Effective sub-typing (also known as grouping or clustering) of patients using their electronic health record (EHR) data can greatly inform precision medicine efforts. However, subtyping temporal EHR datasets is known to be challenging due to inherent EHR issues, including complexity and irregularity. In this study, we propose a self-supervised Mamba-based model that learns effective EHR representations and enables enhanced patient subtyping. We evaluate the proposed model on public and private real-world EHR datasets to classify the data based on the available labels and subtype patients based on the representations learned from the model. Through an extensive set of experiments, we demonstrate that our model's design choices lead to better performance compared to competitive baseline models for prediction. Moreover, we evaluate several clustering techniques to demonstrate that our findings offer valuable insights into subtyping patients based on temporal records from EHR models\footnote{Our implementations are available at https://github.com/healthylaife/triplet_mamba.

Survival analysis is a critical tool for modeling time-to-event data. Recent deep learning-based models have reduced various modeling assumptions including proportional hazard and linearity. However, a persistent challenge remains in incorporating longitudinal covariates, with prior work largely focusing on cross-sectional features, and in assessing calibration of these models, with research primarily focusing on discrimination during evaluation. We introduce TraCeR, a transformer-based survival analysis framework for incorporating longitudinal covariates. Based on a factorized self-attention architecture, TraCeR estimates the hazard function from a sequence of measurements, naturally capturing temporal covariate interactions without assumptions about the underlying data-generating process. The framework is inherently designed to handle censored data and competing events. Experiments on multiple real-world datasets demonstrate that TraCeR achieves substantial and statistically significant performance improvements over state-of-the-art methods. Furthermore, our evaluation extends beyond discrimination metrics and assesses model calibration, addressing a key oversight in literature.

Data collection often reflects human decisions. In healthcare, for instance, a referral for a diagnostic test is influenced by the patient's health, their preferences, available resources, and the practitioner's recommendations. Despite the extensive literature on the informativeness of missingness, its implications on the performance of Large Language Models (LLMs) have not been studied. Through a series of experiments on data from Columbia University Medical Center, a large urban academic medical center, and MIMIC-IV, we demonstrate that patterns of missingness significantly impact zero-shot predictive performance. Notably, the explicit inclusion of missingness indicators at prompting benefits some while hurting other LLMs' zero-shot predictive performance and calibration, suggesting an inconsistent impact. The proposed aggregated analysis and theoretical insights suggest that larger models benefit from these interventions, while smaller models can be negatively impacted. The LLM paradigm risks obscuring the impact of missingness, often neglected even in conventional ML, even further. We conclude that there is a need for more transparent accounting and systematic evaluation of the impact of representing (informative) missingness on downstream performance.

Intensive care unit (ICU) data are highly irregular, heterogeneous, and temporally fragmented, posing challenges for generalizable clinical prediction. We present PULSE-ICU, a self-supervised foundation model that learns event-level ICU representations from large-scale EHR sequences without resampling or manual feature engineering. A unified embedding module encodes event identity, continuous values, units, and temporal attributes, while a Longformer-based encoder enables efficient modeling of long trajectories. PULSE-ICU was fine-tuned across 18 prediction tasks, including mortality, intervention forecasting, and phenotype identification, achieving strong performance across task types. External validation on eICU, HiRID, and P12 showed substantial improvements with minimal fine-tuning, demonstrating robustness to domain shift and variable constraints. These findings suggest that foundation-style modeling can improve data efficiency and adaptability, providing a scalable framework for ICU decision support across diverse clinical environments.

Clinical notes in Electronic Health Records (EHRs) capture rich temporal information on events, clinician reasoning, and lifestyle factors often missing from structured data. Leveraging them for predictive modeling can be impactful for timely identification of chronic diseases. However, they present core natural language processing (NLP) challenges: long text, irregular event distribution, complex temporal dependencies, privacy constraints, and resource limitations. We present two complementary methods for temporally and contextually grounded risk prediction from longitudinal notes. First, we introduce HiTGNN, a hierarchical temporal graph neural network that integrates intra-note temporal event structures, inter-visit dynamics, and medical knowledge to model patient trajectories with fine-grained temporal granularity. Second, we propose ReVeAL, a lightweight, test-time framework that distills the reasoning of large language models into smaller verifier models. Applied to opportunistic screening for Type 2 Diabetes (T2D) using temporally realistic cohorts curated from private and public hospital corpora, HiTGNN achieves the highest predictive accuracy, especially for near-term risk, while preserving privacy and limiting reliance on large proprietary models. ReVeAL enhances sensitivity to true T2D cases and retains explanatory reasoning. Our ablations confirm the value of temporal structure and knowledge augmentation, and fairness analysis shows HiTGNN performs more equitably across subgroups.

Large-scale clinical databases offer opportunities for medical research, but their complexity creates barriers to effective use. The Medical Information Mart for Intensive Care (MIMIC-IV), one of the world's largest open-source electronic health record databases, traditionally requires both SQL proficiency and clinical domain expertise. We introduce M3, a system that enables natural language querying of MIMIC-IV data through the Model Context Protocol. With a single command, M3 retrieves MIMIC-IV from PhysioNet, launches a local SQLite instance or connects to hosted BigQuery, and allows researchers to pose clinical questions in plain English. We evaluated M3 using one hundred questions from the EHRSQL 2024 benchmark with two language models: the proprietary Claude Sonnet 4 achieved 94% accuracy, while the open-source gpt-oss-20B (deployable locally on consumer hardware) achieved 93% accuracy. Both models translate natural language into SQL, execute queries against MIMIC-IV, and return structured results alongside the underlying query for verification. Error analysis revealed that most failures stemmed from complex temporal reasoning or ambiguous question phrasing rather than fundamental architectural limitations. The comparable performance of a smaller open-source model demonstrates that privacy-preserving local deployment is viable for sensitive clinical data analysis. M3 lowers technical barriers to critical care data analysis while maintaining security through OAuth2 authentication, query validation, and comprehensive audit logging.