Electronic Health Records

Published medical case reports serve as a crucial medical information carrier, documenting discoveries in rare diseases, diagnostic methods, and innovative treatments. Despite the wealth of clinical knowledge in millions of case reports in the public medicine literature database (PubMed), accessing relevant information efficiently is hindered by the limitations of traditional keyword-based retrieval tools on unstructured and diverse case reports. To address the above issues, we introduce a comprehensive multimodal information system for case reports integrating structured clinical summaries of patients including medical images and biomedical named entities from 52949 open-access case reports published from 2000 to 2021. The multimodal essential information is organized in a well-structured medical ontology. Also, a powerful interface for searching and browsing case reports is designed to assist junior clinicians in retrieving cases effectively and improving the identification and diagnosis of rare diseases.

Longitudinal electronic health records (EHRs) capture years of patient history across notes, codes, labs, and procedures, and contain evidence needed to reason about likely clinical outcomes. However, comprehensive clinician review of these records is impractical, and LLM-based processing is costly and often unreliable, missing some relevant observations while hallucinating others. We therefore propose EviGen, a three-layer framework for verifiable clinical rationale generation that addresses these challenges. The first layer is a patient-conditioned retriever that uses learnable queries to find evidence predictive of, not just textually relevant to, a clinical outcome and ranks it by prediction attribution scores. The second layer is an LLM generator that consumes this ranked evidence as a scaffold to produce a clinical rationale grounded in the retrieved spans. The third layer is a process-supervised verifier that checks the generated rationale at the reasoning-step level, flagging unreliable claims. Across three medical prediction datasets, EviGen improves prediction performance and rationale faithfulness over full-context LLM and RAG baselines, and is preferred by clinical reviewers in a usability evaluation.

Methodological progress in artificial intelligence (AI) for electronic health records (EHRs) depends on our ability to determine which algorithms work better, and under which conditions. However, such progress is thought to be hindered by difficulties in reproducibility and in defining clinically meaningful evaluation tasks. We empirically study these barriers by re-implementing 12 historical and recent algorithms within a shared evaluation framework and evaluating them on two clinical datasets, MIMIC-IV and NWICU. We compare two complementary task families: expert-authored clinically meaningful tasks and generated tasks defined from randomly sampled event codes and prediction horizons. We ask whether relative algorithms comparisons transfer across task families and datasets, whether residual task heterogeneity contains useful methodological structure, and what a controlled comparison reveals about progress over the last decade. We find that aggregate pairwise comparisons transfer strongly across evaluation settings, including from randomly generated tasks to clinically meaningful tasks and across datasets. At the same time, clinically meaningful tasks exhibit greater task-method interaction, providing preliminary evidence that task properties can help explain when particular modeling choices are advantageous. Finally, newer algorithms do not consistently outperform earlier approaches: gradient-boosted trees remain highly competitive when paired with a modern, wide and sparse representation of the EHR. Together, these results suggest that useful methodological knowledge may require less task engineering than commonly assumed, while highlighting the importance of understanding the structured heterogeneity that remains across tasks and methods.

AI and large language models can recover clinically meaningful features from electronic health records (EHRs), but predictive usefulness does not establish admissibility for causal inference. We introduce information set emulation: an AI typed lift attaches source evidence, clinical and recording times, decision-time availability, representation version, proposed causal roles, and unresolved ambiguity to extracted features under a locked target trial. Causal certificates record auditable evidence for those roles. Features with unresolved downstream roles are routed to compatible reporting or separate analyses. Typed evidence defines an observational fiber of causal worlds consistent with the observed law. The locked scalar estimand maps this fiber to a compatible image whose squared Chebyshev radius equals the residual minimax mean squared error when the image is nonempty and compact. This classical identity provides a target-specific measure of information ambiguity. The contribution is its integration with a joint EHR observation map and an auditable certificate architecture. Under explicit exchangeability, positivity, and nuisance-consistency conditions, we give identification and cross-fitted augmented inverse probability weighted estimation, distinguishing empirical and population targets. An EHR compression-drift identity separates the roles of frame presence, treatment assignment, and outcome observation. Artificial simulations and a common-law finite-world example illustrate estimation failures and information-radius reduction. Synthetic Phase 0 notes demonstrate audit diagnostics; a separate role-specific analysis spread illustrates routing and is not an exact fiber radius. All experiments are synthetic. The framework specifies when reconstructed information can support a point claim and when compatible reporting is required.

Recent approaches to 30-day hospital readmission prediction rely on pre-trained language models applied to discharge summaries. Although these methods achieve strong performance, they depend on the availability of clinical notes, incur substantial computational costs, and yield representations that lack interpretability. We propose a knowledge-enriched feature representation that augments structured Electronic Health Record (EHR) data with four medical knowledge sources: disease ontology mapping, procedure classification, drug ingredient vocabulary, and organ system laboratory aggregation, without using clinical notes. Each feature dimension corresponds to a named clinical concept, yielding a sparse and interpretable patient representation. The approach is evaluated with six classifiers on a MIMIC-IV v2.2 cohort. Under 20-fold cross-validation, the best configuration achieves an AUROC of 0.743. This performance is comparable to that of previously reported methods on this dataset, including both those using only structured data and those incorporating clinical notes, while requiring considerably less computational cost. Interpretability analysis shows that demographics, organ system labs, drug ingredient features, and first-level ontology disease categories drive prediction, while deeper hierarchy levels contribute negligibly. These findings indicate that knowledge-enriched structured features offer a competitive and efficient alternative to embeddings from clinical notes for 30-day readmission prediction.

Memory-augmented and tool-using agents expose exact private values when remote LLMs process retrieved memory, tool actions, and intermediate observations. One-way masking limits direct exposure but removes values needed for trusted execution and can leak them through later observations. We propose Trustworthy Virtual Memory (TVM), a closed-loop runtime that keeps exact-value state local while presenting a protected view to the remote model. Within this single runtime, Rule-TVM replaces whole protected fields with locally recoverable handles, and Semantic-TVM instead replaces only sensitive spans predicted by a trusted local model, preserving surrounding task-relevant context. On Memory-EHR and Memory-RAP across two providers, span-level projection recovers most of the EHR utility lost under whole-field replacement (Task Success 84.17% vs. 52.33% on DeepSeek) while measured exposure stays low and workflows remain executable.

Electronic health record (EHR) foundation models trained on longitudinal patient trajectories have demonstrated strong performance across diverse clinical prediction tasks. However, their clinical reasoning capabilities remain constrained by next-token prediction on limited and incomplete EHR data. To address this, we propose a reinforcement learning (RL) fine-tuning framework that treats EHR foundation models as generative policies over patient trajectories. We formulate common clinical prediction problems (e.g., hospital readmission) as event-conditioned, time-windowed reasoning tasks. We then design time-aware, rollout-sensitive rewards to account for finite rollout lengths and temporally inconclusive outcomes. We find that RL fine-tuning consistently improves over pre-trained backbones and strong baselines. Notably, it enables smaller models to surpass larger pre-trained models in data-limited regimes and induces positive transfer across tasks. Further analysis shows that RL fine-tuned models generate trajectories with stronger structural and semantic alignment to ground truth and greater downstream utility.

