Primal--Dual Alternating Neural Learning for Timely Classification with Performance Guarantees

Timely risk classification is essential in many clinical monitoring settings, where decisions must balance the benefit of classifying patients early for subsequent intervention against the value of observing additional data. Yet most existing statistical and machine-learning methods are designed for fully observed trajectories and offer limited control over key operating characteristics such as sensitivity, specificity, and monitoring cost. We cast the sequential classification problem within a multi-objective optimization framework targeting these three criteria. We characterize the optimal decision rule through a value recursion that quantifies, at each time point, the trade-off between immediate classification and continued monitoring. To estimate the rule from data, we formulate a constrained optimization problem that maximizes specificity while enforcing prespecified sensitivity and monitoring-cost constraints. We then develop an estimation procedure that employs a recurrent neural network to approximate the evolving value processes and a primal--dual updating scheme to satisfy the performance constraints. Through simulation studies and an application to continuous glucose monitoring for hypoglycemia risk prediction, we demonstrate that the proposed method yields accurate and timely sequential decision rules that adhere to the desired operating characteristics.

Structured Evidence Routing for Incident Risk Prediction from Multimodal Longitudinal EHRs

Incident risk prediction from longitudinal electronic health records (EHRs) is challenging because relevant signals are multimodal, weak in isolation, and distributed across irregular patient histories. We propose structured evidence routing, a router-predictor-reviewer workflow that separates full-record access from disease-specific assessment. The router organizes the complete pre-index EHR into a compact summary and targeted evidence slices; the predictor uses this evidence to form an evidence-linked risk assessment, which the reviewer critiques. For comparison with supervised EHRSHOT baselines, we pair the routed evidence summaries with a supervised classifier readout. Across five 1-year incident diagnosis tasks, our method reaches the AUROC range of established supervised EHRSHOT baselines and remains competitive on AUPRC, while exposing a patient-specific evidence trail. Internal pre-readout ablations further suggest that routing, laboratory evidence, task guidance, and review each contribute to performance.

Random Hazard Forests

Clinical data sources such as electronic health records and wearable sensors record patient status repeatedly over follow-up, often at irregular times and on different schedules for different measurements. These data create opportunities for continuously updated, individualized risk prediction. Existing approaches, however, often simplify the temporal structure before modeling it. We introduce Random Hazard Forests (RHF), a survival tree ensemble that learns how a patient's hazard changes in continuous time as new measurements become available. RHF formulates the estimation problem directly through a nonparametric hazard likelihood for predictable covariate processes. An efficient working model guides tree construction, after which flexible time-varying hazards are estimated for each terminal node. Given any predictable covariate path, each tree follows the path through its terminal nodes over time and assembles the corresponding node-level hazards into a trajectory. Averaging these trajectories across trees yields the RHF pathwise hazard estimate. Because routing at each time uses only the covariate state available immediately beforehand, RHF accommodates internal longitudinal covariates without lookahead. Simulations and an intensive care application show that RHF accurately estimates changing risk under irregular and asynchronous covariate updates.

A Two-Stage Time-Aware Transformer for Short-Horizon AECOPD Risk Prediction

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) can worsen rapidly, making timely prediction a clinical priority. Most existing machine learning approaches rely on episodically collected clinical variables, introducing delays that limit their practical utility in home monitoring settings. Home ventilators offer a lower-latency alternative, producing a near-continuous record of respiratory status during daily use. However existing ventilator-based approaches either compress the waveform into handcrafted features or focus primarily on binary risk classification, leaving the timing of an impending event unresolved. In this paper, we present a two-stage framework that operates directly on raw pressure and flow waveforms from the most recent seven days of home ventilator use. The first-stage classification model identifies patients at high risk of a severe exacerbation. The second-stage regression model then estimates how many days remain before the event occurs. Our experimental results demonstrate that the two-stage model outperforms traditional baseline models on both risk classification and time-to-event estimation, with our selected Stage 1 classifier achieving F1 = 0.91 and our Stage 2 regression model achieving RMSE = 1.00 days and R^2 = 0.76, giving clinicians both an early warning and actionable lead time before a severe exacerbation occurs.

A Statistical Framework for Data-Driven Discovery of Differential Performance in Clinical Risk Prediction Models

Predictive models employing artificial intelligence (AI) and machine learning (ML) are increasingly being used for decision support in healthcare settings. These models may exhibit differential performance across population subgroups defined by race, age, sex, and other factors and cause disparate clinical impacts, leading to intensive recent study of what has been termed "model fairness". While many methods have been proposed to assess risk prediction model fairness, these techniques generally require that the end user pre-specify the groups across which fairness is to be evaluated. In real-world settings, however, important model performance disparities may arise in unknown subgroups defined by multiple intersecting characteristics. To address this problem, we propose the unfairness tree (utree), a data-driven recursive partitioning framework for identifying subgroups with differential model performance. In simulations, the utree exhibits nominal empirical type I error rates and good ability to detect, quantify, and characterize performance discrepancies defined by higher-order variable interactions. In six mortality risk models fit to the GUSTO-I acute myocardial infarction trial dataset, utrees identified subgroup-specific performance patterns, with age, sex, blood pressure, and Killip class consistently associated with differential model performance.

