Longitudinal EHR Modeling

Early sepsis warning from ICU records can be cast as a structure-preserving prediction problem. A model needs to detect deterioration from irregular measurements while keeping each alert connected to the physiological signals that support it. Many temporal models fuse clinical variables into a patient-level representation, supporting scalar risk prediction but weakening the structure needed for clinical decomposition. We present SepsisLens, which preserves variable-indexed temporal states until risk composition. Observation-aware representations encode each variable's dynamics and measurement history, while a shared temporal encoder models each trajectory without collapsing the variable axis. The StructuredRiskHead composes multi-horizon risk from explicit variable-level and organ-level components. We evaluate SepsisLens on three public ICU cohorts and one private-hospital cohort under a common pre-onset protocol. SepsisLens achieves strong discrimination on all four cohorts and lower alert burden at matched event recall on MIMIC-IV. Structural ablations support the design, while input-side masking shows that the ranked components reflect variables with greater influence on prediction.

Synthetic patient data generation is a promising solution to the dual challenge of data scarcity and privacy constraints in healthcare machine learning. Realistic synthesis of patient-level clinical data requires jointly modeling heterogeneous static covariates, irregularly sampled longitudinal trajectories, and informative observation times - three tightly coupled components in practice yet rarely addressed together. We propose HyperNSDE, a continuous-time generative model that conditions a latent Neural SDE on static patient representations through a hypernetwork, allowing baseline characteristics to shape trajectory evolution beyond the initial condition without requiring a trajectory encoder, while stochastic latent dynamics capture realistic variability in generated paths. Observation times are modeled jointly through a latent-state-dependent intensity process, and training on irregular stochastic paths is stabilized via a deterministic-stochastic path decomposition with a non-adversarial signature-kernel objective. Experiments on simulated and real clinical datasets show improved observation-time fidelity and competitive performance, while matched-grid analyses reveal that forecasting and correlation metrics are affected by observation-grid regularity and trajectory smoothness.

A patient-timeline reconstruction system is auditable only if it keeps the mentions behind each answer, records how facts were revised, and declines to answer when the evidence is not in the text. This study tests these three properties on a fully synthetic corpus (1,000 patients, 3,353 notes, 220 revision edges). Two provenance-aware Evidence Graph operators reduced the node-plus-edge count to 67% and 63% (77-78% of serialized size) while preserving every answer and mention link across 6,813 query points answerable by recency; a fixed-window baseline returned no value for 53.4% of points, unflagged. On evidence-unavailable controls that announce the omission, a BioClinicalBERT gate and a zero-shot LLM gate responded mainly to the announcement. On marker-free controls, BERT abstained on 0 of 81 notes while its accuracy fell from 93.8% to 59.3% across all three relation classes; the LLM's coverage fell from 75.6% to 27.7% on notes its own model family judged undeterminable. Against 482 regenerated gold spans, the LLM's cited evidence reached recall 0.850 and precision 0.864; BERT's span head, trained without span labels, did not localize evidence. A temporally versioned provenance graph stored abstentions as typed, queryable edges. The clean task admits a 0.651-accuracy shortcut, and results describe implementation behaviour on synthetic data, not clinical performance.

Human health is a continuous, dynamic trajectory shaped by the cumulative interplay of biological processes, clinical events, behaviors and environmental exposures across the life course. Unifying the full breadth of lifelong health information, including longitudinal records, genetic variation, molecular profiles and environmental histories, is essential for whole-person modeling and remains a major challenge. We introduce LifeLong Digital Twin, a unified, event-driven modeling paradigm that organizes Life Events into daily Health States and accumulates them into Lifelong Health Context. An accompanying Agent Harness incorporates multimodal evidence beyond the language model's textual context. We evaluate four language models across 25 disease endpoints on three tasks: Disease Trajectory Forecasting, Disease Risk Ranking and Multi-horizon Disease Prediction. The approach yields marked gains over the reference condition: model-averaged F1 increases by 22.0% for disease identification in trajectory forecasting and 18.3% for five-year disease outcomes; thyroid-disease F1 reaches 0.669. The framework provides a foundation for whole-person digital twins and research on personalized lifelong disease prevention.