Electronic health records (EHRs) may incompletely capture patient-reported factors associated with opioid use disorder (OUD). We evaluated whether survey data improve prediction of a first recorded OUD diagnosis among 267,747 All of Us participants with documented opioid exposure, including 15,287 OUD cases. We compared EHR-only and EHR+survey models across 6-, 12-, and 24-month look-back windows using logistic regression, random forest, XGBoost, LightGBM, multilayer perceptron, LSTM, GRU, and Transformer. Survey augmentation improved PR-AUC across all 24 model-window combinations by 0.0087-0.0505; the best 24-month LightGBM model improved from 0.6219 to 0.6603. Survey coverage increased with longer windows and differed by OUD status (24 months: 21.7% OUD-positive vs. 60.7% OUD-negative). Permutation analysis ranked survey features as the second most important information domain at 24 months in both evaluated models. Patient-reported data provide complementary predictive signals beyond structured EHRs while highlighting the importance of survey availability.

Clinical timelines support treatment-window analysis and leakage-free modeling, but discharge summaries often obscure chronology and structured EHR tables describe only part of the patient course. We present a UID-preserving framework that links each narrative event occurrence to its source span and retains that identity through text-only estimation, structured-evidence retrieval, timestamped source-row grounding, and joint revision. We also present GAVEL, an LLM judge that compares two UID-aligned timelines against the narrative and structured record, to augment prior matching and temporal assessments. Across six open-weight models and 40 mixed-critical-care summaries, the GLM 5.2 multimodal revision, as compared to its text-only variant, improved temporal agreement without reducing event recovery and performed competitively with clinician annotations, while other model revisions showed smaller gains and lower overall performance. Ablations showed that UIDs primarily preserve event retention, whereas source-row linkage supports temporal placement. Blinded human review upheld most GAVEL findings, and controlled adjudication favored multimodal over text-only GLM 5.2 but did not for DeepSeek V3.2. In developing the UID and judge pipeline, we are able to demonstrate 43% increased event recovery, a framework competitive with clinician annotations, and a system with occurrence-level provenance for both reconstruction and evaluation.

The application of large language models (LLMs) to personalized medical assistants has garnered growing interest. However, existing medical benchmarks largely rely on static question answering with pre-selected evidence, leaving unclear whether LLMs can make reliable clinical decisions from real longitudinal electronic health records (EHRs). To bridge this gap, we introduce ObGynLongBench, a rule-grounded long-context EHR benchmark for obstetric and gynecologic decision-making, comprising 1,500 clinical decision-point cases from 976 real pregnancy EHR histories and traceable rules. Each case is anchored to a patient, a pregnancy-timeline point, and a pre-decision information boundary, enabling Evidence-only, Visit-level EHR, and History-level EHR evaluation. Evaluating 17 LLMs reveals a substantial Evidence-to-EHR Gap: models perform well when evidence is directly provided, but accuracy drops when evidence must be extracted from same-day records or full pre-decision EHR histories. Further analyses identify evidence utilization as a key bottleneck: performance decreases with longer EHR contexts and more complex evidence requirements, and earlier failures often predict later failures within the same patient history. Finally, active-search agents perform best among EHR access strategies, highlighting patient-specific evidence utilization as a central challenge for reliable personalized medical assistants. Resources are available at https://github.com/xiangjun2003/ObgynLongbench.

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.

Electronic health-record interoperability is a boundary problem: legacy systems, generative models, terminology services, identity systems, and human reviewers may each expose rich internal states, while operational exchange requires a narrow shared interface of typed claims, bounded uncertainty, provenance, and explicit admission or abstention. This paper details a mathematical and engineering architecture for that interface. The organizing idea is the logit boundary: a discovery model may propose pre-threshold scores over a local categorical decision, but a deterministic judgment substrate decides whether the proposal is admissible, requires review, or must be quarantined before any Fast Healthcare Interoperability Resources (FHIR) transaction is constructed. The resulting Geometric Belief Interface (GBI) combines finite boundary semantics, local Dirichlet evidence, cellular-sheaf and mapping-cone diagnostics, advisory geometric audit charts, and a Decentralized Cryptographic Sheaf-Enclave (DCSE) protocol sketch for fail-closed deployment. The framework does not establish clinical truth, global representation alignment, or end-to-end safety; it defines certificate-producing checks at a model-to-system boundary. A companion frozen synthetic benchmark, GBI BoundaryBench v0.1, evaluated Qwen3-4B-Instruct-2507 on 256 held-out tasks across three evidence modes (768 canonical executions). All executions completed, but none produced an output accepted by the benchmark contract: 369 were rejected during safe parsing and 399 during schema validation, yielding zero coverage and deterministic quarantine. This empirical result is deliberately narrow - one 4B open-weight model under one frozen interface - and is reported as evidence about the admission boundary, not as a general claim about LLM capability or clinical safety. A Julia appendix verifies numerical certificates using standard libraries.

Emergency-department (ED) triage requires clinicians to rapidly identify patients who need immediate attention, determine who can safely wait, and prioritize limited clinical resources. At presentation, however, information may be limited to a chief complaint and initial vital signs. Clinically important details, including symptom onset and progression, associated symptoms, medical history, and medication use, are often obtained through focused conversation. Effective triage therefore requires clinicians to identify information gaps, ask appropriate follow-up questions, and update their assessment as new evidence becomes available. Most existing ED benchmarks evaluate acuity prediction from a fixed clinical snapshot. Although this formulation measures predictive performance after patient information has been assembled, it does not capture the interactive process through which triage-relevant evidence is elicited and interpreted. Existing medical dialogue datasets support the study of clinical communication, but dialogue statements are not always linked to temporally ordered events in the electronic health record (EHR). We introduce EHR2Dial-Triage, an agentic conversation-generation framework and benchmark grounded in MIMIC-IV-ED. The framework constructs triage conversations under explicit role-based and temporal information boundaries. Each accepted patient disclosure is linked to its supporting EHR event and the first dialogue turn at which it becomes available. EHR2Dial-Triage enables controlled evaluation of information elicitation, evidence use, five-level Emergency Severity Index prediction, and patient-facing communication across models and patient personas. It provides a structured setting for studying conversational triage as a dynamic process of clinical information acquisition, reasoning, and communication.

