Import What You Need: Learning When and How to Augment EHR Graphs with External Knowledge

Longitudinal prediction from electronic health records (EHRs) is limited by the sparsity and irregularity in patient trajectories, and knowledge augmentation with external knowledge graphs (KGs) offers a promising way to alleviate these issues. However, most existing methods perform fixed, context-agnostic topology augmentation by adding the same KG nodes and edges regardless of a patient's evolving state. We propose ReTA, a Reinforcement learning-based dynamic Topology Augmentation framework that casts KG import as a per-visit, budget-aware policy. ReTA first constructs an offline refined pool of KG-grounded templates, then learns a policy to select one augment action per visit from three options: Soft Import, which enriches node features without modifying graph topology, Hard Import, which grafts a compact KG subgraph onto the visit graph to create message-passing shortcuts, and Skip, which leaves the visit unaugmented when the base encoder is already confident. To stabilize learning, ReTA employs a decoupled encoder that processes semantic and structural signals in separate channels and fuses them via adaptive gating. Experiments on MIMIC-III and MIMIC-IV across diagnosis prediction, mortality, and readmission show that ReTA consistently outperforms strong baselines while remaining efficient, transfers across datasets and knowledge graphs, and yields interpretable augmentation patterns. The robust gains under sparse supervision highlight the advantage of ReTA's dynamic decision to import knowledge, boosting accuracy while curbing costs.

DIASENTINEL: An Auditable Multi-Agent System for Guideline-Grounded Diabetes Risk Screening

Large language models (LLMs) offer promising clinical decision support but remain vulnerable to hallucinated facts, unsupported recommendations, and citation errors. We present DIASENTINEL, a fully on-premise multi-agent system for one-year type 2 diabetes mellitus (T2DM) risk screening and guideline-grounded report generation from electronic health records (EHRs). The system integrates calibrated risk prediction, deterministic clinical signal extraction, Reciprocal Rank Fusion over American Diabetes Association (ADA) guidelines, and a hybrid verification layer combining rule-based checks with LLM entailment. The demonstration provides a real-time batch-screening dashboard and an interactive patient report interface with cited recommendations, verification results, and raw EHR comparison. DIASENTINEL demonstrates a practical framework for reliable, auditable, and privacy-preserving LLM-based clinical decision support.

FedEHR-Agents: Federated Agentic Optimization for Automated EHR Modeling

Recent advances in large language models are enabling autonomous clinical agents to perform increasingly complex electronic health record (EHR) modeling workflows. However, agents deployed at individual hospitals remain constrained by institution-specific data and modeling environments, while direct cross-hospital collaboration is restricted by the sensitivity of patient-level EHR data. Although federated learning (FL) provides a natural foundation for privacy-preserving collaboration, existing approaches remain predominantly model-centric, limiting federation to prediction models or their updates while overlooking the richer modeling experience accumulated by autonomous agents. To address this limitation, we propose FedEHR-Agents, an experience-centric federated agentic optimization framework for automated EHR modeling. Each hospital deploys an autonomous clinical EHR agent that performs data preprocessing and model development while refining local clinical modeling experience through historical memory, task-specific evaluation, and TextGrad-based prompt refinement. The federated server performs evidence-guided experience aggregation to integrate reliable and complementary modeling experience across heterogeneous hospitals and distills the aggregated experience into global meta-prompts for subsequent local refinement. Extensive experiments on real-world multi-hospital EHR benchmarks demonstrate that FedEHR-Agents consistently outperforms local and federated baselines across diverse clinical prediction tasks and remains robust across different federation scales and LLM backbones. These results establish clinical modeling experience as a promising collaborative object beyond conventional parameter-centric FL and point toward federated autonomous clinical intelligence.

Hierarchical MoE for Multi-Modal ILD Diagnosis

Mixture-of-experts (MoE) models combine specialized predictors under learned routing, offering a principled mechanism for leveraging heterogeneity in medical data. We present a hierarchical multimodal MoE for interstitial lung disease (ILD) classification that integrates a frozen, pre-trained imaging expert with structured electronic health records (EHR) via two-stage gating. A modality-level gate assigns patient-specific weights to imaging and EHR predictions, while a sub-gating module decomposes the EHR branch into clinically defined feature groups with learned, group-specific contributions. This design preserves stable imaging representations while enabling input-dependent clinical weighting and explicit EHR specialization. Under strict patient-level cross-validation, the model achieved the highest mean AUC among the evaluated methods (0.8750 +- 0.0443), compared with 0.8646 for imaging-only REN and 0.7685 for SwinUNETR. The framework extends interpretability across anatomical regions, imaging--EHR utilization, and clinically defined EHR feature groups.