Cross-system transfer of longitudinal Electronic Health Record (EHR) representations is challenging because clinical coding, patient populations, and healthcare workflows differ substantially across institutions and countries. We introduce Asymmetric Supervised Contrastive Learning (Asymmetric SupCon), a task-specific pre-training objective motivated by the heterogeneity of negative clinical outcomes. The objective clusters patients sharing a target positive outcome without explicitly attracting negative trajectories toward one another. We pre-train temporal Transformer encoders on longitudinal records from 3.98 million patients in the Taiwanese National Health Insurance Research Database (NHIRD) and transfer them to two U.S. EHR datasets, MIMIC-IV and EHRSHOT. A hybrid semantic mapping pipeline combining direct mappings with embedding-based retrieval enables transfer across heterogeneous clinical vocabularies. On MIMIC-IV, NHIRD pre-training consistently improves over random initialization while substantially narrowing the performance gap to task-specific in-domain pre-training. On EHRSHOT, the transferred models show particularly strong few-shot performance for incident disease prediction. A controlled objective ablation under a matched pre-training scale shows that Asymmetric SupCon achieves higher mean AUPRC than direct supervised BCE transfer on all four evaluated tasks and Standard SupCon on three of four, with a 0.003 AUPRC deficit on readmission. These results support asymmetric contrastive pre-training as an effective approach for task-specific cross-national EHR representation transfer. Code is available at https://github.com/qingYzhang/Asymmetric_SupCon.

Structured electronic health records (EHRs) contain a patient's clinical trajectory as a sequence of clinical codes. Answering clinical questions from such records requires both the context of the whole trajectory and the specific events that support the answer. We introduce GLoC-EHR, a multimodal language model that reads a contextual encoding of the record through a fixed-size global memory of the trajectory and a local memory of selected events. The model learns to generate hospital-course summaries from the global memory and descriptions of masked concepts from the local memory, aligning both with clinical text. It is then trained to cite evidence before answering, through rationale fine-tuning followed by group relative policy optimization (GRPO) with rewards for correct answers and record-supported evidence. On three MIMIC-IV outcome tasks, GLoC-EHR attains the highest macro AUROC among the compared models when it answers directly, whereas zero-shot LLMs reading the serialized record fall far behind. With evidence-cited reasoning, it stays close to its direct multi-task counterpart in macro AUROC, and the evidence terms of the objective reduce unsupported evidence at a similar macro AUROC. The local memory adds distinct supported findings, particularly under strict matching, without a detectable change in macro AUROC. Without retraining, GLoC-EHR transfers to EHRSHOT on par with EHR-BERT and answers two unseen laboratory questions better than zero-shot prompting of its own backbone.

Opioid overdose remains a major clinical and public health burden, highlighting the need for scalable approaches to identify patients at high risk. Here, we investigate diagnosis-specific adaptation for 180-day opioid overdose risk prediction from patients' preceding one-year longitudinal ICD histories. We develop OODMAMBA and OODQWEN through continued pretraining on longitudinal diagnostic sequences followed by task-specific fine-tuning. Building on the stronger Qwen-based predictors, we further propose OVERDOSEMOE, a multi-expert framework that integrates models of different scales using complementary expert-weighting strategies. Diagnosis-specific adaptation consistently improved predictive performance over general-purpose language-model baselines, with OODQWEN achieving an AUPRC of 24.47 and an AUROC of 68.56. OVERDOSEMOE further improved discrimination and precision, achieving an AUPRC of 25.17 and an AUROC of 69.49 while outperforming the strongest single-model baselines. Among patients ranked in the top 5% of predicted risk, OVERDOSEMOE identified substantially enriched overdose risk, achieving a PPV of 25.38% while retaining meaningful recall. Evaluation on an independent MIMIC-IV cohort further demonstrated cross-cohort robustness, with complementary weighting strategies showing advantages across different performance measures. These findings demonstrate that diagnosis-specific language-model adaptation combined with multi-expert integration can improve opioid overdose risk stratification and support more robust prediction across heterogeneous electronic health record populations.

