Longitudinal Patient Records

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.

Large language models can convert medical documents into structured data, but plausible output may still be unsupported by the source. Persisting such output in a longitudinal health record, a record that accumulates patient information over time, therefore creates an integrity risk: unverified data may influence later summaries, trends, or preventive-care computations. We introduce an evidence-gated trust-promotion model that keeps generated data provisional until a deterministic monitor verifies it against the source document. The monitor admits a candidate for a specified downstream use only when the source contains a unique supporting quotation, the relevant fields occur within the same laboratory row, and the required provenance is preserved. The generator cannot approve its own output, missing or ambiguous evidence causes refusal, and refused candidates remain available for human review rather than being silently discarded. We implement the model in Medical DataCloud, a personal health-record application, and evaluate it through automated tests and a replay of saved extraction outputs. All 22 conformance and mutation tests pass. The replay covers nine historical laboratory PDF reports containing 102 manually labelled rows. The reports produce 97 numeric candidates: schema validation accepts all 97, an earlier packet-level evidence check accepts 94, and the hardened quotation- and row-level policy admits 72 while retaining 25 for review. The study evaluates system integrity rather than clinical correctness or clinical safety. The results demonstrate the technical feasibility of an enforceable boundary that prevents generated claims from authorizing their own reuse in a longitudinal health record.

Computed tomography (CT) is widely used for clinical diagnosis and longitudinal follow-up, yet automatically generating accurate and complete radiology reports from three-dimensional (3D) CT remains challenging. Existing methods improve fine-grained correspondence between images and text by modeling anatomical regions, but remain centered on the current examination. Consequently, patient-specific longitudinal changes within individual regions remain insufficiently modeled. Meanwhile, interval changes are often distributed across multiple anatomical regions, complicating a coherent assessment of the overall longitudinal state. We propose Anatomically Localized Temporal Evidence Representation (ALTER) to address these limitations. Global Prior Integration (GPI) incorporates the prior CT and report to establish historical context for the current examination. Regional Proxy Differencing (RPD) enables each current anatomical region to retrieve a historical proxy from a single shared encoding of the prior volume and to derive localized interval evidence. Interval Change Fusion (ICF) further combines current abnormality states with region-distributed differences, converting their joint representation into change-aware soft prompts that guide report generation. ALTER achieves state-of-the-art results on most evaluation metrics across the RadGenome-ChestCT validation and CTRG-Chest-548K test sets. Code and data preprocessing details are available at https://github.com/peytonkarlie/ALTER/tree/main.

Detecting anomalies in longitudinal clinical profiles is clinically important but difficult: abnormal evidence is often sparse, patient histories have unequal length, and expert explanations are costly. We propose INCLAIR, a framework that scores each observation against multiple historical contexts, aggregates evidence at the profile level, and generates grounded natural-language explanations under limited expert supervision. Under stated within-profile exchangeability assumptions, the complete mean subsequence score takes an order-$l$ U-statistic form, yielding a variance decomposition and an incomplete-subset approximation that controls combinatorial inference cost independently of profile length. The same analysis shows that mean aggregation attenuates localized anomalies by a factor set by the anomaly support and profile length, motivating validation-selected top-$k$ pooling. Across three clinical datasets, INCLAIR consistently outperforms state-of-the-art baselines. We further validate practical relevance through a case study on longitudinal steroid profiles, comparing INCLAIR's predictions and explanations against domain-expert assessments supported by DNA analysis. The results show that INCLAIR enables clinically actionable anomaly detection under limited expert supervision.

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

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.

Color Fundus Photography (CFP) is a primary non-invasive imaging modality for large-scale screening of ophthalmic and systemic diseases. Existing surveys mainly summarize task-specific algorithms, datasets, or preprocessing techniques independently, lacking a unified perspective on their co-evolution with modern artificial intelligence. This review provides an integrated overview of CFP AI through the interplay of dataset evolution, preprocessing paradigms, and modeling frameworks. We show that CFP datasets have evolved from small single-center collections with task-specific labels to large multi-center resources featuring multimodal pairings and longitudinal clinical records. Preprocessing has progressed from conventional image enhancement to neural data-engineering pipelines, hardware-aware token optimization, and self-supervised imputation for incomplete electronic health records (EHRs). Meanwhile, modeling has advanced from convolutional neural networks (CNNs) to vision foundation models, state space models (SSMs), and multimodal expert architectures. At the multimodal frontier, CFP is increasingly integrated with EHRs and longitudinal patient information, enabling more comprehensive clinical reasoning beyond isolated image analysis. We conclude that future progress depends on the collaborative optimization of datasets, preprocessing, and multimodal modeling, providing a roadmap toward robust clinical deployment, improved cross-domain generalization, and resource-efficient edge intelligence.