A Structural FHMM for Interpretable Disease Trajectories in T2DM

In this work, we propose a structural variant of the Factorial Hidden Markov Model (FHMM) for the analysis of disease trajectories in patients with Type 2 diabetes mellitus (T2DM). The model represents a patient's latent health state as a combination of multiple independent, simultaneously evolving components, associated with comorbidities and lab results. This structured latent representation facilitates the identification of clinically meaningful patient states and clustering of common disease trajectories. We evaluate the proposed approach using The IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records (EHR), identifying patients with a first-ever prescription for a non-insulin antidiabetic drug (NIAD) between January 2006 and December 2019. The model identifies multiple clinically coherent latent components corresponding to known patterns of diabetes-related complications and reveals heterogeneous progression pathways, including distinct microvascular-dominant and multi-organ trajectories associated with elevated comorbidity burden and mortality. These results demonstrate that the proposed framework captures meaningful longitudinal structure in EHR data and provides interpretable insights into the evolution of T2DM and its comorbidities.

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.

Role-Specialized Mixture-of-Agents with Open-Weight LLMs for Clinical Prediction

Large Language Models (LLMs) are increasingly applied to clinical prediction tasks such as in-hospital mortality and readmission from electronic health records (EHRs). Privacy and compliance constraints motivate systems that can be deployed locally, which has increased interest in open-weight multi-agent designs. However, most medical multi-agent systems are evaluated as a single block, leaving unclear which agent role contributes to prediction and whether retrieval drives observed gains. We study a role-specialized Mixture-of-Agents (MoA) that combines medical knowledge retrieval with contrastive similar-patient reasoning. By varying the role design while holding the retrieval setup fixed, we localize the main effect to the final integrator. Pairing large open-weight analysts with a small open-weight integrator matches closed-model prompting on F1 for mortality prediction while flagging substantially more true high-risk patients. Mechanism analysis shows the role assignment directly yields a high-recall operating point without threshold tuning. The effect is task-dependent, with smaller gains for readmission because the available records correlate weakly with this longer-horizon outcome. These results position role design as a key factor in privacy-constrained, training-free clinical LLM prediction.

ATHENA: Knowledge-guided agentic neural architecture search for AutoFormer-based electronic health record modeling

Transformer-based models are widely used for clinical prediction from electronic health records (EHRs), yet their architectures require manual tuning, and the optimal configuration may vary across tasks and hospitals. Neural architecture search (NAS) automates architecture design, but conventional methods are computationally costly for Transformer-based EHR models. Recent large language model (LLM)-guided NAS methods reduce manual search design but conduct each search independently, without reusing architecture knowledge across hospitals. In this study, we propose ATHENA (Agentic Transfer across Hospitals for EHR Neural Architecture Search), a knowledge-guided agentic NAS framework for Transformer-based EHR modeling. ATHENA uses a weight-sharing supernet that is pretrained once per hospital, allowing candidate architectures to be instantiated as inherited subnetworks and evaluated through fine-tuning rather than independent pretraining. It incorporates a two-layer cross-hospital architecture prior. The first layer retrieves high-performing architecture examples from source sites based on task descriptors, while the second estimates the effects of architectural components using SHapley Additive exPlanations (SHAP)-based meta-regression. These priors guide a multi-agent LLM search using validation feedback from the target hospital. Across six clinical prediction tasks evaluated at one held-out OneFlorida+ site and one external MIMIC-IV site, ATHENA significantly outperforms all four baselines in 9 of 12 site-task evaluations under a strict equal-compute comparison. Using a common pretrained AutoFormer supernet for candidate evaluation, ATHENA ranks first in 9 of 12 evaluations at a search budget of 30. It also shows more consistent architecture selection across repeated searches. ATHENA provides a practical approach for reducing manual architecture tuning in Transformer-based EHR modeling.

Predicting Early Functional Decline from Longitudinal Laboratory and Vital Sign Trajectories: A Large-Scale Study Using the All of Us Research Program

Functional decline in older adults is typically recognized only after falls or observable gait impairment, closing the window for prevention. We investigated whether temporal trajectories of routine biomarkers, already recorded but rarely analyzed longitudinally, can identify patients in the pre-clinical phase of mobility decline. Using the All of Us Research Program (N = 297,861; 11.1% cases), we derived trajectory features (slope, variability, delta, mean) for twelve biomarkers over a three-year pre-index window. LightGBM models incorporating trajectories significantly outperformed static laboratory summaries (AUROC 0.797 vs. 0.755; DeLong p < 0.001; AUPRC 0.380 vs. 0.304). A 1:1 age- and sex-matched analysis confirmed an independent trajectory signal (AUROC 0.727 vs. demographics-only 0.680). A horizon analysis demonstrated sustained prediction 3-12 months before decline onset (AUROC 0.768-0.740). Because the model uses only measurements already ordered in routine care, it supports passive, zero-burden EHR integration for early detection of pre-clinical functional decline.

