Severe heatwaves in urban areas significantly threaten public health, calling for establishing early warning strategies. Despite predicting occurrence of heatwaves and attributing historical mortality, predicting an incoming deadly heatwave remains a challenge due to the difficulty in defining and estimating heat-related mortality. Furthermore, establishing an early warning system imposes additional requirements, including data availability, spatial and temporal robustness, and decision costs. To address these challenges, we propose DeepTherm, a modular early warning system for deadly heatwave prediction without requiring heat-related mortality history. By highlighting the flexibility of deep learning, DeepTherm employs a dual-prediction pipeline, disentangling baseline mortality in the absence of heatwaves and other irregular events from all-cause mortality. We evaluated DeepTherm on real-world data across Spain. Results demonstrate consistent, robust, and accurate performance across diverse regions, time periods, and population groups while allowing trade-off between missed alarms and false alarms.

Tokenization strategies shape how models process electronic health records, yet fair comparisons of their effectiveness remain limited. We present a systematic evaluation of tokenization approaches for clinical time series modeling using transformer-based architectures, revealing task-dependent and sometimes counterintuitive findings about temporal and value feature importance. Through controlled ablations across four clinical prediction tasks on MIMIC-IV, we demonstrate that explicit time encodings provide no consistent statistically significant benefit for the evaluated downstream tasks. Value features show task-dependent importance, affecting mortality prediction but not readmission, suggesting code sequences alone can carry sufficient predictive signal. We further show that frozen pretrained code encoders dramatically outperform their trainable counterparts while requiring dramatically fewer parameters. Larger clinical encoders provide consistent improvements across tasks, benefiting from frozen embeddings that eliminate computational overhead. Our controlled evaluation enables fairer tokenization comparisons and demonstrates that simpler, parameter-efficient approaches can, in many cases, achieve strong performance, though the optimal tokenization strategy remains task-dependent.

Timely and personalized treatment decisions are essential across a wide range of healthcare settings where patient responses can vary significantly and evolve over time. Clinical data used to support these treatment decisions are often irregularly sampled, where missing data frequencies may implicitly convey information about the patient's condition. Existing Reinforcement Learning (RL) based clinical decision support systems often ignore the missing patterns and distort them with coarse discretization and simple imputation. They are also predominantly model-free and largely depend on retrospective data, which could lead to insufficient exploration and bias by historical behaviors. To address these limitations, we propose medDreamer, a novel model-based reinforcement learning framework for personalized treatment recommendation. medDreamer contains a world model with an Adaptive Feature Integration module that simulates latent patient states from irregular data and a two-phase policy trained on a hybrid of real and imagined trajectories. This enables learning optimal policies that go beyond the sub-optimality of historical clinical decisions, while remaining close to real clinical data. We evaluate medDreamer on both sepsis and mechanical ventilation treatment tasks using two large-scale Electronic Health Records (EHRs) datasets. Comprehensive evaluations show that medDreamer significantly outperforms model-free and model-based baselines in both clinical outcomes and off-policy metrics.

Intensive care unit (ICU) data are highly irregular, heterogeneous, and temporally fragmented, posing challenges for generalizable clinical prediction. We present PULSE-ICU, a self-supervised foundation model that learns event-level ICU representations from large-scale EHR sequences without resampling or manual feature engineering. A unified embedding module encodes event identity, continuous values, units, and temporal attributes, while a Longformer-based encoder enables efficient modeling of long trajectories. PULSE-ICU was fine-tuned across 18 prediction tasks, including mortality, intervention forecasting, and phenotype identification, achieving strong performance across task types. External validation on eICU, HiRID, and P12 showed substantial improvements with minimal fine-tuning, demonstrating robustness to domain shift and variable constraints. These findings suggest that foundation-style modeling can improve data efficiency and adaptability, providing a scalable framework for ICU decision support across diverse clinical environments.

Transformers have defined the state-of-the-art for clinical prediction tasks involving electronic health records (EHRs). The recently introduced Mamba architecture outperformed an advanced Transformer (Transformer++) based on Llama in handling long context lengths, while using fewer model parameters. Despite the impressive performance of these architectures, a systematic approach to empirically analyze model performance and efficiency under various settings is not well established in the medical domain. The performances of six sequence models were investigated across three architecture classes (Transformers, Transformers++, Mambas) in a large Swedish heart failure (HF) cohort (N = 42820), providing a clinically relevant case study. Patient data included diagnoses, vital signs, laboratories, medications and procedures extracted from in-hospital EHRs. The models were evaluated on three one-year prediction tasks: clinical instability (a readmission phenotype) after initial HF hospitalization, mortality after initial HF hospitalization and mortality after latest hospitalization. Ablations account for modifications of the EHR-based input patient sequence, architectural model configurations, and temporal preprocessing techniques for data collection. Llama achieves the highest predictive discrimination, best calibration, and showed robustness across all tasks, followed by Mambas. Both architectures demonstrate efficient representation learning, with tiny configurations surpassing other large-scaled Transformers. At equal model size, Llama and Mambas achieve superior performance using 25% less training data. This paper presents a first ablation study with systematic design choices for input tokenization, model configuration and temporal data preprocessing. Future model development in clinical prediction tasks using EHRs could build upon this study's recommendation as a starting point.