Large language models perform strongly on medical knowledge benchmarks, but reliable clinical deployment requires agents to conduct defensible investigations over heterogeneous, longitudinal records: determining what evidence is needed, retrieving and reconciling structured and free-text data, grounding conclusions in verifiable evidence, and deferring cases that cannot be resolved reliably. We introduce CliniCARE-Bench (Clinical Calibrated Audit of Medical Reasoning in EHR), a benchmark for retrospective clinical audit: 25 clinician-validated scenarios instantiated as 750 patient-specific cases over real-patient-derived MIMIC-IV data. Systems investigate each case through a governed, logged tool environment for record retrieval, computation, and policy access, and return one of four verdicts---Yes, No, Indeterminate: Lack of Data, or Indeterminate: Medically Ambiguous---the last two separating missing evidence from residual medical ambiguity. Beyond verdict accuracy, we score patient-evidence and policy grounding, process adherence, calibrated abstention, reliability, and efficiency against case-level reference verdicts produced by independent multi-model adjudication and calibrated against Clinical Board review. Every retrieval, computation, and report is replayable, so the investigation trace is inspectable and scorable. To our knowledge, CliniCARE-Bench is the first deployment-oriented clinical-agent benchmark to jointly evaluate real longitudinal EHR investigation, claim-level evidence grounding, governing-policy use, process adherence, and calibrated abstention within a common patient-level adjudication framework. Across 16 agentic systems, four-way accuracy spans 65.3-76.1%, but raw accuracy overstates investigation quality. Defect-free accuracy, which credits a verdict only when correct and free of prohibited shortcuts, is 4.8-14.8 points lower and reorders the leaderboard.

Electronic health record (EHR) feature engineering is a major bottleneck in clinical research and AI, accounting for 39-45% of data scientists' workload. This is especially pronounced in heart failure, which affects an estimated 6.7 million U.S. adults and requires integrating fragmented EHR data with disease-specific, guideline-based clinical reasoning. Existing rule-based and large language model (LLM)-based approaches offer only partial automation with limited maintainability and evidence traceability. We developed the Nimblemind Multi-Agent System (nMAS), an evidence-linked, rubric-grounded pipeline for automated heart-failure feature engineering, and evaluated it on 500 dummy patient records from nine EHR source tables. nMAS generated 132 structured and 70 rubric-scored aggregated features, verified for structural integrity, rubric compliance, and provenance, and audited by a restricted LLM. Adding the aggregated features improved held-out AUROC from 0.895 to 0.963 for HFrEF and 0.870 to 0.910 for HFpEF phenotyping, and an independent LLM-based rubric assessment of evidence support and methodological soundness scored the features at 81.5% of maximum points. These results demonstrate the feasibility of automated, auditable feature engineering for complex cardiovascular EHR data, though evaluation was limited to a single-institution cohort and external validation is needed.

Electrocardiography (ECG) is one of the most widely used non-invasive tools for diagnosing cardiovascular disease, but transforming multi-lead ECG recordings into reliable clinical reports remains challenging. Automating ECG report generation could reduce clinicians' interpretive workload, improve diagnostic efficiency, and expand access to cardiac assessment in underserved communities. Unlike image-based report-generation tasks, ECG interpretation requires the analysis of subtle temporal morphologies, followed by coherent diagnostic reasoning expressed in dense clinical terminology. Existing systems predominantly focus on classification, while current report-generation methods often produce outputs that remain inadequate for practical clinical use. To address these challenges, we propose ECG-LENS, an end-to-end ECG report-generation framework that jointly integrates multi-lead signal modeling, diagnosis-aware representations, and clinically grounded text generation. ECG-LENS combines lead-wise encoders that preserve localized waveform morphology with a global encoder that captures inter-lead dependencies. To guide report generation, we fuse signal representations with clinically enriched textual prompts that condition a GPT-2 decoder. We further introduce an ECG-specific report-preprocessing strategy that helps the model focus on clinically meaningful findings. Finally, because lexical metrics may under- or overestimate report quality, we propose F1-ECGBERT, a BERT-based, ECG-specific metric that measures agreement between diagnostic labels extracted from generated and reference reports. In-domain experiments on PTB-XL and cross-domain evaluation on MIMIC-IV-ECG show that ECG-LENS consistently outperforms state-of-the-art methods, with absolute gains of 4.0%, 6.3%, and 11.5% in METEOR, ROUGE-L, and F1-ECGBERT, respectively, over the strongest baselines.

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.

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.

Feature selection is a critical step in electronic health record (EHR)-based predictive modeling, where input variables are often high-dimensional, sparse, noisy, and redundant. Large feature sets not only increase computational burden and overfitting risk, but also make model interpretation difficult, leading to limited usefulness in clinical settings. In this study, we focus on diagnosis-related features and compare five feature selection paradigms for opioid use disorder (OUD) prediction: recurrence enrichment, NTK-motivated early gradient sensitivity, LightGBM-SHAP, Elastic Net, and large language model (LLM)-guided semantic selection. We use a unified preprocessing and evaluation framework and assess each method by downstream predictive performance, resampling stability, and representation of infrequent diagnosis codes. Our results demonstrate that performance improves with larger feature budgets with diminishing returns beyond a moderate size. NTK sensitivity provides the best overall balance of accuracy and stability, and LLM-guided selection contributes complementary clinically meaningful signals despite lower standalone performance.

Emergency triage requires reliable decisions within a short time period. However, the available electronic health record (EHR) data, including structured data and clinical text, are often incomplete, unreliable, and inconsistent. This makes machine learning (ML)-based triage prediction more challenging, as existing ML models typically rely on complete and reliable EHR data to accurately predict patients' acuity levels. To address this, we propose confidence- and reliability-aware selective triage (CRS-Triage) to predict patients' acuity levels with a confidence score. By comparing the confidence score with a predefined threshold, CRS-Triage can selectively determine whether the model should make the decision or defer the case. Specifically, CRS-Triage separately evaluates the reliability of structured data and clinical text and then jointly considers the consistency between the two modalities to estimate the confidence of each prediction. Moreover, to reduce the risk of missing high-acuity patients, namely under-triage, CRS-Triage prefers to assign patients slightly higher acuity levels, namely over-triage, by penalizing under-triage errors. Experiments on the MIMIC-IV-ED dataset show that CRS-Triage achieves strong predictive performance. It also provides a better risk-coverage trade-off and remains reliable when the available EHR data are incomplete, degraded, or inconsistent across modalities.

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.