Explainable Transformer Models for Clinical Prediction Tasks on Structured Electronic Health Records

Predictive models over structured electronic health records (EHRs) remain central to machine learning for healthcare, but few have jointly emphasized quantitative laboratory information and interpretability with respect to input medical events. We present BERT-LER, a BERT-style model for coded EHR timelines pretrained and fine-tuned from a de-identified EHR dataset of 75 million patients, that encodes laboratory test results as discrete tokens while retaining graded information through percentile-based binning, paired with Integrated Gradients for token-level attributions grounded in the input EHR sequence. We benchmark our approach on the public EHRShot benchmark suite and on an asthma severity progression study based on real-world data. This addresses a methodological gap in EHR foundation-style modeling by unifying laboratory value representation and explainability in a single framework, while assessing whether both predictive performance and explanations generalize beyond standard clinical prediction tasks. Across EHRShot and asthma tasks, BERT-LER achieves predictive performance that is competitive with, and on laboratory-related tasks often exceeds, publicly available benchmark models, and provides attributions that align with clinically known risk factors. Our architecture and explainability approach can be applied to many therapeutic areas and prediction tasks using language models trained on structured EHRs.

Institution-Specific LLM Prompting Recovers PHI That De-identification Systems and Their Gold Standards Both Miss

Secondary use of electronic health records requires de-identification, yet existing systems miss \emph{institutionally situated} protected health information (PHI) such as hospital abbreviations, building names, and internal codes whose status is locally determined. We ask whether large language models (LLMs) with in-context learning (ICL) can close this gap and control the precision--recall trade-off. On 100 annotated pediatric oncology notes (5,322 PHI spans) from Texas Children's Hospital, we benchmarked eight LLMs against two purpose-built systems (Stanford TiDE, OpenMed PII) and two pattern-based baselines. Each LLM ran under three prompts of increasing specificity: (1) a HIPAA-aligned baseline, (2) baseline plus the institutional PHI categories it missed, and (3) prompt 2 plus instructions against over-redacting clinical content. We then compared 14~multi-agent and ensemble configurations against the best single prompt, with recall the primary safety metric. LLMs outperformed the purpose-built systems (best F1=0.918$\pm$0.001 vs.\ TiDE 0.779), with advantages concentrated in contextual categories. Naming the missed categories recovered 79\% (48/61) of them, and discouraging over-redaction restored precision. No agentic architecture beat calibrated single-pass prompting (F1 0.906--0.907), but LLM outputs surfaced 414~candidate annotation gaps; re-annotation confirmed 227~PHI spans, against which the final prompt reached recall=0.981 (F1=0.907$\pm$0.002). Well-calibrated ICL resolves both the institutional PHI gap and the precision--recall trade-off in one LLM call per note. LLMs cost more to run than traditional methods, but that cost buys a way to audit the reference standard. LLMs are a legitimate, adaptable alternative to purpose-built de-identification systems; institution-specific prompt development should be the primary adaptation strategy.

Foresight-England: Development of a National-Scale Generative AI Model of Electronic Health Records for Medical Event Prediction across the COVID-19 Pandemic

Foresight-England (Foresight-E) is the first national-scale generative foundation model of electronic health records (EHRs), developed as a research pilot strictly for COVID-19 research. We evaluated its ability to model the direct and indirect effects of the pandemic. Trained from scratch entirely within the NHS England Secure Data Environment, Foresight-E is a 243-million-parameter transformer decoder. It was trained and evaluated on de-identified, longitudinal EHRs of approximately 61 million individuals, integrating primary/secondary care, death registrations, and COVID-19 data. Training and validation used a 90% subset (54.9 million) spanning November 2018 to December 2022; the remaining 10% (6.1 million) was held out for evaluation. Foresight-E models patient timelines autoregressively, predicting the next medical event given their prior history. At inference, it operates zero-shot, predicting any concept in its ~40,000-code vocabulary without task-specific training. Our tokenisation scheme retains the clinical granularity of ICD-10, OPCS-4, and SNOMED CT codes, jointly representing absolute and relative timing. We designed an evaluation framework for 30-day COVID-19 hospitalisation and mortality, including subgroup analyses by demographic factors and vaccination status. To assess generalisation to unseen future data and the pandemic's indirect effects, we tested the model on medical events from 2023 (beyond its training period), benchmarking against logistic regression and XGBoost. As detailed in the Project Status section, NHS England has paused access to data for the Foresight-E project, meaning quantitative results are currently unavailable. Instead, we share our strategy for tokenisation, architecture, training, inference, and evaluation as a methodological template and case study in the challenges of building population-scale EHR foundation models.

