Electronic Health Records

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.

The extraction of structured clinical information from unstructured EHR notes is a persistent bottleneck in healthcare informatics. While large language models (LLMs) offer high performance, their deployment in clinical settings is hindered by privacy risks, inference costs, and the tendency to hallucinate beyond textual evidence. We address these challenges for the CL4Health 2026 Case Report Form (CRF) filling task by proposing a fully local, domain-adapted pipeline using the MedGemma-27B model. Our two-stage architecture, which separates binary presence classification from value extraction, enforces strict adherence to textual evidence and ensures deterministic outputs for negated, uncertain, or unknown states. By leveraging item-specific, few-shot in-context learning without external API calls or fine-tuning, our approach achieves a macro-F1 score of 0.55 on the official English test track. This result secures second place among all locally-hosted, open-source submissions. Our work demonstrates that privacy-preserving, on-premise LLM pipelines can achieve near-competitive performance with proprietary frontier models, providing a practical, data-sovereign framework for clinical NLP.

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.

CARE-link is an open-source, web-based clinical support platform designed to improve the management of gestational diabetes by linking clinicians and patients through an LLM-mediated workflow. The system aggregates patient-generated data outside the hospital, summarizes relevant clinical information, and delivers context-aware decision support to clinicians. For patients, CARE-link provides clear explanations of management plans and delivers timely lifestyle guidance through a WhatsApp interface. The integrated dual-facing design aims to promote continuous monitoring, support individualized care, and reduce the burden of in-clinic follow-ups. Built with a modular architecture, the platform can be adapted to other chronic conditions requiring longitudinal tracking and behavioral support. CARE-link has the potential to enhance clinical oversight, promote patient compliance, and strengthen continuity of care particularly in resource-constrained settings.

Electronic health records (EHRs) are central to clinical prediction, but existing methods either rely on correlation-driven deep models or use single large language models (LLMs), making it difficult to support multidisciplinary clinical reasoning. Recent multi-agent systems (MAS) provide a promising alternative, yet current EHR-grounded MAS methods still suffer from weak evidence differentiation across agents and redundant multi-round interaction. We propose D2MDT, a Department-aware MultiDisciplinary Team Consultation with Deliberation for Efficient clinical prediction. D2MDT first constructs structured EHR evidence and consultation-ready semantic evidence for multi-agent consultation. It then assigns patient-specific department perspectives to doctor agents and retrieves complementary evidence for collaborative consultation. To improve efficiency, D2MDT further introduces residual deliberation, which updates only unresolved consensus rather than replaying the full discussion history. Finally, D2MDT fuses the refined consensus report with structured EHR representations for prediction. Experiments on mortality prediction show that D2MDT improves both predictive performance and consultation efficiency. We release the code online to ease the reproducibility of this paper.

While large language models (LLMs) are increasingly used for clinical applications, many existing pipelines require sending raw sensitive health information to remote servers for processing, which heightens the risk of privacy leakage. A natural approach to mitigate this risk is to encrypt the data before transmission. However, straightforward solutions such as encrypting the entire dataset introduce prohibitive computational, alignment, and communication overheads, rendering large-scale practical deployment infeasible. To preserve privacy while maintaining usability, we present Healthcare Encryption & Redaction via Adaptive Linguistic Decomposition (HERALD), a token-level cryptographic redaction framework designed to achieve this balance by encrypting only sensitive tokens while preserving the surrounding context for downstream model utility. HERALD combines medical named-entity recognizer (NER) with part-of-speech (POS) driven policies to select candidate tokens, performs targeted lemmatization to stabilize surface forms, and substitutes each protected token with a deterministic ciphertext wrapped in explicit delimiters. Notably, HERALD is model-agnostic and operates entirely on the client side, ensuring that sensitive content remains encrypted throughout storage, transmission, and processing without requiring changes to downstream models. We evaluated HERALD on both classification and medical question answering (MQA) tasks on public datasets. Across different tasks, experiments illustrate that fully secured baselines suffer significant utility loss, whereas HERALD consistently recovers performance close to plaintext. Overall, HERALD provides a novel utilization pipeline.

Modeling patient trajectories from longitudinal electronic health records (EHRs) requires reasoning over sparse, noisy, and long-context multimodal sequences. Existing LLM-based multi-agent systems address context length but process patients in isolation, failing to mirror how clinicians leverage accumulated experience from similar prior cases. We present Traj-Evolve, a self-evolving multi-agent system with two complementary evolving mechanisms. First, an Experience Pool (ExPool) acts as a non-parametric memory, indexing rejection-sampled reasoning traces to retrieve similar patients as few-shot contexts. Second, multi-agent reinforcement learning (MARL) via reward-ranked fine-tuning parametrically optimizes inter-agent and agent-memory collaboration. A leave-one-out cross-retrieval strategy unifies the two, aligning training- and inference-time behavior under retrieval augmentation. On a lung cancer prediction task utilizing up to five years of multimodal EHRs, Traj-Evolve outperforms 9 strong baselines on the overall population and a challenging never-smoker population. Analysis of the evolving dynamics highlights three key findings: (1) expanding the ExPool shifts optimal retrieval from diverse to specific samples; (2) under MARL, the manager agent's prediction loss converges quickly while the worker agents' temporal reasoning continues to benefit from more verified patients; and (3) the two mechanisms are complementary on the predicted risk, where ExPool improves specificity while MARL improves sensitivity.

Large language models (LLMs) exhibit strong natural-language reasoning abilities for clinical decision support, but struggle to effectively model structured longitudinal electronic health records (EHRs). In contrast, EHR foundation models can learn predictive patient representations, yet lack interpretable language-based reasoning. To bridge this gap, we propose ChatHealthAI, a multimodal reasoning framework that aligns structured EHR representations from a pretrained EHR foundation model with the semantic space of a frozen LLM through a task-aware resampler. By integrating longitudinal patient representations with refined clinical event descriptions, ChatHealthAI enables clinically grounded natural-language reasoning while maintaining accurate patient prediction. We evaluated ChatHealthAI on three clinical predictive tasks from the EHRSHOT benchmark. Results show that ChatHealthAI improves reasoning quality and interpretability while preserving competitive predictive performance. These findings highlight the potential of integrating EHR foundation models with pretrained LLMs for interpretable clinical prediction.

Clinical practice is not the selection of an answer from enumerated options: a physician gathers heterogeneous information incrementally and commits to sequential, irreversible decisions under uncertainty. Static benchmarks cannot probe and existing interactive medical benchmarks each compromise on at least one of them. We present ClinEnv, an interactive benchmark that evaluates LLMs as attending physicians over real inpatient admissions under a paradigm we term Longitudinal Inpatient Simulation. Each case is automatically constructed into an ordered sequence of decision stages; at every stage the model must actively query four specialized agents before committing to medications, procedures, and diagnoses. ClinEnv scores both what the model decides, through deterministic ontology-grounded matching, and how it gathers information. Across seven models, the strongest reaches only 0.31 decision F1, and outcome quality is sharply decoupled from process quality. Difficulty concentrates in management decisions and later stages, where models recover discharge diagnoses far more reliably than management actions (0.51 vs. 0.17 F1) and continue to issue redundant queries as cases progress. ClinEnv makes this information-acquisition gap, invisible to outcome-only evaluation, directly measurable.

