Kenneth Hornbuckle

A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States.

Treatment-emergent diabetes mellitus (DM) has been described for conventional and atypical antipsychotics. In our study, antipsychotic prescription claims from AdvancePCSs database were used to identify patients starting antipsychotic monotherapy. The relative risk of developing DM was determined using prescription claims for antidiabetic agents in the following cohorts: AdvancePCS general patient population, combined conventional antipsychotics, and combined atypical antipsychotics. Cox proportional hazards regression was used to adjust for differences in age, gender, and duration of antipsychotic exposure between cohorts in the estimation of risk of developing diabetes. Hazard ratios for developing DM in the combined conventional, combined atypical, and individual conventional and atypical antipsychotic treatment cohorts were greater than the AdvancePCS general patient population cohort. An increased risk of developing diabetes compared with the AdvancePCS general patient population was observed during treatment with conventional or atypical antipsychotics.

Retrospective Cohort Study of Diabetes Mellitus and Antipsychotic Treatment in a Geriatric Population in the United States

OBJECTIVES The objective of this study was to investigate risk of diabetes among elderly patients during treatment with antipsychotic medications. DESIGN We conducted a longitudinal, retrospective study assessing the incidence of new prescription claims for antihyperglycemic agents during antipsychotic therapy. SETTING Prescription claims from the AdvancePCS claim database were followed for 6 to 9 months. PARTICIPANTS Study participants consisted of patients in the United States aged 60+ and receiving antipsychotic monotherapy. The following cohorts were studied: an elderly reference population (no antipsychotics: n = 1,836,799), those receiving haloperidol (n = 6481) or thioridazine (n = 1658); all patients receiving any conventional antipsychotic monotherapy (n = 11,546), clozapine (n = 117), olanzapine (n = 5382), quetiapine (n = 1664), and risperidone (n = 12,244), and all patients receiving any atypical antipsychotic monotherapy (n = 19,407). MEASUREMENTS We used Cox proportional hazards regression to determine the risk ratio of diabetes for antipsychotic cohorts relative to the reference population. Covariates included sex and exposure duration. RESULTS New antihyperglycemic prescription rates were higher in each antipsychotic cohort than in the reference population. Overall rates were no different between atypical and conventional antipsychotic cohorts. Among individual antipsychotic cohorts, rates were highest among patients treated with thioridazine (95% confidence interval [CI], 3.1- 5.7), lowest with quetiapine (95% CI, 1.3-2.9), and intermediate with haloperidol, olanzapine, and risperidone. Among atypical cohorts, only risperidone users had a significantly higher risk (95% CI, 1.05-1.60; P = 0.016) than for haloperidol. Conclusions about clozapine were hampered by the low number of patients. CONCLUSION These data suggest that diabetes risk is elevated among elderly patients receiving antipsychotic treatment. However, causality remains to be demonstrated. As a group, the risk for atypical antipsychotic users was not significantly different than for users of conventional antipsychotics.

Risk of Hepatic Events in Patients Treated with Vancomycin in Clinical Studies

AbstractBackground: Routine surveillance of spontaneous reporting data and subsequent disproportionality analyses have indicated that the use of vancomycin might be associated with an increased risk of hepatic events. Objective: To conduct a meta-analysis of published randomized controlled clinical trials (RCTs) to better understand if the use of vancomycin is potentially associated with an increased risk of hepatic events. Data Sources: A comprehensive search and review of published clinical studies indexed in MEDLINE, PubMed, International Pharmaceutical Abstracts and the Cochrane Library from 1950 to June 2010 was conducted. Study Selection: The inclusion criteria consisted of (i) published RCTs comparing vancomycin with/without other additional treatments to other comparators; and (ii) studies that reported hepatic events. Data Extraction: The data related to any hepatic events reported in RCTs were extracted and examined. The quality of selected studies was assessed based on the Jadad scale. The effect size was presented as a risk ratio (RR) with a 95% CI and number needed to harm. The pooled RRs were calculated by using both fixed-effects and random-effects models. The impact of publication bias was assessed by funnel plot and the Egger’s test. Data Synthesis: A total of 20 RCTs, including 7419 patients, met the study inclusion criteria and were selected. An increased incidence of hepatic events, specifically elevated serum aminotransferase levels, was observed in patients receiving vancomycin, when compared with other comparators (pooled RR= 1.95; 95% CI 1.62, 2.36; ps< 0.001), but the majority of the events were mild to moderate in nature. No evidence is currently available suggesting that the use of vancomcycin confers a risk of progressive or severe drug-induced liver injury. Conclusions: Continuous monitoring of hepatic events on a routine basis among patients with the use of vancomycin is suggested.