MiGHT-EHR: A Multi-task Graph Transformer for Heterogeneous Temporal Electronic Health Records

Learning from Electronic Health Records (EHRs) has gained significant attention due to its potential to improve clinical prediction. However, effective learning remains challenging because EHRs encode heterogeneous, temporally ordered clinical interactions. In particular, EHRs contain: (i) heterogeneous clinical entities, including patients, visits, diagnoses, prescriptions, and procedures, together with their heterogeneous interactions, (ii) longitudinal patient trajectories across hospital visits and (iii) shared statistical dependencies across related clinical prediction tasks. Existing EHR learning methods capture only a subset of these properties. To bridge this gap, we propose Multi-task Graph transformer for Heterogeneous Temporal EHRs (MiGHT-EHR), which jointly models all three within a unified representation learning method. MiGHT-EHR constructs a heterogeneous graph from EHRs in which nodes represent clinical entities and edges connect statistically associated entities identified via normalized point-wise mutual information. Across MIMIC-III and MIMIC-IV datasets, MiGHT-EHR outperforms state-of-the-art methods on average across four tasks: drug recommendation, prediction of length-of-stay, mortality, and readmission, with particularly strong improvements in mortality and readmission prediction. Furthermore, a post-hoc analysis of the learned representations reveals that patient neighborhoods are organized by clinical outcomes, salient medical concepts are recoverable as linear directions in the representation space, and task probabilities are well calibrated. Collectively, these findings demonstrate that MiGHT-EHR representations support diverse prediction tasks while preserving clinically interpretable structure.

Mr.Dec: Daily-Scale Longitudinal Multimodal Modeling for 30-Day Readmission Prediction

Predicting 30-day hospital readmission is essential for assessing patient stability and optimizing healthcare resources. As clinical risk evolves with the accumulation of evidence during hospitalization, capturing these dynamic trajectories is essential. However, many existing approaches compress the complex longitudinal history into fixed representations, often losing the granular, day-level clinical signals that reflect a patient's evolving physiological state. To address this, we propose Mr.Dec (Multimodal Readmission-risk prediction Decoder), which models each admission as a natural chronological sequence of daily multimodal events. By leveraging a Transformer Decoder, Mr.Dec integrates daily Electronic Health Record(EHR) updates and intermittent Chest X-ray(CXR) findings in a time-aligned stream, reflecting the actual clinical workflow. To ensure robustness, we utilize Disease-Specific Supervised Contrastive Learning as an auxiliary regularization to induce a diagnosis-aware structure in the latent space. Evaluations on the MIMIC-IV and MIMIC-CXR datasets show that Mr.Dec achieves state-of-the-art performance by preserving the integrity of the clinical sequence. Furthermore, our model identifies "Critical Days" within an admission, providing actionable and clinically grounded interpretations for real-time risk stratification. Code is available at: https://github.com/yejix-ai/MR.DEC

Patients-like-me: A Variational LM--GNN Framework for Explainable Clinical Prediction

Language models (LMs) offer strong textual representations for electronic health records (EHRs), but they encode patient sequences in isolation and provide limited explainability. Graph neural networks (GNNs) complement LMs by incorporating inter-patient relationships and enabling reference-patient attribution, yet they rely on high-quality patient representations. We propose Patients-like-me (PLM), a unified LM--GNN framework that integrates local patient semantics with global cohort structure. To train PLM efficiently, we introduce a Variational Expectation-Maximization algorithm that alternates LM and GNN updates under a supervised variational objective. Extensive experiments on MIMIC-III and MIMIC-IV show that PLM consistently outperforms state-of-the-art methods, with improvements generalizing across encoder-only and decoder-only LM backbones. These gains are achieved with only modest additional computational overhead. PLM also provides reference-patient explanations by retrieving influential similar patients, while edge-masking experiments confirm that the highest-ranked references have the greatest impact on model predictions.

Federated generative event models for tokenized electronic health records

Electronic health record foundation models are limited by institutionally siloed data and substantial performance degradation under cross-site transfer. We evaluated federated training of tokenized generative event models (GEMs) across 122,251 intensive care hospitalizations from three independent health systems harmonized to the Common Longitudinal ICU Data Format. Models were assessed on 12 post-24-hour clinical prediction tasks using within-site, cross-site, centralized, and federated training configurations. GEMs achieved the highest mean within-site and cross-site ROC-AUC and were substantially more transportable than conventional supervised models: their average cross-site penalties were 0.025 ROC-AUC and 0.027 PR-AUC, compared with 0.079 and 0.089 for LightGBM. Federated Learning (FedAvg and FedAvgM) approached the performance of centralized GEM training, with most gains obtained within 5-10 communication rounds. However, centralized multi-site training provided only modest improvements over complete local training. Multi-site models were most useful when local training data were limited, with their advantage narrowing as institutional data accumulated. These findings show that federated GEM training is technically feasible and preserves most centralized performance, but that the main open challenge is learning transportable representations to translate larger, but heterogeneous data from multiple health systems into a reliable target-site benefit.

