Efficient Variance-reduced Estimation from Generative EHR Models: The SCOPE and REACH Estimators

Generative models trained using self-supervision of tokenized electronic health record (EHR) timelines show promise for clinical outcome prediction. This is typically done using Monte Carlo simulation for future patient trajectories. However, existing approaches suffer from three key limitations: sparse estimate distributions that poorly differentiate patient risk levels, extreme computational costs, and high sampling variance. We propose two new estimators: the Sum of Conditional Outcome Probability Estimator (SCOPE) and Risk Estimation from Anticipated Conditional Hazards (REACH), that leverage next-token probability distributions discarded by standard Monte Carlo. We prove both estimators are unbiased and that REACH guarantees variance reduction over Monte Carlo sampling for any model and outcome. Empirically, on hospital mortality prediction in MIMIC-IV using the ETHOS-ARES framework, SCOPE and REACH match 100-sample Monte Carlo performance using only 10-11 samples (95% CI: [9,11]), representing a ~10x reduction in inference cost without degrading calibration. For ICU admission prediction, efficiency gains are more modest (~1.2x), which we attribute to the outcome's lower "spontaneity," a property we characterize theoretically and empirically. These methods substantially improve the feasibility of deploying generative EHR models in resource-constrained clinical settings.

Thinking Like a Doctor: Conversational Diagnosis through the Exploration of Diagnostic Knowledge Graphs

Conversational diagnosis requires multi-turn history-taking, where an agent asks clarifying questions to refine differential diagnoses under incomplete information. Existing approaches often rely on the parametric knowledge of a model or assume that patients provide rich and concrete information, which is unrealistic. To address these limitations, we propose a conversational diagnosis system that explores a diagnostic knowledge graph to reason in two steps: (i) generating diagnostic hypotheses from the dialogue context, and (ii) verifying hypotheses through clarifying questions, which are repeated until a final diagnosis is reached. Since evaluating the system requires a realistic patient simulator that responds to the system's questions, we adopt a well-established simulator along with patient profiles from MIMIC-IV. We further adapt it to describe symptoms vaguely to reflect real-world patients during early clinical encounters. Experiments show improved diagnostic accuracy and efficiency over strong baselines, and evaluations by physicians support the realism of our simulator and the clinical utility of the generated questions. Our code will be released upon publication.

Trustworthy Blockchain-based Federated Learning for Electronic Health Records: Securing Participant Identity with Decentralized Identifiers and Verifiable Credentials

The digitization of healthcare has generated massive volumes of Electronic Health Records (EHRs), offering unprecedented opportunities for training Artificial Intelligence (AI) models. However, stringent privacy regulations such as GDPR and HIPAA have created data silos that prevent centralized training. Federated Learning (FL) has emerged as a promising solution that enables collaborative model training without sharing raw patient data. Despite its potential, FL remains vulnerable to poisoning and Sybil attacks, in which malicious participants corrupt the global model or infiltrate the network using fake identities. While recent approaches integrate Blockchain technology for auditability, they predominantly rely on probabilistic reputation systems rather than robust cryptographic identity verification. This paper proposes a Trustworthy Blockchain-based Federated Learning (TBFL) framework integrating Self-Sovereign Identity (SSI) standards. By leveraging Decentralized Identifiers (DIDs) and Verifiable Credentials (VCs), our architecture ensures only authenticated healthcare entities contribute to the global model. Through comprehensive evaluation using the MIMIC-IV dataset, we demonstrate that anchoring trust in cryptographic identity verification rather than behavioral patterns significantly mitigates security risks while maintaining clinical utility. Our results show the framework successfully neutralizes 100% of Sybil attacks, achieves robust predictive performance (AUC = 0.954, Recall = 0.890), and introduces negligible computational overhead (<0.12%). The approach provides a secure, scalable, and economically viable ecosystem for inter-institutional health data collaboration, with total operational costs of approximately $18 for 100 training rounds across multiple institutions.