Clinic notes and structured electronic health record (EHR) medication history often contain different medication information. Same-visit disagreement between these sources may result from note-side normalization errors, differences in terminology or timing, or actual differences in documentation. We developed a note-grounded approach that uses large language model (LLM) assisted reference construction, targeted and random human review, deterministic medication normalization, and semantic and temporal comparisons with structured medication history. We evaluated all normalization results on a patient-level held-out test set to limit adaptation to the study cohort. On 5,403 held-out mention rows, exact canonical agreement improved from 0.7226 with surface-exact matching to 0.8429 after lexical cleanup and curated alias mapping. In a random audit of previously unaudited rows, canonical-label agreement was 0.9210 among evaluable valid medication mentions, whereas treatment-action attribution was lower at 0.5326. In the full-cohort characterization analysis, only 16.44% of note-derived rows had same-visit exact overlap with structured medication history, but 55.17% had same-visit semantic overlap, 90.34% had same-visit or +/-30-day overlap, and only 3.97% remained in the strict no-structured-overlap bucket under broad project-level mapping. An ontology-backed sensitivity analysis further showed that held-out strict Observational Medical Outcomes Partnership (OMOP)-backed no-overlap fell from 43.99% to 36.68% after a development-derived alias supplement. These results show that note-to-structured-medication mismatch can arise from normalization errors, differences in terminology, and differences in documentation timing.

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.

Clinical data-science agents must transform heterogeneous longitudinal records into auditable analyses, yet existing benchmarks largely isolate medical question answering, structured-table reasoning, or generic scientific repositories. We introduce CLINLENS, a benchmark of 200 executable tasks over five linked MIMIC resources spanning structured electronic health records, notes, electrocardiograms, chest radiographs, and echocardiograms. A 4 x 5 taxonomy crosses four patient-time scopes with five analysis capabilities. Program-first reverse synthesis pairs each bounded semi-raw package with an evaluator-private reference workflow and checks required artifacts, cohort and temporal semantics, and the final answer. On a fixed 126-task suite, the strongest of 24 standardized model-scaffold configurations achieves 56.3% scope-macro STRICTPASS despite 100% EXECSUCCESS. For reference, a separately configured coding agent solves 83 of 126 tasks, while five biomedical systems adapted to GPT-4o-mini reach at most 2.9% scope-macro STRICTPASS. These results expose a substantial gap between runnable submissions and correct clinical analyses.

Medical world models offer a framework for extending medical artificial intelligence beyond static prediction by representing evolving patient states and modelling how they change over time and in response to clinical interventions. This Review defines the conceptual boundaries, technical foundations, application domains, and evidence requirements of the field through a structured narrative synthesis with reproducible evidence mapping. We screened 1,455 unique records and assembled a corpus of 98 sources, including 14 studies that met a strict empirical definition of a medical world model. The field is organised around four capabilities: patient state representation, temporal dynamics modelling, intervention-conditioned simulation, and clinician-supervised planning. Evidence spans medical imaging, longitudinal electronic health records, treatment response modelling, physiological and multimodal state modelling, ultrasound and surgical interaction, and population and health-system simulation; clinical digital twins are treated as a cross-cutting integration framework. Current studies provide early evidence of technical feasibility for trajectory forecasting and comparison of candidate interventions, but most remain retrospective, task-specific, or preclinical. The evidence base is further limited by incomplete longitudinal intervention data, inconsistent action semantics, limited causal identifiability, long-horizon error accumulation, inadequate uncertainty estimation, and limited external validation. Clinical translation will therefore depend on precise intervention representations, robust causal and mechanistic grounding, calibrated trajectory-level uncertainty, safety-constrained planning, and prospective multicentre validation against clinically meaningful endpoints.

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.

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 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.

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.

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.

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.

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.

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.

Generative modeling of longitudinal Electronic Health Records is increasingly important for privacy-preserving research, yet standard autoregressive models tend to underrepresent the co-occurrence structure of tail events (i.e., diseases, symptoms), reducing the fidelity and faithfulness of generated data for rare subpopulations. To this end, we propose AdaPCLA framework, which enables generative models to adaptively fit and generate EHR data through a data distribution-aware training strategy; this is achieved by internalizing data knowledge parameters by simulated annealing training. It also supports training-free adaptation to a diverse clinical population for generation through zero-shot distribution control. Moreover, our theoretical analysis characterizes rare-code logit updates through the label-wise empirical NTK and derives a prior-internalization bound for how annealing speed and NTK conditioning affect retained prior signals. Experiments on real-world data show that AdaPCLA achieves consistent gains in tail plausibility, downstream utility, and zero-shot control; in particular, it improves TailPairSeen over HALO by 114.2% on MIMIC-III and 65.1% on MIMIC-IV, outperforms GPT-style generation by 3.5% F1 for zero-shot cross-population adaptation.

We study interaction-aware mixture-of-experts for post-stroke rigidity prediction using multi-level views of structured health records. Despite minimal performance gains, routing attribution reveals systematic importance differences across views, underscoring view construction as key to interpretability.

Survival models can model time-to-event outcomes using partially observed data. They are widely used in clinical prediction, including cancer risk, disease progression, treatment response, and mortality. Recent models often rely on rich inputs collected at a specific clinical encounter, such as medical images, laboratory tests, electronic health record snapshots, or sensor measurements. In large retrospective datasets, these inputs are usually collected over many calendar years. As a result, they may contain clues about when they were acquired through changes in devices, protocols, documentation, patient mix, or clinical practice. This creates a potential failure mode when outcomes are observed only up to a fixed study end date. More recent records necessarily have less potential follow-up than older records. A model that can infer the record date from the input may therefore learn to predict how much follow-up was available rather than the patient's true risk of experiencing the event. We call this failure mode administrative-cutoff leakage. In this paper, we characterize when this leakage can occur, distinguish it from classical informative censoring and genuine temporal changes in risk, and propose practical ways to detect it. In simulations, we show that administrative-cutoff leakage can inflate fixed-horizon AUC and can also affect Harrell's C-index under realistic follow-up patterns. We then demonstrate the same behavior in a real mammography cohort. These results motivate a simple design principle for survival prediction: for an n-year prediction task, the dataset should provide at least n years of potential follow-up after the latest input date. Otherwise, the models may be subject to bias induced by administrative-cutoff leakage.

Electronic health record (EHR) data are inherently multimodal, and leveraging multiple modalities can improve predictive performance. However, most existing approaches rely on deep fusion, which obscures how individual modalities contribute to predictions and limits the interpretability of multimodal reasoning. We propose an explicit multimodal routing framework for clinical prediction that enables interpretable, robust, and auditable reasoning across three EHR modalities: structured longitudinal variables (L), clinical notes (N), and chest X-rays (I). Our model constructs discrete unimodal, directional bimodal, and trimodal routes to capture both individual modality signals and asymmetric cross-modal interactions. To audit multimodal reasoning and assess robustness, we introduce inference-time route masking, which simulates missing modalities and reweights the remaining routes without retraining. We analyze changes in performance and routing weights under these scenarios to understand model decision-making. We evaluate our framework on multi-label phenotype prediction (K = 25) and binary ICU mortality prediction using trimodal patient stays from MIMIC-IV, revealing systematic differences in modality reliance across clinical condition groups. Overall, our framework offers a transparent, auditable, and practical approach to multimodal clinical prediction, providing interpretability, robustness, and insights into how different data sources drive model decisions.