CT-HEG: A Bidirectional, Timestamp-Attributed Event Graph for ICU In-Hospital Mortality Prediction - An Architectural Ablation Study

Accurate ICU mortality prediction requires modeling irregular clinical observations across heterogeneous entity types. Existing sequence models handle irregular sampling but ignore typed relational structure; existing graph models assume fixed-interval inputs. We introduce the Continuous-Time Heterogeneous EHR Graph (CT-HEG) schema and evaluate which architectural choices drive predictive performance. CT-HEG encodes each ICU stay as a typed, timestamped graph with three node types (visit, vital, lab_event) and 2D edge attributes (t_hours/48, value_norm) encoding timing and value without imputation. We instantiate CT-HEG as CHIRP-Net, a four-layer heterogeneous GATv2Conv network, evaluated on MIMIC-IV v3.1 (31,142 ICU stays, LOS>=48h, 13.4% mortality) with five seeds and bootstrapped confidence intervals, against logistic regression, mTAND, a Transformer, and GRU-D, plus an ablation study. CHIRP-Net achieved 5-seed mean AUROC 0.8449+/-0.0071 (AUPRC 0.4958+/-0.0209); the ensemble achieved AUROC 0.8618 (95% CI: 0.8485-0.8745). Removing reverse edges disconnected observation nodes from the visit readout, cutting AUROC by 0.1968+/-0.0073. Time-attentive edge features contributed 0.0247+/-0.0093 AUROC. Collapsing heterogeneous edge types into one relation (7x fewer parameters) outperformed the full model on all seeds. Post-calibration ECE was 0.0307. Temporal and demographic subgroup analyses were explored but not reported here, pending follow-up work. Bidirectional connectivity was necessary for the model to use its inputs at all, and CT-HEG was reasonably well calibrated after validation-fitted temperature scaling. These results support CT-HEG for irregular EHR data, while external validation, a pre-specified temporal evaluation, and a demographic fairness audit remain necessary before any claim of robustness. Code: https://github.com/nasiruddinstudents-ctrl/chirp-net-mimic-iv.

LUNG-KGMM: Knowledge-Guided Multimodal Learning for Lung Cancer Incidence Prediction

Early identification of lung cancer risk is critical for timely intervention, yet existing prediction models are limited by their reliance on single data modalities and their inability to leverage structured clinical knowledge. We propose LUNG-KGMM, a knowledge-guided multimodal framework that integrates longitudinal electronic health records, radiology reports, chest radiograph representations, and guideline-derived knowledge for 1-to-6-year incident lung cancer prediction. To address modality heterogeneity and potential data leakage, we develop a leakage-sanitized report processing pipeline and a horizon-masked cumulative training objective that handles incomplete follow-up. We further introduce a knowledge-graph representation of clinical guidance that encodes report-triggered finding-attribute-action relations as an auditable knowledge stream. We build a multimodal development cohort from the publicly available MIMIC databases and construct a real-world validation cohort from the Xiamen Medical Big Data Platform. Extensive experiments on the MIMIC cohort demonstrate that LUNG-KGMM achieves superior performance over state-of-the-art methods, and validation on the Xiamen cohort further characterizes its cross-cohort portability and the need for local adaptation. The MIMIC development cohort is publicly accessible; the Xiamen cohort is governed by local data privacy regulations.

What Is Missing in Surgical Risk Stratification and Outcome Prediction: A Scoping Review of End-to-End Machine Learning Approaches

Postoperative adverse events, including mortality and morbidity, remain a major global burden, many of which are preventable through early identification of high-risk patients and targeted perioperative care. Accurate risk stratification is therefore essential. With the growing availability of large-scale electronic health records (EHRs), machine learning (ML) provides a data-driven approach to model complex clinical patterns. However, existing studies vary widely in design, and methodological practices remain fragmented. This scoping review characterizes ML pipelines for surgical risk stratification and outcome prediction using EHR data. We reviewed 190 studies covering the ML workflow, including data preprocessing, algorithm selection, model evaluation, and explainability. Most studies relied on single-center private datasets with limited data modalities, while the scarcity of open-access surgical datasets constrained reproducibility and generalizability. Reporting of key preprocessing steps, including missing data handling, feature selection, and class imbalance, was often incomplete. Conventional ML models and simple neural networks predominated, whereas deep learning and multimodal approaches remained uncommon. Benchmark datasets and standardized evaluation protocols were largely absent, hindering cross-study comparisons. Only about one-third of studies incorporated explainability methods. This review identifies methodological gaps limiting clinically robust postoperative ML tools and provides a structured reference to support more rigorous, reproducible, and clinically meaningful ML development for perioperative care.