Low-dose chest computed tomography (LDCT) inherently captures both pulmonary and cardiac structures, offering a unique opportunity for joint assessment of lung and cardiovascular health. However, most existing approaches treat these domains as independent tasks, overlooking their physiological interplay and shared imaging biomarkers. We propose an Explainable Cross-Disease Reasoning Framework that enables interpretable cardiopulmonary risk assessment from a single LDCT scan. The framework introduces an agentic reasoning process that emulates clinical diagnostic thinking-first perceiving pulmonary findings, then reasoning through established medical knowledge, and finally deriving a cardiovascular judgment with explanatory rationale. It integrates three synergistic components: a pulmonary perception module that summarizes lung abnormalities, a knowledge-guided reasoning module that infers their cardiovascular implications, and a cardiac representation module that encodes structural biomarkers. Their outputs are fused to produce a holistic cardiovascular risk prediction that is both accurate and physiologically grounded. Experiments on the NLST cohort demonstrate that the proposed framework achieves state-of-the-art performance for CVD screening and mortality prediction, outperforming single-disease and purely image-based baselines. Beyond quantitative gains, the framework provides human-verifiable reasoning that aligns with cardiological understanding, revealing coherent links between pulmonary abnormalities and cardiac stress mechanisms. Overall, this work establishes a unified and explainable paradigm for cardiovascular analysis from LDCT, bridging the gap between image-based prediction and mechanism-based medical interpretation.

Recent attempts to achieve fairness in predictive models focus on the balance between fairness and accuracy.

Objective: Current ICU enteral feeding remains sub-optimal due to limited personalization and ongoing uncertainty about appropriate calorie, protein, and fluid targets--particularly in the context of rapidly changing metabolic demands and heterogeneous responses to therapeutic interventions. This study introduces DeepEN, a novel reinforcement learning (RL)-based framework designed to dynamically personalize enteral nutrition (EN) dosing for critically ill patients using electronic health record data. Methods: DeepEN was trained on data from over 11,000 ICU patients in the MIMIC-IV database to generate 4-hourly, patient-specific targets for caloric, protein, and fluid intake. The model's state space integrates demographics, comorbidities, vital signs, laboratory measurements, and recent interventions considered relevant to nutritional management. The reward function was designed with domain expertise to balance short-term physiological and nutrition-related goals with long-term survival outcomes, reflecting real-world clinical priorities. The framework employs a dueling double deep Q-network with Conservative Q-Learning regularization to ensure safe and reliable policy learning from retrospective data. Model performance was benchmarked against both clinician-derived and guideline-based policies. Results: DeepEN outperformed both clinician and guideline-based policies, achieving a 3.7 0.17 percentage-point absolute reduction in estimated morarXiv:2510.08350v2 [cs.LG] 19 Nov 2025 tality compared with the clinician policy (18.8% vs 22.5%) and higher expected returns relative to the gold-standard guideline policy (11.89 vs 8.11). Control of key nutritional biomarkers was also improved under the learned policy.

Objective: Machine learning (ML) predictive models are often developed without considering downstream value trade-offs and clinical interpretability. This paper introduces a cost-aware prediction (CAP) framework that combines cost-benefit analysis assisted by large language model (LLM) agents to communicate the trade-offs involved in applying ML predictions. Materials and Methods: We developed an ML model predicting 1-year mortality in patients with heart failure (N = 30,021, 22% mortality) to identify those eligible for home care. We then introduced clinical impact projection (CIP) curves to visualize important cost dimensions - quality of life and healthcare provider expenses, further divided into treatment and error costs, to assess the clinical consequences of predictions. Finally, we used four LLM agents to generate patient-specific descriptions. The system was evaluated by clinicians for its decision support value. Results: The eXtreme gradient boosting (XGB) model achieved the best performance, with an area under the receiver operating characteristic curve (AUROC) of 0.804 (95% confidence interval (CI) 0.792-0.816), area under the precision-recall curve (AUPRC) of 0.529 (95% CI 0.502-0.558) and a Brier score of 0.135 (95% CI 0.130-0.140). Discussion: The CIP cost curves provided a population-level overview of cost composition across decision thresholds, whereas LLM-generated cost-benefit analysis at individual patient-levels. The system was well received according to the evaluation by clinicians. However, feedback emphasizes the need to strengthen the technical accuracy for speculative tasks. Conclusion: CAP utilizes LLM agents to integrate ML classifier outcomes and cost-benefit analysis for more transparent and interpretable decision support.

Recent attempts to achieve fairness in predictive models focus on the balance between fairness and accuracy.