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Abstract AimsTo develop machine‐learning algorithms for predicting the risk of a hospitalization or emergency department (ED) visit for opioid use disorder (OUD) (i.e. OUD acute events) in Pennsylvania Medicaid enrollees in the Opioid Use Disorder Centers of Excellence (COE) program and to evaluate the fairness of model performance across racial groups. MethodsWe studied 20 983 United States Medicaid enrollees aged 18 years or older who had COE visits between April 2019 and March 2021. We applied multivariate logistic regression, least absolute shrinkage and selection operator models, random forests, and eXtreme Gradient Boosting (XGB), to predict OUD acute events following the initial COE visit. Our models included predictors at the system, patient, and regional levels. We assessed model performance using multiple metrics by racial groups. Individuals were divided into a low, medium and high‐risk group based on predicted risk scores. ResultsThe training (n = 13 990) and testing (n = 6993) samples displayed similar characteristics (mean age 38.1 ± 9.3 years, 58% male, 80% White enrollees) with 4% experiencing OUD acute events at baseline. XGB demonstrated the best prediction performance (C‐statistic = 76.6% [95% confidence interval = 75.6%–77.7%] vs. 72.8%–74.7% for other methods). At the balanced cutoff, XGB achieved a sensitivity of 68.2%, specificity of 70.0%, and positive predictive value of 8.3%. The XGB model classified the testing sample into high‐risk (6%), medium‐risk (30%), and low‐risk (63%) groups. In the high‐risk group, 40.7% had OUD acute events vs. 16.5% and 5.0% in the medium‐ and low‐risk groups. The high‐ and medium‐risk groups captured 44% and 26% of individuals with OUD events. The XGB model exhibited lower false negative rates and higher false positive rates in racial/ethnic minority groups than White enrollees. ConclusionsNew machine‐learning algorithms perform well to predict risks of opioid use disorder (OUD) acute care use among United States Medicaid enrollees and improve fairness of prediction across racial and ethnic groups compared with previous OUD‐related models. 

OBJECTIVES:The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. DESIGN:We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. SETTING:Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. PATIENTS:Adult patients presenting to the emergency department with severe sepsis or septic shock. INTERVENTIONS:EGDT vs. usual care. MEASUREMENTS AND MAIN RESULTS:A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p< 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], –8% [–19% to 4%] and relative risk reduction, 1.34 [0.89–2.01] in quintile 1 suggesting harm from EGDT, and 12% [1–23%] and 0.64 [0.42–0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. CONCLUSIONS:Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE. 

Summary With rapid development of techniques to measure brain activity and structure, statistical methods for analyzing modern brain-imaging data play an important role in the advancement of science. Imaging data that measure brain function are usually multivariate high-density longitudinal data and are heterogeneous across both imaging sources and subjects, which lead to various statistical and computational challenges. In this article, we propose a group-based method to cluster a collection of multivariate high-density longitudinal data via a Bayesian mixture of smoothing splines. Our method assumes each multivariate high-density longitudinal trajectory is a mixture of multiple components with different mixing weights. Time-independent covariates are assumed to be associated with the mixture components and are incorporated via logistic weights of a mixture-of-experts model. We formulate this approach under a fully Bayesian framework using Gibbs sampling where the number of components is selected based on a deviance information criterion. The proposed method is compared to existing methods via simulation studies and is applied to a study on functional near-infrared spectroscopy, which aims to understand infant emotional reactivity and recovery from stress. The results reveal distinct patterns of brain activity, as well as associations between these patterns and selected covariates.