Longitudinal clinical cohorts are multimodal, irregularly sampled and pervasively incomplete: in ADNI, positron emission tomography and cerebrospinal fluid assays are absent from roughly half of all visits. Linear state-space models handle irregular sampling gracefully but treat a missing modality by masking the input, leaving the transition operator untouched. We prove that this is a representational limitation: the latent state of any linear state-space layer whose transition operator does not depend on the availability pattern is an additive function of the availability indicators, so no such layer can represent an interaction between two modalities being jointly present or jointly absent. We propose CAMOS, which gives each modality a bank of second-order oscillators coupled through a matrix that sits inside the differential equation and is gated by availability, so the transition operator itself becomes a function of which measurements were taken. Coupling invalidates the analysis of uncoupled oscillatory models, and we restore it: a per-channel Gershgorin budget makes the effective stiffness positive definite uniformly over all $2^M$ availability patterns and all gaps, an energy argument charges amplification to availability transitions rather than sequence length, and a channel factorization preserves exact associative parallel scans. On ADNI, CAMOS outperforms uncoupled oscillatory state-space models and clinical fusion models on same-visit staging, landmark prediction and longitudinal forecasting, and under zero-shot transfer to OASIS-3 it is the only model that avoids collapse to the majority class.

Large language model (LLM) agents that reason over clinical records must track changes in a patient's state while preserving the history needed to understand them. Simply accumulating memories leaves it unclear which information still applies, whereas overwriting earlier memories can erase evidence needed to reconstruct treatment history and clinical trajectories. We introduce STAM, a state-transition-aware memory framework that records state changes as new clinical entries arrive. STAM combines semantic retrieval with typed clinical relations to identify affected memories, maintaining current information in Active and superseded or resolved information in History. At read time, a query-dependent gate selectively serves historical memory. Across four longitudinal clinical benchmarks, we evaluate STAM with downstream question answering, direct state-maintenance diagnostics, and comparisons at approximately matched context lengths.

Longitudinal electronic health record (EHR) modeling requires integrating new visits with an expanding patient history. Yet the continual accumulation of clinical information imposes increasing computational and memory costs on large language models (LLMs) when they process and retain complete patient histories. A practical alternative is visit-wise recurrent compression, which incorporates each incoming visit into a compact, continually updated patient memory. However, under a fixed memory budget, successive updates must integrate new information without progressively losing critical historical evidence needed to subsequent tasks. To address this challenge, we introduce Recurrent Longitudinal Memory (ReLMem), a framework that learns to maintain fixed-capacity patient memory for efficient downstream prediction with a frozen LLM. ReLMem equips this LLM with lightweight compression adapters to recurrently update the memory from its previous state and each incoming visit, without rereading earlier records. Specifically, we develop a multi-granularity optimization strategy to preserve task-relevant information throughout recurrent updates and support downstream prediction from the final memory. The intermediate supervision aligns attention outputs from compressed memory and the full history under identical queries, while prediction supervision minimizes cross-entropy with ground truth answers conditioned on the final memory. On EHR-based medication prediction, ReLMem approaches the F1 scores of full-history baseline while reducing average retained historical storage by 97.1%. Under the same memory budget, it improves macro- and micro-F1 over the strongest compressed-memory baseline by 4.66 and 4.75 percentage points, respectively. These results highlight the value of learning recurrent patient memory for efficient longitudinal EHR modeling.

