The intensive care unit (ICU) manages critically ill patients, many of whom face a high risk of mortality. Early and accurate prediction of in-hospital mortality within the first 24 hours of ICU admission is crucial for timely clinical interventions, resource optimization, and improved patient outcomes. Traditional scoring systems, while useful, often have limitations in predictive accuracy and adaptability. Objective: This review aims to systematically evaluate and benchmark innovative methodologies that leverage data available within the first day of ICU admission for predicting in-hospital mortality. We focus on advancements in machine learning, novel biomarker applications, and the integration of diverse data types.
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.
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.
Integrating modern machine learning and clinical decision-making has great promise for mitigating healthcare's increasing cost and complexity. We introduce the Enhanced Transformer for Health Outcome Simulation (ETHOS), a novel application of the transformer deep-learning architecture for analyzing high-dimensional, heterogeneous, and episodic health data. ETHOS is trained using Patient Health Timelines (PHTs)-detailed, tokenized records of health events-to predict future health trajectories, leveraging a zero-shot learning approach. ETHOS represents a significant advancement in foundation model development for healthcare analytics, eliminating the need for labeled data and model fine-tuning. Its ability to simulate various treatment pathways and consider patient-specific factors positions ETHOS as a tool for care optimization and addressing biases in healthcare delivery. Future developments will expand ETHOS' capabilities to incorporate a wider range of data types and data sources. Our work demonstrates a pathway toward accelerated AI development and deployment in healthcare.
Background: Stroke is second-leading cause of disability and death among adults. Approximately 17 million people suffer from a stroke annually, with about 85% being ischemic strokes. Predicting mortality of ischemic stroke patients in intensive care unit (ICU) is crucial for optimizing treatment strategies, allocating resources, and improving survival rates. Methods: We acquired data on ICU ischemic stroke patients from MIMIC-IV database, including diagnoses, vital signs, laboratory tests, medications, procedures, treatments, and clinical notes. Stroke patients were randomly divided into training (70%, n=2441), test (15%, n=523), and validation (15%, n=523) sets. To address data imbalances, we applied Synthetic Minority Over-sampling Technique (SMOTE). We selected 30 features for model development, significantly reducing feature number from 1095 used in the best study. We developed a deep learning model to assess mortality risk and implemented several baseline machine learning models for comparison. Results: XGB-DL model, combining XGBoost for feature selection and deep learning, effectively minimized false positives. Model's AUROC improved from 0.865 (95% CI: 0.821 - 0.905) on first day to 0.903 (95% CI: 0.868 - 0.936) by fourth day using data from 3,646 ICU mortality patients in the MIMIC-IV database with 0.945 AUROC (95% CI: 0.944 - 0.947) during training. Although other ML models also performed well in terms of AUROC, we chose Deep Learning for its higher specificity. Conclusions: Through enhanced feature selection and data cleaning, proposed model demonstrates a 13% AUROC improvement compared to existing models while reducing feature number from 1095 in previous studies to 30.
Objective: Sepsis is a life-threatening condition. Sequential Organ Failure Assessment (SOFA) score is commonly used to assess organ dysfunction and predict ICU mortality, but it is taken as a static measurement and fails to capture dynamic changes. This study aims to investigate the relationship between dynamic changes in SOFA scores over the first 72 hours of ICU admission and patient outcomes. Design, setting, and participants: 3,253 patients in the Medical Information Mart for Intensive Care IV database who met the sepsis-3 criteria and were admitted from the emergency department with at least 72 hours of ICU admission and full-active resuscitation status were analysed. Group-based trajectory modelling with dynamic time warping and k-means clustering identified distinct trajectory patterns in dynamic SOFA scores. They were subsequently compared using Python. Main outcome measures: Outcomes including hospital and ICU mortality, length of stay in hospital and ICU, and readmission during hospital stay, were collected. Discharge time from ICU to wards and cut-offs at 7-day and 14-day were taken. Results: Four clusters were identified: A (consistently low SOFA scores), B (rapid increase followed by a decline in SOFA scores), C (higher baseline scores with gradual improvement), and D (persistently elevated scores). Cluster D had the longest ICU and hospital stays, highest ICU and hospital mortality. Discharge rates from ICU were similar for Clusters A and B, while Cluster C had initially comparable rates but a slower transition to ward. Conclusion: Monitoring dynamic changes in SOFA score is valuable for assessing sepsis severity and treatment responsiveness.
Extensive bedside monitoring in Intensive Care Units (ICUs) has resulted in complex temporal data regarding patient physiology, which presents an upscale context for clinical data analysis. In the other hand, identifying the time-series patterns within these data may provide a high aptitude to predict clinical events. Hence, we investigate, during this work, the implementation of an automatic data-driven system, which analyzes large amounts of multivariate temporal data derived from Electronic Health Records (EHRs), and extracts high-level information so as to predict in-hospital mortality and Length of Stay (LOS) early. Practically, we investigate the applicability of LSTM network by reducing the time-frame to 6-hour so as to enhance clinical tasks. The experimental results highlight the efficiency of LSTM model with rigorous multivariate time-series measurements for building real-world prediction engines.