Radiologists routinely compare current and prior chest X-rays to track disease progression, producing follow-up reports that describe multiple findings, each localised to an anatomical region and annotated with a temporal change status. Existing automated methods either generate reports from a single image without modelling temporal context, or incorporate temporal information but do not ground their outputs spatially. The few approaches that combine temporal reasoning with spatial grounding are restricted to single-finding descriptions, leaving multi-finding reports with mixed change directions unaddressed. We present GRCD, a framework for grounded report generation from chest X-ray pairs in the multi-finding setting. We first construct a rigorously cleaned dataset of temporal chest X-ray pairs by identifying and correcting two systematic labelling errors in the source annotations. We then introduce a Region-Guided Change Token module that encodes per-region temporal change across anatomical structures and injects this signal into a language model through a dual-pathway strategy combining prepended spatial tokens with gated cross-attention. On a multi-finding test set, GRCD outperforms existing baselines on text generation and clinical accuracy metrics, with gains in change detection. Ablation studies confirm that the dual-pathway design outperforms either integration strategy in isolation on text and clinical metrics, and that region-level change encoding is necessary for multi-finding generation. Code is available at https://github.com/UTSA-VIRLab/GRCD

The verbose context problem occurs when structured concepts have token-inefficient textual representations. This bottleneck is acute in population health: cohort-level analysis of longitudinal patient records requires reasoning over thousands of medically-coded events, often exceeding 400K tokens in total. We present PopMedQA, a benchmark isolating this problem through computational tasks on groups of longitudinal patient records. We construct the benchmark using neopatient, a new library for language-controlled generation of artificial patient records. Through extensive ablations -- including prompting strategies, prompt compression, and agentic decomposition -- we find that domain-independent methods fail to alleviate the verbose context problem. There remains significant opportunity to exploit domain-specific structure in language model inputs for population-scale reasoning.

In longitudinal clinical practice, every chest X-ray is read in the context of the patients prior exam, and much of what the radiologist communicates is the change from one visit to the next. To the best of our knowledge, we present the first training-free best-of-N sampling scheme for pre-trained chest X-ray report generators that is explicitly aware of this longitudinal prior to current transition. We call it transition-aware best-of-N sampling, each report is split into sentences and embedded into an unordered set in Rd; each (prior, current) pair is reduced to a fixed-dim directional vector via a set-to-set distance designed to encode the change between the two sets; and candidates are scored by cosine distance from their candidate transition vector to a cached bank of ground-truth training transition vectors, aggregated as min or kNN. We instantiate the framework with four directional set distances (mean-shift, novelty residual, directed-Hausdorff anchor, and cost-weighted optimal transport) and evaluate on a multi-visit AP-PA cohort, running inference under three prompts on three vision-language generators. Transition-aware best-of-N outperforms random selection across the board, with the largest relative gains on the Impression section.

Sleep diaries are central to behavioral sleep medicine and cognitive behavioral therapy for insomnia, yet daily completion is difficult to sustain, and static forms often provide limited context for interpreting night-to-night sleep variation. We designed an LLM-powered conversational voice diary that delivers clinically grounded morning and evening sleep diary questions through proactive smart-speaker prompts, structured conversational intake, and adaptive follow-up dialogue. We evaluated the system in a four-week between-subjects field study with 30 university students, comparing it with a text-based mobile diary using matched diary items, reporting windows, and reminder intervals. Compared with the text-based diary, the conversational voice diary showed higher adherence and elicited more detailed contextual self-report about routines, stressors, environmental conditions, and other sleep-related factors. Participants also described the voice diary as easier to integrate into daily routines, despite longer perceived completion time. However, voice-based conversational intake produced lower completeness for some structured diary fields, revealing a trade-off between expressive richness and structured precision. These findings show both the promise and the challenge of using LLM-powered conversational voice assistants for longitudinal health self-report.

