No abstract

Purpose Bleeding complications are a serious adverse effect of medications that prevent abnormal blood clotting. To facilitate epidemiologic investigations of bleeding complications, we developed and validated an automated database case definition for bleeding-related hospitalizations. Methods The case definition utilized information from an in-progress retrospective cohort study of warfarin-related bleeding in Tennessee Medicaid enrollees 30 years of age or older. It identified inpatient stays during the study period of January 1990 through December 2005 with diagnoses and/or procedures that indicated a current episode of bleeding. The definition was validated by medical record review for a sample of 236 hospitalizations. Results We reviewed 186 hospitalizations that had medical records with sufficient information for adjudication. Of these, 165 (89% [95% CI, 83%-92%]) were clinically confirmed bleeding-related hospitalizations. An additional 19 hospitalizations (10% [7%-15%]) were adjudicated as possibly bleeding-related. Of the 165 clinically confirmed bleeding-related hospitalizations, the automated database and clinical definitions had concordant anatomical sites (gastrointestinal, cerebral, genitourinary, other) for 163 (99% [96%-100%]). For those hospitalizations with sufficient information to distinguish between upper/lower gastrointestinal bleeding, the concordance was 89%(76%-96%) for upper gastrointestinal sites and 91%(77%-97%) for lower gastrointestinal sites. Conclusion A case definition for bleeding-related hospitalizations suitable for automated databases had a positive predictive value of between 89% and 99% and could distinguish specific bleeding sites.

These data support other findings indicating that a clinically significant risk for serious ulcer disease is associated with the use of nonaspirin nonsteroidal anti-inflammatory drugs. The data show that this risk increases with dose and recency of use and that use of these drugs may be responsible for a large proportion of peptic ulcer disease among elderly persons.

Background Proton-pump inhibitors (PPIs) and clopidogrel are frequently co-prescribed though the benefits and harms of their concurrent use are unclear. Objective To examine the association between concurrent PPI and clopidogrel use and the risks for gastroduodenal bleeding hospitalizations and serious cardiovascular disease. Design Retrospective cohort study that used automated data to identify patients who received clopidogrel between 1999 through 2005 following hospitalization for coronary heart disease. Setting Tennessee Medicaid Program Patients 20,596 patients (including 7593 concurrent users of clopidogrel and PPIs) hospitalized for myocardial infarction, coronary artery revascularization, or unstable angina pectoris. Measurements Baseline and followup drug use assessed from automated records of dispensed prescriptions. Primary outcomes were hospitalizations for gastroduodenal bleeding and serious cardiovascular disease (fatal or nonfatal myocardial infarction/sudden cardiac death, stroke, or other cardiovascular death). Results Pantoprazole and omeprazole accounted for 62% and 9% of the concurrent PPI use. Adjusted gastroduodenal bleeding hospitalization incidence in concurrent PPI users was 50% lower than that in nonusers (HR, 0.50 [95% CI, 0.39 to 0.65]). For patients at highest risk of bleeding, PPI use was associated with an absolute reduction of 28 (12 to 37) gastroduodenal bleeding hospitalizations per 1000 person years. The hazard ratio associated with concurrent PPI use for risk of serious cardiovascular disease was 0.99 (CI, 0.82 to 1.19) and was 1.01 (CI, 0.77 to 1.30) among patients who had percutaneous coronary interventions with stenting. Limitations There was possible unmeasured confounding and misclassification of exposure (no information on adherence or over-the-counter use of drugs) and endpoints (not confirmed by medical record review). Because many patients entered the cohort from hospitals with relatively few cohort members, the analysis relied on the assumption that after adjusting for observed covariates, PPI users from one such hospital could be compared with nonusers from a different hospital. Conclusion Among patients with serious coronary heart disease treated with clopidogrel, concurrent PPI use was associated with reduced incidence of gastroduodenal bleeding hospitalizations. The corresponding point estimate for serious cardiovascular disease was not increased; however, the 95% confidence interval included a clinically important increased risk. Funding Agency for Healthcare Quality and Research, National Heart Lung and Blood Institute.

ncreasing antipsychotic use among children and youth 1-4 raises the concern that this practice increases the risk of type 2 diabetes mellitus in this vulnerable population. 5-7 For adults, there is considerable evidence linking antipsychotic use to increased risk of type 2 diabetes. Several antipsychotics have metabolic effects, such as weight gain, increased glucose level, and insulin resistance, that are thought to be precursors to diabetes. 8 Epidemiologic studies have confirmed an increased risk for type 2 diabetes for individuals using some types of antipsychotics, particularly the atypical antipsychotic drugs. 9-11 However, the evidence for children and youth is less extensive. Although metabolic studies of children suggest that antipsychotic use might increase the risk of type 2 diabetes, 12,13 epidemiologic data are more limited. 5-7 Obstacles to studies of this population include the lower incidence of type 2 diabetes, the need to distinguish between type 1 and type 2 diabetes, and the identification of appropriate comparison groups. Prior to the introduction of the atypical antipsychotic drugs, the primary indications for antipsychotics in pediatric or adolescent populations were schizophrenia and other psychotic disorders. Subsequently, use expanded to include bipolar disorders, affective disorders, and symptoms related to behavior and conduct, which now account for the majority of prescriptions. 2-4,14 There are other well-recognized alternative medications for each of these conditions; indeed, antipsychotics are often a secondary or off-label therapeutic choice. 14-17 Thus, an increased risk of diabetes conferred by an-IMPORTANCE The increased prescribing of antipsychotics for children and youth has heightened concerns that this practice increases the risk of type 2 diabetes mellitus. OBJECTIVE To compare the risk of type 2 diabetes in children and youth 6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity score-matched controls who had recently initiated another psychotropic medication. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of the Tennessee Medicaid program with 28 858 recent initiators of antipsychotic drugs and 14 429 matched controls. The cohort excluded patients who previously received a diagnosis of diabetes, schizophrenia, or some other condition for which antipsychotics are the only generally recognized therapy. MAIN OUTCOMES AND MEASURES Newly diagnosed diabetes during follow-up, as identified from diagnoses and diabetes medication prescriptions. RESULTS Users of antipsychotics had a 3-fold increased risk for type 2 diabetes (HR = 3.03 [95% CI = 1.73-5.32]), which was apparent within the first year of follow-up (HR = 2.49 [95% CI = 1.27-4.88]). The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95% CI = 1.06-4.27), 3.42 (95% CI = 1.88-6.24), and 5.43 (95% CI = 2.34-12.61) for respective cumulative doses (gram equivalents of chlorpromazine) of more than 5 g, 5 to 99 g, and 100 g or more (P < .04). The risk remained ele...