Generating a plausible clinical trajectory does not establish what would happen under a different treatment. We present ADMIT, a framework combining irregular multimodal representations, treatment-conditioned latent diffusion and explicit constraints on generated states or actions. We formulate its interventional target through sequential g-computation and distinguish causal assumptions from constraint satisfaction. Its admissibility mechanism translates physiological prior knowledge into explicit constraints on generated states and proposed actions. Treatment-exposure dynamics condition latent transitions, while state projection or action gating applies the constraints during rollout so that they influence subsequent trajectory generation. In our preliminary experiments, multimodal inputs improved supervised hidden-state recovery and reduced treatment-contrast error. In a simulated dosing-schedule experiment with leak-free history encoding, ADMIT predicted most of the tumor-volume change caused by redistributing a fixed total dose. An exposure input improved these predictions around a temporary dose reduction whether or not the assumed clearance rate was correct, but reduced the predicted size of a dose effect, and a deterministic recurrent baseline matched ADMIT's average predictions. Exposure projection reduced constraint violations, although enforcement remained incomplete. Semi-synthetic experiments using eICU context illustrated treatment-response generation under fixed and adaptive policies. Observational examples further characterize model treatment sensitivity. ADMIT provides a framework for testing whether complementary observations and physiological restrictions improve intervention trajectories, with representation recovery, effect accuracy and rule enforcement assessed separately.

Electronic health records (EHRs) encode clinical histories as (time, modality, code) tuples, whereas pretrained language models expect text tokens. Serializing them as text inflates sequence length and redundantly encodes structure. We introduce EHRAdapt, an adapter that maps tuples directly into a frozen language model's embedding space. Modality receives a learned embedding, time gaps enter through learned attention biases, and event codes receive dedicated vectors. Learning event vectors is the central challenge: clinical vocabularies are long-tailed, leaving rare events too few observations for reliable estimates. EHRAdapt therefore represents each event vector as the sum of a semantic prior and an evidence residual. The prior is a frozen embedding of the event's clinical description from a biomedical language model trained on clinical ontologies, mapped into the model's input space by a shared learned projection, so it supplies clinical meaning even when observations are scarce. The residual, a learned low-rank event-specific correction, refines it as evidence accumulates. We run continued pretraining on about 4 million patients' records with three frozen LLM backbones (OLMo2 1B, Llama3.2 1B, and OLMo2 7B), training only the adapter (0.1--0.6% of all parameters). The full adapter outperforms all ablations in held-out next-event prediction on every backbone. Removing the semantic pathway hurts rare events over ten times more than the most frequent ones, whereas removing the residual hurts overall prediction but improves it for the rarest events. On reportable infectious-disease and syndromic downstream classification tasks, EHRAdapt outperforms text-based LLM and count-based baselines, and both pathways improve rare-disease discrimination. The two pathways therefore play complementary roles, visible only when results are broken down by event frequency rather than averaged.

Representation learning from medical code sequences in electronic health records and medical claims data has been successful in various clinical applications, such as those regarding disease prediction. However, significant challenges remain in extending this approach to the discovery of scientific hypotheses. One reason is that many existing BERT-based models fail to adequately capture the hierarchical structure of medical codes and the complex interactions between diagnoses and treatments. To address these limitations, we propose a new unified pre-training framework that explicitly integrates hierarchical sub-token aggregation, partial masking, and cross-reference mechanisms. The proposed model consistently outperformed existing methods on both pre-training objectives and downstream clinical event prediction tasks, including the onset of dementia and hospitalization. We also conducted an in silico drug repositioning case study targeting Alzheimer's disease. In the hypothesis generation step, our approach successfully rediscovered known promising drugs in a data-driven manner without relying on such external knowledge sources as the literature. Subsequently, in the hypothesis prioritization step, we introduced a Task-Adaptive Representation Approach to alleviate the over-encoding of historical prescription information within diagnostic vectors, enabling the robust prioritization of generated hypotheses. This study establishes an exploratory screening workflow for hypothesis generation and prioritization based on observational associations. Importantly, this framework is not intended to provide causal evidence, but rather to identify promising candidates for subsequent rigorous causal inference. Overall, this study demonstrates that domain-informed representation learning combined with task-adaptive representation control can enable a practical hypothesis discovery workflow.

