Decisions about managing patients on the heart transplant waitlist are currently made by committees of doctors who consider multiple factors, but the process remains largely ad-hoc. With the growing volume of longitudinal patient, donor, and organ data collected by the United Network for Organ Sharing (UNOS) since 2018, there is increasing interest in analytical approaches to support clinical decision-making at the time of organ availability. In this study, we benchmark machine learning models that leverage longitudinal waitlist history data for time-dependent, time-to-event modeling of waitlist mortality. We train on 23,807 patient records with 77 variables and evaluate both survival prediction and discrimination at a 1-year horizon. Our best model achieves a C-Index of 0.94 and AUROC of 0.89, significantly outperforming previous models. Key predictors align with known risk factors while also revealing novel associations. Our findings can support urgency assessment and policy refinement in heart transplant decision making.
Traumatic Brain Injury (TBI) is a major contributor to mortality among older adults, with geriatric patients facing disproportionately high risk due to age-related physiological vulnerability and comorbidities. Early and accurate prediction of mortality is essential for guiding clinical decision-making and optimizing ICU resource allocation. In this study, we utilized the MIMIC-III database to identify geriatric TBI patients and applied a machine learning framework to develop a 30-day mortality prediction model. A rigorous preprocessing pipeline-including Random Forest-based imputation, feature engineering, and hybrid selection-was implemented to refine predictors from 69 to 9 clinically meaningful variables. CatBoost emerged as the top-performing model, achieving an AUROC of 0.867 (95% CI: 0.809-0.922), surpassing traditional scoring systems. SHAP analysis confirmed the importance of GCS score, oxygen saturation, and prothrombin time as dominant predictors. These findings highlight the value of interpretable machine learning tools for early mortality risk stratification in elderly TBI patients and provide a foundation for future clinical integration to support high-stakes decision-making in critical care.
Real-world medical data often includes measurements from multiple signals that are collected at irregular and asynchronous time intervals. For example, different types of blood tests can be measured at different times and frequencies, resulting in fragmented and unevenly scattered temporal data. Similar issues of irregular sampling of different attributes occur in other domains, such as monitoring of large systems using event log files or the spread of fake news on social networks. Effectively learning from such data requires models that can handle sets of temporally sparse and heterogeneous signals. In this paper, we propose Graph Mixing Additive Networks (GMAN), a novel and interpretable-by-design model for learning over irregular sets of temporal signals. Our method achieves state-of-the-art performance in real-world medical tasks, including a 4-point increase in the AUROC score of in-hospital mortality prediction, compared to existing methods. We further showcase GMAN's flexibility by applying it to a fake news detection task. We demonstrate how its interpretability capabilities, including node-level, graph-level, and subset-level importance, allow for transition phases detection and gaining medical insights with real-world high-stakes implications. Finally, we provide theoretical insights on GMAN expressive power.
There is a long history of building predictive models in healthcare using tabular data from electronic medical records. However, these models fail to extract the information found in unstructured clinical notes, which document diagnosis, treatment, progress, medications, and care plans. In this study, we investigate how answers generated by GPT-4o-mini (ChatGPT) to simple clinical questions about patients, when given access to the patient's discharge summary, can support patient-level mortality prediction. Using data from 14,011 first-time admissions to the Coronary Care or Cardiovascular Intensive Care Units in the MIMIC-IV Note dataset, we implement a transparent framework that uses GPT responses as input features in logistic regression models. Our findings demonstrate that GPT-based models alone can outperform models trained on standard tabular data, and that combining both sources of information yields even greater predictive power, increasing AUC by an average of 5.1 percentage points and increasing positive predictive value by 29.9 percent for the highest-risk decile. These results highlight the value of integrating large language models (LLMs) into clinical prediction tasks and underscore the broader potential for using LLMs in any domain where unstructured text data remains an underutilized resource.
The temporal complexity of electronic health record (EHR) data presents significant challenges for predicting clinical outcomes using machine learning. This paper proposes ChronoFormer, an innovative transformer based architecture specifically designed to encode and leverage temporal dependencies in longitudinal patient data. ChronoFormer integrates temporal embeddings, hierarchical attention mechanisms, and domain specific masking techniques. Extensive experiments conducted on three benchmark tasks mortality prediction, readmission prediction, and long term comorbidity onset demonstrate substantial improvements over current state of the art methods. Furthermore, detailed analyses of attention patterns underscore ChronoFormer's capability to capture clinically meaningful long range temporal relationships.