Reliable quantification of malaria dynamics in sub-Saharan Africa is hindered by short, noisy, and spatially heterogeneous surveillance records. In Ghana, health-facility data from 2014 to 2023 reveal non-linear and age-specific fluctuations in hospital admissions, yet existing approaches struggle to capture stochastic variability or provide credible uncertainty bounds. This study develops a Bayesian nonlinear inference framework that integrates a cubic baseline with a damped oscillatory kernel, estimated via an affine-invariant ensemble Markov Chain Monte Carlo sampler. The framework accommodates limited data, models parameter uncertainty, and generates probabilistic forecasts for children under five years and individuals aged five years or more. Results show strong empirical adequacy ($R^2 = 0.9958$ for $<5$ years; $R^2 = 0.9956$ for $\geq 5$ years) with residual errors below $2\%$ and well-mixed posteriors confirming convergence. District-level analysis reveals pronounced spatial heterogeneity, with coefficients of variation ranging from $<0.07$ in urban centres such as Kumasi to $>3.3$ in peripheral districts such as Mpohor and Bia East. Forecasts for 2024-2026 indicate a gradual resurgence: from 137,000 to 149,000 cases among children under five years and from 348,000 to 375,000 cases among older individuals, with uncertainty widening over time. By producing probabilistic forecasts, this Bayesian framework provides a principled tool for anticipating malaria fluctuations and strengthening data-driven decision-making in Ghana's national malaria control strategy.

Clinical decision-making (CDM) is central to real-world clinical workflows, where clinicians infer diagnoses, select treatments, or anticipate future health outcomes under incomplete evidence. LLMs are increasingly used to support these decisions due to strong language capabilities, broad biomedical knowledge, and efficiency, yet the reliability of LLMs on real-world clinical decision tasks remains insufficiently understood. To evaluate CDM models, especially LLM-based models, an ideal and practical medical decision benchmark should be constructed via an automated yet reliable pipeline to ensure both scale and quality. Moreover, the grounding of a CDM benchmark in real patient EHRs can better support evaluation on practical CDM tasks that require substantive biomedical knowledge and clinical inference. To fill the gaps, we introduce EHRBench, an automated and reliable EHR-grounded benchmark for evaluating LLM-based clinical decision-making at scale. To ensure scalability and reliability, EHRBench is constructed through an EHR-LLM-KB(knowledge-base) interaction pipeline. For efficiency, we use a specialized LLM to automatically convert encounter-level EHR trajectories into structured templates and deterministically instantiate the templates into QA items. In parallel, we apply systematic KB-based verification and enrichment to filter hallucinated or ambiguous relations and to improve reliability. Using this pipeline, we construct nearly 1M (960,067) QA items spanning three core inference-required clinical decision tasks: diagnosis, treatment, and prognosis. We benchmark more than 30 representative LLMs on EHRBench and provide detailed analyses of performance and robustness. The results show consistent capability trends across settings, further validating the reliability of EHRBench and highlighting actionable gaps toward clinically reliable LLM systems.

Large language models (LLMs) show promise for clinical reasoning and decision support, but evaluation in structured, electronic health record-congruent settings remains limited. Existing benchmarks often rely on static datasets or unstructured inputs that do not reflect the interoperable data formats used in clinical systems. We introduce a reusable pipeline for generating terminology-grounded HL7 FHIR R4 bundles from unstructured text, enabling controllable evaluation of clinical decision support systems over structured inputs. The pipeline combines staged LLM generation with terminology-grounded validation and repair to eliminate hallucinated codes and enforce structural and semantic consistency. Applying this approach to MedCaseReasoning, we construct MedCase-Structured, a synthetic dataset of 1,732 FHIR bundles derived from clinician-authored diagnostic cases, producing complete, valid bundles for 97.1% of attempted cases. Evaluation on MedCase-Structured reveals consistently lower diagnostic accuracy for LLMs on structured FHIR inputs than with plain text, highlighting the importance of deployment-aligned benchmarking.

Synthetic Electronic Health Record (EHR) generation provides a promising avenue for data augmentation and cross-hospital modeling in privacy-constrained healthcare settings. However, most existing EHR generative models are centralized and require pooling data across hospitals, which is often infeasible when real-world data sharing is restricted. While federated EHR generation offers a natural solution, direct federated modeling often collapses or diverges due to the high dimensionality, sparsity, and cross-hospital heterogeneity of EHR data. In this work, we propose FedEHR-Gen, the first federated framework for synthetic time-series EHR generation across distributed hospitals. FedEHR-Gen uses a two-stage learning paradigm. First, we introduce a federated autoencoder that projects high-dimensional and sparse EHR features onto a compact latent space. To ensure semantic consistency across hospitals, we develop a layer-wise matching aggregation mechanism that aligns local encoders into a unified global latent space. Second, operating on this aligned latent space, we train a federated temporal conditional variational autoencoder (TCVAE) with distribution-aware aggregation, enabling stable temporal generative modeling under severe cross-hospital heterogeneity. Extensive experiments on the eICU and MIMIC-III datasets demonstrate that FedEHR-Gen achieves generation fidelity, downstream utility, and privacy risk comparable to centralized training, while consistently outperforming the standard federated baseline.

Data consistency between unstructured clinical notes and structured tables in Electronic Health Records (EHRs) is essential for patient safety and clinical decision-making. However, existing work on note-table consistency verification mainly relies on surface-level matching of numeric values or simple events. Such approaches fail to capture the reasoning underlying real-world EHR documentation, including clinical interpretation, event relations, and temporal changes. To address this gap, we introduce EHR-ReasonCon, a reasoning-intensive benchmark for note-table consistency verification. Built on MIMIC-III with expert-guided annotations, it comprises 8,048 entities derived from clinical notes and provides high-quality ground-truth labels. The annotation protocol is supported by specialized table-exploration tools to ensure systematic evidence retrieval and reliable consistency assessment. We also propose EHR-Inspector, an LLM-based framework that segments notes, extracts anchor entities and temporal references, and uses table-exploration tools to verify consistency against structured tables. Evaluated using expert-validated LLM-as-a-judge metrics under harsh and lenient criteria, EHR-Inspector achieves state-of-the-art performance across multiple model backbones. Analyses further demonstrate the effectiveness of its components and highlight differences from human verification.

Understanding the effects of interventions is central to scientific progress, with randomized controlled trials (RCTs) regarded as the gold standard for causal inference in many applied fields. However, RCTs are costly, time-consuming, and often constrained by ethical or practical limitations, motivating the need for causal methods able to draw conclusions from observational data. While such data is collected at ever larger scale, making its use for causal inference is often hindered by the fact that not all variables affecting treatment allocation and the outcome are observed: an issue known as unobserved confounding. In this paper, we introduce a new study design called confounder detection via treatment intent. The idea is to query a human expert who makes treatment decisions, and ask them to compare pairs of units proposed by a principled matching strategy, with the goal of eliciting unobserved variables that explain why treatment decisions differ. We provide a theoretical basis for such a procedure, ascertaining conditions under which such a study design may elicit unobserved confounders. Building on this newly established foundations, we study treatment effects of interventions in the intensive care unit (ICU). First, we show empirical evidence strongly indicating that electronic health records (EHRs) collected in ICUs are subject to unobserved confounding. By using clinical text notes as a proxy for physicians' knowledge and leveraging natural language processing, we provide a proof of concept for our methodology in a semi-synthetic environment with a known ground truth.