Motivation: Rare disease (RD) diagnosis is frequently delayed due to the similarities in symptoms to common disease variants. Machine Learning Algorithms applied to Electronic Health Records show promise for accelerating the diagnosis; however, legal and privacy concerns pose significant barriers. To address these issues, Synthetic Data Generation is an alternative method for obtaining Electronic Health Records and can be applied with any Machine Learning algorithm for benchmarking and development purposes. Despite the availability of Synthetic Data Generation algorithms, support for generating a subset of patients that differ in a definable degree from the majority to simulate patients with RD is often lacking. Results: We present SYNRARE, a graphical user interface based on the Synthea framework that enables easier modification and generation of synthetic Electronic Health Records of RD patients, which differ only to a definable degree from patients with common diseases, thereby enabling the benchmarking and testing of algorithms under controlled technical conditions. SYNRARE enables researchers to rapidly benchmark their Machine Learning algorithms across any scenario. Availability and implementation: SYNRARE, including detailed instructions for installing, is available at https://gitlab.sdu.dk/screen4care/synrare.

Electrocardiography (ECG) is one of the most widely used tests for diagnosing cardiovascular disease. Yet several remote clinics still utilize paper ECG printouts for their analysis due to limited connectivity and computational capacity. As a result, vast numbers of physical ECGs obtained in remote areas still remain incapable of being accessed by contemporary artificial-intelligence (AI)-based decision support as they require high computational resources or strong high-speed internet connectivity. This causes several cases where conditions like acute coronary occlusion (ACS) is overlooked and reperfusion therapy delayed. Although prior work has tackled digitization and diagnosis separately, and utilized advanced AI models for them, there still remains a lack of a compute-light, on-device framework that reconstructs paper ECGs at high fidelity, while accurately supporting multiple clinically relevant endpoints. We address this need with an end-to-end lightweight on-device digitization-to-diagnosis pipeline that converts a smartphone photo or scan of a paper ECG into a calibrated 12-lead signal and screens for Myocardial Infarction (MI) pathologies, with SHapley Additive exPlanations (SHAP) to support interpretability. Trained and evaluated on 21,799 ECGs from the PTB-XL dataset and further validated on hospital-acquired ECG-Matrix dataset, the complete system runs in <30 s per ECG on CPU-only resources, achieving 95.51% accuracy (F1 = 0.9519) for MI detection on PTB-XL and 88.89% accuracy (F1 = 0.8862) for OMI detection on ECG-Matrix. This work showcases that legacy paper records can be reliably democratized in any part of the world, providing a scalable decision support when digital ECG export, connectivity, or high-end compute are unavailable

A shared electrocardiogram (ECG) is itself a biometric fingerprint that can re-identify a patient and reveal personal information. Recent ECG anonymizers transform the signal before sharing to reduce privacy leakage. However, existing methods still face a privacy--utility trade-off, in which preserving privacy often compromises utility while preserving utility reveals personal information. We propose \emph{REAN} (\emph{RE}construction-aware ECG \emph{AN}onymizer), a raw ECG signal anonymizer, to address this privacy--utility trade-off. REAN reconstructs the signal using a 1-D U-Net trained with losses from frozen privacy and utility classifiers to reduce privacy leakage while preserving utility. The privacy and utility gradients are near-orthogonal ($\approx$93.8$^\circ$), so reducing privacy leakage leaves utility almost unchanged. On four public PhysioNet databases, REAN achieves the strongest privacy--utility balance among raw ECG signal baselines. It drives re-identification to chance (0.96$\to$0.00), keeps arrhythmia macro-AUROC at the clean level (Clean 0.9982 vs.\ REAN 0.9991), and maintains re-identification protection under unseen privacy-classifier architectures.

Background: Disease severity is a multidimensional construct difficult to capture with rule-based approaches in Electronic Healthcare Records (EHR). Agentic large language model (LLM) systems could synthesise clinical evidence and reason over EHRs, but remain unevaluated for this task. Methods: MOSAIC is a two-phase agentic LLM framework for severity phenotyping, using type 2 diabetes (T2D) as a proof-of-concept. MOSAIC was evaluated on a synthetic cohort (SyntheticMass; open-weight N = 4,886; closed-weight N = 200) against three algorithmic ground truths (DCSI, DiSSCo, Cooper) and against all-cause mortality and incident complications. Open-weight (locally deployable) and proprietary pipelines were also compared. Results: The generated framework spanned domains absent from the comparators, including biomarker-based glycaemic staging, beta-cell function, and social determinants of health. Open-weight MOSAIC matched the proprietary pipeline (closed- vs open-weight weighted kappa = 0.773) and reached moderate agreement with Cooper (kappa = 0.597) and DCSI (kappa = 0.534) and fair agreement with DiSSCo (kappa = 0.320). Agent-based (Type 1) tiers showed significant separation of all-cause mortality (log-rank p < 0.001; crude hazard ratios 1.6-2.4 for non-Baseline tiers), with non-monotonic separation at the upper tiers, and an inverse gradient for incident complications (log-rank p < 0.001) consistent with depletion of susceptibles. Agentic classification also diverged from deterministic execution of the same rubric (MOSAIC Frozen; kappa = 0.428), indicating reasoning beyond fixed rules. Conclusion: MOSAIC shows agentic LLM systems can generate and apply clinically meaningful severity phenotypes from structured EHR data in T2D. Extending it to other diseases with similarly multidimensional severity warrants further research.

Complete digital 12-lead electrocardiograms (ECGs) are essential for AI-enabled cardiovascular assessment, yet many clinical ECG records, particularly those digitized from ECG images, remain incomplete because of short display formats, incomplete waveform digitization, lead loss, or signal corruption. We developed ImputeECG, a mask-conditioned one-dimensional Transformer autoencoder that completes 12-lead, 10-s ECGs while retaining all observed samples. The model was trained on PTB-XL and evaluated on PTB-XL and CPSC2018 under simulated incomplete settings, with additional real-world validation in a 43,633-record Kailuan clinical cohort after ECG image digitization. Metrics were computed over originally missing regions, with analyses of morphology and downstream diagnostic utility. On PTB-XL, ImputeECG reduced missing-region MAE by 41.7-51.0% and MSE by 54.0-63.7% versus the strongest baseline, with lower errors in R-peak timing, RR interval, QRS duration, QT interval, and P-wave, QRS-complex, and T-wave reconstruction. On CPSC2018, ImputeECG reduced MAE by 49.7-51.9%, supporting external generalization. In downstream multi-label classification, ImputeECG restored performance to 92.28% AUROC and 33.88% AUPRC in the most incomplete PTB-XL setting, approaching complete-ECG performance. On CPSC2018, completed ECGs achieved 94.75-95.89% AUROC and 78.83-81.86% AUPRC across settings. In Kailuan, ECG completion improved zero-shot sex prediction AUROC from 82.6% to 85.8% and reduced age prediction MAE from 10.72 to 9.87 years after image-based ECG digitization. These findings support ECG completion as a practical strategy for converting incomplete ECG records into AI-ready 12-lead, 10-s digital signals and extending the usable scope of ECG archives for digital cardiac assessment.

