulatory action regarding cisapride use had no material effect on contraindicated cisapride use. More effective ways to communicate new information about drug safety are needed. [ABSTRACT FROM AUTHOR]

Purpose: The Infectious Diseases Society of America and US CDC recommend 60 days of ciprofloxacin, doxycycline, or amoxicillin for anthrax prophylaxis. It is not possible to determine severe adverse drug event (ADE) risks from the few people thus far exposed to anthrax prophylaxis. This study's objective was to estimate risks of severe ADEs associated with long-term ciprofloxacin, doxycycline, and amoxicillin exposure using three large databases: one electronic medical record (General Practice Research Database) and two claims databases (UnitedHealthcare, HMO Research Network)., Methods: We include office visit, hospital admission and prescription data for 1/1/1999-6/30/2001. Exposure variable was oral antibiotic person-days (pds). Primary outcome was hospitalization during exposure with ADE diagnoses: anaphylaxis, phototoxicity, hepatotoxicity, nephrotoxicity, seizures, ventricular arrhythmia, or infectious colitis., Results: We randomly sampled 999,773, 1047,496, and 1819,004 patients from Databases A, B, and C respectively. 33,183 amoxicillin, 15,250 ciprofloxacin and 50,171 doxycycline prescriptions continued > or =30 days. ADE hospitalizations during long-term exposure were not observed in Database A. ADEs during long-term amoxicillin were seen only in Database C with 5 ADEs or 1.2(0.4-2.7) ADEs/100,000 pds exposure. Long-term ciprofloxacin showed 3 and 4 ADEs with 5.7(1.2-16.6) and 3.5(1.0-9.0) ADEs/100,000 pds in Databases B and C, respectively. Only Database B had ADEs during long-term doxycycline with 3 ADEs or 0.9(0.2-2.6) ADEs/100,000 pds. For most events, the incidence rate ratio, comparing >28 versus 1-28 pds exposure was <1, showing limited evidence for cumulative dose-related ADEs from long-term exposure., Conclusions: Long-term amoxicillin, ciprofloxacin, and doxycycline appear safe, supporting use of these medications if needed for large-scale post-exposure anthrax prophylaxis.

Introduction: Published literature suggests that attention-deficit/hyperactivity disorder (ADHD) affects 4% of adults and that as many as 60% of children with a diagnosis of ADHD will continue to have problems with inattention and impulsivity in adulthood. We analyzed cross-sectional prescription claims data and data from a national survey of office-based physicians for further inference on the likelihood of treatment with ADHD medications into adulthood., Methods: This study used data from a proprietary, national survey of office-based physicians (the IMS Health National Disease and Therapeutic Index, NDTI) to describe the indication associated with office visits with mention of common stimulant medications and atomoxetine. Enrollment and prescription claims data maintained by a large national health-care company were analyzed for age-specific utilization of these same agents., Results: Data from the NDTI suggest that the vast majority of visits associated with a stimulant medication or atomoxetine was coded with a diagnosis consistent with a mental health condition and not obesity/weight loss. The health plans included in this study processed 222,096 prescriptions for stimulant medications and atomoxetine among 43,175 unique patients aged 1-64 years during the calendar year 2004. Analyses of pharmacy claims data showed a steep increase in use through age 11 (prevalence=70.3 per 1,000 covered lives) followed by a marked decrease and plateau from age 25 through age 64 years (prevalence=5 to 10 per 1,000 covered lives)., Conclusions: On the basis of comparison of the prevalence rate peak of 70 per 1,000 around age 11 years to a plateau of 7 per 1,000 during the early career years, our results are consistent with a prediction that at least one child in 10 placed on an ADHD medication in childhood will receive treatment in to adulthood. The decrease in the prevalence of use of these medications with advancing age as seen in this cross-sectional study may reflect upon several clinical and secular factors.

Background: From July to September 1999, due to a concern of toxicity from exposure to thimerosal-containing vaccines, the American Academy of Pediatrics and U.S. Public Health Service temporarily recommended delaying the administration of first dose of hepatitis B vaccine until the age of 2-6 months for infants born to hepatitis B surface antigen negative mothers. Our objectives were to determine whether the recommendation affected the rate of perinatal hepatitis B infection in a multistate managed care population; to describe neonatal and early childhood cases of hepatitis B infection and to evaluate a possible role of the recommendation; and to assess the timeliness, with respect to the U.S. childhood immunization schedule, of vaccinations during the first 2 years of life., Methods: We identified 3 cohorts of infants born before (July 1998 to June 1999), during (July 1999 to September 1999) and after (October 1999 to September 2000) the recommendation period. We used automated claims data to identify possible neonatal and early childhood hepatitis B cases using specific ICD-9 diagnosis and CPT procedure codes and validated cases through medical record review. Using Health Plan Employer Data and Information Set (HEDIS) data, we calculated vaccination coverage for the first dose of hepatitis B vaccine at 3-month intervals from January 1999 to September 2000., Results: The eligible populations in the "before," "during" and "after" cohorts were 29,347, 7791 and 29,215 infants, respectively. Of 41 possible hepatitis B cases identified in the 3 cohorts, we confirmed 1 case in the after cohort with medical record review. Despite receiving the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12-24 hours of birth, the infant was diagnosed with laboratory-confirmed chronic hepatitis B at age of 9 months. An analysis of HEDIS data showed that vaccination coverage for the first dose of hepatitis B vaccine was 98% (January to March 1999) and 96% (April to June 1999) for the "before" cohort and 66% for the "during" cohort. For the "after" cohort the coverage was 72% (October to December 1999), 83% (January to March 2000), 91% (April to June 2000) and 95% (July to September 2000)., Conclusions: This study did not identify any perinatal hepatitis B transmission among health plan enrollees associated with the 1999 recommendation. The recommendation did result in a delay of hepatitis B birth dose in the "during" cohort as intended for infants born to hepatitis B surface antigen negative mothers. Six months after the recommendation was rescinded there was still a delay in the timing of first dose of hepatitis B vaccine, but the timing had returned to the prerecommendation level after 9-12 months.