Early prediction of respiratory failure is critical for timely clinical intervention in intensive care units. Existing electronic health record (EHR)-based models can continuously monitor physiologic deterioration, but they may not fully capture pulmonary pathophysiology reflected in chest radiographs (CXRs). In this study, we ask whether CXR information improves prospective prediction of invasive mechanical ventilation beyond EHR signals alone. We develop a gated multimodal framework that integrates structured EHR time-series data with CXR foundation-model representations. The gating module adaptively controls the contribution of imaging features based on patient-specific clinical context, allowing the model to selectively rely on imaging information when it is informative. We prospectively evaluate the framework for predicting invasive mechanical ventilation within 24 hours in ICU patients and compare it with an established EHR-only model (Ventio), physician predictions obtained at matched clinical time points, and alternative multimodal variants. The gated multimodal models achieved higher discrimination than the EHR-only baseline, with AUROC values of 0.860 and 0.858 using REMEDIS and MedInsight CXR representations, respectively, compared with 0.752 for Ventio. Relative to physician predictions, the multimodal framework substantially improved sensitivity while maintaining favorable specificity. Compared with the EHR-only model, multimodal integration increased specificity and positive predictive value, suggesting that CXR information can refine risk estimation in selected patients. These findings support adaptive multimodal fusion as a practical strategy for incorporating imaging into prospective respiratory failure prediction.

This study presents a methodology for constructing a clinically verified dataset of dermatoscopic images for medical informatics research. The relevance of the work is driven by the fact that the performance of automated diagnostic support systems depends not only on the volume of images, but also on the reproducibility of the image acquisition procedure, the completeness of structured metadata, and the reliability of diagnostic labels. International collections were primarily created under conditions that differ substantially from routine Russian outpatient practice and mobile dermatoscopy. The proposed methodology integrates three interconnected components: (1) a standard operating procedure (SOP) for acquiring images via mobile dermatoscopy, (2) an information model comprising 16 structured metadata fields organized into six clinically oriented blocks in ISIC-compatible notation, and (3) a multi-stage expert verification of diagnostic labels (initial clinical annotation, consensus review by three specialists, and histological confirmation of all malignant neoplasms). Using this methodology, a dataset of 1,026 unique dermatoscopic images from 443 patients was collected between June 2025 and May 2026. From 1,044 initial records, 18 duplicates were excluded. The dataset includes nine nosological categories; all 39 malignant lesions (18 melanomas, 15 basal cell carcinomas, and 6 squamous cell carcinomas) were histologically verified. Patient age ranged from 2 to 90 years (median 38), with 279 females (63%) and 164 males (37%). Each image is accompanied by expert-annotated dermatoscopic structures and an explicit verification_stage field indicating the level of diagnostic confirmation. The resulting dataset serves as a pilot clinically verified resource suitable for independent model evaluation, domain shift analysis, interpretability studies, and further expansion.

Machine learning methods provide a methodological innovation that can help screen for cardiovascular disease through noninvasive and readily available measurement modalities. Recent investments in using electrocardiogram (ECG) data to screen for structural heart disease (SHD) are one example, where ECGs provide a low-cost, available modality for screening. This has led to the EchoNext dataset, a paired ECG-echocardiogram data repository for testing new methods of SHD detection. However, relatively few studies have investigated how more probabilistic classification through Bayesian inference may improve uncertainty quantification in this setting. Moreover, few studies have considered how triage systems can be developed to alleviate healthcare bottlenecks, such as the review of data from underserved, rural clinics by expert sonographers for SHD assessment. In this study, we leverage existing ECG-echocardiogram data to compare frequentist and Bayesian neural network classifiers. We show that the Bayesian approach is comparable or better than frequentist methods in SHD classification, and that they have a more robust uncertainty quantification attached to them. We provide an example of how this uncertainty-aware classification scheme can be used for screening SHD, providing a proof-of-concept for how machine learning can help with triage in getting individuals expert sonographer input when SHD is highly likely or measurements are highly uncertain.

Antimicrobial stewardship (AMS) is critical in pediatric intensive care units (PICUs), where diagnostic uncertainty often drives broad-spectrum antibiotic use, increasing antimicrobial resistance and potential long-term harms. Machine learning offers a promising approach for identifying patient-level opportunities for stewardship interventions from electronic health record data, yet prior work has focused largely on adult populations and static tabular representations. We present a systematic benchmarking study of AMS intervention prediction in the PICU across the public Paediatric Intensive Care database a private cohort from the University Children's Hospital Zurich, Switzerland. We define four clinically relevant proxy targets for reducing antibiotic exposure: intravenous-to-oral switching, de-escalation, discontinuation, and short-course therapy. Under a unified evaluation framework, we compare tabular, sequence-based, and graph-based temporal models at multiple temporal resolutions. We find that predictive performance is driven primarily by target prevalence and dataset characteristics rather than model complexity. Sequence models improve the precision-recall trade-off over tabular approaches at coarse (24-hour) resolution, while finer temporal modeling provides limited additional benefit. However, these gains come at the cost of poorer calibration, with simpler tabular models yielding more reliable probability estimates. Our findings highlight the importance of target design, temporal representation, and calibration in clinical machine learning, and provide practical guidance for developing reliable decision support systems for pediatric AMS.

Graph-based Retrieval Augmented Generation (GraphRAG) extends retrieval-augmented generation to support structured reasoning over complex corpora, but its reliability under resource-constrained, privacy-sensitive deployments remains unclear. In healthcare, where Electronic Health Record (EHR) data is complex and strictly regulated, reliance on cloud-based large language models (LLMs) introduces challenges in cost, latency, and compliance. In this work, we present a systematic evaluation of GraphRAG for EHR schema retrieval using locally deployed open-source LLMs. We implement the Microsoft GraphRAG pipeline on real-world EHR schema documentation and benchmark four models, including Llama 3.1 (8B), Mistral (7B), Qwen 2.5 (7B), and Phi-4-mini (3.8B), each deployed via Ollama on a single consumer GPU (8 GB VRAM). We evaluate indexing efficiency, knowledge graph construction, query latency, answer quality, and hallucination under both global and local retrieval modes. Our results reveal substantial differences: Llama 3.1 produces the richest knowledge graph (1,172 entities), Qwen 2.5 achieves the best answer quality (3.3/5), Phi-4-mini fails to complete the pipeline due to structured-output errors, and Mistral exhibits degenerate repetition behavior. We further show that GraphRAG exhibits a practical capacity threshold, where models below approximately 7B parameters fail to reliably produce valid structured outputs and cannot complete the pipeline. In addition, indexing and answer quality are decoupled across models, and local retrieval consistently outperforms global summarization in both latency and factual grounding, with reduced hallucination. These findings demonstrate that GraphRAG is feasible on consumer hardware while highlighting the importance of model selection and retrieval design for robust deployment in regulated settings.

Numerical time-series models can effectively process irregular electronic health record (EHR) trajectories, but they do not naturally expose the measurements and temporal patterns supporting each risk estimate as readable evidence. Existing text-based interfaces improve readability, but typically rely on either raw serialization, which is lengthy and redundant, or patient-level free-form summaries, which are difficult to trace to source measurements and time windows. To bridge this gap, we introduce TreeText-CTS (Clinical Time-Series), which converts irregular EHR trajectories into human-readable, compact, source-traceable tree-path evidence units without patient-level summarization or inference-time autoregressive decoding. TreeText-CTS routes multi-scale window summaries through frozen XGBoost models and verbalizes activated tree paths as deterministic, source-traceable evidence units composed of threshold conditions. An evidence selector assembles an informative subset of these units, which a language-model encoder then integrates for prediction. Across PhysioNet 2012 mortality, MIMIC-III mortality, and PhysioNet 2019 sepsis-onset forecasting, TreeText-CTS achieves the best AUROC and AUPRC among evaluated text-based EHR time-series interfaces, improving AUPRC by 6.0 to 9.7 absolute percentage points over the strongest prior text-based interface while remaining competitive with numerical time-series models. Ablations show that tree-path evidence construction, evidence selection, and language-model composition each contribute to performance. Because every span passed to the language-model encoder is constructed from activated tree-path threshold conditions, TreeText-CTS makes the evidence supplied to the final predictor inspectable and source-traceable.