On Safer Reinforcement Learning Policies for Sedation and Analgesia in Intensive Care

Pain management in intensive care usually involves complex trade-offs between therapeutic goals and patient safety, since both inadequate and excessive treatment may induce serious sequelae. Reinforcement learning can help address this challenge by learning medication dosing policies from retrospective data. However, prior work on sedation and analgesia has optimized for objectives that do not value patient survival while relying on algorithms unsuitable for imperfect information settings. We investigated the risks of these design choices by implementing a deep reinforcement learning framework to suggest hourly medication doses under partial observability. Using data from 47,144 ICU stays in the MIMIC-IV database, we trained policies to prescribe opioids, propofol, benzodiazepines, and dexmedetomidine according to two goals: reduce pain or jointly reduce pain and mortality. We found that, although the two policies were associated with lower pain, actions from the first policy were positively correlated with mortality, while those proposed by the second policy were negatively correlated. This suggests that valuing long-term outcomes could be critical for safer treatment policies, even if a short-term goal remains the primary objective.

Robust Multimodal Representation Learning in Healthcare

Medical multimodal representation learning aims to integrate heterogeneous data into unified patient representations to support clinical outcome prediction. However, real-world medical datasets commonly contain systematic biases from multiple sources, which poses significant challenges for medical multimodal representation learning. Existing approaches typically focus on effective multimodal fusion, neglecting inherent biased features that affect the generalization ability. To address these challenges, we propose a Dual-Stream Feature Decorrelation Framework that identifies and handles the biases through structural causal analysis introduced by latent confounders. Our method employs a causal-biased decorrelation framework with dual-stream neural networks to disentangle causal features from spurious correlations, utilizing generalized cross-entropy loss and mutual information minimization for effective decorrelation. The framework is model-agnostic and can be integrated into existing medical multimodal learning methods. Comprehensive experiments on MIMIC-IV, eICU, and ADNI datasets demonstrate consistent performance improvements.

Embracing Aleatoric Uncertainty in Medical Multimodal Learning with Missing Modalities

Medical multimodal learning faces significant challenges with missing modalities prevalent in clinical practice. Existing approaches assume equal contribution of modality and random missing patterns, neglecting inherent uncertainty in medical data acquisition. In this regard, we propose the Aleatoric Uncertainty Modeling (AUM) that explicitly quantifies unimodal aleatoric uncertainty to address missing modalities. Specifically, AUM models each unimodal representation as a multivariate Gaussian distribution to capture aleatoric uncertainty and enable principled modality reliability quantification. To adaptively aggregate captured information, we develop a dynamic message-passing mechanism within a bipartite patient-modality graph using uncertainty-aware aggregation mechanism. Through this process, missing modalities are naturally accommodated, while more reliable information from available modalities is dynamically emphasized to guide representation generation. Our AUM framework achieves an improvement of 2.26% AUC-ROC on MIMIC-IV mortality prediction and 2.17% gain on eICU, outperforming existing state-of-the-art approaches.

From Generative Modeling to Clinical Classification: A GPT-Based Architecture for EHR Notes

The increasing availability of unstructured clinical narratives in electronic health records (EHRs) has created new opportunities for automated disease characterization, cohort identification, and clinical decision support. However, modeling long, domain-specific clinical text remains challenging due to limited labeled data, severe class imbalance, and the high computational cost of adapting large pretrained language models. This study presents a GPT-based architecture for clinical text classification that adapts a pretrained decoder-only Transformer using a selective fine-tuning strategy. Rather than updating all model parameters, the majority of the GPT-2 backbone is frozen, and training is restricted to the final Transformer block, the final layer normalization, and a lightweight classification head. This approach substantially reduces the number of trainable parameters while preserving the representational capacity required to model complex clinical language. The proposed method is evaluated on radiology reports from the MIMIC-IV-Note dataset using uncertainty-aware CheXpert-style labels derived directly from report text. Experiments cover multiple problem formulations, including multi-label classification of radiographic findings, binary per-label classification under different uncertainty assumptions, and aggregate disease outcome prediction. Across varying dataset sizes, the model exhibits stable convergence behavior and strong classification performance, particularly in settings dominated by non-mention and negated findings. Overall, the results indicate that selective fine-tuning of pretrained generative language models provides an efficient and effective pathway for clinical text classification, enabling scalable adaptation to real-world EHR data while significantly reducing computational complexity.