In mental health care, reasoning over patient journeys is a key task for clinicians. Yet these journeys, encompassing a longitudinal progression of biological, psychological, and social events, are often spread across disparate unstructured text narratives, making temporal recovery challenging. We present CliniCIRCA, a multi-stage LLM framework for Calendar-anchored, Imprecision-aware Reconstruction of Clinical Annals. To our knowledge, CliniCIRCA is the first to temporally classify clinical events across unstructured discharge summaries without event-level timestamps. From 14,882 MIMIC-III mental health admissions, we first construct a benchmark of 52 discharge summaries on which CliniCIRCA produces 15,891 temporally tagged events. After correcting 629 errors based on a clinician-in-the-loop evaluation, we produce verified gold-standard labels. Finally, the corrected timelines drive a temporally grounded summarization stage that compresses each source 1.52 times into a date-grouped chronological record. We then scale the framework to generate 1,000 silver-standard timelines and evaluate them as training data. Compared with zero- and few-shot prompting, instruction tuning generally improves five open-weight models on event extraction, temporal tagging, and summarization across silver and clinician-verified evaluations.

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.

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.

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 digitization of healthcare has generated vast, longitudinal, and multimodal patient records over a lifetime, yet fully exploiting these data to represent and predict patient state trajectories remains a critical challenge. Current AI models often struggle to capture the complex, irregular temporal dynamics and inherent stochasticity of real-world multimodal patient data. Existing AI approaches for modeling longitudinal patient records are predominantly discriminative, limited to a few modalities, constrained by closed categorical vocabularies, treating time as a monotonic inductive bias, or they are limited in forecasting future patient states. We introduce NOAH, a time-aware, task-agnostic, generative transformer model representing and forecasting the full multimodal patient journey. NOAH features a novel bidirectional time integration and a variational latent space to capture the continuous evolution of patient states and the stochasticity of clinical trajectories. Built from over 559 million clinical events from 431,000 hospital visits of 299,000 patients across the MIMIC dataset family, NOAH natively processes medical images, time-series and numeric signals, categorical events, as well as structured and unstructured clinical records. NOAH is the first truly holistic generative model in its field, enabling autoregressive forecasting with optional time control, zero-shot classification, and counterfactual intervention simulation. It generates highly informative and predictive patient state representations that demonstrate strong performance in probing for clinical outcomes, 15 ICD chapters, and 29 comorbidities, as well as in time-to-event prediction. Seamlessly handling diverse modalities and complex temporal dynamics, NOAH provides a versatile, task-agnostic, scalable foundation for intelligent predictive systems in personalized clinical care and digital medicine.

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.

Clinical data sources such as electronic health records and wearable sensors record patient status repeatedly over follow-up, often at irregular times and on different schedules for different measurements. These data create opportunities for continuously updated, individualized risk prediction. Existing approaches, however, often simplify the temporal structure for model fitting. We introduce Random Hazard Forests (RHF), a survival tree ensemble that estimates how a patient's hazard changes in continuous time as new measurements become available. The method formulates the estimation problem directly through a nonparametric hazard likelihood for predictable covariate processes. An efficient working model guides tree construction, after which flexible time-varying hazards are estimated for each terminal node. Given any predictable covariate path, each tree follows the path through its terminal nodes over time and assembles the corresponding node-level hazards into a trajectory. Averaging these trajectories across trees yields the pathwise hazard estimate. Because routing at each time uses only the covariate state available immediately beforehand, the construction accommodates internal longitudinal covariates without lookahead. Simulations and an intensive care application show that the forest accurately estimates changing risk under irregular and asynchronous covariate updates.

