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.

The integration of multimodal Electronic Health Records (EHR) data has notably advanced clinical predictive capabilities. However, current models that utilize clinical notes and multivariate time-series EHR data often lack the necessary medical context for precise clinical tasks. Previous methods using knowledge graphs (KGs) primarily focus on structured knowledge extraction. To address this, we propose EMERGE, a Retrieval-Augmented Generation (RAG) driven framework aimed at enhancing multimodal EHR predictive modeling. Our approach extracts entities from both time-series data and clinical notes by prompting Large Language Models (LLMs) and aligns them with professional PrimeKG to ensure consistency. Beyond triplet relationships, we include entities' definitions and descriptions to provide richer semantics. The extracted knowledge is then used to generate task-relevant summaries of patients' health statuses. These summaries are fused with other modalities utilizing an adaptive multimodal fusion network with cross-attention. Extensive experiments on the MIMIC-III and MIMIC-IV datasets for in-hospital mortality and 30-day readmission tasks demonstrate the superior performance of the EMERGE framework compared to baseline models. Comprehensive ablation studies and analyses underscore the efficacy of each designed module and the framework's robustness to data sparsity. EMERGE significantly enhances the use of multimodal EHR data in healthcare, bridging the gap with nuanced medical contexts crucial for informed clinical predictions.

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.

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.

Analyzing the health status of patients based on Electronic Health Records (EHR) is a fundamental research problem in medical informatics. The presence of extensive missing values in EHR makes it challenging for deep neural networks to directly model the patient's health status based on EHR. Existing deep learning training protocols require the use of statistical information or imputation models to reconstruct missing values; however, the protocols inject non-realistic data into downstream EHR analysis models, significantly limiting model performance. This paper introduces Learnable Prompt as Pseudo Imputation (PAI) as a new training protocol. PAI no longer introduces any imputed data but constructs a learnable prompt to model the implicit preferences of the downstream model for missing values, resulting in a significant performance improvement for all EHR analysis models. Additionally, our experiments show that PAI exhibits higher robustness in situations of data insufficiency and high missing rates. More importantly, in a real-world application involving cross-institutional data with zero-shot evaluation, PAI demonstrates stronger model generalization capabilities for non-overlapping features.

Electronic Health Record (EHR) data, while rich in information, often suffers from sparsity, posing significant challenges in predictive modeling. Traditional imputation methods inadequately distinguish between real and imputed data, leading to potential inaccuracies in models. Addressing this, we introduce PRISM, a novel approach that indirectly imputes data through prototype representations of similar patients, thus ensuring denser and more accurate embeddings. PRISM innovates further with a feature confidence learner module, which evaluates the reliability of each feature in light of missing data. Additionally, it incorporates a novel patient similarity metric that accounts for feature confidence, avoiding overreliance on imprecise imputed values. Our extensive experiments on the MIMIC-III and MIMIC-IV datasets demonstrate PRISM's superior performance in predicting in-hospital mortality and 30-day readmission tasks, showcasing its effectiveness in handling EHR data sparsity. For the sake of reproducibility and further research, we have made the code publicly available at https://github.com/yhzhu99/PRISM.

Due to the limited information about emerging diseases, symptoms are hard to be noticed and recognized, so that the window for clinical intervention could be ignored. An effective prognostic model is expected to assist doctors in making right diagnosis and designing personalized treatment plan, so to promptly prevent unfavorable outcomes. However, in the early stage of a disease, limited data collection and clinical experiences, plus the concern out of privacy and ethics, may result in restricted data availability for reference, to the extent that even data labels are difficult to mark correctly. In addition, Electronic Medical Record (EMR) data of different diseases or of different sources of the same disease can prove to be having serious cross-dataset feature misalignment problems, greatly mutilating the efficiency of deep learning models. This article introduces a domain-invariant representation learning method to build a transition model from source dataset to target dataset. By way of constraining the distribution shift of features generated in disparate domains, domain-invariant features that are exclusively relative to downstream tasks are captured, so to cultivate a unified domain-invariant encoder across various task domains to achieve better feature representation. Experimental results of several target tasks demonstrate that our proposed model outperforms competing baseline methods and has higher rate of training convergence, especially in dealing with limited data amount. A multitude of experiences have proven the efficacy of our method to provide more accurate predictions concerning newly emergent pandemics and other diseases.

Irregularly sampled time series are ubiquitous, presenting significant challenges for analysis due to missing values. Despite existing methods address imputation, they predominantly focus on leveraging intra-series information, neglecting the potential benefits that inter-series information could provide, such as reducing uncertainty and memorization effect. To bridge this gap, we propose PRIME, a Prototype Recurrent Imputation ModEl, which integrates both intra-series and inter-series information for imputing missing values in irregularly sampled time series. Our framework comprises a prototype memory module for learning inter-series information, a bidirectional gated recurrent unit utilizing prototype information for imputation, and an attentive prototypical refinement module for adjusting imputations. We conducted extensive experiments on three datasets, and the results underscore PRIME's superiority over the state-of-the-art models by up to 26% relative improvement on mean square error.

Deep learning algorithms, especially Transformer-based models, have achieved significant performance by capturing long-range dependencies and historical information. However, the power of convolution has not been fully investigated. Moreover, most existing works ignore the dynamic interaction among variables and evolutionary noise in series. Addressing these issues, we propose a Hierarchical Memorizing Network (HMNet). In particular, a hierarchical convolution structure is introduced to extract the information from the series at various scales. Besides, we propose a dynamic variable interaction module to learn the varying correlation and an adaptive denoising module to search and exploit similar patterns to alleviate noises. These modules can cooperate with the hierarchical structure from the perspective of fine to coarse grain. Experiments on five benchmarks demonstrate that HMNet significantly outperforms the state-of-the-art models by 10.6% on MSE and 5.7% on MAE. Our code is released at https://github.com/yzhHoward/HMNet.

Predicting health risks from electronic health records (EHR) is a topic of recent interest. Deep learning models have achieved success by modeling temporal and feature interaction. However, these methods learn insufficient representations and lead to poor performance when it comes to patients with few visits or sparse records. Inspired by the fact that doctors may compare the patient with typical patients and make decisions from similar cases, we propose a Progressive Prototypical Network (PPN) to select typical patients as prototypes and utilize their information to enhance the representation of the given patient. In particular, a progressive prototype memory and two prototype separation losses are proposed to update prototypes. Besides, a novel integration is introduced for better fusing information from patients and prototypes. Experiments on three real-world datasets demonstrate that our model brings improvement on all metrics. To make our results better understood by physicians, we developed an application at http://ppn.ai-care.top. Our code is released at https://github.com/yzhHoward/PPN.