Public AI evaluations are often read as terminal leaderboards, yet the underlying evidence is a selective time series shaped by reporting rules, benchmark revisions, and missingness. Repeated public archives for LiveBench and Open LLM Leaderboard v2 serve as the primary longitudinal record; LMArena provides a preference stress test; and GAIA and tau-bench contribute limited agentic pilots. Together, these archives instantiate a Bayesian inference problem: under a fixed reporting convention, one constructed terminal-only example over $1{,}000$ systems is compatible with two pre-terminal histories, yielding times of $23.03$ or $75.13$ to reach within $0.05$ of the ceiling under the same terminal-tail model. In synthetic posterior comparisons, action-facing diagnostics differ across observation regimes. The candidate selection-aware frontier model fails synthetic recovery, objective-archive prediction, preference transfer, and uncertainty calibration; correspondingly, fixed audit gates reject its stronger claims. An archive-and-adjudication protocol reconstructs public evaluation histories, isolates a verified timing boundary, and falsifies unsupported frontier claims.

Accurate estimation of long-term care transition probabilities is central to disability insurance pricing, reserving, and solvency assessment. Classical actuarial multi-state models commonly rely on Markov, semi-Markov, or proportional-hazard specifications, which provide a direct connection to cohort projection but may be restrictive for irregular longitudinal health data with nonlinear aging patterns and heterogeneous covariate histories. This paper develops a well-calibrated estimator of multi-state transition probabilities for irregular longitudinal health data. The model learns from individual health history, incorporates the time elapsed between observations, and conditions transition probabilities on demographic and socioeconomic attributes. It produces a valid probability distribution over the next observed health state, with four possible states: healthy, mild disability, severe disability, and death. Individual probabilities are aggregated by age group and origin state to form transition matrices compatible with actuarial cohort projection. Using longitudinal data from the Health and Retirement Study, we compare the proposed estimator with logistic regression, gradient-boosted trees, a recurrent neural network, and a last-state persistence benchmark. The evaluation considers probabilistic accuracy, endpoint discrimination and calibration for severe disability and death, risk concentration, and transition matrix error after aggregation. The proposed estimator improves severe disability discrimination relative to logistic regression and gradient-boosted tree benchmarks, maintains strong calibration, and yields the lowest transition matrix error among the evaluated models in the held-out test analysis. Results show that a structured machine learning estimator can support long-term care transition modeling when judged by calibration and projection fidelity, beyond discrimination.

Huntington's disease (HD) is a progressive brain disorder that gradually affects movement, cognitive function, and behavior. Identifying the stage of the disease accurately and consistently is important for understanding its course, grouping patients, personalized care, and discovering treatment. Existing clinical staging frameworks rely primarily on predefined clinical measurement thresholds and clinical expert decisions, yet these discrete cut-offs may obscure meaningful intra-stage variability and remain vulnerable to inter-rater differences, especially in motor and functional assessments. To address these limitations, we developed an unsupervised machine learning framework based on dynamic graph representation learning to capture temporal relationships within and across patients from longitudinal clinical measurements. Using the learned representations, we applied K-means++ clustering to identify well-separated groups. We then iteratively increased the number of clusters (k), using stability analysis to assess robustness and reveal additional meaningful clusters beyond the initial optimal solution. We applied the framework to 302 individuals from the Enroll-HD cohort (1,477 visits, 44 clinical variables per visit; 80% manifest participants), enabling data-driven discovery of HD stages reflecting natural clinical progression. Despite the limited cohort size, the proposed framework achieved robust clustering performance using a four-dimensional latent space, identifying four meaningful and statistically distinct disease stages through clustering stability analysis. Each stage corresponded to well-defined clinical measurement boundaries, with minimal overlap compared to previously established clinical staging methods.

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.

Medical treatment recommendation poses several challenges to reinforcement learning (RL): patient physiology evolves in continuous time, measurements and interventions are performed at irregular intervals, and treatment effects vary substantially across individuals. Existing RL formulations and simulated environments, however, are based on discrete-time MDPs with fixed decision intervals. Thus, it remains difficult to evaluate whether RL methods can handle time-interval-dependent disease progression, personalized treatment response, and safety between consecutive measurement points. To address this gap, we introduce MedGym, a benchmark environment for dynamic treatment recommendation. MedGym models longitudinal patient evolution in a continuous-time framework and constructs a configurable medical RL benchmark from clinical data by using Physics-Informed Neural Networks. The resulting benchmark enables direct comparison between discrete-time and continuous-time methods under irregular treatment timing and patient-specific dynamics. Furthermore, MedGym supports evaluation from clinically important perspectives, such as personalization and trajectory-level safety. By providing a standardized and configurable benchmark for continuous-time dynamic treatment, MedGym enables more realistic and informative evaluation of medical RL methods.

