Improving Patient Subtyping on Longitudinal Data using Representations from Mamba-based Architecture

Electronic health Records (EHRs) have become a cornerstone in modern-day healthcare. They are a crucial part for analyzing the progression of patient health; however, their complexity, characterized by long, multivariate sequences, sparsity, and missing values poses significant challenges in traditional deep learning modeling. While Transformer-based models have demonstrated success in modeling EHR data and predicting clinical outcomes, their quadratic computational complexity and limited context length hinder their efficiency and practical applications. On the other hand, State Space Models (SSMs) like Mamba present a promising alternative offering linear-time sequence modeling and improved efficiency for handling long sequences, but focus mostly on mixing sequence-level information rather than channel-level data. To overcome these challenges, we propose HyMaTE (A Hybrid Mamba and Transformer Model for EHR Representation Learning), a novel hybrid model tailored for representing longitudinal data, combining the strengths of SSMs with advanced attention mechanisms. By testing the model on predictive tasks on multiple clinical datasets, we demonstrate HyMaTE's ability to capture an effective, richer, and more nuanced unified representation of EHR data. Additionally, the interpretability of the outcomes achieved by self-attention illustrates the effectiveness of our model as a scalable and generalizable solution for real-world healthcare applications. Codes are available at: https://github.com/healthylaife/HyMaTE.

Autoregressive foundation models for electronic health records (EHRs) typically inherit pretraining methods from language modeling, where patient trajectories are concatenated into a single token stream and windows are sampled from that stream. In EHR data, this choice is consequential: windows may mix multiple patients, and patients with longer records contribute more optimization updates, potentially introducing bias. We propose Patient Sampling, a pretraining sequence-construction method that allows us to control how training signal is distributed across patients. We compare this method to the standard approach, which we refer to as Global Stream. We show that stochastic Patient Sampling with controllable weighting improves performance on real-world EHR data. Across downstream clinical tasks on MIMIC-IV v2.2 and v3.1, Patient Sampling improves Macro AUROC and AUPRC over the Global Stream baseline. These results identify training and validation sequence construction as important and underexplored design choices for autoregressive EHR foundation models.

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