Background: Registrational studies of patients treated with tegaserod for irritable bowel syndrome (IBS) suggest an increased risk for cholecystectomy versus treatment with placebo., Objective: To study cholecystectomy rates in association with tegaserod within a large administrative medical claims database., Methods: Patients were drawn from a large population within the US with commercial medical insurance. The primary analysis consisted of a comparison of the observed incidence rate for cholecystectomy claims among a large cohort of new-to-therapy tegaserod users with an incidence rate published for tegaserod-naive patients classified with IBS within the same insured population., Results: An inception cohort of 7475 individuals with up to 103 weeks of claims history following initiation of therapy with tegaserod was identified. After a follow-up of 3 months (and thus similar to the longest registrational trials), the observed cholecystectomy incidence rate was 340 per 10,000 person-years (95% CI 258, 442). The rate of cholecystectomy was highest in the earliest months of observation following initiation of tegaserod. The observed cholecystecomy incidence rate is 2.9 times higher than an IBS-specific rate of 119 per 10,000 person-years as published for patients so classified within the same insured population., Conclusion: Based on a large, inception cohort, we report a strong temporal association between the initiation of tegaserod therapy and an increased rate for cholecystectomy. The effect size at 3 months was similar to the relative risk for cholecystectomy reported in registrational studies comparing tegaserod with placebo. As misclassification of initial diagnosis for patients presenting with biliary colic-like symptoms may occur, precise measurements of tegaserod-related relative risk for cholecystectomy from observational studies are problematic and will require prospective studies.

Objective: The aim of this study was to determine the incidence rate for new-onset and idiopathic thrombotic thrombocytopenic purpura (TTP) among adults 20-64 years old, the validity of diagnostic criteria, and potential risk factors for TTP., Methods: This retrospective observational study analyzed automated administrative data from 11 geographically dispersed U.S. health plans. Cases of TTP were identified based on the presence of an inpatient hospital claim for TTP (ICD-9-CM 446.6) between 1/1/97 and 12/31/01 and confirmed by medical record review. Pharmacy and medical claims were used to evaluate outpatient drug exposure and comorbidities preceding hospitalization for TTP. Cases and the base population were screened so as to result in an incidence rate for idiopathic TTP., Results: We confirmed new-onset and idiopathic TTP in 9 of 15 presumptive cases for an incidence density of 1.4 per million person-years (95% CI: 0.6-2.6). The rate increased to 1.8 per million person-years after projection and age-standardization. The highest incidence rate of TTP was found in patients 50-64 years old (2.8 per million person-years; 95% CI: 0.8-7.1). These 9 patients had no apparent risk factors for TTP based on claims and medical record data., Conclusions: In a general U.S. population, the incidence rate of confirmed new-onset and idiopathic TTP was lower than previously reported, but appears to be on the rise. Our findings suggest that administrative claims data are useful for identifying outpatient drug exposures and comorbidities potentially associated with TTP., (Published 2006 Wiley-Liss, Inc.)

Objective: We evaluated the positive predictive values (PPVs) of specific criteria based upon International Classification of Diseases, 9th revision (ICD-9-CM) codes documented in health plan administrative databases for identification of cases of serious myopathy and rhabdomyolysis., Study Design and Setting: We conducted a retrospective study among patients enrolled in 11 geographically dispersed managed care organizations. Cohorts of new users of specific statins and fibrates were identified by selecting patients with an initial dispensing of the drug during the period 1 January 1998 to 30 June 2001. Potential cases of serious myopathy or rhabdomyolysis were identified using specific criteria based upon ICD-9-CM codes suggesting a muscle disorder or acute renal failure., Results: A total of 194 hospitalizations meeting the criteria for chart review selection were identified among 206,732 new users of statins and 15,485 new users of fibrates. Overall, 31 cases of serious, clinically important myopathy or rhabdomyolysis (18%) were confirmed through chart review. Of these, 26 (84%) had a claim including codes for myoglobinuria (ICD-9-CM 791.3) or other disorders of muscle, ligament, and fascia (ICD-9-CM 728.89). A PPV of 74% (26 of 35 patients meeting criteria) was found for a composite definition that included (1) a primary or secondary discharge code for myoglobinuria, (2) a primary code for "other disorders of muscle," or (3) a secondary code for "other disorders of muscle" accompanied by a claim for a CK test within 7 days of hospitalization or a discharge code for acute renal failure., Conclusion: For rare adverse events such as serious myopathy or rhabdomyolysis, large population-based databases that include diagnosis and laboratory test claims data can facilitate epidemiologic research.