GRAIN: Molecules Are Not the Right Granularity -- Active-Ingredient Modeling for Safe Medication Recommendation

Medication recommendation from electronic health records must balance predictive accuracy against the risk of adverse drug-drug interactions (DDIs) under polypharmacy. Existing safety-aware recommenders operate at one of two granularities: the drug code, which treats each medication as an indivisible token, or the molecular substructure, which is finer than pharmacological interaction knowledge is actually organized. We argue that the active ingredient is the missing granularity, and introduce GRAIN, a medication recommendation framework built around it. GRAIN encodes longitudinal patient trajectories (diagnoses, procedures, past medications) with a selective state space backbone that handles long, irregular visit sequences in linear time. On top of it we introduce a joint objective unifying three knowledge sources aligned to a common medication vocabulary: a drug-level DDI graph, an ingredient-level DDI graph obtained by normalizing medication codes to active ingredients via RxNorm, and an EHR-derived co-prescription graph. A proportional controller adapts the accuracy-safety trade-off to the observed validation DDI rate rather than fixing it a priori. Under strictly matched settings -- identical preprocessing, cohort, vocabulary, split, and evaluation code -- GRAIN improves over a re-implemented MambaHealth baseline on MIMIC-IV across all standard multi-label metrics (Jaccard 0.4488 to 0.4983, PRAUC 0.6911 to 0.7485, F1 0.5989 to 0.6453) while reducing the drug-level DDI rate from 0.1875 to 0.0948. We further define an ingredient-level DDI rate, a safety measure invisible to drug-code-level evaluation. The results indicate that ingredient-level normalization recovers predictive signal erased by code-level aggregation, and that it is complementary to, rather than in competition with, accurate sequence modeling.

Fracture Risk Prediction in Adults Over 50 Years Old Using DXA and EHR: Comparison of Traditional and Machine Learning Models in Two Large Cohorts

Accurate fracture risk prediction is important for osteoporosis management, but commonly used clinical tools may not fully use information available in electronic health records (EHRs) and dual-energy X-ray absorptiometry (DXA) reports. We developed and externally validated time-to-event fracture prediction models among adults aged 50 years or older with clinically obtained DXA reports in 2 US health care systems. The development cohort was derived from NewYork-Presbyterian/Weill Cornell Medical Center and the external validation cohort from the Indiana Network for Patient Care. Predictors included demographics, lifestyle factors, prior fracture, comorbidities, medication exposures, osteoporosis treatment history, and DXA-derived T-scores extracted from radiology reports. The outcome was time from index DXA to first incident fragility fracture identified from structured diagnosis codes. We evaluated penalized Cox regression, random survival forest, gradient-boosting survival, and XGBoost survival models using 2 prespecified predictor settings and compared discrimination with clinically reported FRAX major osteoporotic fracture probabilities. The development cohort included 11,510 adults, of whom 858 sustained incident fragility fractures; the external validation cohort included 1,932 adults, of whom 180 sustained fractures. In internal validation, the expanded Cox model achieved a mean Harrell C-index of 0.779, compared with 0.653 for FRAX. In external validation, the corresponding Cox model achieved a Harrell C-index of 0.714, compared with 0.590 for FRAX; gradient-boosting survival had the highest external discrimination (0.725). EHR- and DXA-enhanced models showed better discrimination than clinically reported FRAX scores in this DXA-tested population, but calibration assessment, prospective evaluation, and implementation workflow assessment are needed before clinical use.

Toward Automated Detection of Documentation Inconsistencies in Electronic Health Records

Objective: To characterize the kinds of internal documentation inconsistencies a general-domain large language model (LLM) can surface from real-world discharge summaries, and to identify recurring failure modes that limit reliability at scale. Materials and Methods: We applied a two-stage LLM pipeline---open-ended candidate identification (Gemini 2.5 Pro) followed by context-grounded verification (Gemini 2.5 Flash)---to 3,000 randomly sampled MIMIC-IV-Note discharge summaries. A subset of the pipeline output was then reviewed manually by clinical experts. Results: Our pipeline surfaced 3,460 candidate inconsistencies, affecting 69.7% of admissions. Representative examples spanned demographics, allergies, procedures, diagnoses, laboratory, medications, and care-planning domains, with direct implications for clinical reasoning or patient safety. Expert review also revealed recurring failure modes that arise when verification requires temporal reasoning, evolving-diagnosis context, or knowledge of outpatient-prescribing conventions the model does not natively possess. Discussion: Detection is highly context-dependent: many flagged pairs require anchoring each statement to its source section and clinical domain, then assessing whether the conflict reflects a true contradiction or missing context. We propose a graded ontology spanning strict contradiction and ambiguity, with a schema characterizing each flagged case by category, section, domain, and inconsistency axis. Conclusion: This formative study establishes a methodological foundation and conceptual framework to guide subsequent validated, large-scale EHR-inconsistency analysis.

Autoregressive EHR Foundation Models with Multimodal Inputs

Autoregressive foundation models trained on tokenized electronic health records (EHRs) can support zero-shot clinical prediction, yet most operate on structured event codes alone, and do not incorporate multiple modalities in a principled way. We present a framework for conditioning such models on auxiliary clinical modalities, including ECG waveforms, chest X-ray images, and clinical notes, using modality-specific latent compression and gated cross-attention with temporal alignment. We investigate two key design choices: (1) how to compress long per-modality sequences (e.g., ECG time series) before they enter the multi-modal cross-attention. This feature may be essential to reduce compute overheads and may be beneficial for generalization; (2) how the choice of pretrained encoder for each modality impacts downstream performance. Through controlled ablations on MIMIC-IV, we show that the best latent-compression configurations outperforms both uncompressed cross-attention and mean pooling. Encoder choice has a clear within-modality effect, with stronger pretrained encoders consistently outperforming weaker alternatives. We further show that merely adding auxiliary modalities does not guarantee improvement on ICU mortality prediction over an EHR-only baseline. This implies that careful design of the fusion architecture and an appropriate evaluation in the clinical context are required.

