ColaCare: Enhancing Electronic Health Record Modeling through Large Language Model-Driven Multi-Agent Collaboration

We introduce ColaCare, a framework that enhances Electronic Health Record (EHR) modeling through multi-agent collaboration driven by Large Language Models (LLMs). Our approach seamlessly integrates domain-specific expert models with LLMs to bridge the gap between structured EHR data and text-based reasoning. Inspired by clinical consultations, ColaCare employs two types of agents: DoctorAgent and MetaAgent, which collaboratively analyze patient data. Expert models process and generate predictions from numerical EHR data, while LLM agents produce reasoning references and decision-making reports within the collaborative consultation framework. We additionally incorporate the Merck Manual of Diagnosis and Therapy (MSD) medical guideline within a retrieval-augmented generation (RAG) module for authoritative evidence support. Extensive experiments conducted on four distinct EHR datasets demonstrate ColaCare's superior performance in mortality prediction tasks, underscoring its potential to revolutionize clinical decision support systems and advance personalized precision medicine. The code, complete prompt templates, more case studies, etc. are publicly available at the anonymous link: https://colacare.netlify.app.

Is larger always better? Evaluating and prompting large language models for non-generative medical tasks

The use of Large Language Models (LLMs) in medicine is growing, but their ability to handle both structured Electronic Health Record (EHR) data and unstructured clinical notes is not well-studied. This study benchmarks various models, including GPT-based LLMs, BERT-based models, and traditional clinical predictive models, for non-generative medical tasks utilizing renowned datasets. We assessed 14 language models (9 GPT-based and 5 BERT-based) and 7 traditional predictive models using the MIMIC dataset (ICU patient records) and the TJH dataset (early COVID-19 EHR data), focusing on tasks such as mortality and readmission prediction, disease hierarchy reconstruction, and biomedical sentence matching, comparing both zero-shot and finetuned performance. Results indicated that LLMs exhibited robust zero-shot predictive capabilities on structured EHR data when using well-designed prompting strategies, frequently surpassing traditional models. However, for unstructured medical texts, LLMs did not outperform finetuned BERT models, which excelled in both supervised and unsupervised tasks. Consequently, while LLMs are effective for zero-shot learning on structured data, finetuned BERT models are more suitable for unstructured texts, underscoring the importance of selecting models based on specific task requirements and data characteristics to optimize the application of NLP technology in healthcare.

Adaptive Activation Steering: A Tuning-Free LLM Truthfulness Improvement Method for Diverse Hallucinations Categories

Recent studies have indicated that Large Language Models (LLMs) harbor an inherent understanding of truthfulness, yet often fail to express fully and generate false statements. This gap between "knowing" and "telling" poses a challenge for ensuring the truthfulness of generated content. To address this, we introduce Adaptive Activation Steering (ACT), a tuning-free method that adaptively shift LLM's activations in "truthful" direction during inference. ACT addresses diverse categories of hallucinations by utilizing diverse steering vectors and adjusting the steering intensity adaptively. Applied as an add-on across various models, ACT significantly improves truthfulness in LLaMA ($\uparrow$ 142\%), LLaMA2 ($\uparrow$ 24\%), Alpaca ($\uparrow$ 36\%), Vicuna ($\uparrow$ 28\%), and LLaMA2-Chat ($\uparrow$ 19\%). Furthermore, we verify ACT's scalability across larger models (13B, 33B, 65B), underscoring the adaptability of ACT to large-scale language models.

Prompting Large Language Models for Zero-Shot Clinical Prediction with Structured Longitudinal Electronic Health Record Data

The inherent complexity of structured longitudinal Electronic Health Records (EHR) data poses a significant challenge when integrated with Large Language Models (LLMs), which are traditionally tailored for natural language processing. Motivated by the urgent need for swift decision-making during new disease outbreaks, where traditional predictive models often fail due to a lack of historical data, this research investigates the adaptability of LLMs, like GPT-4, to EHR data. We particularly focus on their zero-shot capabilities, which enable them to make predictions in scenarios in which they haven't been explicitly trained. In response to the longitudinal, sparse, and knowledge-infused nature of EHR data, our prompting approach involves taking into account specific EHR characteristics such as units and reference ranges, and employing an in-context learning strategy that aligns with clinical contexts. Our comprehensive experiments on the MIMIC-IV and TJH datasets demonstrate that with our elaborately designed prompting framework, LLMs can improve prediction performance in key tasks such as mortality, length-of-stay, and 30-day readmission by about 35\%, surpassing ML models in few-shot settings. Our research underscores the potential of LLMs in enhancing clinical decision-making, especially in urgent healthcare situations like the outbreak of emerging diseases with no labeled data. The code is publicly available at https://github.com/yhzhu99/llm4healthcare for reproducibility.

