Adam Cross

Junyi Gao, Chaoqi Yang, George Heintz et al.

The COVID-19 pandemic has caused devastating economic and social disruption, straining the resources of healthcare institutions worldwide. This has led to a nationwide call for models to predict hospitalization and severe illness in patients with COVID-19 to inform distribution of limited healthcare resources. We respond to one of these calls specific to the pediatric population. To address this challenge, we study two prediction tasks for the pediatric population using electronic health records: 1) predicting which children are more likely to be hospitalized, and 2) among hospitalized children, which individuals are more likely to develop severe symptoms. We respond to the national Pediatric COVID-19 data challenge with a novel machine learning model, MedML. MedML extracts the most predictive features based on medical knowledge and propensity scores from over 6 million medical concepts and incorporates the inter-feature relationships between heterogeneous medical features via graph neural networks (GNN). We evaluate MedML across 143,605 patients for the hospitalization prediction task and 11,465 patients for the severity prediction task using data from the National Cohort Collaborative (N3C) dataset. We also report detailed group-level and individual-level feature importance analyses to evaluate the model interpretability. MedML achieves up to a 7% higher AUROC score and up to a 14% higher AUPRC score compared to the best baseline machine learning models and performs well across all nine national geographic regions and over all three-month spans since the start of the pandemic. Our cross-disciplinary research team has developed a method of incorporating clinical domain knowledge as the framework for a new type of machine learning model that is more predictive and explainable than current state-of-the-art data-driven feature selection methods.

Yongda Fan, John Wu, Andrea Fitzpatrick et al.

Clinical decisions are high-stakes and require explicit justification, making model interpretability essential for auditing deep clinical models prior to deployment. As the ecosystem of model architectures and explainability methods expands, critical questions remain: Do architectural features like attention improve explainability? Do interpretability approaches generalize across clinical tasks? While prior benchmarking efforts exist, they often lack extensibility and reproducibility, and critically, fail to systematically examine how interpretability varies across the interplay of clinical tasks and model architectures. To address these gaps, we present a comprehensive benchmark evaluating interpretability methods across diverse clinical prediction tasks and model architectures. Our analysis reveals that: (1) attention when leveraged properly is a highly efficient approach for faithfully interpreting model predictions; (2) black-box interpreters like KernelSHAP and LIME are computationally infeasible for time-series clinical prediction tasks; and (3) several interpretability approaches are too unreliable to be trustworthy. From our findings, we discuss several guidelines on improving interpretability within clinical predictive pipelines. To support reproducibility and extensibility, we provide our implementations via PyHealth, a well-documented open-source framework: https://github.com/sunlabuiuc/PyHealth.

Paul Landes, Pranav Herur, Adam Cross et al.

Large Language Models (LLMs) are optimized to produce distributionally plausible continuations rather than to explicitly verify whether generated propositions are entailed by source documents. This inductive bias enables generalization, but it does not encode whether responses are grounded with respect to a reference. These issues limit the use of LLMs in domains where strict factual correctness is crucial, such as clinical decision support. Existing hallucination detection approaches improve factuality through retrieval augmentation, self-consistency, or claim verification, but generally do not learn directly over alignment topology. To leverage alignment topology as an inductive bias, we construct aligned bipartite graphs between reference information and LLM outputs and train a graph neural network (GNN) to model alignment structure using message passing. The method achieves state-of-the-art results on four diverse hallucination and question-answering datasets, outperforming all compared methods, including foundational LLMs such as GPT-4o.

John Wu, Adam Cross, Jimeng Sun

Rare diseases affect 1 in 10 Americans, yet standard ICD coding systems fail to capture these conditions in electronic health records (EHR), leaving crucial information buried in clinical notes. Current approaches struggle with medical abbreviations, miss implicit disease mentions, raise privacy concerns with cloud processing, and lack clinical reasoning abilities. We present Rare Disease Mining Agents (RDMA), a framework that mirrors how medical experts identify rare disease patterns in EHR. RDMA connects scattered clinical observations that together suggest specific rare conditions. By handling clinical abbreviations, recognizing implicit disease patterns, and applying contextual reasoning locally on standard hardware, RDMA reduces privacy risks while improving F1 performance by upwards of 30\% and decreasing inferences costs 10-fold. This approach helps clinicians avoid the privacy risk of using cloud services while accessing key rare disease information from EHR systems, supporting earlier diagnosis for rare disease patients. Available at https://github.com/jhnwu3/RDMA.