Patient-managed Personal Health Records (PHRs) promises to empower patients to better understand their health; but information in the record is complex, potentially hindering insights. In this study, we assess the potential of large language models (LLMs, Gemini 3.0 Flash) to provide helpful answers to user health queries, when provided clinical data from PHRs as context. A total of 2,257 user queries were drawn from 3 different distributions to represent patient questions: shorter web search queries, longer questions derived from templates of chatbot conversations, and questions patients asked to their healthcare team (patient calls). Queries were matched with de-identified PHRs (from a pool of 1,945). Gemini responses were generated (1) without PHR context; (2) with a basic summary of demographics, conditions, and medications; (3) with full, extensive clinical notes. For evaluation, we leveraged an existing rating framework (SHARP), and developed a new framework for specific error modes when interpreting PHRs. Evaluation was performed using autoraters for the full set, and with clinician ratings for a subset (n=95), with both sets of raters knowing the full PHR context. We see significant improvements in the helpfulness of answers to all question types with PHR data (p < 0.001, paired t-test). We also observe potential gains in safety, accuracy, relevance and personalization of answers. Our PHR evaluation framework further identifies gaps in LLM understanding of particular aspects of complex PHRs, such as temporal disorientation, and rare but meaningful confabulations. These results suggest potential for PHR data to help people with a wide range of user needs; and provide a framework for monitoring for gaps in LLM answers based on PHR context. This study motivates further work to assess and realize potential benefits to users from understanding their health records.

Tabular foundation models (TFMs) achieve strong performance on health datasets, but their inference cost and infrastructure requirements limit practical use. We study whether their predictive behavior can be transferred to lightweight tabular models through knowledge distillation. Since in-context TFMs condition on the training set at inference time, naive distillation can introduce context leakage; we address this with stratified out-of-fold teacher labeling. Across $19$ healthcare datasets, $6$ TFM teachers, $4$ student families, and several multi-teacher ensembles, we find that distilled students retain at least $90\%$ of teacher AUC, outperforming teachers in some cases, while running at least $26\times$ faster on CPU and preserving calibration and fairness critical for health applications. Moreover, multi-teacher averaging does not consistently improve over the best single teacher. Leakage-aware distillation is thus a viable route for bringing TFM-quality predictions into inference-constrained health settings.

Rare diseases such as inborn errors of immunity (IEI) require early diagnosis to prevent end organ damage and improve quality of life. Hurdles in accessing and curating large scale electronic health record (EHR) data limit routine data driven analyses to remain on the forefront of IEI and other rare disease trends. Development of machine learning (ML) algorithms in IEI for pattern recognition as well as published methodology examining how to systematically process and integrate complex medical data is limited. Our proposed pipeline, including data curation and ML clustering algorithms, is designed to recognize novel rare disease patterns and extract IEI- associated features from a national data registry. Our methodology for EHR data formatting and processing presents the pipeline that transforms raw immunologic lab data into vectors. This is further combined with hyperparameter tuning for diseases pattern recognition via clustering. This study refines IEI feature awareness, develops data tool kits for rare disease populations analysis, and expands on transforming complex medical records in data structures interpretable by unsupervised ML.

As large language models empower healthcare, intelligent clinical decision support has developed rapidly. Longitudinal electronic health records (EHR) provide essential temporal evidence for accurate clinical diagnosis and analysis. However, current large language models have critical flaws in longitudinal EHR reasoning. First, lacking fine-grained statistical reasoning, they often hallucinate clinical trends and metrics when quantitative evidence is textually implied, biasing diagnostic inference. Second, non-uniform time series and scarce labels in longitudinal EHR hinder models from capturing long-range temporal dependencies, limiting reliable clinical reasoning. To address the above limitations, this work presents the Probabilistic Chain-of-Thought Completion Agent (COTCAgent), a hierarchical reasoning framework for longitudinal electronic health records. It consists of three core modules. The Temporal-Statistics Adapter (TSA) converts analytical plans into executable code for standardized trend output. The Chain-of-Thought Completion (COTC) layer leverages a symptom-trend-disease knowledge base with weighted scoring to evaluate disease risk, while the bounded completion module acquires structured evidence through standardized inquiries and iterative scoring constraints to ensure rigorous reasoning. By decoupling statistical computation, feature matching, and language generation, the framework eliminates reliance on complex multi-modal inputs and enables efficient longitudinal record analysis with lower computational overhead. Experimental results show that COTCAgent powered by Baichuan-M2 achieves 90.47% Top-1 accuracy on the self-built dataset and 70.41% on HealthBench, outperforming existing medical agents and mainstream large language models. The code is available at https://github.com/FrankDengAI/COTCAgent/.

Accurate disease trajectory prediction is critical for early intervention, resource allocation, and improving long-term outcomes. While electronic health records (EHRs) provide a rich longitudinal view of patient health in clinical environments, models trained on curated research cohorts may not reflect routine deployment settings, and those trained on single-hospital datasets capture only fragments of each patient's trajectory. This highlights the importance of leveraging large, multi-hospital health systems for training and validation to better reflect real-world clinical complexity. In this work, we develop DT-Transformer, a foundation model trained on 57.1M structured EHR entries over 1.7M patients from Mass General Brigham (MGB), spanning 11 hospitals and a broad network of outpatient clinics. DT-Transformer achieves strong discrimination in both held-out and prospective validation settings. Next-event prediction achieves a median age- and sex-stratified AUC of 0.871 across 896 disease categories, with all categories exceeding AUC 0.5. These results support health system-scale training as a path toward foundation models suited to real-world clinical forecasting.

Fast Healthcare Interoperability Resources (FHIR) is the dominant standard for interoperable exchange of healthcare data. In FHIR, electronic health records form a directed graph of resources. Answering clinically meaningful questions over FHIR requires agents to perform multi-step reasoning, filtering, and aggregation across multiple resource types. Prior work shows that even tool-augmented LLM agents (retrieval, code execution, multi-turn planning) often select the wrong resources or violate traversal constraints. We study this problem in the context of FHIR-AgentBench, a benchmark for realistic question answering over real-world hospital data, and frame reasoning on FHIR as a sequential decision-making problem over a queryable structured graph. We implement a multi-turn CodeAct agent and post-train it with reinforcement learning using a custom harness and tools. A LLM Judge provides execution-grounded rewards. Compared to prompt-based, closed-model baselines, RL post-training improves performance while enforcing data-integrity constraints. Empirically, our approach improves answer correctness from 50% (o4-mini) to 77% on FHIR-AgentBench using a smaller and cheaper Qwen3-8B model. We present an end-to-end post-training pipeline (environment building, harness construction, model training and custom evaluation) that reliably improves multi-turn reasoning over structured clinical graphs.

Drug development and pharmacovigilance are frequently bottlenecked by legacy clinical reporting pipelines. These monolithic systems encode regulatory-grade logic but resist AI integration by producing opaque output with no machine-readable intermediate layer. Existing modernization approaches force a choice between full rewrites and incremental refactoring that preserves structural barriers. We present a non-destructive methodological framework achieving AI-driven pharmacoinformatics readiness without altering legacy source code. A metadata layer--comprising a bridge map, a typed Intermediate Representation (IR), and an orchestrator--wraps existing components and re-exposes their outputs as structured data consumable by LLMs. It enables optional incremental consolidation, replacing selected legacy components with metadata-configured core routines while the remainder operates unchanged. Validated on a 558-component SAS reporting library (373,000 lines of code), the framework demonstrated immediate AI-readiness under coexistence mode, yielding machine-readable output. Where consolidation was elected, the modernized core achieved a 92% reduction in proprietary code. Parity validation on 14 report types from a Phase III study achieved cell-level parity of 80% or above on 11 reports (mean 82.7%, best 99.2%). A benchmark using CDISC CDISCPilot01 data achieved 100% parity across 5 reports. LLM experiments confirmed the IR enables automated pharmacovigilance, table summarization, and trial configuration generation. The framework offers a regulation-aware path to AI-integrated clinical reporting, accelerating drug development without interrupting regulatory submissions.

