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Drug-drug interactions (DDIs) are a common cause of adverse drug events (ADEs). The electronic medical record (EMR) database and the FDA's adverse event reporting system (FAERS) database are the major data sources for mining and testing the ADE associated DDI signals. Most DDI data mining methods focus on pair-wise drug interactions, and methods to detect high-dimensional DDIs in medical databases are lacking. In this paper, we propose 2 novel mixture drug-count response models for detecting high-dimensional drug combinations that induce myopathy. The "count" indicates the number of drugs in a combination. One model is called fixed probability mixture drug-count response model with a maximum risk threshold (FMDRM-MRT). The other model is called count-dependent probability mixture drug-count response model with a maximum risk threshold (CMDRM-MRT), in which the mixture probability is count dependent. Compared with the previous mixture drug-count response model (MDRM) developed by our group, these 2 new models show a better likelihood in detecting high-dimensional drug combinatory effects on myopathy. CMDRM-MRT identified and validated (54; 374; 637; 442; 131) 2-way to 6-way drug interactions, respectively, which induce myopathy in both EMR and FAERS databases. We further demonstrate FAERS data capture much higher maximum myopathy risk than EMR data do. The consistency of 2 mixture models' parameters and local false discovery rate estimates are evaluated through statistical simulation studies. [ABSTRACT FROM AUTHOR]

Objective: Develop and validate a surveillance model to identify outpatient surgical adverse events (AEs) based on previously developed electronic triggers.Data Sources: Veterans Health Administration's Corporate Data Warehouse.Study Design: Six surgical AE triggers, including postoperative emergency room visits and hospitalizations, were applied to FY2012-2014 outpatient surgeries (n = 744,355). We randomly sampled trigger-flagged and unflagged cases for nurse chart review to document AEs and measured positive predictive value (PPV) for triggers. Next, we used chart review data to iteratively estimate multilevel logistic regression models to predict the probability of an AE, starting with the six triggers and adding in patient, procedure, and facility characteristics to improve model fit. We validated the final model by applying the coefficients to FY2015 outpatient surgery data (n = 256,690) and reviewing charts for cases at high and moderate probability of an AE.Principal Findings: Of 1,730 FY2012-2014 reviewed surgeries, 350 had an AE (20 percent). The final surveillance model c-statistic was 0.81. In FY2015 surgeries with >0.8 predicted probability of an AE (n = 405, 0.15 percent), PPV was 85 percent; in surgeries with a 0.4-0.5 predicted probability of an AE, PPV was 38 percent.Conclusions: The surveillance model performed well, accurately identifying outpatient surgeries with a high probability of an AE. [ABSTRACT FROM AUTHOR]