Antipsychotic Use and Stroke: A Retrospective Comparative Study in a Non-Elderly Population.

OBJECTIVE: To evaluate stroke risk among users of typical antipsychotics compared to users of atypical antipsychotics in a non-elderly and non-demented US population. METHODS: New users of antipsychotics aged 18-64 years without dementia were identified via electronic health care data from 13 health plans participating in the Sentinel System from January 2001 to September 2015. The risk of hospitalized stroke events, identified via ICD-9-CM diagnostic criteria, was compared between typical and atypical antipsychotic users using 1:1 matching on propensity score. Adjusted hazard ratios (HRs) and 95% CIs during the entire follow-up period and during 1- to 15-day and 16- to 90-day risk windows were estimated. The risk associated with haloperidol use was estimated separately. RESULTS: A total of 45,495 typical antipsychotic users were matched 1:1 to atypical antipsychotic users. While unmatched HRs suggest an increased stroke risk among typical antipsychotic users compared to atypical antipsychotic users, no increased risk was observed after matching during the entire follow-up period (HR = 0.87; 95% CI, 0.54-1.41), the 1- to 15-day risk window (HR = 1.16; 95% CI, 0.41-3.32), or the 16- to 90-day risk window (HR = 0.52; 95% CI, 0.20-1.36). The adjusted HR for haloperidol was 1.31 (95% CI, 0.54-3.21). CONCLUSION: These findings were not suggestive of an increased stroke risk in typical antipsychotic users compared to atypical antipsychotic users in a non-elderly and non-demented population.

Evaluation of the US Food and Drug Administration Sentinel Analysis Tools Using a Comparator with a Different Indication: Comparing the Rates of Gastrointestinal Bleeding in Warfarin and Statin Users.

BACKGROUND: The US Food and Drug Administration's Sentinel System was established to monitor safety of regulated medical products. Sentinel investigators identified known associations between drugs and adverse events to test reusable analytic tools developed for Sentinel. This test case used a comparator with a different indication. OBJECTIVE: We tested the ability of Sentinel's reusable analytic tools to identify the known association between warfarin and gastrointestinal bleeding (GIB). Statins, expected to have no effect on GIB, were the comparator. We further explored the impact of analytic features, including matching ratio and stratifying Cox regression analyses, on matched pairs. METHODS: This evaluation included data from 14 Sentinel Data Partners. New users of warfarin and statins, aged 18 years and older, who had not received other anticoagulants or had recent GIB were matched on propensity score using 1:1 and 1:n variable ratio matching, matching statin users with warfarin users to estimate the average treatment effect in warfarin-treated patients. We compared the risk of GIB using Cox proportional hazards regression, following patients for the duration of their observed continuous treatment or until a GIB. For the 1:1 matched cohort, we conducted analyses with and without stratification on matched pair. The variable ratio matched cohort analysis was stratified on the matched set. RESULTS: We identified 141,398 new users of warfarin and 2,275,694 new users of statins. In analyses stratified on matched pair/set, the hazard ratios (HR) for GIB in warfarin users compared with statin users were 2.78 (95% confidence interval [CI] 2.36-3.28) in the 1:1 matched cohort and 3.10 (95% CI 2.76-3.49) in the variable ratio matched cohort. The HR was lower in the analysis of the 1:1 matched cohort not stratified by matched pair (2.22, 95% CI 1.97-2.49), and highest early in treatment. Follow-up for warfarin users tended to be shorter than for statin users. CONCLUSIONS: This study identified the expected GIB risk with warfarin compared with statins using an analytic tool developed for Sentinel. Our findings suggest that comparators with different indications may be useful in surveillance in select circumstances. Finally, in the presence of differential censoring, stratification by matched pair may reduce the potential for bias in Cox regression analyses.

Use of tumor necrosis factor-alpha inhibitors during pregnancy among women who delivered live born infants.

PURPOSE: To describe the use of tumor necrosis factor-alpha inhibitors (TNFis) among pregnancies ending in a live birth and with a diagnosis of ankylosing spondylitis (AS), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ulcerative colitis (UC). METHODS: We identified pregnancies among women aged 15 to 54 years between 01/01/2004 and 09/30/2015 from 16 health plans participating in Sentinel. We inferred indication using ICD-9-CM codes in the 183-day period before conception. We assessed proportion of infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab by calendar year, indication, and maternal age, and compared them to proportions in an age-matched, indication-matched, and date-matched non-pregnant cohort. RESULTS: Among 19 681 pregnancies with at least one chronic inflammatory condition, 2990 (15.2%) received a TNFi. In both pregnancies and matched non-pregnant cohort, TNFi use was highest (34.4%; 55.8%) for PsA patients and lowest (6.2%; 13.4%) for PsO patients. Etanercept was most frequently used among AS/JIA/PsA/PsO/RA patients, while infliximab was the preferred TNFi for CD/UC patients. Except for infliximab and certolizumab, TNFi use during pregnancy decreased after the first trimester. Pregnancies among older pregnant women (45-54 years) were more likely to be treated compared with the matched non-pregnant cohort. CONCLUSION: There was a preference for etanercept among pregnancies with AS/JIA/PsA/PsO/RA, despite the availability of other TNFis. Decline in TNFi use after the first trimester may be related to the desire to reduce TNFis transplacental transfer and to minimize infection risk to the fetus or baby associated with live vaccine immunizations after birth.

Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study Using the Sentinel Distributed Database.

Importance: Continuous/extended cyclic estrogen use (84/7 or 365/0 days cycles) in combined oral contraceptives (COCs) could potentially expose women to an increased cumulative dose of estrogen, compared with traditional cyclic regimens (21/7 days cycle), and may increase the risk for venous thromboembolism (VTE). Objective: To determine, while holding the progestogen type constant, whether the risk for VTE is higher with use of continuous/extended COCs than with cyclic COCs among women who initiated a COC containing ethinyl estradiol and levonorgestrel. Design, Setting, and Participants: Incident user retrospective cohort study of primarily commercially insured US population identified from the Sentinel Distributed Database. Participants were women aged 18 to 50 years at the time of initiating a study COC between May 2007 and September 2015. Using a propensity score approach and Cox proportional hazards regression models, we estimated the hazard ratios of VTE overall and separately by ethinyl estradiol dose and age groups. Exposures: Initiation of continuous/extended or traditional cyclic COCs containing ethinyl estradiol or levonorgestrel of any dose. Main Outcomes and Measures: First VTE hospitalization that occurred during the study follow-up, identified by an inpatient International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 415.1, 415.1x, 453, 453.x, or 453.xx. Results: We identified 210 691 initiators of continuous/extended COCs (mean [SD] age, 30.4 [8.6] years) and 522 316 initiators of cyclic COCs (mean [SD] age, 28.8 [8.3] years), with a mean of 0.7 person-years at risk among continuous/extended and cyclic users. Baseline cardiovascular and metabolic conditions (7.2% vs 4.7%), gynecological conditions (39.7% vs 32.3%), and health services utilization were slightly higher among continuous/extended cyclic than cyclic COC users. Propensity score matching decreased the hazard ratio estimates from 1.84 (95% CI, 1.53-2.21) to 1.32 (95% CI, 1.07-1.64) for continuous/extended use compared with cyclic COC use. The absolute risk difference (0.27 per 1000 persons) and the incidence rate difference (0.35 cases per 1000 person-years [1.44 vs 1.09 cases per 1000 person-years]) between the 2 propensity score-matched cohorts remained low, which may not translate into a clinically significant risk differences between cyclic and noncyclic estrogen use. Conclusions and Relevance: Holding the progestogen type constant (levonorgestrel), we observed a slightly elevated VTE risk in association with continuous/extended COC use when compared with cyclic COC use. However, due to the small absolute risk difference and potential residual confounding, our findings did not show strong evidence supporting a VTE risk difference between continuous/extended and cyclic COC use.

Outpatient influenza antivirals in a distributed data network for influenza surveillance.

Electronic data collected from routine health care can be used for public health surveillance. To examine the Sentinel System, a distributed data network of health plans, as a source for influenza surveillance, we compared trends in outpatient prescription dispensings of influenza antivirals in Sentinel to trends in CDC's ILINet and NREVSS systems over five seasons. There were 2 102 885 dispensed prescriptions of oseltamivir capsules, 494 188 of oseltamivir powder, and 7955 of zanamivir. Across all seasons, the magnitude and timing of peaks in drug utilization were highly comparable to those in ILINet and NREVSS. Oseltamivir capsules and powder were well correlated with ILINet and NREVSS. This lays the foundation for further exploration of Sentinel's utility for influenza surveillance.

Design of a prostate cancer patient navigation intervention for a Veterans Affairs hospital.

BACKGROUND: Patient navigation programs have been launched nationwide in an attempt to reduce racial/ethnic and socio-demographic disparities in cancer care, but few have evaluated outcomes in the prostate cancer setting. The National Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims to implement and evaluate the efficacy of a patient navigation intervention for predominantly low-income minority patients with an abnormal prostate cancer screening test at a Veterans Affairs (VA) hospital in Chicago. METHODS/DESIGN: From 2006 through 2010, C-PNRP implemented a quasi-experimental intervention whereby trained social worker and lay health navigators worked with veterans with an abnormal prostate screen to proactively identify and resolve personal and systems barriers to care. Men were enrolled at a VA urology clinic and were selected to receive navigated versus usual care based on clinic day. Patient navigators performed activities to facilitate timely follow-up such as appointment reminders, transportation coordination, cancer education, scheduling assistance, and social support as needed. Primary outcome measures included time (days) from abnormal screening to diagnosis and time from diagnosis to treatment initiation. Secondary outcomes included psychosocial and demographic predictors of non-compliance and patient satisfaction. Dates of screening, follow-up visits, and treatment were obtained through chart audit, and questionnaires were administered at baseline, after diagnosis, and after treatment initiation. At the VA, 546 patients were enrolled in the study (245 in the navigated arm, 245 in the records-based control arm, and 56 in a subsample of surveyed control subjects). DISCUSSION: Given increasing concerns about balancing better health outcomes with lower costs, careful examination of interventions aimed at reducing healthcare disparities attain critical importance. While analysis of the C-PNRP data is underway, the design of this patient navigation intervention will inform other patient navigation programs addressing strategies to improve prostate cancer outcomes among vulnerable populations.