Wearable devices enable continuous monitoring of physiological signals such as ECG and PPG, but existing mHealth systems are largely limited to task-specific prediction pipelines or reactive question answering over static summaries. They lack the ability to support temporal reasoning, persistent physiological context, and proactive monitoring over long-term signal streams. We propose VitalAgent, a tool-augmented agentic framework for ECG/PPG-based mHealth that supports both reactive question answering and proactive monitoring. VitalAgent is built on a longitudinal physiological memory and a tool-augmented reasoning interface that enables dynamic computation over raw signals. We further introduce VitalBench, a longitudinal physiological monitoring benchmark dataset comprising 1,862 QA pairs for reactive question answering and 90.2 hours of continuous ECG/PPG recordings for proactive monitoring, covering cardiac, physical activity, and stress-related tasks. Experiments demonstrate that VitalAgent achieves over 25% improvement over prompt-based and ReAct baselines in reactive evaluation and supports proactive alert monitoring over long-term physiological signals, highlighting the importance of dynamic tool use and long-term physiological monitoring.

Chronic dermatologic diseases such as pemphigus require long-term follow-up, generating extensive longitudinal clinical documentation that is difficult to review comprehensively during routine visits and increasing clinician workload as well as the risk of missing critical historical information. We evaluated whether a locally deployed, privacy-preserving small language model (SLM) could retrieve structured clinical features and generate longitudinal summaries from long-term dermatology follow-up records. In this retrospective case series, thirty pemphigus patients contributed 541 visit notes that were aggregated into full longitudinal records (89,336 words); 56 clinically relevant features were annotated by two expert dermatologists. The locally deployed SLM (Qwen3 4B Thinking 2507) was queried with each complete record to retrieve 56 features and generate one final report summaries. Across 1,680 feature retrieval tasks, mean accuracy was 82.25%. Dermatologists' ratings of AI-generated summaries were high for overall quality (8.23-8.47), clinical accuracy (7.93-8.20), and usefulness (8.47-8.50), with no significant inter-evaluator differences and an overall preference for AI summaries in 53.3% of evaluations. These findings suggest that privacy-preserving, locally deployed SLMs can outperform medical experts and reliably generate clinically meaningful longitudinal summaries. SLMs may support clinical decision-making when integrated with appropriate oversight.

A critical challenge facing clinicians managing chronic disease interventions is sustaining long-run patient health given limited information and resources. Digital therapeutics (DTs) provide a cost-effective way to manage interventions at scale through repeated interactions (e.g. daily treatment recommendations), but patient success is highly dependent on their adherence. Behavioral psychology suggests that both treatment recommendations and past adherence affect future adherence, yet existing decision support frameworks for DTs model only recommendation effects or treat adherence as exogenous context, leaving a key gap in model and algorithm development. To address this gap, we present a DT decision support framework that captures both recommendation and adherence effects, allowing clinicians to better plan treatment recommendations. We model a patient's time-varying capacity for engagement with treatment using a linear dynamical system (LDS) that captures both recommendation and adherence effects, endogenously connected to adherence behavior with a logit link. We establish finite-time identification guarantees for this model, extending LDS results to our setting. Next, we propose an optimism-based algorithm, UCB-BOLD, for online treatment selection and prove that it achieves sublinear regret. We evaluate UCB-BOLD against benchmarks via ablation studies on a synthetic patient cohort generated using micro-randomized trial data. DT decision support tools can include dynamical models to enable decision makers to efficiently use the data in DT settings to improve patient health through effective resource allocation. While myopic or heuristic approaches suffice for some patient types, the benefits of explicitly planning around recommendation and adherence effects are significant for others; UCB-BOLD achieves 2-3x lower conditional value-at-risk regret than the next-best benchmark.