Recent advances in the data-driven medicine approach, which integrates ethically managed and explainable artificial intelligence into clinical decision support systems (CDSS), are critical to ensure reliable and effective patient care. This paper focuses on comparing novel agent system designs that use modular agents to analyze laboratory results, vital signs, and clinical context, and to predict and validate results. We implement our agent system with the eICU database, including running lab analysis, vitals-only interpreters, and contextual reasoners agents first, then sharing the memory into the integration agent, prediction agent, transparency agent, and a validation agent. Our results suggest that the multi-agent system (MAS) performed better than the single-agent system (SAS) with mortality prediction accuracy (59%, 56%) and the mean error for length of stay (LOS)(4.37 days, 5.82 days), respectively. However, the transparency score for the SAS (86.21) is slightly better than the transparency score for MAS (85.5). Finally, this study suggests that our agent-based framework not only improves process transparency and prediction accuracy but also strengthens trustworthy AI-assisted decision support in an intensive care setting.
Objectives: Administrative data is commonly used to inform chronic disease prevalence and support health informatics research. This study assessed the validity of coding comorbidity in the International Classification of Diseases, 10th Revision (ICD-10) administrative data. Methods: We analyzed three chart review cohorts (4,008 patients in 2003, 3,045 in 2015, and 9,024 in 2022) in Alberta, Canada. Nurse reviewers assessed the presence of 17 clinical conditions using a consistent protocol. The reviews were linked with administrative data using unique identifiers. We compared the accuracy in coding comorbidity by ICD-10, using chart review data as the reference standard. Results: Our findings showed that the mean difference in prevalence between chart reviews and ICD-10 for these 17 conditions was 2.1% in 2003, 7.6% in 2015, and 6.3% in 2022. Some conditions were relatively stable, such as diabetes (1.9%, 2.1%, and 1.1%) and metastatic cancer (0.3%, 1.1%, and 0.4%). For these 17 conditions, the sensitivity ranged from 39.6-85.1% in 2003, 1.3-85.2% in 2015, and 3.0-89.7% in 2022. The C-statistics for predicting in-hospital mortality using comorbidities by ICD-10 were 0.84 in 2003, 0.81 in 2015, and 0.78 in 2022. Discussion: The under-coding could be primarily due to the increase of hospital patient volumes and the limited time allocated to coders. There is a potential to develop artificial intelligence methods based on electronic health records to support coding practices and improve coding quality. Conclusion: Comorbidities were increasingly under-coded over 20 years. The validity of ICD-10 decreased but remained relatively stable for certain conditions mandated for coding. The under-coding exerted minimal impact on in-hospital mortality prediction.
Accurate patient mortality prediction enables effective risk stratification, leading to personalized treatment plans and improved patient outcomes. However, predicting mortality in healthcare remains a significant challenge, with existing studies often focusing on specific diseases or limited predictor sets. This study evaluates machine learning models for all-cause in-hospital mortality prediction using the MIMIC-III database, employing a comprehensive feature engineering approach. Guided by clinical expertise and literature, we extracted key features such as vital signs (e.g., heart rate, blood pressure), laboratory results (e.g., creatinine, glucose), and demographic information. The Random Forest model achieved the highest performance with an AUC of 0.94, significantly outperforming other machine learning and deep learning approaches. This demonstrates Random Forest's robustness in handling high-dimensional, noisy clinical data and its potential for developing effective clinical decision support tools. Our findings highlight the importance of careful feature engineering for accurate mortality prediction. We conclude by discussing implications for clinical adoption and propose future directions, including enhancing model robustness and tailoring prediction models for specific diseases.
Data-driven AI is establishing itself at the center of evidence-based medicine. However, reports of shortcomings and unexpected behavior are growing due to AI's reliance on association-based learning. A major reason for this behavior: latent bias in machine learning datasets can be amplified during training and/or hidden during testing. We present a data modality-agnostic auditing framework for generating targeted hypotheses about sources of bias which we refer to as Generalized Attribute Utility and Detectability-Induced bias Testing (G-AUDIT) for datasets. Our method examines the relationship between task-level annotations and data properties including protected attributes (e.g., race, age, sex) and environment and acquisition characteristics (e.g., clinical site, imaging protocols). G-AUDIT automatically quantifies the extent to which the observed data attributes may enable shortcut learning, or in the case of testing data, hide predictions made based on spurious associations. We demonstrate the broad applicability and value of our method by analyzing large-scale medical datasets for three distinct modalities and learning tasks: skin lesion classification in images, stigmatizing language classification in Electronic Health Records (EHR), and mortality prediction for ICU tabular data. In each setting, G-AUDIT successfully identifies subtle biases commonly overlooked by traditional qualitative methods that focus primarily on social and ethical objectives, underscoring its practical value in exposing dataset-level risks and supporting the downstream development of reliable AI systems. Our method paves the way for achieving deeper understanding of machine learning datasets throughout the AI development life-cycle from initial prototyping all the way to regulation, and creates opportunities to reduce model bias, enabling safer and more trustworthy AI systems.