Many clinical prediction models treat post-intervention outcomes as a one-step mapping from baseline measurements to a future endpoint. However, recovery after a procedure often unfolds as an irregular trajectory: clinical observations, medication changes, repeat interventions, and physiological measurements are recorded asynchronously and can change risk assessment over time. We propose an intervention-aware clinical world model that represents each patient with a structured latent state and evolves it through time-ordered post-intervention events. The model first encodes baseline imaging into a 3D spatial latent state. It then updates this state using procedural context, static covariates, elapsed time, and peri-event physiological embeddings. Follow-up imaging provides training-only supervision through a latent forecasting objective. We apply the framework to atrial fibrillation ablation. During the 90-day recovery window, irregular post-procedure records provide clinically meaningful evidence for long-term recurrence risk. In repeated internal cross-validation on DECAAF-II, our model achieves AUROC 0.756 and AUPRC 0.777 for recurrence prediction. It also achieves a scar-extent MAE of 2.971 percentage points without requiring follow-up MRI intensities at inference. The learned state supports recurrence-risk queries at different horizons and retrospective input editing of blanking-period records.

Cardiac arrest remains one of the most lethal conditions encountered in intensive care units. Despite the growing availability of electronic health record data, existing mortality prediction studies in this population largely depend on static summaries derived from early admission. Such approaches ignore the temporal progression of physiological deterioration and recovery that unfolds throughout a patient's ICU stay. To address this limitation, we introduce QuanTiMedAI, a quantum-agentic framework developed for cardiac arrest mortality prediction using agentic AI guided quantum enhancement time series model. The proposed system combines an agentic large language model (LLM) for clinically informed feature discovery with a compact quantum recurrent network for temporality aware mortality prediction. Our findings demonstrate that agentic LLM-guided feature selection consistently outperforms conventional feature selection approaches, and the proposed quantum architecture achieves competitive predictive performance through nonlinear feature enhancement while keeping the number of parameters very low. Through extensive experimentation on a MIMIC-IV cohort of cardiac arrest patients, QuanTiMedAI's quantum-enhanced architecture attains an AUROC of 0.852 using only 605 parameters, an improvement of approximately 2.9% over a current state-of-the-art baseline for this task. A structured ablation study systematically validates the contribution of each architectural design choice. These results show that quantum-enhanced sequential modeling can exceed classical recurrent networks while using substantially fewer parameters.

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.

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.

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

Many time-series forecasts depend not only on prior observations but also on actions specified during the forecast period. In intensive care units (ICUs), future vital signs and laboratory values are influenced by treatments such as vasopressors. However, models that predict the full future sequence all at once make little use of these treatments, whereas autoregressive models can accumulate errors. We introduce DRIFT, a hybrid framework in which a direct model produces the primary forecast and a recursive, action-conditioned model contributes constrained corrections. We evaluate DRIFT on 6,046 admissions from MIMIC-IV and 8,345 admissions from eICU-CRD. Averaged across the 8-, 24-, and 48-hour forecast endpoints, DRIFT reduces mean absolute error for mean arterial pressure (MAP) by 0.673% relative to an action-conditioned Temporal Fusion Transformer (TFT-action) on MIMIC-IV and achieves the lowest corresponding error among the compared models on eICU-CRD. Although the overall accuracy improvement is modest, a MIMIC-IV audit restricted to windows in which the supplied treatment sequence was altered showed that DRIFT achieved lower observed-target MAP error than TFT-action at 8 and 24 hours. Treatment-sequence alteration increased DRIFT's MAP error by 0.21-0.26 mmHg more than it increased TFT-action's error, with prediction changes occurring primarily after the supplied paths diverged. In a separate robustness experiment, the MAP advantage persisted under three shared checkpoint-selection rules emphasizing overall endpoint error, MAP error, or both equally.

Understanding disease trajectories from longitudinal clinical data remains challenging due to complex temporal dynamics and heterogeneous patient cohorts. Here, we present a contrastive representation learning framework that models multivariate disease trajectories as temporal graphs and learns representations using contrastive graph neural networks. Nodes represent patient observations over time, while edges capture temporal continuity and structural similarity between trajectories. Structure-aware random walks guide contrastive learning to generate embeddings that preserve temporal context and trajectory topology. The resulting representations enable robust clustering of patients with similar disease progression patterns and reveal latent structure in longitudinal data.

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.