Electronic Health Records (EHR) contain rich longitudinal patient information and are widely used in predictive modeling applications. However, effectively leveraging historical data remains challenging due to long trajectories, heterogeneous events, temporal irregularity, and the varying relevance of past clinical context. Existing approaches often rely on fixed windows or uniform aggregation, which can obscure clinically important signals. In this work, we introduce EHR-RAGp, a retrieval-augmented foundation model that dynamically integrates the most relevant patient history across diverse clinical event types. We propose a prototype-guided retrieval module that acts as an alignment mechanism and estimates the relevance of retrieved historical chunks with respect to a given prediction task, guiding the model towards the most informative context. Across multiple clinical prediction tasks, EHR-RAGp consistently outperforms state-of-the-art EHR foundation models and transformer-based baselines. Furthermore, integrating EHR-RAGp with existing clinical foundation models yields substantial performance gains. Overall, EHR-RAGp provides a scalable and efficient framework for leveraging long-range clinical context to improve downstream performance.

By processing electronic health records (EHRs) as natural language sequences, large language models (LLMs) have shown potential in clinical prediction tasks such as mortality prediction and phenotyping. However, longitudinal or highly frequent EHRs often yield excessively long token sequences that result in high computational costs and even reduced performance. Existing solutions either add modules for compression or remove less important tokens, which introduce additional inference latency or risk losing clinical information. To achieve lossless compression of token sequences without additional cost or loss of performance, we propose Medical Token-Pair Encoding (MedTPE), a layered method that extends standard tokenisation for EHR sequences. MedTPE merges frequently co-occurring medical token pairs into composite tokens, providing lossless compression while preserving the computational complexity through a dependency-aware replacement strategy. Only the embeddings of the newly introduced tokens of merely 0.5-1.0% of the LLM's parameters are fine-tuned via self-supervised learning. Experiments on real-world datasets for two clinical scenarios demonstrate that MedTPE reduces input token length by up to 31% and inference latency by 34-63%, while maintaining or even improving both predictive performance and output format compliance across multiple LLMs and four clinical prediction tasks. Furthermore, MedTPE demonstrates robustness across different input context lengths and generalisability to scientific and financial domains and different languages.

Automated question answering (QA) over electronic health records (EHRs) demands precise evidence retrieval, faithful answer generation, and explicit grounding of answers in clinical notes. In this work, we present Neural1.5, our method for the ArchEHR-QA 2026 shared task at CL4Health@LREC 2026, which comprises four subtasks: question interpretation, evidence identification, answer generation, and evidence alignment. Our approach decouples the task into independent, modular stages and employs DSPy"s MIPROv2 optimizer to automatically discover high-performing prompts, jointly tuning instructions and few-shot demonstrations for each stage. Within every stage, self-consistency voting over multiple stochastic inference runs suppresses spurious errors and improves reliability, while stage-specific verification mechanisms (e.g., self-reflection and chain-of-verification for alignment) further refine output quality. Among all teams that participated in all four subtasks, our method ranks second overall (mean rank 4.00), placing 4th, 1st, 4th, and 7th on Subtasks 1-4, respectively. These results demonstrate that systematic, per-stage prompt optimization combined with self-consistency mechanisms is a cost-effective alternative to model fine-tuning for multifaceted clinical QA.

ML models in healthcare are typically evaluated using curated real-world EHR data. A key limitation of such evaluations is that they may fail to assess the robustness of ML models to changes in the data at deployment, which is a common issue because EHR data used for ML model development cannot capture all such changes. Mass casualty incidents (MCIs) caused by disasters are critical instances where this will be an issue, as they induce rare, uncertain, and novel changes to routine system conditions. Because real-world EHR data from MCIs are often limited or unavailable, assessing ML robustness under such conditions before deployment remains challenging. Here, we propose an agent-based modelling approach for generating synthetic EHR data to evaluate the robustness of ML models under MCI scenarios. We use real-world EHR data to develop and calibrate an agent-based model (ABM) of an emergency department (ED) that explicitly models patient arrivals, resource capacity, and clinical workflow. By changing these system conditions to reflect plausible MCI scenarios, the ED model generates synthetic versions of the real-world EHR data that exhibit shifts in system behaviour. Using these synthetic data, we test ML models for predicting length of stay. We observed consistent declines in recall under MCI conditions relative to baseline system conditions, resulting in an increase in the number of patients with prolonged length of stay that were missed by the ML models. These results highlight the impact of changes in system conditions on patient outcomes, EHR data, and ML model performance. Our work establishes ABM-based synthetic EHR data generation as a proactive and systematic approach for evaluating the robustness of ML models under MCI or other system conditions not captured in real-world EHR data, supporting the safer and more effective deployment of ML models in healthcare systems.

Representation learning in electronic health records (EHR) has largely followed paradigms inherited from natural language processing, relying on sequence modeling and reconstruction based objectives that treat clinical labels as ground truth. However, real world clinical supervision is inherently weak, arising from heterogeneous, noisy, and institution specific labeling processes such as billing codes, heuristic phenotypes, and incomplete annotations. In this work, we propose WISTERIA, a weakly supervised representation learning framework that models labels as stochastic observations of an underlying latent clinical state. Instead of optimizing against a single supervision signal, WISTERIA constructs multiple weak supervision operators and learns representations by enforcing consistency across their induced label distributions. This multi view formulation induces an implicit denoising mechanism, allowing the model to recover clinically meaningful structure by reconciling disagreement between noisy labelers. We further incorporate ontology aware regularization in the label space to impose semantic structure over supervision signals. Empirically, WISTERIA improves predictive performance across standard EHR benchmarks, demonstrates strong robustness to label noise, and exhibits superior cross institutional generalization compared to sequence based pretraining objectives. These results suggest that explicitly modeling the supervision process rather than treating labels as fixed targets provides a more appropriate inductive bias for learning robust and clinically meaningful representations from EHR data.

Epilepsy diagnosis and treatment require evidence-intensive reasoning across heterogeneous clinical knowledge, including biosignal patterns, genetic mechanisms, pharmacogenomics, treatment strategies, and patient outcomes. In this work, we present \textsc{EpiGraph}, a large-scale epilepsy knowledge graph and benchmark for evaluating knowledge-augmented clinical reasoning. \textsc{EpiGraph} integrates 48,166 peer-reviewed papers and seven clinical resources into a heterogeneous graph containing 24,324 entities and 32,009 evidence-grounded triplets across five clinical layers. Built upon this graph, \textsc{EpiBench} defines five clinically motivated tasks spanning clinical decision-making, EEG report generation, pharmacogenomic precision medicine, treatment recommendation, and deep research planning. We evaluate six LLMs under both standard and Graph-RAG settings. Results show that integrating \textsc{EpiGraph} consistently improves performance across all tasks, with the largest gains observed in pharmacogenomic reasoning (+30--41%). Our findings demonstrate that structured epilepsy knowledge substantially enhances evidence-grounded clinical reasoning and provides a practical benchmark framework for evaluating knowledge-augmented LLMs in real-world neurological settings. Our code is available at: https://github.com/LabRAI/EEG-KG.