Longitudinal chest X-ray (CXR) interpretation requires reasoning over disease evolution across multiple patient visits, yet most existing medical VQA benchmarks focus on single images or short-horizon image pairs. We introduce MI-CXR, a benchmark for standardized evaluation of Multi-Interval longitudinal reasoning over multi-visit CXR sequences, without requiring free-form report generation or additional clinical context. MI-CXR comprises five-way multiple-choice questions over five-visit patient timelines and instantiates three complementary task families: Temporal Event Localization, Interval-wise Change Reasoning, and Global Trajectory Summarization, which assess clinically grounded visual reasoning over time. Evaluating 14 state-of-the-art vision-language models (VLMs) shows low overall performance, with an average accuracy of 29.3%, only modestly above random guessing. Using stage-wise diagnostic probing, we find that models often produce locally plausible interval descriptions but fail to enforce temporal constraints or compose evidence into globally consistent decisions over the full timeline. These findings reveal key limitations of current VLMs and establish MI-CXR as a principled benchmark for longitudinal medical reasoning. The benchmark is available at https://github.com/AIDASLab/MI-CXR

Wearable devices capture physiological and behavioral data with increasing fidelity, but the psychological context shaping these outcomes is difficult to recover from sensor data alone, limiting passive sensing utility for digital health. We examined whether ultra-brief naturalistic concern text could serve as a scalable complement to passive sensing. In a year-long study of 458 university students (3,610 person-waves) tracked with Oura rings, participants responded bimonthly to an open-ended prompt about what concerned them most; responses had a median length of three words. We compared dictionary-based, general pretrained, and domain-adapted NLP approaches using within-person mixed-effects models across nine sleep and physical activity outcomes. Weeks dominated by academic concern framing were associated with lower physical activity; weeks characterized by emotional exhaustion language were associated with poorer sleep quality and lower heart rate variability. General pretrained embeddings outperformed domain-adapted models for most outcomes, with domain adaptation showing relative advantage for autonomic outcomes. Zero-shot classification of concern topics produced no significant associations, while affective dimensions across all three methods were consistently associated with outcomes, indicating emotional register rather than topical content carries the signal. These findings offer design guidance: ultra-brief affective prompts enrich the psychological interpretability of passive physiological data at minimal burden.

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.

Personalized healthcare decisions require reasoning about how physiological and behavioral variables influence an individual patient over time. Existing temporal causal discovery methods are poorly matched to this setting: cohort-level models provide stable but non-personalized structures, while per-patient discovery is unreliable because individual trajectories are short, noisy, irregular, and non-stationary. This creates a fundamental gap between population-level causal modeling and the patient-specific, time-varying mechanisms needed for intervention reasoning. We introduce PerCaM-Health, a framework for learning personalized dynamic causal graphs from longitudinal health data. The framework learns a knowledge-guided population temporal graph, then conservatively adapts and evolves it using patient-specific temporal evidence and rolling-window updates, producing interpretable and auditable graph sequences. By coupling these graphs with temporal structural equations, the framework enables patient-level counterfactual queries, such as estimating short-horizon outcome changes under hypothetical behavioral interventions. Experiments on a semi-synthetic dynamic health benchmark show that PerCaM-Health improves graph recovery, dynamic edge tracking, and intervention direction accuracy compared to cohort-level, per-patient, and non-personalized temporal baselines. These results demonstrate that jointly modeling personalization and temporal evolution yields more reliable causal structure and intervention reasoning.

As Large Language Model (LLM) agents transition from single-session tools to persistent systems managing longitudinal healthcare journeys, their memory architectures face a critical challenge: reconciling two imperfect sources of truth. The patient's evolving self-report is current but prone to recall bias, while the Electronic Health Record (EHR) is medically validated but frequently stale. General-purpose agent memory systems optimize for coherence by overwriting older facts with the user's latest statement, a pattern that risks safety failures when applied to clinical data. We introduce a Dual-Stream Memory Architecture that strictly separates the patient narrative from the structured clinical record (FHIR), governed by a dedicated Reconciliation Engine that evaluates every extracted memory against the patient's FHIR profile and classifies discrepancies by type, severity, and the specific FHIR resources involved. We evaluate this architecture on 26 patients across 675 longitudinal wellness coaching sessions, using a hybrid dataset that interleaves real provider-patient transcripts with synthetic, FHIR-grounded clinical scenarios. In isolated testing, the engine detects 84.4% of designed clinical discrepancies with 86.7% safety-critical recall. By coupling extraction and reconciliation evaluation on the same data, we directly quantify a 13.6% error cascade, tracing the degradation to clinical details lost during memory extraction from unstructured conversation rather than to downstream classification errors. These findings establish that validating patient-reported memories against clinical records is both feasible and necessary for safe deployment of longitudinal health agents.