A Latent ODE Approach to Spatiotemporal Modeling of Cine Cardiac MRI

Cardiac magnetic resonance imaging (CMR) captures rich spatiotemporal information about ventricular structure and motion, but conventional risk models use only a few image-derived indices from selected cardiac phases. We present a latent dynamical model that encodes bi-ventricular anatomy and full-cycle cine motion as a continuous latent trajectory, using heart-rate-aware neural ordinary differential equation (ODE) dynamics and a graph-based mesh autoencoder to reconstruct anatomically consistent 3D+t ventricular motion. A covariate-conditioned prior defines the expected end-diastolic latent state, and a Cox proportional hazards model tests whether deviations from this prior predict incident heart failure. We studied 72,386 UK Biobank participants without baseline cardiovascular disease, including 367 incident heart failure events. In a held-out evaluation subset, adding the latent score to refitted pooled cohort equations improved the stratified C-index from 0.704 to 0.785, compared with 0.764 for seven established cardiac markers. Compared with non-graph and non-ODE approaches, the proposed model gave the best trade-off between reconstruction fidelity, generative realism, and downstream prognostic performance. These results suggest that continuous full-cycle modeling of ventricular motion provides informative cardiac phenotypes beyond conventional CMR summaries, while external validation in more representative patient cohorts is required before clinical risk-prediction use.

Deployment-Centered Evaluation: Predicting Query-Level Rejection Risk in a Clinical LLM System

Large language models (LLMs) are increasingly integrated into clinical systems, making it essential to evaluate the real-world utility of these systems. However, static benchmarks tend to measure correctness rather than user acceptance, aggregate performance across queries, and require densely annotated datasets -- leading to major blind spots for evaluating clinical systems. In this work, we perform a deployment-centered evaluation of an LLM system embedded within electronic health records at an academic medical center, where user feedback is sparse but closely reflects the deployment conditions. Specifically, we train a pre-response classifier that estimates the risk that a future interaction will result in the user rejecting the LLM response, based on query content and deployment-specific context available before generation. We conduct a prospective analysis of our model over 4.5 months of user feedback, finding that our prediction model achieves an AUROC of 0.719. Further, we estimate the benefit of such predictions in two downstream use cases (guardrail triggering and abstention). Our key conceptual insight is that making use of deployment-specific context (i.e., the provider type, department name, language model used for response), as opposed to only query content, improves the ability to predict whether the user will reject the system output. Altogether, our empirical case study demonstrates the feasibility of predicting user rejection using deployment-specific context, opening the door to targeted guardrails.

Pre-AF 13: An Interpretable Atrial Fibrillation Risk Score Mined from Discharge Reports

Background. Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and a major determinant of prognosis. Established AF risk scores rely on factors (older age, hypertension) nearly ubiquitous among patients with cardiovascular disease (CVD), offering limited stratification in this high-risk group. Most target long-term (5-10 year) rather than medium-term prediction. We developed interpretable ML models predicting AF risk over a 24-month and entire follow-up horizon in CVD patients using routinely collected hospital data. Methods. Single-center retrospective study of electronic health records from the National Research Cardiology Center (Russia) for patients aged >=18 with CVD but without pre-existing AF, hospitalized more than once between January 2012 and May 2019. A custom NLP pipeline transformed unstructured discharge reports into 73 structured features, combining a rule-based parser with transformer-based NER. Using LightAutoML we built a full model (73 features), a simple model (reduced subset), and a linear model for a bedside risk score. Performance was assessed by ROC AUC, compared with CHARGE-AF, C2HEST, MHS, and HAVOC, and interpreted via SHAP. Results. Of 80,576 records from 45,000 patients, 17,562 met inclusion criteria; 1,438 (8.19%) developed AF. The full model reached ROC AUC 0.735 (24-month) and 0.696 (entire follow-up); the simple model was nearly identical (0.725, 0.696). All non-linear models outperformed the four clinical risk scores (ROC AUC 0.53-0.64). The simple model uses 13 features and is named Pre-AF 13. SHAP identified age and left atrial volume as dominant predictors. A linear risk score (Pre-AF 9) stratified observed 24-month AF incidence from ~7% to 36%. Conclusion. Interpretable ML models built from routinely collected EHR data identify high-AF-risk CVD patients, outperforming established clinical risk scores.

External Validation of Deep Learning Models for BI-RADS Breast Density Prediction from Ultrasound Images

We externally validated three deep learning models (DenseNet121, ViT-B/32, and ResNet50) for predicting mammographic breast density from breast ultrasound exams on an independent cohort. The external validation set comprised 2,000 ultrasound exams, including 500 cancer cases defined by an initial negative exam (BI-RADS 1 or 2) followed by a cancer diagnosis within 6 months to 10 years, and 1,500 negative controls matched by manufacturer and study year. Performance was measured using patient-level AUROC across four density categories: A (fatty), B (scattered), C (heterogeneous), and D (extremely dense). As a downstream assessment, we also evaluated 10-year risk prediction by incorporating age and AI-derived density into the Tyrer-Cuzick model and comparing performance against a reference model using age and mammography-reported density. All three models performed best in extremely dense breasts (AUROC 0.868-0.899), with strong performance in fatty (0.814-0.838) and scattered density (0.764-0.799), and lower performance in heterogeneously dense breasts (0.699-0.729). DenseNet121 achieved the highest overall performance (micro-averaged AUROC 0.885), and performance across categories was comparable between internal and external testing. For risk modeling, age combined with AI-derived density yielded a lower AUROC than age combined with mammography-reported density (0.541 vs. 0.570; p = 0.23), with no statistically significant difference. These findings indicate that deep learning models generalize well to external data with different racial composition for breast density assessment. While performance is strongest in extremely dense breasts, heterogeneously dense remains more challenging, highlighting the need for targeted optimization.