Clinical reports are often fragmented across healthcare institutions because privacy regulations and data silos limit direct information sharing. When patients seek care at a different hospital, they often carry paper or scanned reports from prior visits. This hinders EHR integration and longitudinal review, and downstream applications that depend on more complete patient records, such as patient management, follow-up care, real-world studies, and clinical-trial matching. Although OCR can digitize such reports, reliable extraction remains challenging because clinical documents are heterogeneous, OCR text is noisy, and many healthcare settings require low-cost on-premise deployment. We formulate this problem as canonical key-conditioned extractive question answering over OCR-derived clinical reports. Because the key fields are neither fixed nor known in advance, the key space is open. We maintain a canonical key inventory through iterative key mining, normalization, clustering, and lightweight human verification, and introduce key coverage as a metric to quantify inventory completeness. Using a 0.2B BERT-based model, experiments on real-world reports from more than 20 hospitals show performance improves monotonically with key coverage. The model achieves F1 scores of 0.839 and 0.893 under exact match and boundary-tolerant matching, respectively, once the Top-90 canonical keys are covered. These results show that key coverage is a dominant factor for end-to-end performance. At Top-90 coverage, our model outperforms a fine-tuned Qwen3-0.6B baseline under exact match. Although our annotated corpus is Chinese, the method relies on the language-agnostic key-value organization of semi-structured clinical reports and can be adapted to other settings given an appropriate canonical key inventory and alias mapping.

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management decisions using past patient cases stored in electronic health records (EHRs). Our hypothesis is that a patient-management decision that is unusual with respect to past patient care may be due to an error and that it is worthwhile to generate an alert if such a decision is encountered. We evaluate this hypothesis using data obtained from EHRs of 4486 post-cardiac surgical patients and a subset of 222 alerts generated from the data. We base the evaluation on the opinions of a panel of experts. The results of the study support our hypothesis that the outlier-based alerting can lead to promising true alert rates. We observed true alert rates that ranged from 25% to 66% for a variety of patient-management actions, with 66% corresponding to the strongest outliers.

Target trial emulation (TTE) enables causal questions to be studied with observational data when randomized controlled trials (RCTs) are infeasible. Yet treatment-effect methods often address causal estimation, missingness, and temporal structure separately, limiting their robustness in electronic health records (EHRs), where time-varying confounding and missing-not-at-random (MNAR) biomarkers can reach 50%--80%. We propose a two-stage pipeline for treatment effect estimation from incomplete longitudinal EHRs. First, CausalFlow-T, a directed acyclic graph (DAG)-constrained normalizing flow with long short-term memory (LSTM)-encoded patient history, performs exact invertible counterfactual inference, avoiding approximation errors from variational inference and separating confounding through explicit causal structure. Ablations on four synthetic and one semi-synthetic benchmark with known counterfactuals show that DAG constraints and exact inference address distinct failure modes: neither compensates for the other. Second, because CausalFlow-T requires completed inputs, we introduce an LLM-driven evolutionary imputer that proposes executable imputation operators rather than individual entries, and evaluate it with three large language model (LLM) backends, including two open-source models. Across 30%--80% MNAR missingness, this imputer achieves the best pooled rank over biomarker and causal metrics, leading in point-wise accuracy and temporal extrapolation while preserving average treatment effect (ATE) recovery as statistical baselines degrade. On Swiss primary-care EHRs from adults with type 2 diabetes initiating a GLP-1 receptor agonist or SGLT-2 inhibitor, the pipeline estimates a per-protocol weight-loss difference of -0.98 kg [95% CI -1.01, -0.96] favoring GLP-1 receptor agonists, consistent with randomized evidence and obtained from realistically incomplete real-world EHRs.

We develop and evaluate a data-driven approach for detecting unusual (anomalous) patient-management actions using past patient cases stored in an electronic health record (EHR) system. Our hypothesis is that patient-management actions that are unusual with respect to past patients may be due to a potential error and that it is worthwhile to raise an alert if such a condition is encountered. We evaluate this hypothesis using data obtained from the electronic health records of 4,486 post-cardiac surgical patients. We base the evaluation on the opinions of a panel of experts. The results support that anomaly-based alerting can have reasonably low false alert rates and that stronger anomalies are correlated with higher alert rates.

Today, advances in medical technology extensively utilize 3D volume data for accurate and efficient diagnostics. However, sharing these data across networks in telemedicine poses significant security risks of data tampering and unauthorized copying. To address these challenges, this paper proposes a novel reversible-zero watermarking approach, termed Vol-Mark, for medical volume data to protect their ownership and authenticity in telemedicine. The proposed Vol-Mark method offers two key benefits: 1) it designs a volume data feature extractor that leverages contrastive learning to efficiently extract discriminative and stable volumetric features, ensuring robustness against 3D attacks; 2) it introduces the cubic difference expansion (c-DE) technique, which leverages the 3D integer wavelet transform to embed watermark bits into neighboring voxels within cubes at low-frequency coefficients. The voxel differences within each cube are expanded to create embedding space, and a majority voting mechanism is employed during extraction to enhance reliability. The embedding process incurs low distortion and supports lossless removal, thereby preserving the integrity and diagnostic accuracy of medical volume data. Through these two benefits, Vol-Mark enables both integrity verification and ownership verification. Integrity verification is first performed, and ownership verification through hypothesis testing is further conducted to enhance reliability, particularly under data tampering or watermark removal attacks. Comprehensive experimental results show the effectiveness of the proposed method and its superior robustness against conventional, geometric, and hybrid attacks on medical volume data. In particular, through multiple tasks evaluations, Vol-Mark consistently achieves an ACC above 0.90 in most attack scenarios, outperforming existing methods by a clear margin.

The objective of this paper is to understand what characteristics and features of clinical data influence physician's decision about ordering laboratory tests or prescribing medications the most. We conduct our analysis on data and decisions extracted from electronic health records of 4486 post-surgical cardiac patients. The summary statistics for 335 different lab order decisions and 407 medication decisions are reported. We show that in many cases, physician's lab-order and medication decisions can be well predicted from a small subset of all features.

Discharge summaries require extracting critical information from lengthy electronic health records (EHRs), a process that is labor-intensive when performed manually. Large language models (LLMs) can improve generation efficiency; however, they are prone to producing faithfulness hallucinations, statements that contradict source records, posing direct risks to patient safety. To address this, we present CuraView, a multi-agent framework for sentence-level detection and evidence-grounded explanation of faithfulness hallucinations in discharge summaries. CuraView constructs a GraphRAG-based knowledge graph from patient-level EHRs and implements a closed-loop generation-detection pipeline with sentence-level evidence retrieval and classification spanning four evidence grades from strong support to direct contradiction (E1-E4), yielding structured and interpretable evidence chains. We evaluate CuraView on a subset of 250 patients from the Discharge-Me benchmark, with 50 patients held out for testing. Our fine-tuned Qwen3-14B detection model achieves an F1 of 0.831 on the safety-critical E4 metric (90.9% recall, 76.5% precision) and an F1 of 0.823 on E3+E4, representing a 50.0% relative improvement over the base model and outperforming RAGTruth-style and QAGS-style baselines. These results demonstrate that evidence-chain-based graph retrieval verification substantially improves the factual reliability of clinical documentation, while simultaneously producing reusable annotated datasets for downstream model training and distillation.