Background: Sepsis-Associated Acute Kidney Injury (SA-AKI) leads to high mortality in intensive care. This study develops machine learning models using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database to predict Intensive Care Unit (ICU) mortality in SA-AKI patients. External validation is conducted using the eICU Collaborative Research Database. Methods: For 9,474 identified SA-AKI patients in MIMIC-IV, key features like lab results, vital signs, and comorbidities were selected using Variance Inflation Factor (VIF), Recursive Feature Elimination (RFE), and expert input, narrowing to 24 predictive variables. An Extreme Gradient Boosting (XGBoost) model was built for in-hospital mortality prediction, with hyperparameters optimized using GridSearch. Model interpretability was enhanced with SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME). External validation was conducted using the eICU database. Results: The proposed XGBoost model achieved an internal Area Under the Receiver Operating Characteristic curve (AUROC) of 0.878 (95% Confidence Interval: 0.859-0.897). SHAP identified Sequential Organ Failure Assessment (SOFA), serum lactate, and respiratory rate as key mortality predictors. LIME highlighted serum lactate, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, total urine output, and serum calcium as critical features. Conclusions: The integration of advanced techniques with the XGBoost algorithm yielded a highly accurate and interpretable model for predicting SA-AKI mortality across diverse populations. It supports early identification of high-risk patients, enhancing clinical decision-making in intensive care. Future work needs to focus on enhancing adaptability, versatility, and real-world applications.
This study addresses the critical issue of reliability for AI-assisted medical diagnosis. We focus on the selection prediction approach that allows the diagnosis system to abstain from providing the decision if it is not confident in the diagnosis. Such selective prediction (or abstention) approaches are usually based on the modeling predictive uncertainty of machine learning models involved. This study explores uncertainty quantification in machine learning models for medical text analysis, addressing diverse tasks across multiple datasets. We focus on binary mortality prediction from textual data in MIMIC-III, multi-label medical code prediction using ICD-10 codes from MIMIC-IV, and multi-class classification with a private outpatient visits dataset. Additionally, we analyze mental health datasets targeting depression and anxiety detection, utilizing various text-based sources, such as essays, social media posts, and clinical descriptions. In addition to comparing uncertainty methods, we introduce HUQ-2, a new state-of-the-art method for enhancing reliability in selective prediction tasks. Our results provide a detailed comparison of uncertainty quantification methods. They demonstrate the effectiveness of HUQ-2 in capturing and evaluating uncertainty, paving the way for more reliable and interpretable applications in medical text analysis.
Electronic Health Records (EHRs) offer considerable potential for clinical prediction, but their complexity and heterogeneity present significant challenges for traditional machine learning methods. Recently, domain-specific EHR foundation models trained on large volumes of unlabeled EHR data have shown improved predictive accuracy and generalization. However, their development is constrained by limited access to diverse, high-quality datasets, and by inconsistencies in coding standards and clinical practices. In this study, we explore the use of general-purpose Large Language Models (LLMs) to encode EHR into high-dimensional representations for downstream clinical prediction tasks. We convert structured EHR data into markdown-formatted plain text documents by replacing medical codes with natural language descriptions. This enables the use of LLMs and their extensive semantic understanding and generalization capabilities as effective encoders of EHRs without requiring access to private medical training data. We show that LLM-based embeddings can often match or even surpass the performance of a specialized EHR foundation model, CLMBR-T-Base, across 15 diverse clinical tasks from the EHRSHOT benchmark. To demonstrate generalizability, we further evaluate the approach on the UK Biobank (UKB) cohort, a population distinct from that used to train CLMBR-T-Base. Notably, one of the tested LLM-based models achieves superior performance for disease onset, hospitalization, and mortality prediction, highlighting robustness to shifts in patient populations. Our findings suggest that repurposed general-purpose LLMs for EHR encoding provide a scalable and generalizable alternative to domain-specific models for clinical prediction.