Planner-Auditor Twin: Agentic Discharge Planning with FHIR-Based LLM Planning, Guideline Recall, Optional Caching and Self-Improvement

Objective: Large language models (LLMs) show promise for clinical discharge planning, but their use is constrained by hallucination, omissions, and miscalibrated confidence. We introduce a self-improving, cache-optional Planner-Auditor framework that improves safety and reliability by decoupling generation from deterministic validation and targeted replay. Materials and Methods: We implemented an agentic, retrospective, FHIR-native evaluation pipeline using MIMIC-IV-on-FHIR. For each patient, the Planner (LLM) generates a structured discharge action plan with an explicit confidence estimate. The Auditor is a deterministic module that evaluates multi-task coverage, tracks calibration (Brier score, ECE proxies), and monitors action-distribution drift. The framework supports two-tier self-improvement: (i) within-episode regeneration when enabled, and (ii) cross-episode discrepancy buffering with replay for high-confidence, low-coverage cases. Results: While context caching improved performance over baseline, the self-improvement loop was the primary driver of gains, increasing task coverage from 32% to 86%. Calibration improved substantially, with reduced Brier/ECE and fewer high-confidence misses. Discrepancy buffering further corrected persistent high-confidence omissions during replay. Discussion: Feedback-driven regeneration and targeted replay act as effective control mechanisms to reduce omissions and improve confidence reliability in structured clinical planning. Separating an LLM Planner from a rule-based, observational Auditor enables systematic reliability measurement and safer iteration without model retraining. Conclusion: The Planner-Auditor framework offers a practical pathway toward safer automated discharge planning using interoperable FHIR data access and deterministic auditing, supported by reproducible ablations and reliability-focused evaluation.

ReToP: Learning to Rewrite Electronic Health Records for Clinical Prediction

Electronic Health Records (EHRs) provide crucial information for clinical decision-making. However, their high-dimensionality, heterogeneity, and sparsity make clinical prediction challenging. Large Language Models (LLMs) allowed progress towards addressing this challenge by leveraging parametric medical knowledge to enhance EHR data for clinical prediction tasks. Despite the significant achievements made so far, most of the existing approaches are fundamentally task-agnostic in the sense that they deploy LLMs as EHR encoders or EHR completion modules without fully integrating signals from the prediction tasks. This naturally hinders task performance accuracy. In this work, we propose Rewrite-To-Predict (ReToP), an LLM-based framework that addresses this limitation through an end-to-end training of an EHR rewriter and a clinical predictor. To cope with the lack of EHR rewrite training data, we generate synthetic pseudo-labels using clinical-driven feature selection strategies to create diverse patient rewrites for fine-tuning the EHR rewriter. ReToP aligns the rewriter with prediction objectives using a novel Classifier Supervised Contribution (CSC) score that enables the EHR rewriter to generate clinically relevant rewrites that directly enhance prediction. Our ReToP framework surpasses strong baseline models across three clinical tasks on MIMIC-IV. Moreover, the analysis of ReToP shows its generalizability to unseen datasets and tasks with minimal fine-tuning while preserving faithful rewrites and emphasizing task-relevant predictive features.

Learning temporal embeddings from electronic health records of chronic kidney disease patients

We investigate whether temporal embedding models trained on longitudinal electronic health records can learn clinically meaningful representations without compromising predictive performance, and how architectural choices affect embedding quality. Model-guided medicine requires representations that capture disease dynamics while remaining transparent and task agnostic, whereas most clinical prediction models are optimised for a single task. Representation learning facilitates learning embeddings that generalise across downstream tasks, and recurrent architectures are well-suited for modelling temporal structure in observational clinical data. Using the MIMIC-IV dataset, we study patients with chronic kidney disease (CKD) and compare three recurrent architectures: a vanilla LSTM, an attention-augmented LSTM, and a time-aware LSTM (T-LSTM). All models are trained both as embedding models and as direct end-to-end predictors. Embedding quality is evaluated via CKD stage clustering and in-ICU mortality prediction. The T-LSTM produces more structured embeddings, achieving a lower Davies-Bouldin Index (DBI = 9.91) and higher CKD stage classification accuracy (0.74) than the vanilla LSTM (DBI = 15.85, accuracy = 0.63) and attention-augmented LSTM (DBI = 20.72, accuracy = 0.67). For in-ICU mortality prediction, embedding models consistently outperform end-to-end predictors, improving accuracy from 0.72-0.75 to 0.82-0.83, which indicates that learning embeddings as an intermediate step is more effective than direct end-to-end learning.