Bayesian fusion forests for heterogeneous treatment effects on survival from randomised and real-world data

We develop the Bayesian fusion forest, a nonparametric framework to estimate heterogeneous treatment effects on survival outcomes by combining a randomised controlled trial and real-world data. The framework relaxes the unconfoundedness assumption on the real-world data by assuming instead that the treatment effect transports across the two sources. Our method opens up right- and interval-censored outcomes to data fusion. We model the survival time with an accelerated failure time decomposition into a shared baseline prognosis, a source-specific deviation, a treatment effect, and a confounding function. The confounding function absorbs the confounding bias in the real-world data. Each component receives a Bayesian tree ensemble prior. The shared baseline prognosis borrows strength across sources, while the deviation captures between-source heterogeneity. A hierarchical Dirichlet process mixture models the error distribution nonparametrically. A simulation study shows efficiency gains over a trial-only analysis across varying levels of confounding and between-source heterogeneity. We combine the ACTG 175 trial with the Multicenter AIDS Cohort Study to estimate the effect of combination antiretroviral therapy for HIV. The fusion identifies a benefit for nearly every patient whereas the trial alone is inconclusive.

Bayesian Mediation Analysis for Individualized Treatment Rules

The value of an individualized treatment rule (ITR), defined as the expected outcome under treatment assignment according to the rule, is useful for assessing average clinical benefit but does not explain how the benefit of a rule is generated. We propose a causal mediation framework for decomposing the value contrast between a prespecified candidate ITR and a clinically meaningful reference rule into direct and indirect components. Using rule-specific nested potential outcomes, we define natural direct and indirect rule effects that quantify the extent to which the improvement in value arises through pathways operating directly on the outcome versus through a specified mediator. We give identification conditions under which these components are identified by a rule-level mediation g-formula. For estimation, we adapt Bayesian causal mediation forests to obtain posterior inference for the value contrast and its path-specific components. Our simulations demonstrate that the proposed estimator achieved near-nominal credible interval coverage with decreasing bias and root mean squared error as sample size increased in settings with varying direct and mediated contributions. We further illustrate the method using data from the TRIUMPH trial, decomposing the cognitive benefit of a lifestyle intervention rule through candidate neurovascular, cardiorespiratory, and behavioral mediators. The proposed framework complements optimal ITR learning with explanation using mediation, providing a natural approach for mechanistic evaluation of ITRs.

A specialized reasoning large language model for accelerating rare disease diagnosis: a randomized AI physician assistance trial

Rare diseases affect millions of individuals worldwide, yet timely diagnosis remains a major public health challenge due to scarcity of specialized clinical expertise. While large language models (LLMs) show promise to support rare disease diagnosis, current models are constrained by insufficient clinical deployability, limited clinically grounded evidence, and scarcity of training data. Here we present RaDaR (Rare Disease navigatoR), an open-source, compact reasoning LLM (32B parameters) for rare disease diagnosis. RaDaR was trained with 49,170 publicly available free-text cases and 104,666 synthetic cases with reasoning-enhanced training. RaDaR showed the strongest performance among evaluated open-source models, including the 671B DeepSeek-R1, across public benchmarks and four external validation centers. In a retrospective cohort, RaDaR prioritized the final diagnosis before documented clinical suspicion in 61.06 percent of cases, corresponding to a potential lead time of 1.87 months and 50.18 percent of the within-center interval. In a randomized physician-assistance trial, RaDaR assistance improved physicians' rare-disease diagnostic accuracy by 21.44 percentage points compared with internet search alone. Synthetic-data ablations suggested that phenotype-anchored narratives provide useful training signal for long-tail rare diseases, with a monotonic scaling trend within the tested data range. Together, RaDaR and its development and validation framework provide a deployable rare-disease reasoning model and a reproducible development framework for diagnostic AI under data scarcity.

Ride, Track, and Recover: Pilot Randomized Trial of a Wearable Digital Self-Management Intervention During a Veteran Endurance-Cycling Program

Post-traumatic stress disorder (PTSD) in veterans is characterized by persistent hyperarousal and comorbid anxiety and depressive symptoms that are difficult to monitor and manage outside clinical settings. Thirteen veterans participating in a Project Hero cycling event in Texas were randomized by computer-generated sequence in a naturalistic setting to two arms: (1) digital intervention plus physical activity, or (2) physical activity only, plus a third at-home monitoring control cohort consisting of 7 veterans selected from the broader Project Hero veteran community. Continuous smartwatch sensing combined heart rate and accelerometer features to detect hyperarousal events, which were confirmed in real time by participants. Weekly self-report measures of anxiety, depression, and PTSD severity were collected. Generalized additive mixed models characterized nonlinear trajectories over time. Baseline-normalized hyperarousal trajectories differed significantly across conditions, with the digital intervention group (n=7) showing structured stabilization compared to late-study escalation in the physical-only group (n=3). Both cycling groups exhibited acute symptom improvements during the endurance event; however, the digital intervention group demonstrated a higher overall maintenance of gains. The at-home control group (n=4) showed gradual symptom declines. Perceived precision of ML detections varied substantially across individuals and was positively associated with symptom severity, with higher-severity participants confirming a greater proportion of detected events. These results suggest that coupling wearable detection with digital self-management tools may support stabilization of hyperarousal and symptom improvement while emphasizing the importance of personalization and human-centered design in wearable mental health systems.