SynPre-FL: Synthetic data-driven pretraining integrated Federated Learning training framework

Federated learning (FL) offers a promising approach to privacy-preserving clinical risk prediction, but its deployment remains limited by restricted data sharing, client heterogeneity, class imbalance, and the lack of realistic tabular electronic health record (EHR) benchmarks. Synthetic data generation may alleviate data scarcity, yet its integration with federated optimisation has received limited systematic study. We propose SynPre-FL, a unified framework combining high-fidelity synthetic EHR generation with synthetic-pretrained FL for robust prediction under non-IID conditions. A latent autoencoder-diffusion model generates privacy-preserving synthetic cohorts, which are used to warm-start federated training. This pretraining is followed by heterogeneity-aware optimisation using class-balanced local objectives, proximal regularisation, and adaptive server aggregation. Post-hoc calibration and federated-safe explainability support reliable and interpretable risk estimates. Experiments show that the synthetic generator preserves univariate, bivariate, and multivariate structure while protecting against membership-inference and reconstruction attacks. The generated data achieve strong downstream utility under TSTR, TRTS, and model-based evaluations. Across federated settings with 5, 10, and 15 heterogeneous clients, SynPre-FL consistently improves robustness and scalability over baseline methods, especially under severe non-IID fragmentation. Calibration improves probability reliability, while SHAP analysis produces stable and clinically coherent feature attributions across federation sizes. SynPre-FL therefore provides a practical and reproducible framework for combining synthetic data with FL to enable privacy-aware, interpretable, and robust clinical prediction from distributed tabular EHR data.

An unsupervised clustering analysis of breast cancer data derived from electronic health records enhanced through UMAP dimensionality reduction

Breast cancer is one of the most widespread types of cancer, affecting approximately 8 million women worldwide. Electronic health records of patients diagnosed with this disease can serve as valuable datasets for computational analyses, enabling the discovery of new insights about the pathology. Unsupervised clustering, in particular, can identify groups of patients with medically significant features, revealing data trends that might otherwise go unnoticed by medical doctors. In this study, we first applied the DBSCAN density-based clustering method to three independent datasets derived from electronic medical records of patients with mammary carcinoma. Subsequently, to enhance our results, we preceded the DBSCAN application with a dimensionality reduction phase using UMAP. We evaluated our clustering outcomes using three statistical indices (DBCV, DCSI, and DISCO). Our results confirm the effectiveness of combining UMAP with DBSCAN for clustering data derived from electronic health records, paving the way for the medical interpretation of the patient groups identified by our approach.

Using binary silver labels in electronic health records-based computable phenotyping algorithms

Gold-standard phenotype labels are often unavailable at scale in electronic health record (EHR) studies because they require manual chart review. Weakly supervised phenotyping methods instead use silver-standard labels, such as diagnosis-code counts, natural language processing (NLP) mentions, medication indicators, or laboratory thresholds. PheNorm is widely used for this purpose, but its original formulation was designed for count-valued silver labels and relies on log transformation, utilization normalization, and Gaussian mixture modeling. These steps are not directly suited to binary silver labels, which are common and may be highly informative. We propose Binary PheNorm, an extension that uses binary silver labels directly in the corruption-and-regression denoising step and produces a continuous phenotype score without EM calibration. We also consider a lasso-regularized version for high-dimensional EHR settings and combined models using both binary and count labels. In simulations, Binary PheNorm achieved strong discrimination using binary labels alone and often improved performance when combined with count labels. In anaphylaxis, AUC increased from 0.793 for an epinephrine-mention indicator to 0.891-0.892 after Binary PheNorm. In acute pancreatitis, AUC increased from 0.736 for a lipase-threshold indicator to 0.805-0.819. These results support Binary PheNorm as a practical weakly supervised approach when informative binary silver labels are available.