M$^3$Fair: Mitigating Bias in Healthcare Data through Multi-Level and Multi-Sensitive-Attribute Reweighting Method

In the data-driven artificial intelligence paradigm, models heavily rely on large amounts of training data. However, factors like sampling distribution imbalance can lead to issues of bias and unfairness in healthcare data. Sensitive attributes, such as race, gender, age, and medical condition, are characteristics of individuals that are commonly associated with discrimination or bias. In healthcare AI, these attributes can play a significant role in determining the quality of care that individuals receive. For example, minority groups often receive fewer procedures and poorer-quality medical care than white individuals in US. Therefore, detecting and mitigating bias in data is crucial to enhancing health equity. Bias mitigation methods include pre-processing, in-processing, and post-processing. Among them, Reweighting (RW) is a widely used pre-processing method that performs well in balancing machine learning performance and fairness performance. RW adjusts the weights for samples within each (group, label) combination, where these weights are utilized in loss functions. However, RW is limited to considering only a single sensitive attribute when mitigating bias and assumes that each sensitive attribute is equally important. This may result in potential inaccuracies when addressing intersectional bias. To address these limitations, we propose M3Fair, a multi-level and multi-sensitive-attribute reweighting method by extending the RW method to multiple sensitive attributes at multiple levels. Our experiments on real-world datasets show that the approach is effective, straightforward, and generalizable in addressing the healthcare fairness issues.

Mortality Prediction with Adaptive Feature Importance Recalibration for Peritoneal Dialysis Patients: a deep-learning-based study on a real-world longitudinal follow-up dataset

Objective: Peritoneal Dialysis (PD) is one of the most widely used life-supporting therapies for patients with End-Stage Renal Disease (ESRD). Predicting mortality risk and identifying modifiable risk factors based on the Electronic Medical Records (EMR) collected along with the follow-up visits are of great importance for personalized medicine and early intervention. Here, our objective is to develop a deep learning model for a real-time, individualized, and interpretable mortality prediction model - AICare. Method and Materials: Our proposed model consists of a multi-channel feature extraction module and an adaptive feature importance recalibration module. AICare explicitly identifies the key features that strongly indicate the outcome prediction for each patient to build the health status embedding individually. This study has collected 13,091 clinical follow-up visits and demographic data of 656 PD patients. To verify the application universality, this study has also collected 4,789 visits of 1,363 hemodialysis dialysis (HD) as an additional experiment dataset to test the prediction performance, which will be discussed in the Appendix. Results: 1) Experiment results show that AICare achieves 81.6%/74.3% AUROC and 47.2%/32.5% AUPRC for the 1-year mortality prediction task on PD/HD dataset respectively, which outperforms the state-of-the-art comparative deep learning models. 2) This study first provides a comprehensive elucidation of the relationship between the causes of mortality in patients with PD and clinical features based on an end-to-end deep learning model. 3) This study first reveals the pattern of variation in the importance of each feature in the mortality prediction based on built-in interpretability. 4) We develop a practical AI-Doctor interaction system to visualize the trajectory of patients' health status and risk indicators.