Multiple myeloma is managed through sequential lines of therapy over years to decades, with each decision depending on cumulative disease history distributed across dozens to hundreds of heterogeneous clinical documents. Whether LLM-based systems can synthesise this evidence at a level approaching expert agreement has not been established. A retrospective evaluation was conducted on longitudinal clinical records of 811 myeloma patients treated at a tertiary centre (2001-2026), covering 44,962 documents and 1,334,677 laboratory values, with external validation on MIMIC-IV. An agentic reasoning system was compared against single-pass retrieval-augmented generation (RAG), iterative RAG, and full-context input on 469 patient-question pairs from 48 templates at three complexity levels. Reference labels came from double annotation by four oncologists with senior haematologist adjudication. Iterative RAG and full-context input converged on a shared ceiling (75.4% vs 75.8%, p = 1.00). The agentic system reached 79.6% concordance (95% CI 76.4-82.8), exceeding both baselines (+3.8 and +4.2 pp; p = 0.006 and 0.007). Gains rose with question complexity, reaching +9.4 pp on criteria-based synthesis (p = 0.032), and with record length, reaching +13.5 pp in the top decile (n = 10). The system error rate (12.2%) was comparable to expert disagreement (13.6%), but severity was inverted: 57.8% of system errors were clinically significant versus 18.8% of expert disagreements. Agentic reasoning was the only approach to exceed the shared ceiling, with gains concentrated on the most complex questions and longest records. The greater clinical consequence of residual system errors indicates that prospective evaluation in routine care is required before these findings translate into patient benefit.

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.

Longitudinal information in radiology reports refers to the sequential tracking of findings across multiple examinations over time, which is crucial for monitoring disease progression and guiding clinical decisions. Many recent automated radiology report generation methods are designed to capture longitudinal information; however, validating their performance is challenging. There is no proper tool to consistently label temporal changes in both ground-truth and model-generated texts for meaningful comparisons. Large language models (LLMs) offer a promising annotation alternative, as they are capable of capturing nuanced linguistic patterns and semantic similarities without extensive manual intervention. They also adapt well to new contexts. In this study, we therefore propose an LLM-based pipeline to automatically annotate longitudinal information in radiology reports. The pipeline first identifies sentences containing relevant information and then extracts the progression of diseases. We evaluate and compare five mainstream LLMs on these two tasks using 500 manually annotated reports. Considering both efficiency and performance, Qwen2.5-32B was subsequently selected and used to annotate another 95,169 reports from the public MIMIC-CXR dataset. Our Qwen2.5-32B-annotated dataset provided us with a standardized benchmark for evaluating report generation models. Using this new benchmark, we assessed seven state-of-the-art report generation models. Our LLM-based annotation method outperforms existing annotation solutions, achieving 11.3% and 5.3% higher F1-scores for longitudinal information detection and disease tracking, respectively. The source code is available at https://github.com/wxinyi1996/Standardizing-Longitudinal-Chest-X-ray-Report-Evaluation-via-Large-Language-Model-Annotation.git.

Clinical care often relies on key laboratory indicators, yet real-world patient visits are sparse and tests are ordered irregularly, leading to pervasive missingness. While many imputation methods improve average accuracy, they provide limited guidance on which imputed values are reliable enough for high-stakes downstream use. In this work, we study reliable clinical imputation, aiming to produce accurate imputations while selectively releasing the reliable results, with statistical control over clinically unacceptable errors. To achieve this goal, we propose SafeImpute, a reliable imputation framework for irregular and sparse clinical longitudinal records. SafeImpute constructs an event graph that captures both intra-patient temporal trajectories and inter-patient clinical similarity, and learns imputations with a two-relation GNN and adaptive fusion, regularized by an auxiliary masked reconstruction objective. For reliability guarantees, SafeImpute converts a proxy risk score into conformal p-values and applies the Benjamini--Hochberg procedure to control the false discovery rate (FDR) of unacceptable errors among released imputations at a user-specified tolerance. Experiments on our Mayo Clinic data, the public MIMIC-III and MIMIC-IV datasets show that SafeImpute achieves strong imputation accuracy while providing reliable error control, outperforming diverse baselines in both standard imputation evaluation and FDR-controlled selective-release evaluation.