Optimizing Clinical Trial Protocols Using EHR-Derived Heterogeneous Treatment Effects

Traditional randomized trials often obscure clinically meaningful heterogeneity in treatment response by focusing on average effects. Leveraging real-world data to emulate clinical trials and estimate heterogeneous treatment effects (HTEs) offers a promising path toward more precise and efficient trial design. In this study, we emulate the DAPA-HF trial using electronic health records from the Mayo Clinic Cloud (MCC) to investigate whether HTE-guided stratification can identify patient subgroups with distinct treatment responses to dapagliflozin versus placebo in patients with heart failure with reduced ejection fraction. All-cause mortality was evaluated using Cox proportional hazards models, with HTEs estimated using a Meta-S learner and subgroups defined using a decision tree-based thresholding approach. In the overall cohort of the emulation, no significant treatment difference was observed (HR, 1.681; 95% CI, 0.828-3.413; p = 0.1507). However, compared with the overall emulated cohort, in which dapagliflozin showed no statistically significant survival benefit, HTE-driven stratification identified subgroups with significant and directionally distinct treatment effects. The beneficial (low-HTE) subgroup showed a significant survival benefit from dapagliflozin (HR = 0.203, 95% CI, 0.087-0.476, p = 0.0002), whereas the harmful (high-HTE) subgroup showed a significant harmful association with markedly increased mortality risk (HR = 6.680, 95% CI, 2.759-16.171, p < 0.0001). These findings indicate that HTE-guided stratification can uncover clinically meaningful beneficial and harmful treatment-effect patterns that are masked in the full-cohort emulation.

A Framework for Early Sepsis Prediction via Self-Supervised (JEPA) and Federated Representation Learning

Early sepsis prediction from electronic health records is challenged by irregular sampling, high missingness, and class imbalance. We systematically compare four modeling paradigms -- self-supervised Joint Embedding Predictive Architecture (JEPA) via masked latent prediction, self-supervised VICReg (variance-invariance-covariance regularization) with two-view augmentation, semi-supervised fine-tuning of a VICReg-pretrained encoder, and supervised Temporal Convolutional Network (TCN) -- alongside raw-feature baselines. All models share a common preprocessing pipeline of hourly binning with forward-fill imputation applied to 7 biomarkers selected via sparsity analysis from the MIMIC-III dataset. Our best model (JEPA + XGBoost + mean pooling) achieves AUPRC 0.636 at the time of onset (H0), approaching the SupMix benchmark (0.667) while using 83\% fewer biomarkers. The Tier 1 pipeline -- VICReg pretraining followed by semi-supervised fine-tuning and XGBoost -- achieves AUPRC 0.510 at H0, a 3.1$\times$ improvement over the raw-feature baseline (0.165) and a 7.6\% improvement over the end-to-end supervised TCN (0.474). Crucially, the fine-tuned VICReg encoder exhibits the most temporally persistent representations, degrading only 16.8\% from H0 to H10 compared to 47.5\% for supervised TCN and 65.3\% for JEPA, demonstrating that self-supervised pretraining with task-aware fine-tuning yields features that are both sharp near onset and robust across prediction horizons.

Multimodal Attention-based Deep Learning for Emergency Triage with Electronic Health Records

Accurate emergency triage decision is critical to avoid clinical deterioration, morbidity, and mortality. Machine learning-based triage system involves acquiring the main presenting complaint in text form and assessing vital signs in numerical data, enabling an automated and efficient analysis of patient information for timely and accurate prioritization of medical attention. However, modelling the intricacies of both data types requires a comprehensive understanding of the temporal structure and dependencies within the data. Thus, the aim of this study is to propose a multimodal deep learning architecture that can effectively handle both tabular and textual data. Furthermore, the proposed model exploits self-attention to to capture both local and global relationships between the features. A dataset consisting of 11,102 triage data collected from emergency department of Hospital Universiti Sains Malaysia is used for model development and validation. The proposed model demonstrated an increase of 1.95% in accuracy, 2.49% in F1-score, and 1.41% in ROC AUC compared to the baseline model. The experimental results demonstrated the potential of the proposed model in predicting triage decisions.

LLM4EHR: Aligning Clinical Time Series with Medical Event Sequences via Large Language Models

Recent research in clinical machine learning, focusing on outcome predictions in intensive care unit (ICU), has shifted from bespoke supervised models to foundation models, utilising modern representation learning methods. Here, foundation models are pre-trained on mixtures of complex clinical data modalities, useful for various downstream tasks. Existing works often utilise Electronic Health Records (EHR) to provide rich and diverse patient observations to train clinical foundation models. However, existing methods do not sufficiently explore the shared temporal structures between clinical events and time series (TS) observations recorded in EHRs. This limitation potentially leads to less robust and adaptive clinical foundation models, resulting in reduced performance on downstream tasks. To fully exploit this temporal structure, we propose LLM4EHR, a new clinical foundation model trained on ICU EHR data. Combining domain adapted large language models with a transformer TS encoder, we pre-trained LLM4EHR by temporally aligning the EHR events and TS. For this, we propose a regularised contrastive objective to learn robust EHR TS representations conditioned on EHR event embeddings produced by the domain adapted LLM. Supported by an ablation study, we find that learnt EHR TS embeddings from LLM4EHR improve performance on various downstream clinical tasks with competitive performance. Further, we empirically demonstrate that LLM4EHR learns transferable clinical TS embeddings that can be deployed to new cohorts via k-shot adaptation. These findings provide a step towards building more generalisable and performant clinical foundation models.