Objective: To assess whether primary care physicians, via referrals or other mechanisms, are now providing proportionally less care for children with specific common diagnoses, thus driving greater demand for specialist services., Study Design: Secondary data analysis (1993-2001) from one of the largest commercial healthcare organizations in the United States. Evaluation and management (E/M) common procedural terminology (CPT) visit codes and International Classification of Diseases (ICD) codes pertaining to asthma, constipation, headache, and heart murmurs were selected. Visits were then assigned to the specialty of physician providing care. Significant differences between and among categories of physicians were tested using logistic regression., Results: Overall, pediatrician generalists and specialists provided a greater proportion of E/M visits to children in 2001 than in 1993, compared with nonpediatrician providers. However, although the absolute increase in the proportion of all E/M visits by children <18 years of age to pediatrician generalists was greater than that of pediatrician subspecialists (4.77% vs 0.69%; P <.0001), the relative increase was much smaller for the generalists (8.9% vs 19.7%; P <.0001). Findings were consistent for most of the specific diagnoses examined., Conclusions: The increases in both the proportion and number of visits made to specialists has not been accompanied by a decrease in visits to generalists.

Context: Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available., Objective: To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting., Design, Setting, and Patients: Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy., Main Outcome Measure: Incidence rates of rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis., Results: In 252,460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10,000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate., Conclusions: Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.

Objectives: To use a national population-based automated claims database to study the testing rate, prevalence, and prescribing patterns for chronic hepatitis C., Study Design: A retrospective descriptive study that analyzes medical and pharmacy automated claims from affiliated health plans in 4 regions of the United States., Methods: Data were collected from 11 UnitedHealth Group-affiliated health plans (3.9 million members) from January 1, 1997, to December 31, 1999. Medical claims were used to identify persons tested for hepatitis C virus (HCV). Persons with chronic HCV were identified through medical and pharmacy claims. Patterns of drug use and treatment were analyzed, including prescribing physician specialty and proportion of patients receiving baseline and follow-up testing., Results: Of 27,871 members tested for HCV (0.7%), 1869 (6.7%) were diagnosed as having chronic HCV. Tested patients were more likely to be female (odds ratio [OR], 1.1) and older (> or = 25 years; OR, 4.1). Of 3259 patients with HCV, most were male (OR, 1.8) and older (> or = 25 years; OR, 32.0). Of these patients, 33.6% (n = 670) of men and 25.2% (n = 319) of women received treatment. Combination therapy users were more likely to undergo baseline (OR, 4.8) and follow-up (OR, 6.2) testing compared with interferon alfa monotherapy users., Conclusions: Of the total population, 0.7% were tested for HCV, of whom 6.7% were diagnosed as having chronic HCV. Although women were more likely to undergo testing, prevalence and therapy rates for chronic HCV were higher in men. Most patients did not receive recommended baseline and follow-up testing, and the approximate 30% therapy rate suggested that many patients with HCV remain untreated.

The aim of this study was to quantify ambulatory use of ticlopidine and clopidogrel in association with percutaneous coronary revascularization procedures (PTCA, atherectomy, stent) in a national managed care organization. Retrospective administrative claims data over a 3-year period (1996-1998) from 12 UnitedHealth Group-affiliated health plans in four geographic regions were collected. Pharmacy and medical claims data were used to determine the patients exposed to ticlopidine and clopidogrel between January 1, 1996 and December 31, 1998, the duration of use, prescriptions within 2 weeks of a coronary procedure, and stent patients prescribed either drug within 2 weeks of stent placement in 1998. Substantial short-term use of ticlopidine and clopidogrel was found. The percentage of members with duration of use < or = 30 days ranged from 50.4% in 1996 to 56.9% in 1998 for ticlopidine and was 52.7% for clopidogrel. In 1998, 46% and 33% of ticlopidine and clopidogrel users, respectively, had a medical claim for a coronary procedure that fell within 2 weeks of a prescription. The rate was lower for Medicare beneficiaries. In 1998, 78% of stent patients filled a prescription for either drug within 2 weeks of stent implantation. Although little difference was found overall in the use of these agents across geographic regions, a higher proportion of stent patients in the Southeast were prescribed ticlopidine within this time frame. The findings suggest that during the study time period ticlopidine and clopidogrel are frequently used off-label in association with percutaneous coronary revascularization procedures. These results were important in considering the overall benefit-risk profile.