Deploying Large Language Models (LLMs) in high-stakes clinical settings remains limited by structural hallucinations, weak deterministic reasoning over tabular patient data, and omissions in vector retrieval. This paper presents the architecture and validation of Medi-Gemma, a Clinical Decision Support System (CDSS) for wound pathology triage and workflow automation. The platform introduces a decoupled framework that separates clinical perception from data orchestration while preserving traceable reasoning. Medi-Gemma uses a multi-stage pipeline coordinated by a centralized ClinicalOrchestrator. Data requests are handled without generative inference by a DataManager that cleans unstructured Electronic Medical Record (EMR) files through type coercion. Natural language queries are processed by a hierarchical IntentRouter, which routes requests to deterministic analytics paths executed by a PandasQueryEngine or to patient-specific reasoning managed by a ClinicalRAGEngine using a CPU-optimized vector store. A key contribution is the Ground Truth Injection Module, which intercepts patient-specific queries, extracts numeric identification tokens, queries the structured dataframe via Pandas, retrieves the latest validated clinical state, and embeds this snapshot as an overriding context block in the LLM prompt before generation. Safety compliance is enforced by a deterministic ProtocolManager that maps clinical terminology to fixed evidence-based risk pathways, while a SafetyVerifier phrase filter prevents output rule violations. Validation shows that this architecture eliminates semantic context drift, prevents database compilation crashes, and improves factual adherence to backend clinical repositories. These results support Medi-Gemma as a safer pattern for LLM-based clinical decision support where structured data fidelity, retrieval grounding, and deterministic safeguards are essential.

Extracting textual information from scanned medical documents, such as external laboratory reports and manually filled forms, has been a major challenge in modern electronic health records (EHRs). Recent advancements in vision language models (VLMs) have shown great promise over traditional OCR tools. However, at this point, most clinical OCR studies were conducted on private, institutional data. To our knowledge, there are few publicly available datasets for evaluating OCR models in the clinical domain. Furthermore, common scanning artifacts that undermine OCR performance are not reflected in those datasets, leaving a systematic evaluation unfeasible. Therefore, we release a publicly available, realistic-looking OCR benchmark dataset, ClinOCR-Bench, with 384 scanned images across 6 subsets: Normal, Handwriting, Poor Quality, Rotation, Tables, and Mix-artifacts. ClinOCR-Bench features: 1) diverse document types and layouts, 2) full coverage of common EHR scan artifacts, 3) protected health information-free, 4) template-aware train/test split, and 5) adequate sample size for OCR benchmarking. Baseline OCR performance was evaluated using state-of-the-art open-weight and proprietary VLMs. The dataset and documentation are available on GitHub (https://github.com/ClinOCR-Bench/ClinOCR-Bench).

How do we encode numeric values in transformer-based sequence processing, particularly in electronic health record (EHR) data? We systematically compare discrete, continuous, and hybrid value encoding strategies using synthetic arithmetic tasks embedded within real-world EHR data, as well as real-world clinical prediction tasks. Our study reveals trade-offs between numeric precision, optimisation stability, and architectural flexibility. We find that approaches that explicitly model value-concept interactions perform best on precision-sensitive arithmetic tasks when architectural constraints permit. Hybrid token-based approaches that retain numeric values but apply binning prior to projection provide a more robust and broadly applicable alternative, with the optimal number of bins following a simple empirically derived power-law in dataset size. Across tasks, models consistently exhibit reliable "good enough" numeric computation rather than exact arithmetic, while clinical gains from incorporating laboratory values are task-dependent. This suggests that robustness and deployability often outweigh maximal numeric precision in practice, motivating hybrid token-based approaches as a practical default.

Objective: ICD codes are central to reimbursement, research, and population health surveillance, yet automated coding systems often struggle to integrate diagnostic signals from both clinical narratives and structured electronic health record (EHR) variables. We evaluated whether frozen medical large language model (LLM) representations can serve as a shared embedding space for multimodal primary diagnosis category prediction. Materials and Methods: We constructed a MIMIC-IV cohort of 13,645 admissions from the 10 most frequent primary ICD-10 codes, consolidated into seven categories. Structured variables were serialized into clinical narratives and combined with leakage-pruned discharge notes. Using a frozen MedFound-Llama3-8B-finetuned backbone, we extracted hidden states from five transformer layers and trained linear probes for structured-only, unstructured-only, and combined inputs, comparing against XGBoost and information-matched PLM-ICD baselines and evaluating MIMIC-III adaptation with a compact bottleneck adapter. Results: The combined probe performed best on MIMIC-IV (87.69% strict; 91.45% medical accuracy), exceeding both single-modality probes and baselines. The structured-only probe outperformed its standard baseline by 6.19 points in medical accuracy. Diagnostic information became increasingly linearly separable in deeper layers, and a 2M-parameter adapter restored cross-dataset transfer to MIMIC-III using only 5% of target labels. Discussion: LLM embeddings can unify structured and narrative EHR information for multimodal diagnosis prediction, supporting efficient reuse of clinical representations across modalities and datasets through a small representation-level module. Conclusion: Multimodal probing of frozen medical LLM representations provides a practical approach for studying EHR modalities and adapting clinical representations across datasets.

Most electronic health record (EHR) foundation models encode clinical events as discrete event tokens from a fixed vocabulary and therefore cannot directly represent events containing unseen concepts or new combinations of concepts and attributes such as numeric values. This limits transfer across institutions and even across deployment pipelines within the same institution. We introduce PORTER, a language-grounded structured EHR foundation model that decouples event representation from this fixed vocabulary. PORTER represents events through their descriptions using a frozen text encoder, integrates numeric values through a dedicated pathway, and learns clinical dynamics over patient timelines with an autoregressively pretrained temporal backbone. Across 74 clinical prediction tasks at a pediatric hospital, PORTER matched the mean AUROC of a fixed-vocabulary model with the same temporal backbone and pretraining objective. When the same patient timelines were rendered using event descriptions not seen during pretraining, PORTER transferred without retraining or vocabulary mapping, recovering 97.1% of the mean AUROC of a model trained directly on the target vocabulary. When transferred to MIMIC, PORTER outperformed the fixed-vocabulary model, which dropped 69% of events because their tokens were unseen. Mechanistic analyses showed cross-vocabulary transfer tracked preservation of patient-level representation geometry rather than the scale of the text encoder, and the numeric pathway improved sensitivity to magnitude without disrupting clinical concept identity. PORTER also achieved higher AUROC than a task-specific text serialization comparator, at 329-fold lower amortized compute. PORTER is a step toward vocabulary-independent EHR foundation models that reduce the need for vocabulary harmonization while preserving in-domain performance and enabling efficient cross-task reuse.