A Comprehensive Benchmark for COVID-19 Predictive Modeling Using Electronic Health Records in Intensive Care: Choosing the Best Model for COVID-19 Prognosis

The COVID-19 pandemic has posed a heavy burden to the healthcare system worldwide and caused huge social disruption and economic loss. Many deep learning models have been proposed to conduct clinical predictive tasks such as mortality prediction for COVID-19 patients in intensive care units using Electronic Health Record (EHR) data. Despite their initial success in certain clinical applications, there is currently a lack of benchmarking results to achieve a fair comparison so that we can select the optimal model for clinical use. Furthermore, there is a discrepancy between the formulation of traditional prediction tasks and real-world clinical practice in intensive care. To fill these gaps, we propose two clinical prediction tasks, Outcome-specific length-of-stay prediction and Early mortality prediction for COVID-19 patients in intensive care units. The two tasks are adapted from the naive length-of-stay and mortality prediction tasks to accommodate the clinical practice for COVID-19 patients. We propose fair, detailed, open-source data-preprocessing pipelines and evaluate 17 state-of-the-art predictive models on two tasks, including 5 machine learning models, 6 basic deep learning models and 6 deep learning predictive models specifically designed for EHR data. We provide benchmarking results using data from two real-world COVID-19 EHR datasets. Both datasets are publicly available without needing any inquiry and one dataset can be accessed on request. We provide fair, reproducible benchmarking results for two tasks. We deploy all experiment results and models on an online platform. We also allow clinicians and researchers to upload their data to the platform and get quick prediction results using our trained models. We hope our efforts can further facilitate deep learning and machine learning research for COVID-19 predictive modeling.

MedML: Fusing Medical Knowledge and Machine Learning Models for Early Pediatric COVID-19 Hospitalization and Severity Prediction

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.

CovidCare: Transferring Knowledge from Existing EMR to Emerging Epidemic for Interpretable Prognosis

Due to the characteristics of COVID-19, the epidemic develops rapidly and overwhelms health service systems worldwide. Many patients suffer from systemic life-threatening problems and need to be carefully monitored in ICUs. Thus the intelligent prognosis is in an urgent need to assist physicians to take an early intervention, prevent the adverse outcome, and optimize the medical resource allocation. However, in the early stage of the epidemic outbreak, the data available for analysis is limited due to the lack of effective diagnostic mechanisms, rarity of the cases, and privacy concerns. In this paper, we propose a deep-learning-based approach, CovidCare, which leverages the existing electronic medical records to enhance the prognosis for inpatients with emerging infectious diseases. It learns to embed the COVID-19-related medical features based on massive existing EMR data via transfer learning. The transferred parameters are further trained to imitate the teacher model's representation behavior based on knowledge distillation, which embeds the health status more comprehensively in the source dataset. We conduct the length of stay prediction experiments for patients on a real-world COVID-19 dataset. The experiment results indicate that our proposed model consistently outperforms the comparative baseline methods. CovidCare also reveals that, 1) hs-cTnI, hs-CRP and Platelet Counts are the most fatal biomarkers, whose abnormal values usually indicate emergency adverse outcome. 2) Normal values of gamma-GT, AP and eGFR indicate the overall improvement of health. The medical findings extracted by CovidCare are empirically confirmed by human experts and medical literatures.

COMPOSE: Cross-Modal Pseudo-Siamese Network for Patient Trial Matching

Clinical trials play important roles in drug development but often suffer from expensive, inaccurate and insufficient patient recruitment. The availability of massive electronic health records (EHR) data and trial eligibility criteria (EC) bring a new opportunity to data driven patient recruitment. One key task named patient-trial matching is to find qualified patients for clinical trials given structured EHR and unstructured EC text (both inclusion and exclusion criteria). How to match complex EC text with longitudinal patient EHRs? How to embed many-to-many relationships between patients and trials? How to explicitly handle the difference between inclusion and exclusion criteria? In this paper, we proposed CrOss-Modal PseudO-SiamEse network (COMPOSE) to address these challenges for patient-trial matching. One path of the network encodes EC using convolutional highway network. The other path processes EHR with multi-granularity memory network that encodes structured patient records into multiple levels based on medical ontology. Using the EC embedding as query, COMPOSE performs attentional record alignment and thus enables dynamic patient-trial matching. COMPOSE also introduces a composite loss term to maximize the similarity between patient records and inclusion criteria while minimize the similarity to the exclusion criteria. Experiment results show COMPOSE can reach 98.0% AUC on patient-criteria matching and 83.7% accuracy on patient-trial matching, which leads 24.3% improvement over the best baseline on real-world patient-trial matching tasks.