We introduce PhysicianBench, a benchmark for evaluating LLM agents on physician tasks grounded in real clinical setting within electronic health record (EHR) environments. Existing medical agent benchmarks primarily focus on static knowledge recall, single-step atomic actions, or action intent without verifiable execution against the environment. As a result, they fail to capture the long-horizon, composite workflows that characterize real clinical systems. PhysicianBench comprises 100 long-horizon tasks adapted from real consultation cases between primary care and subspecialty physicians, with each task independently reviewed by a separate panel of physicians. Tasks are instantiated in an EHR environment with real patient records and accessed through the same standard APIs used by commercial EHR vendors. Tasks span 21 specialties (e.g., cardiology, endocrinology, oncology, psychiatry) and diverse workflow types (e.g., diagnosis interpretation, medication prescribing, treatment planning), requiring an average of 27 tool calls per task. Solving each task requires retrieving data across encounters, reasoning over heterogeneous clinical information, executing consequential clinical actions, and producing clinical documentation. Each task is decomposed into structured checkpoints (670 in total across the benchmark) capturing distinct stages of completion graded by task-specific scripts with execution-grounded verification. Across 13 proprietary and open-source LLM agents, the best-performing model achieves only 46% success rate (pass@1), while open-source models reach at most 19%, revealing a substantial gap between current agent capabilities and the demands of real-world clinical workflows. PhysicianBench provides a realistic and execution-grounded benchmark for measuring progress toward autonomous clinical agents.

Accurate prediction of physician referral links is essential for optimizing care coordination and reducing fragmentation in healthcare delivery. However, existing computational methods, ranging from triadic closure heuristics to graph neural networks, fail to capture the intrinsic properties of physician referral networks, including sparsity, disassortative degree mixing, and hub-dominated topology. Here, we propose H3, a healthcare three-hop index that addresses these limitations by modeling indirect referral pathways through intermediate physicians, with degree-based normalization and a redundancy penalty to mitigate hub-mediated noise. Using Medicare Physician Shared Patient Patterns data, we evaluate H3 under two complementary prediction regimes: within-period prediction, which assesses recovery of contemporaneous referral links under sparse conditions, and cross-period prediction, which tests robustness to temporal shift as referral windows expand. Across both regimes, H3 consistently outperforms classical heuristics and deep learning-based baselines. Unlike black-box neural network approaches, H3 produces fully decomposable predictions traceable to specific intermediary physicians, offering a transparent and deployable solution for referral network completion.

Electrocardiogram (ECG) biometrics have emerged as a promising modality for continuous, liveness-aware authentication in wearable systems. However, many prior studies report overly optimistic results due to data leakage (e.g., random splits within the same session). To address this issue, we introduce ECG-biometrics-bench, a modular, reproducible benchmarking framework that standardizes preprocessing, segmentation, and evaluation across seven widely used public ECG datasets spanning clinical, ambulatory, and large-scale cohort settings. The framework supports both closed-set and open-set (i.e., subject-disjoint generalization in this work) evaluation, as well as progressively realistic protocols including cross-session and long-term temporal separation. To facilitate reproducible research in the community, the ECG-biometrics-bench repository will be made publicly accessible on GitHub upon the acceptance of this manuscript. Through a comprehensive multi-dataset analysis, we expose the Random Split Fallacy, demonstrating that intra-session evaluation protocols artificially inflate performance while masking severe degradation caused by temporal drift and unseen identities. Furthermore, by evaluating multiple architectures, including DeepECG, ResNet1D, and CNN-LSTM, we show that these failures are not model-specific but are likely inherent to current supervised feature-learning paradigms. Finally, we demonstrate that performance degradation due to temporal aging can be partially mitigated through a heavy enrollment, lightweight authentication strategy based on dynamic multi-session template fusion. These findings establish a more realistic baseline for ECG biometrics and highlight critical challenges that must be addressed for reliable real-world deployment.

Predicting future clinical outcomes from electronic health records (EHR) remains challenging due to the complexity and heterogeneity of patient data. LLMs have shown strong potential for such predictive tasks, yet existing approaches mainly focus on enhancing medical knowledge through distillation or RAG while relying on the model's internal ability to interpret contextual information. In this work, we present ReMedi (Reasoner for Medical Clinical Prediction), a framework for improving clinical outcome prediction from EHR. ReMedi generates rationale-answer pairs using a challenging sample regeneration mechanism for complex clinical questions, which leverages ground-truth answers as hints to enhance reasoning for further fine-tuning and preference tuning. ReMedi integrates ground-truth outcome guidance into the preference data construction loop, regenerating rationale-answer variants. By tuning on these rationale-answer pairs, the model improves its predictive performance. Experiments on multiple EHR prediction tasks demonstrate substantial gains of up to 19.9 percent over state-of-the-art baselines in terms of F1 score, underscoring ReMedi's effectiveness in real-world clinical prediction.

With the proliferation of Electronic Health Records (EHRs), a critical challenge in building predictive models is determining the optimal historical data time window to maximize accuracy. This study investigates the impact of various observation windows ranging from the day of surgery to three years prior on predicting 30-day readmission following hip and knee arthroplasties. The dataset encompasses both structured encounter records (over 4 million) and unstructured clinical notes (80,000) from 7,174 patients. To extract meaning from the clinical notes, we employed a suite of non neural (BOW, count BOW, TF IDF, LDA) and neural encoders (BERT, 1D CNN, BiLSTM, Average). We subsequently evaluated models utilizing clinical notes alone, structured data alone, and a combination of both modalities. Our results demonstrate that the optimal time window for unstructured clinical notes is significantly shorter than for structured data, maximum predictive performance was achieved using notes from just three to six months prior to surgery. In contrast, performance using structured data improved as the time window lengthened, but strictly plateaued after twelve months. These modality-specific temporal patterns remained consistent regardless of model complexity or encoder type. Ultimately, these findings challenge the general assumption that more historical data inherently yields better machine learning predictions, establishing targeted time-window guidelines for optimizing readmission prediction models.

Patient portals now give individuals direct access to their electronic health records (EHRs), yet access alone does not ensure patients understand or act on the complex clinical information contained in these records. The ArchEHR-QA 2026 shared task addresses this challenge by focusing on grounded question answering over EHRs, and this paper presents the system developed by the HealthNLP_Retrievers team for this task. The proposed approach uses a multi-stage cascaded pipeline powered by the Gemini 2.5 Pro large language model to interpret patient-authored questions and retrieve relevant evidence from lengthy clinical notes. Our architecture comprises four integrated modules: (1) a few-shot query reformulation unit which summarizes verbose patient queries; (2) a heuristic-based evidence scorer which ranks clinical sentences to prioritize recall; (3) a grounded response generator which synthesizes professional-caliber answers restricted strictly to identified evidence; and (4) a high-precision many-to-many alignment framework which links generated answers to supporting clinical sentences. This cascaded approach achieved competitive results. Across the individual tracks, the system ranked 1st in question interpretation, 5th in answer generation, 7th in evidence identification, and 9th in answer-evidence alignment. These results show that integrating large language models within a structured multi-stage pipeline improves grounding, precision, and the professional quality of patient-oriented health communication. To support reproducibility, our source code is publicly available in our GitHub repository

Progression to dialysis or end-stage renal disease is a rare but clinically important outcome. Clinicians need evidence on how medication exposures influence downstream risk. We constructed a fixed-window EHR cohort (90-day observation, 730-day prediction; N=81401; dialysis/ESRD prevalence: 1.1%) and modeled sequences of diagnoses, procedures, and medications with kidney laboratory trends (creatinine, BUN, eGFR). A transformer-based causal multi-head model was trained to estimate drug- and ingredient-level average treatment effects (ATEs) using counterfactual exposure removal and insertion under a full medication history setup. On test set, predictive performance reached an AUC of 0.694 and PR-AUC of 0.094. At the selected decision threshold (0.883), the model achieved an F1 score of 0.201 with a Brier score of 0.018. Post-hoc causal analyses of lab changes (eGFR, creatinine, BUN) using IPTW, AIPW, naive, and covariate-adjusted OLS methods assessed clinical directionality. Results showed partial protective-direction support for ACE/ARB exposures and worsening-direction signals for loop diuretics.