We introduce VISTA Architect, a database-oriented AI architecture for integrating large language models (LLMs) with longitudinal electronic health records (EHRs). At ingestion, it transforms complex clinical documentation into a persistent, provenance-linked knowledge graph, eliminating repeated reprocessing of raw records at query time. The architecture has two layers: a source-faithful MEDS Graph preserving granular EHR structure with full provenance, and a clinically abstracted Timeline Object Architecture (TOA) that uses graph-guided LLM extraction to synthesize a concise timeline of deduplicated, temporally coherent clinical events. This addresses key limitations of direct long-context prompting and retrieval-augmented generation (RAG), which often miss temporal relationships and incur high cost and latency from repeated raw-text processing. By precomputing clinical synthesis once, downstream queries access an organized patient state and traverse to source documentation only when detailed verification is needed. We demonstrate the system in multidisciplinary thoracic oncology tumor boards at Stanford Medicine, where precise reconstruction of patient histories is critical. Across 1,180 patients, VISTA Architect achieved 96.4% accuracy (mean 9.75/10) on 15 tumor board-salient variables (17,700 evaluations; 95% CI 96.1-96.7%), surpassing a matched BM25 RAG baseline and recent benchmarks for LLM-based clinical extraction. An agentic interface reduced preparation for a 30-patient held-out cohort to about 2.2 minutes without sacrificing accuracy. While configured here for thoracic oncology, the modular design adapts to other specialties through customizable event definitions, episode structures, and agentic tools; validation beyond thoracic oncology remains future work.

Pulmonary embolism (PE) is a high risk cardiopulmonary condition whose management requires both timely diagnosis and reliable assessment of future clinical risk. Because PE care routinely combines computed tomography pulmonary angiography (CTPA), radiology interpretation, and longitudinal electronic health record (EHR) evidence, it provides a clinically meaningful setting for evaluating compact multimodal language models. In this work, we build a benchmark using efficient multimodal large language models (MLLMs) on INSPECT, a multimodal PE dataset containing 23,248 CTPA studies from 19,402 patients. We formulate eight diagnostic and prognostic tasks as structured clinical question answering problems and evaluate on typical efficient MLLMs under CTPA-Only, EHR-Only, and CTPA+EHR settings with zero-shot and few-shot prompting. Results show that Gemma4 E4B and Gemma4 E2B perform more strongly when EHR evidence is available, especially under CTPA+EHR input. Task level analysis further shows that PE diagnosis achieves higher performance than prognostic tasks, particularly readmission prediction. These observations suggest that compact multimodal models have the great potential in early stage PE risk detection and explanation.

Foundation models have achieved remarkable performance across medical question answering, imaging, and electronic health record (EHR) tasks, yet reliable clinical deployment remains challenging due to limited interpretability, vulnerability to distribution shift, and weak alignment with clinician reasoning. We argue that these limitations arise because existing approaches prioritize representation learning while treating patient comparison as an emergent property rather than a primary source of clinical evidence. To address this gap, we propose CAFM, a Cohort-Anchored Foundation Model framework that elevates patient cohorts to a first-class object throughout the learning pipeline. The framework consists of four stages: deviation-aware data curation, cohort-conditioned pretraining, multimodal cohort alignment, and clinician-in-the-loop refinement. Together, these stages improve data quality, organize representations around clinically meaningful cohort structure, preserve modality-specific relationships, and support auditable clinical decision-making. The framework is compositional and can augment existing EHR foundation models without modifying their underlying encoders. We illustrate CAFM through four clinical case studies spanning acute kidney injury prediction, cardiovascular risk stratification from electrocardiograms, optic neuropathy triage from orbital imaging, and electroretinogram-grounded report generation. We further present five empirically testable hypotheses and identify open challenges in data quality, irregular temporality, multimodal learning, distribution shift, and evaluation beyond predictive accuracy. We argue that explicitly anchoring foundation models to patient cohorts provides a principled path toward trustworthy clinical AI.

Real-world clinical decision support requires reasoning over heterogeneous and longitudinal patient information rather than answering isolated medical questions. However, current medical large language models and retrieval-augmented generation systems often rely on single-step prompting or retrieval, which can be fragile when clinical evidence is distributed across long electronic health records, medical images, sensor streams, guidelines, and referral constraints. This paper proposes MedRLM, a Recursive Multimodal Health Intelligence framework for long-context clinical reasoning, sensor-guided screening, and community-to-tertiary referral support. Instead of compressing all patient information into one prompt, MedRLM treats the patient case as an external clinical environment that can be recursively inspected, decomposed, retrieved, verified, and synthesized. The framework coordinates specialized agents for clinical text, longitudinal EHR, medical imaging, physiological sensor signals, guideline retrieval, uncertainty auditing, and referral planning. It further introduces a Clinical Evidence Graph Memory to connect patient-specific observations with retrieved evidence, standardized definitions, sensor-derived biomarkers, and referral criteria. A sensor-guided recursive triggering mechanism activates deeper reasoning when abnormal physiological or behavioral patterns are detected, while uncertainty-gated refinement supports clinician review for high-risk or low-confidence cases. We also outline a real-data evaluation design using public and credentialed clinical datasets spanning EHR, radiology, ECG, ICU time series, and referral-proxy outcomes. MedRLM aims to move medical AI from static question answering toward auditable, multimodal, and workflow-aware clinical decision support.

Clinical NLP increasingly relies on electronic health record (EHR) data to detect suicidal behaviors, treating clinical documentation as more reliable ground truth than social media. We argue that this framing obscures how EHR-based suicidality datasets encode a particular operationalization of suicidality, shaped by who authors the data, how episodes are bounded, and how ambiguity is resolved. We ground this argument in a case study of the ScAN dataset, built over MIMIC-III clinical notes. We show how governance constraints, ICD-based cohort selection, single-annotator labeling, and hospital-stay-level aggregation produce labels that reflect clinician-documented judgments, treat suicidality as a bounded episode, and assume that intent can be reliably inferred from documentation. A linguistic analysis demonstrates that identical labels subsume heterogeneous clinical framings differing in temporality, negation, and uncertainty. We argue that clinical NLP should examine the assumptions embedded in suicidality datasets before interpreting their labels as ground truth.

Traditional comorbidity scores (e.g., Charlson and Elixhauser) are widely used for risk adjustment and patient stratification, but they have two key limitations: (i) they are largely mortality-centric and do not align well with other clinical outcomes, and (ii) their linear, rule-based structure cannot capture nonlinear, outcome-specific risk relationships. We propose a Machine-Learned Comorbidity Index (MLCI) that maps diagnosis codes to a single scalar by maximizing the normalized Hilbert-Schmidt Independence Criterion (nHSIC) between the learned score and multiple clinical outcomes. MLCI captures nonlinear risk-outcome dependence and is supported by a theory that characterizes when a unified, informative admission-level ordering can be achieved across outcomes. Empirical results on multiple benchmark electronic health record (EHR) datasets show that MLCI outperforms strong baselines across multiple evaluation metrics.