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products

Optimizing a therapeutic products benefit–risk profile is an on‐going process throughout the products life cycle. Different, yet related, benefit–risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life‐cycle approach to integrated Benefit–Risk Assessment, Communication, and Evaluation (BRACE).

Benefit-Risk Assessment, Communication, and Evaluation (BRACE) throughout the life cycle of therapeutic products : overall perspective and role of the pharmacoepidemiologist

Optimizing a therapeutic products benefit–risk profile is an on‐going process throughout the products life cycle. Different, yet related, benefit–risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life‐cycle approach to integrated Benefit–Risk Assessment, Communication, and Evaluation (BRACE).

Co-possession of phosphodiesterase type-5 inhibitors (PDE5-I) with nitrates

Abstract Objective: Estimate the proportion of phosphodiesterase type-5 inhibitor (PDE5-I) patients who co-possess nitrates and compare the proportion of tadalafil patients dispensed nitrates to a matched control group. Secondarily, examine the percentage of co-possession of PDE5-Is and nitrates where the products were dispensed on the same day or written by the same prescriber. Methods: Male patients aged 18+ years filling PDE5-I prescriptions between December 2003 and March 2006 were identified using a U.S. longitudinal prescription database (IMS Health LRx™). Similar patients not dispensed a PDE5-I during this period were matched to the tadalafil-dispensed cohort using a propensity score approach. Co-possession, as a proxy for concurrent use, was defined as an overlap in time on therapy for a PDE5-I and nitrate and was compared for the three PDE5-Is and for tadalafil to the matched control group. Results: Among 601,063 tadalafil patients, 3.31% were dispensed a nitrate during the study period, compared to 6.18% in control patients (n = 601,063). When co-possessed prescriptions were defined by overlapping exposure periods, the proportion of PDE5-I patients with co-possessed nitrates ranged from 1.44% (tadalafil) to 1.72% (vardenafil) and 2.13% (sildenafil). Co-possession percentages of PDE5-I prescriptions were 0.83% for tadalafil and 1.07% for sildenafil and vardenafil. The majority (54.29%) of co-possessed PDE5-I and nitrate prescriptions had the nitrate dispensed prior to the PDE5-I prescription identified in the study cohort. Conclusions: Keeping in mind the limitations of observational studies, these results suggest that co-dispensing of nitrates and PDE5-Is is low. Compared to control patients, the proportion of nitrate co-possession was lowest for patients filling tadalafil. Tadalafil patients also had the lowest co-possessed proportion among the three PDE5-I cohorts. While the majority of co-possessed drug pairs were prescribed by different providers, the highest percentage of co-prescribing from the same physician was among cardiologists. These results suggest that physicians adhere to contraindications and are careful about co-prescribing of nitrates with PDE-5Is.

P.2.132 A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United Kingdom

OBJECTIVE Treatment-emergent diabetes has been reported during exposure to conventional and atypical antipsychotics. This retrospective cohort study explored the UK General Practice Research Database (GPRD) to determine hazard ratios of diabetes for patients prescribed antipsychotics. METHODS A Cox proportional hazard regression model using age, gender, and obesity (BMI > 30 kg/m2) was used to determine the hazard ratio (HR) of diabetes development in conventional antipsychotic (N = 59,089), atypical antipsychotic (N = 9053), individual antipsychotic, and general patient population cohorts (N = 1,491,548). RESULTS Compared with the general GPRD patient population, patients exposed to conventional or atypical antipsychotics had a higher risk of developing diabetes (atypical antipsychotic cohort: HR = 2.9, CI = 2.0-4.4; and conventional antipsychotic cohort: HR = 1.9, CI = 1.6-2.3). The risk of developing diabetes during thioridazine, risperidone, or olanzapine treatment was significantly higher compared with the general GPRD patient population. CONCLUSION Consistent with other epidemiology studies, this study supports an increased risk of developing diabetes during treatment with antipsychotics.