Feature engineering for Electronic Health Records (EHR) is complicated by irregular observation intervals, variable measurement frequencies, and structural sparsity inherent to clinical time series. Existing automated methods either lack clinical domain awareness or assume clean, regularly sampled inputs, limiting their applicability to real-world EHR data. We present \textbf{FeatEHR-LLM}, a framework that leverages Large Language Models (LLMs) to generate clinically meaningful tabular features from irregularly sampled EHR time series. To limit patient privacy exposure, the LLM operates exclusively on dataset schemas and task descriptions rather than raw patient records. A tool-augmented generation mechanism equips the LLM with specialized routines for querying irregular temporal data, enabling it to produce executable feature-extraction code that explicitly handles uneven observation patterns and informative sparsity. FeatEHR-LLM supports both univariate and multivariate feature generation through an iterative, validation-in-the-loop pipeline. Evaluated on eight clinical prediction tasks across four ICU datasets, our framework achieves the highest mean AUROC on 7 out of 8 tasks, with improvements of up to 6 percentage points over strong baselines. Code is available at github.com/hojjatkarami/FeatEHR-LLM.

Patient-trial matching requires reasoning over long, heterogeneous electronic health records (EHRs) and complex eligibility criteria, posing significant challenges for scalability, generalization, and computational efficiency. Existing approaches either rely on full-document processing with large language models (LLMs), which is computationally expensive, or use traditional machine learning methods that struggle to capture unstructured clinical narratives. In this work, we propose a lightweight framework that combines retrieval-augmented generation and large language model-based modeling for scalable patient-trial matching. The framework explicitly separates two key components: retrieval-augmented generation is used to identify clinically relevant segments from long EHRs, reducing input complexity, while large language models are used to encode these selected segments into informative representations. These representations are further refined through dimensionality reduction and modeled using lightweight predictors, enabling efficient and scalable downstream classification. We evaluate the proposed approach on multiple public benchmarks (n2c2, SIGIR, TREC 2021/2022) and a real-world multimodal dataset from Mayo Clinic (MCPMD). Results show that retrieval-based information selection significantly reduces computational burden while preserving clinically meaningful signals. We further demonstrate that frozen LLMs provide strong representations for structured clinical data, whereas fine-tuning is essential for modeling unstructured clinical narratives. Importantly, the proposed lightweight pipeline achieves performance comparable to end-to-end LLM approaches with substantially lower computational cost.

Protecting patient privacy in clinical narratives is essential for enabling secondary use of healthcare data under regulations such as GDPR and HIPAA. While manual de-identification remains the gold standard, it is costly and slow, motivating the need for automated methods that combine privacy guarantees with high utility. Most automated text de-identification pipelines employed named entity recognition (NER) to identify protected entities for redaction. Although methods based on differential privacy (DP) provide formal privacy guarantees, more recently also large language models (LLMs) are increasingly used for text de-identification in the clinical domain. In this work, we present the first comparative study of DP, NER, and LLMs for Dutch clinical text de-identification. We investigate these methods separately as well as hybrid strategies that apply NER or LLM preprocessing prior to DP, and assess performance in terms of privacy leakage and extrinsic evaluation (entity and relation classification). We show that DP mechanisms alone degrade utility substantially, but combining them with linguistic preprocessing, especially LLM-based redaction, significantly improves the privacy-utility trade-off.

Electronic health record (EHR) question answering is often handled by LLM-based pipelines that are costly to deploy and do not explicitly leverage the hierarchical structure of clinical data. Motivated by evidence that medical ontologies and patient trajectories exhibit hyperbolic geometry, we propose HypEHR, a compact Lorentzian model that embeds codes, visits, and questions in hyperbolic space and answers queries via geometry-consistent cross-attention with type-specific pointer heads. HypEHR is pretrained with next-visit diagnosis prediction and hierarchy-aware regularization to align representations with the ICD ontology. On two MIMIC-IV-based EHR-QA benchmarks, HypEHR approaches LLM-based methods while using far fewer parameters. Our code is publicly available at https://github.com/yuyuliu11037/HypEHR.

We evaluated whether a glaucoma risk assessment (GRA) model trained on All of Us national data can identify patients at high probability of glaucoma using only systemic electronic health records (EHR) at an independent institution. In this cross-sectional study, 20,636 Stanford patients seen from November 2013 to January 2024 were included (15% with glaucoma). A pretrained GRA model was fine-tuned on the Stanford cohort and tested on a held-out set using demographics, systemic diagnoses, medications, laboratory results, and physical examination measurements as inputs. The best model achieved AUROC 0.883 and PPV 0.657. Calibration was consistent with clinical risk: the highest prediction decile showed the greatest glaucoma diagnosis rate (65.7%) and treatment rate (57.0%). Performance improved with more trainable layers up to 15 and with additional data. An EHR-only GRA model may enable scalable and accessible pre-screening without specialized imaging.

Large Language Models (LLMs) have shown strong promise for mining Electronic Health Records (EHRs) by reasoning over longitudinal clinical information to capture context-rich patient trajectories. However, leveraging LLMs for structured EHRs (e.g., standardized diagnosis and medication codes) presents two key challenges. First, translating time-stamped EHR sequences into plain text can obscure both temporal structure and code identities, weakening the ability to capture code co-occurrence and longitudinal regularities. Second, unlike cohort-trained predictive models that learn a shared, task-aligned representation space across patients, LLMs are often applied in a case-isolated inference setting where each patient is processed independently without leveraging population-level patterns. To address these challenges, we introduce RePrompT, a time-aware LLM framework that integrates structured EHR encoders through prompt tuning, without modifying underlying architectures. Specifically, RePrompT recurrently incorporates latent states from prior visits to preserve longitudinal information, and injects population-level information through trainable prompt tokens derived from a cohort-trained, task-aligned EHR encoder. Experiments on MIMIC-III and MIMIC-IV demonstrate that RePrompT consistently outperforms both EHR-based and LLM-based baselines across multiple clinical prediction tasks.

Breast cancer is a leading cause of cancer-related mortality worldwide, and timely accurate diagnosis is critical to improving survival outcomes. While convolutional neural networks (CNNs) have demonstrated strong performance on histopathology image classification, and machine learning models on structured electronic health records (EHR) have shown utility for clinical risk stratification, most existing work treats these modalities in isolation. This paper presents a systematic multimodal framework that integrates patch-level histopathology features from the BreCaHAD dataset with structured clinical data from MIMIC-IV. We train and evaluate unimodal image models (a simple CNN baseline and ResNet-18 with transfer learning), unimodal tabular models (XGBoost and a multilayer perceptron), and an intermediate-fusion model that concatenates latent representations from both modalities. ResNet-18 achieves near-perfect accuracy (1.000) and AUC (1.000) on three-class patch-level classification, while XGBoost achieves 98% accuracy on the EHR prediction task. The intermediate fusion model yields a macro-average AUC of 0.997, outperforming all unimodal baselines and delivering the largest improvements on the diagnostically critical but class-imbalanced mitosis category (AUC 0.994). Grad-CAM and SHAP interpretability analyses validate that model decisions align with established pathological and clinical criteria. Our results demonstrate that multimodal integration delivers meaningful improvements in both predictive performance and clinical transparency.