Understanding how a prediction model will perform in a new environment before deployment is essential to preventing harm when algorithms inform decision-making. Two common sources of model performance degradation are (i) covariate shift, where the target covariate distribution differs from the source, and (ii) selective labels, where the observability of outcomes depends on historical decisions. We study pre-deployment model evaluation under the joint presence of covariate shift and labeling of outcomes selectively based on observed features. In particular, we present a double machine learning procedure for estimating the target risk of an arbitrary black-box prediction model under a general loss function. We show identification of this estimand under standard assumptions and derive a bias-corrected estimator based on the influence function of the target risk. Finally, we evaluate our estimator through experiments using the eICU electronic health records database, showing that it tracks the true target risk more accurately than methods that address either selective labels or covariate shift alone, as well as baselines that combine standard plug-in approaches.

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.

We propose a spectral-based, unsupervised representation learning framework to derive low-dimensional embeddings for clinical concepts and patients in rare disease cohorts from electronic health records, where data are high-dimensional but sample sizes are limited. To overcome this challenge, we incorporate a knowledge matrix extracted from a broader population that shares a partially overlapping subspace with the rare-disease cohort. Our method departs from existing approaches by relaxing restrictive one-to-one signal-alignment assumptions between the latent data matrix and knowledge matrix, allowing more flexible and realistic forms of structured sharing. We introduce a novel two-step spectral embedding procedure: first, we identify and remove irrelevant components from the knowledge matrix; then, we apply a projection-based method to separately recover shared and heterogeneous components. Simulations and an analysis of a real-world multiple sclerosis cohort show that the proposed method outperforms competing approaches, particularly in challenging scenarios where shared signals are weak and only partially aligned, as is common in rare-disease data.

Synthetic healthcare data are widely proposed as privacy-preserving substitutes for real patient data, yet their evaluation remains dominated by statistical similarity and predictive performance that do not reflect clinical validity. We introduce a multi-dimensional evaluation framework grounded in epidemiology, assessing descriptive fidelity, clinical utility, and structural validity, corresponding to descriptive, predictive, and causal questions. We evaluate four representative generative paradigms - GAN-based, VAE-boosted, diffusion-based, and masked modelling - using PRIME-CVD, a 50,000-person cohort with known ground-truth structure. While all models reproduce marginal distributions, none simultaneously preserve subgroup structure, effect estimates, and dependency structure. Notably, models with strong distributional fidelity can exhibit poor calibration and distorted relationships, leading to unreliable inference. These results show that current evaluation practices can overestimate synthetic data quality and motivate domain-informed assessment based on the ability to support valid clinical and scientific conclusions.

Electronic health record (EHR) notes are dense medical documents containing large amounts of information, often filled with complex medical jargon. Highlighting all details in EHRs helps reduce the likelihood of missing crucial information by drawing attention to key content. This study proposes the design of a Cardiology Interface Terminology (CIT) to accurately highlight all details in EHR notes of cardiology patients. We introduce an innovative Machine Learning (ML) technique for the design of CIT. The ML technique requires training data. Manual preparation of such training data is time-consuming and expensive. The process of the CIT design includes three phases. In the first two phases, we innovatively derive a training data CIT to be used by the third phase, ML technique. We start by designing an initial CIT, composed of several components: the cardiology-related sub-hierarchies of SNOMED, other SNOMED concepts mined from EHRs of build set, and necessary components of terms e.g., medical abbreviations and medications. Utilizing an iterative process, fine-grained phrases containing initial CIT concepts are extracted from build set as CIT concept candidates. The candidate concepts are semi-automatically reviewed before being added to CIT, yielding the training data CIT, TCIT. In the third phase, a ML model is trained with TCIT to identify candidates fitting to be concepts in the CIT. This model is used to extract further concepts from build set, yielding the final CIT. The final CIT is then used to highlight the test set and evaluate the extent to which it captures details in an unseen EHR dataset. For this purpose, four evaluation metrics, coverage, breadth, completeness, and conciseness are used. The highlighted test set has a coverage of 74.21%, with a breadth of 1.68. For 20 random notes in test set, the average completeness is 98.2% and average conciseness is 84.2%.

The generation of high-fidelity synthetic Electronic Health Records (EHR) is crucial for advancing medical research while preserving patient privacy. However, head-to-head comparison of existing generative models is hindered by disjointed codebases, incompatible data loaders, conflicting library dependencies, and inconsistent evaluation protocols. To address these gaps, we introduce a lightweight, end-to-end benchmarking framework for reproducible synthetic EHR evaluation, organized as a unified pipeline spanning data ingestion, standardized model training, and architecture-agnostic evaluation. Our current implementation targets the generation of longitudinal ICD diagnosis codes -- the most commonly studied modality in this literature -- and is built on the community-maintained PyHealth library. We reimplement and unify strong baselines (MedGAN, CorGAN, PromptEHR, HALO) under full ICD-9 vocabulary granularity, and add a lightweight GPT-2 baseline from the general-purpose sequence-modeling literature. We contribute a rigorous, architecture-agnostic privacy-utility evaluation suite that applies identically to GAN- and transformer-based generators, and report bootstrapped confidence intervals across all metrics. We further analyze the poor long-tailed performance of existing models and discuss the extensibility of our framework beyond diagnosis codes. By lowering the engineering barrier to running, extending, and evaluating under a single pipeline, we introduce a starting point for community-driven reproducibility and benchmarking synthetic EHR models.

Electronic health records (EHR) pose large-scale multi-disease modeling problems in which many outcomes are rare and strongly influenced by shared risk factors. While modern approaches achieve strong predictive performance, they often treat diseases independently or rely on black-box architectures, offering limited insight into how risk factors organize disease risk and little principled uncertainty quantification. We introduce a Bayesian hypergraph inference framework that reframes multi-disease modeling around latent, risk-factor-modulated disease pathways. Risk factors act on hyperedges, latent disease subsets with shared risk patterns, allowing diseases to participate in multiple distinct pathways and enabling interpretable, higher-order structure beyond pairwise associations. A repulsion prior encourages parsimonious and identifiable structure, while posterior inference provides calibrated uncertainty over both disease groupings and risk-factor influence. To enable scalable inference on large EHR datasets, we develop a structured variational inference algorithm that preserves logical dependencies among hyperedge existence, disease membership, and pathway-level effects. Experiments on simulated data and UK Biobank demonstrate stable and interpretable disease pathway structure, well-calibrated uncertainty, improved estimation for rare diseases, and competitive predictive performance.