Sepsis is a major cause of ICU mortality, where early recognition and effective interventions are essential for improving patient outcomes. However, the vasoactive-inotropic score (VIS) varies dynamically with a patient's hemodynamic status, complicated by irregular medication patterns, missing data, and confounders, making sepsis prediction challenging. To address this, we propose a novel Teacher-Student multitask framework with self-supervised VIS pretraining via a Masked Autoencoder (MAE). The teacher model performs mortality classification and severity-score regression, while the student distills robust time-series representations, enhancing adaptation to heterogeneous VIS data. Compared to LSTM-based methods, our approach achieves an AUROC of 0.82 on MIMIC-IV 3.0 (9,476 patients), outperforming the baseline (0.74). SHAP analysis revealed that SOFA score (0.147) had the greatest impact on ICU mortality, followed by LODS (0.033), single marital status (0.031), and Medicaid insurance (0.023), highlighting the role of sociodemographic factors. SAPSII (0.020) also contributed significantly. These findings suggest that both clinical and social factors should be considered in ICU decision-making. Our novel multitask and distillation strategies enable earlier identification of high-risk patients, improving prediction accuracy and disease management, offering new tools for ICU decision support.
We introduce a novel contextual embedding model med-gte-hybrid that was derived from the gte-large sentence transformer to extract information from unstructured clinical narratives. Our model tuning strategy for med-gte-hybrid combines contrastive learning and a denoising autoencoder. To evaluate the performance of med-gte-hybrid, we investigate several clinical prediction tasks in large patient cohorts extracted from the MIMIC-IV dataset, including Chronic Kidney Disease (CKD) patient prognosis, estimated glomerular filtration rate (eGFR) prediction, and patient mortality prediction. Furthermore, we demonstrate that the med-gte-hybrid model improves patient stratification, clustering, and text retrieval, thus outperforms current state-of-the-art models on the Massive Text Embedding Benchmark (MTEB). While some of our evaluations focus on CKD, our hybrid tuning of sentence transformers could be transferred to other medical domains and has the potential to improve clinical decision-making and personalised treatment pathways in various healthcare applications.
Access to diverse, high-quality datasets is crucial for machine learning model performance, yet data sharing remains limited by privacy concerns and competitive interests, particularly in regulated domains like healthcare. This dynamic especially disadvantages smaller organizations that lack resources to purchase data or negotiate favorable sharing agreements. We present SecureKL, a privacy-preserving framework that enables organizations to identify beneficial data partnerships without exposing sensitive information. Building on recent advances in dataset combination methods, we develop a secure multiparty computation protocol that maintains strong privacy guarantees while achieving >90\% correlation with plaintext evaluations. In experiments with real-world hospital data, SecureKL successfully identifies beneficial data partnerships that improve model performance for intensive care unit mortality prediction while preserving data privacy. Our framework provides a practical solution for organizations seeking to leverage collective data resources while maintaining privacy and competitive advantages. These results demonstrate the potential for privacy-preserving data collaboration to advance machine learning applications in high-stakes domains while promoting more equitable access to data resources.
Chest X-ray (CXR) is the most frequently ordered imaging test, supporting diverse clinical tasks from thoracic disease detection to postoperative monitoring. However, task-specific classification models are limited in scope, require costly labeled data, and lack generalizability to out-of-distribution datasets. To address these challenges, we introduce CheXFound, a self-supervised vision foundation model that learns robust CXR representations and generalizes effectively across a wide range of downstream tasks. We pretrain CheXFound on a curated CXR-1M dataset, comprising over one million unique CXRs from publicly available sources. We propose a Global and Local Representations Integration (GLoRI) module for downstream adaptations, by incorporating disease-specific local features with global image features for enhanced performance in multilabel classification. Our experimental results show that CheXFound outperforms state-of-the-art models in classifying 40 disease findings across different prevalence levels on the CXR-LT 24 dataset and exhibits superior label efficiency on downstream tasks with limited training data. Additionally, CheXFound achieved significant improvements on new tasks with out-of-distribution datasets, including opportunistic cardiovascular disease risk estimation and mortality prediction. These results highlight CheXFound's strong generalization capabilities, enabling diverse adaptations with improved label efficiency. The project source code is publicly available at https://github.com/RPIDIAL/CheXFound.
