Purpose We describe the design, implementation, and use of a large, multiorganizational distributed database developed to support the Mini-Sentinel Pilot Program of the US Food and Drug Administration (FDA). As envisioned by the US FDA, this implementation will inform and facilitate the development of an active surveillance system for monitoring the safety of medical products (drugs, biologics, and devices) in the USA. Methods A common data model was designed to address the priorities of the Mini-Sentinel Pilot and to leverage the experience and data of participating organizations and data partners. A review of existing common data models informed the process. Each participating organization designed a process to extract, transform, and load its source data, applying the common data model to create the Mini-Sentinel Distributed Database. Transformed data were characterized and evaluated using a series of programs developed centrally and executed locally by participating organizations. A secure communications portal was designed to facilitate queries of the Mini-Sentinel Distributed Database and transfer of confidential data, analytic tools were developed to facilitate rapid response to common questions, and distributed querying software was implemented to facilitate rapid querying of summary data. Results As of July 2011, information on 99 260 976 health plan members was included in the Mini-Sentinel Distributed Database. The database includes 316 009 067 person-years of observation time, with members contributing, on average, 27.0 months of observation time. All data partners have successfully executed distributed code and returned findings to the Mini-Sentinel Operations Center. Conclusion This work demonstrates the feasibility of building a large, multiorganizational distributed data system in which organizations retain possession of their data that are used in an active surveillance system.

IntroductionAlthough osteoporosis has been reported to be more common in patients with rheumatoid arthritis (RA), little is known whether the risk of osteoporotic fractures in these patients differs by age, sex, and anatomic site.MethodsA retrospective cohort study was conducted using a health care utilization database. Incidence rates (IRs) and rate ratios (RRs) of osteoporotic fractures with 95% confidence intervals (CIs) were calculated. Multivariable Cox proportional hazards models compared the risk of osteoporotic fracture at typical sites between RA and non-RA patients.ResultsDuring a median 1.63-year follow-up, 872 (1.9%) of 47,034 RA patients experienced a fracture. The IR for osteoporotic fracture at typical sites among RA patients was 9.6 per 1,000 person-years, 1.5 times higher than the rate of non-RA patients. The IR was highest for hip fracture (3.4 per 1,000 person-years) in RA. The IRs across all age groups were higher for women than men and increased with older age in both groups. The RRs were elevated in RA patients across all common sites of osteoporotic fracture: hip (1.62, 95% CI 1.43 to 1.84), wrist (1.15, 95% CI 1.00 to 1.32), pelvis (2.02, 95% CI 1.77 to 2.30), and humerus (1.51, 95% CI 1.27 to 1.84). After confounding adjustment, a modest increase in risk for fracture was noted with RA (hazard ratio 1.26, 95% CI 1.15 to 1.38).ConclusionsOur study showed an increased risk of osteoporotic fractures for RA patients across all age groups, sex and various anatomic sites, compared with non-RA patients.

WHAT'S KNOWN ON THIS SUBJECT:Attention-deficit/ hyperactivity disorder agents increase systolic and diastolic blood pressure and heart rate. Case reports of sudden death in children and adolescents receiving these agents have led to the concern that they might increase the risk of cardiovascular events. WHAT THIS STUDY ADDS:Low rates of validated cardiovascular events and of all-cause death, nonsuicide, and non-accidental death were found in children and adolescents receiving attention-deficit/ hyperactivity disorder medications.abstract OBJECTIVE: The objective of this study was to compare the rate of severe cardiovascular events and death in children who use attentiondeficit/hyperactivity disorder (ADHD) medications versus nonusers. PATIENTS AND METHODS:We performed a large cohort study using data from 2 administrative databases. All children aged 3 to 17 years with a prescription for an amphetamine, atomoxetine, or methylphenidate were included and matched with up to 4 nonusers on the basis of data source, gender, state, and age. Cardiovascular events were validated using medical records. Proportional hazards regression was used to calculated hazard ratios. RESULTS: We identified 241 417 incident users (primary cohort) CONCLUSIONS:The rate of cardiovascular events in exposed children was very low and in general no higher than that in unexposed control subjects. Because of the low number of events, we have limited ability to rule out relative increases in rate.

Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.

BACKGROUND: Thrombotic events (TEs) are rare but often serious adverse events that could occur after administration of immune globulin (IG) products. Our study objective was to assess occurrence of recorded TEs after administration of different US‐licensed IG products and investigate potential risk factors using a large administrative database. STUDY DESIGN AND METHODS: This is a retrospective claims‐based cohort study of individuals exposed to IG products from January 1, 2008, through September 30, 2010, using HealthCore's Integrated Research Database, a longitudinal health care database. IG products were identified by recorded Healthcare Common Procedure Coding System codes. TEs were ascertained via International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for same‐day TEs by IG product, while controlling for confounders. RESULTS: Of 11,785 individuals exposed to IG products in the study period, 122 (1%) had TE(s) recorded on the same day as IG administration. TE rates per 1000 persons exposed ranged from 6.1 to 20.5 for different IG product groups. Vivaglobin users had an increased same‐day TE risk compared to reference Gammagard Liquid users (OR, 3.56; 95% CI, 1.54‐8.23). An increased TE risk was also found with older age (≥45 years), prior TE(s), and hypercoagulable state(s). CONCLUSION: The study suggests potentially elevated TE rates for different IG products, including subcutaneous. It also identifies important recipient TE risk factors and suggests that risk–benefit profiles should be weighed before IG administration. The observed differences may be due to various factors such as dosage, administration rates, and product manufacturing processes that warrant further evaluation.