Explainable Transformer Models for Clinical Prediction Tasks on Structured Electronic Health Records

The growing adoption of electronic health record (EHR) systems has provided unprecedented opportunities for predictive modeling to guide clinical decision making. Structured EHRs contain longitudinal observations of patients across hospital visits, where each visit is represented by a set of medical codes. While sequence-based, graph-based, and graph-enhanced sequence approaches have been developed to capture rich code interactions over time or within the same visits, they often overlook the inherent heterogeneous roles of medical codes arising from distinct clinical characteristics and contexts. To this end, in this study we propose the Disease Trajectory-aware Transformer for EHR (DT-BEHRT), a graph-enhanced sequential architecture that disentangles disease trajectories by explicitly modeling diagnosis-centric interactions within organ systems and capturing asynchronous progression patterns. To further enhance the representation robustness, we design a tailored pre-training methodology that combines trajectory-level code masking with ontology-informed ancestor prediction, promoting semantic alignment across multiple modeling modules. Extensive experiments on multiple benchmark datasets demonstrate that DT-BEHRT achieves strong predictive performance and provides interpretable patient representations that align with clinicians' disease-centered reasoning. The source code is publicly accessible at https://github.com/GatorAIM/DT-BEHRT.git.

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.

Electronic Health Record (EHR) prediction models in the intensive care unit must learn from sparse and irregular measurements while preserving the clinical meaning of time and supporting transparent decision-making. We present INTERVenE, a family of Transformer architectures whose input is an interval-based, knowledge-based temporal abstraction (KBTA), a token stream of named clinical concepts (states, trends, events, contexts) drawn from a curated medical ontology, rather than an unnamed bin index or a raw measurement triplet. This naming layer is what we ask KBTA to do: it makes the model's per-token attributions resolve to clinical concepts by construction. INTERVenE offers two complementary variants: an auto-regressive decoder that generates future abstraction trajectories with a per-step risk readout (localizing when and after which events risk rises), and a bidirectional encoder for single-pass joint risk and time-to-event prediction. Evaluated on 57,078 MIMIC-IV admissions against GRU-D, STraTS, and KarmaLego, INTERVenE-Enc reaches a support-weighted AUPRC$_w$ of 0.672, improving by 0.041 over the strongest neural baseline with non-overlapping 95% bootstrap CIs, while also taking the best AUROC$_w$ (0.901) and length-of-stay MAE (44.4,h). INTERVenE-Ar (AUROC$_w$ $0.854$, AUPRC$_w$ $0.587$ under the same evaluation contract - a strictly harder generative readout) provides a complementary token-level risk trajectory. An input-representation ablation confirms the lift transfers across structured discretizations, positioning KBTA-based intervals as the interpretable substrate that makes per-token attributions resolve to meaningful clinical concepts within the deployed model.