Pulmonary Embolism (PE) is a serious cardiovascular condition that remains a leading cause of mortality and critical illness, underscoring the need for enhanced diagnostic strategies. Conventional clinical methods have limited success in predicting 30-day in-hospital mortality of PE patients. In this study, we present a new algorithm, called PEP-Net, for 30-day mortality prediction of PE patients based on the initial imaging data (CT) that opportunistically integrates a 3D Residual Network (3DResNet) with Extreme Gradient Boosting (XGBoost) algorithm with patient level binary labels without annotations of the emboli and its extent. Our proposed system offers a comprehensive prediction strategy by handling class imbalance problems, reducing overfitting via regularization, and reducing the prediction variance for more stable predictions. PEP-Net was tested in a cohort of 193 volumetric CT scans diagnosed with Acute PE, and it demonstrated a superior performance by significantly outperforming baseline models (76-78\%) with an accuracy of 94.5\% (+/-0.3) and 94.0\% (+/-0.7) when the input image is either lung region (Lung-ROI) or heart region (Cardiac-ROI). Our results advance PE prognostics by using only initial imaging data, setting a new benchmark in the field. While purely deep learning models have become the go-to for many medical classification (diagnostic) tasks, combined ResNet and XGBoost models herein outperform sole deep learning models due to a potential reason for having lack of enough data.
In-hospital mortality (IHM) prediction for ICU patients is critical for timely interventions and efficient resource allocation. While structured physiological data provides quantitative insights, clinical notes offer unstructured, context-rich narratives. This study integrates these modalities with Large Language Model (LLM)-generated expert summaries to improve IHM prediction accuracy. Using the MIMIC-III database, we analyzed time-series physiological data and clinical notes from the first 48 hours of ICU admission. Clinical notes were concatenated chronologically for each patient and transformed into expert summaries using Med42-v2 70B. A multi-representational learning framework was developed to integrate these data sources, leveraging LLMs to enhance textual data while mitigating direct reliance on LLM predictions, which can introduce challenges in uncertainty quantification and interpretability. The proposed model achieved an AUPRC of 0.6156 (+36.41%) and an AUROC of 0.8955 (+7.64%) compared to a time-series-only baseline. Expert summaries outperformed clinical notes or time-series data alone, demonstrating the value of LLM-generated knowledge. Performance gains were consistent across demographic groups, with notable improvements in underrepresented populations, underscoring the framework's equitable application potential. By integrating LLM-generated summaries with structured and unstructured data, the framework captures complementary patient information, significantly improving predictive performance. This approach showcases the potential of LLMs to augment critical care prediction models, emphasizing the need for domain-specific validation and advanced integration strategies for broader clinical adoption.
The task of predicting long-term patient outcomes using supervised machine learning is a challenging one, in part because of the high variance of each patient's trajectory, which can result in the model over-fitting to the training data. Temporal difference (TD) learning, a common reinforcement learning technique, may reduce variance by generalising learning to the pattern of state transitions rather than terminal outcomes. However, in healthcare this method requires several strong assumptions about patient states, and there appears to be limited literature evaluating the performance of TD learning against traditional supervised learning methods for long-term health outcome prediction tasks. In this study, we define a framework for applying TD learning to real-time irregularly sampled time series data using a Semi-Markov Reward Process. We evaluate the model framework in predicting intensive care mortality and show that TD learning under this framework can result in improved model robustness compared to standard supervised learning methods. and that this robustness is maintained even when validated on external datasets. This approach may offer a more reliable method when learning to predict patient outcomes using high-variance irregular time series data.
Accurately predicting blood glucose (BG) levels of ICU patients is critical, as both hypoglycemia (BG < 70 mg/dL) and hyperglycemia (BG > 180 mg/dL) are associated with increased morbidity and mortality. This study presents a proof-of-concept machine learning framework, the Multi-source Irregular Time-Series Transformer (MITST), designed to predict BG levels in ICU patients. In contrast to existing methods that rely heavily on manual feature engineering or utilize limited Electronic Health Record (EHR) data sources, MITST integrates diverse clinical data--including laboratory results, medications, and vital signs without predefined aggregation. The model leverages a hierarchical Transformer architecture, designed to capture interactions among features within individual timestamps, temporal dependencies across different timestamps, and semantic relationships across multiple data sources. Evaluated using the extensive eICU database (200,859 ICU stays across 208 hospitals), MITST achieves a statistically significant ( p < 0.001 ) average improvement of 1.7 percentage points (pp) in AUROC and 1.8 pp in AUPRC over a state-of-the-art random forest baseline. Crucially, for hypoglycemia--a rare but life-threatening condition--MITST increases sensitivity by 7.2 pp, potentially enabling hundreds of earlier interventions across ICU populations. The flexible architecture of MITST allows seamless integration of new data sources without retraining the entire model, enhancing its adaptability for clinical decision support. While this study focuses on predicting BG levels, we also demonstrate MITST's ability to generalize to a distinct clinical task (in-hospital mortality prediction), highlighting its potential for broader applicability in ICU settings. MITST thus offers a robust and extensible solution for analyzing complex, multi-source, irregular time-series data.