Lang Cao, Jimeng Sun, Adam Cross

Rare diseases affect millions worldwide but often face limited research focus due to their low prevalence. This results in prolonged diagnoses and a lack of approved therapies. Recent advancements in Large Language Models (LLMs) have shown promise in automating the extraction of medical information, offering potential to improve medical diagnosis and management. However, most LLMs lack professional medical knowledge, especially concerning rare diseases, and struggle to handle the latest rare disease information. They also cannot effectively manage rare disease data and are not directly suitable for diagnosis and management tasks. Our objective is to create an end-to-end system called AutoRD, which automates the extraction of information from medical texts about rare diseases, focusing on entities and their relations. AutoRD integrates up-to-date structured knowledge and demonstrates superior performance in rare disease extraction tasks. We conduct various experiments to evaluate AutoRD's performance, aiming to surpass common LLMs and traditional methods.

Sharim Khan, Paul Landes, Adam Cross et al.

Social Determinants of Health correlate with patient outcomes but are rarely captured in structured data. Recent attention has been given to automatically extracting these markers from clinical text to supplement diagnostic systems with knowledge of patients' social circumstances. Large language models demonstrate strong performance in identifying Social Determinants of Health labels from sentences. However, prediction in large admissions or longitudinal notes is challenging given long distance dependencies. In this paper, we explore hospital admission multi-label Social Determinants of Health ICD-9 code classification on the MIMIC-III dataset using reasoning models and traditional large language models. We exploit existing ICD-9 codes for prediction on admissions, which achieved an 89% F1. Our contributions include our findings, missing SDoH codes in 139 admissions, and code to reproduce the results.

Paul Landes, Jimeng Sun, Adam Cross

Social Determinants of Health (SDoH) are economic, social and personal circumstances that affect or influence an individual's health status. SDoHs have shown to be correlated to wellness outcomes, and therefore, are useful to physicians in diagnosing diseases and in decision-making. In this work, we automatically extract SDoHs from clinical text using traditional deep learning and Large Language Models (LLMs) to find the advantages and disadvantages of each on an existing publicly available dataset. Our models outperform a previous reference point on a multilabel SDoH classification by 10 points, and we present a method and model to drastically speed up classification (12X execution time) by eliminating expensive LLM processing. The method we present combines a more nimble and efficient solution that leverages the power of the LLM for precision and traditional deep learning methods for efficiency. We also show highly performant results on a dataset supplemented with synthetic data and several traditional deep learning models that outperform LLMs. Our models and methods offer the next iteration of automatic prediction of SDoHs that impact at-risk patients.

Dina Albassam, Adam Cross, Chengxiang Zhai

Electronic Health Records (EHRs) often lack explicit links between medications and diagnoses, making clinical decision-making and research more difficult. Even when links exist, diagnosis lists may be incomplete, especially during early patient visits. Discharge summaries tend to provide more complete information, which can help infer accurate diagnoses, especially with the help of large language models (LLMs). This study investigates whether LLMs can predict implicitly mentioned diagnoses from clinical notes and link them to corresponding medications. We address two research questions: (1) Does majority voting across diverse LLM configurations outperform the best single configuration in diagnosis prediction? (2) How sensitive is majority voting accuracy to LLM hyperparameters such as temperature, top-p, and summary length? To evaluate, we created a new dataset of 240 expert-annotated medication-diagnosis pairs from 20 MIMIC-IV notes. Using GPT-3.5 Turbo, we ran 18 prompting configurations across short and long summary lengths, generating 8568 test cases. Results show that majority voting achieved 75 percent accuracy, outperforming the best single configuration at 66 percent. No single hyperparameter setting dominated, but combining deterministic, balanced, and exploratory strategies improved performance. Shorter summaries generally led to higher accuracy.In conclusion, ensemble-style majority voting with diverse LLM configurations improves diagnosis prediction in EHRs and offers a promising method to link medications and diagnoses in clinical texts.

Pengcheng Jiang, Cao Xiao, Adam Cross et al.

Clinical predictive models often rely on patients' electronic health records (EHR), but integrating medical knowledge to enhance predictions and decision-making is challenging. This is because personalized predictions require personalized knowledge graphs (KGs), which are difficult to generate from patient EHR data. To address this, we propose \textsc{GraphCare}, an open-world framework that uses external KGs to improve EHR-based predictions. Our method extracts knowledge from large language models (LLMs) and external biomedical KGs to build patient-specific KGs, which are then used to train our proposed Bi-attention AugmenTed (BAT) graph neural network (GNN) for healthcare predictions. On two public datasets, MIMIC-III and MIMIC-IV, \textsc{GraphCare} surpasses baselines in four vital healthcare prediction tasks: mortality, readmission, length of stay (LOS), and drug recommendation. On MIMIC-III, it boosts AUROC by 17.6\% and 6.6\% for mortality and readmission, and F1-score by 7.9\% and 10.8\% for LOS and drug recommendation, respectively. Notably, \textsc{GraphCare} demonstrates a substantial edge in scenarios with limited data availability. Our findings highlight the potential of using external KGs in healthcare prediction tasks and demonstrate the promise of \textsc{GraphCare} in generating personalized KGs for promoting personalized medicine.