Background: The predictive Intensive Care Unit (ICU) scoring system plays an important role in ICU management because it predicts important outcomes, especially mortality. Many scoring systems have been developed and used in the ICU. These scoring systems are primarily based on the structured clinical data in the electronic health record (EHR), which may suffer the loss of important clinical information in the narratives and images. Methods: In this work, we build a deep learning based survival prediction model with multi-modality data to predict ICU mortality. Four sets of features are investigated: (1) physiological measurements of Simplified Acute Physiology Score (SAPS) II, (2) common thorax diseases pre-defined by radiologists, (3) BERT-based text representations, and (4) chest X-ray image features. We use the Medical Information Mart for Intensive Care IV (MIMIC-IV) dataset to evaluate the proposed model. Results: Our model achieves the average C-index of 0.7829 (95% confidence interval, 0.7620-0.8038), which substantially exceeds that of the baseline with SAPS-II features (0.7470 (0.7263-0.7676)). Ablation studies further demonstrate the contributions of pre-defined labels (2.00%), text features (2.44%), and image features (2.82%).
This study employed the MIMIC-IV database as data source to investigate the use of dynamic, high-frequency, multivariate time-series vital signs data, including temperature, heart rate, mean blood pressure, respiratory rate, and SpO2, monitored first 8 hours data in the ICU stay. Various clustering algorithms were compared, and an end-to-end multivariate time series clustering system called Time2Feat, combined with K-Means, was chosen as the most effective method to cluster patients in the ICU. In clustering analysis, data of 8,080 patients admitted between 2008 and 2016 was used for model development and 2,038 patients admitted between 2017 and 2019 for model validation. By analyzing the differences in clinical mortality prognosis among different categories, varying risks of ICU mortality and hospital mortality were found between different subgroups. Furthermore, the study visualized the trajectory of vital signs changes. The findings of this study provide valuable insights into the potential use of multivariate time-series clustering systems in patient management and monitoring in the ICU setting.
In the United States, more than 5 million patients are admitted annually to ICUs, with ICU mortality of 10%-29% and costs over $82 billion. Acute brain dysfunction status, delirium, is often underdiagnosed or undervalued. This study's objective was to develop automated computable phenotypes for acute brain dysfunction states and describe transitions among brain dysfunction states to illustrate the clinical trajectories of ICU patients. We created two single-center, longitudinal EHR datasets for 48,817 adult patients admitted to an ICU at UFH Gainesville (GNV) and Jacksonville (JAX). We developed algorithms to quantify acute brain dysfunction status including coma, delirium, normal, or death at 12-hour intervals of each ICU admission and to identify acute brain dysfunction phenotypes using continuous acute brain dysfunction status and k-means clustering approach. There were 49,770 admissions for 37,835 patients in UFH GNV dataset and 18,472 admissions for 10,982 patients in UFH JAX dataset. In total, 18% of patients had coma as the worst brain dysfunction status; every 12 hours, around 4%-7% would transit to delirium, 22%-25% would recover, 3%-4% would expire, and 67%-68% would remain in a coma in the ICU. Additionally, 7% of patients had delirium as the worst brain dysfunction status; around 6%-7% would transit to coma, 40%-42% would be no delirium, 1% would expire, and 51%-52% would remain delirium in the ICU. There were three phenotypes: persistent coma/delirium, persistently normal, and transition from coma/delirium to normal almost exclusively in first 48 hours after ICU admission. We developed phenotyping scoring algorithms that determined acute brain dysfunction status every 12 hours while admitted to the ICU. This approach may be useful in developing prognostic and decision-support tools to aid patients and clinicians in decision-making on resource use and escalation of care.
Intensive Care Units usually carry patients with a serious risk of mortality. Recent research has shown the ability of Machine Learning to indicate the patients' mortality risk and point physicians toward individuals with a heightened need for care. Nevertheless, healthcare data is often subject to privacy regulations and can therefore not be easily shared in order to build Centralized Machine Learning models that use the combined data of multiple hospitals. Federated Learning is a Machine Learning framework designed for data privacy that can be used to circumvent this problem. In this study, we evaluate the ability of deep Federated Learning to predict the risk of Intensive Care Unit mortality at an early stage. We compare the predictive performance of Federated, Centralized, and Local Machine Learning in terms of AUPRC, F1-score, and AUROC. Our results show that Federated Learning performs equally well as the centralized approach and is substantially better than the local approach, thus providing a viable solution for early Intensive Care Unit mortality prediction. In addition, we show that the prediction performance is higher when the patient history window is closer to discharge or death. Finally, we show that using the F1-score as an early stopping metric can stabilize and increase the performance of our approach for the task at hand.
Although Machine Learning (ML) can be seen as a promising tool to improve clinical decision-making for supporting the improvement of medication plans, clinical procedures, diagnoses, or medication prescriptions, it remains limited by access to healthcare data. Healthcare data is sensitive, requiring strict privacy practices, and typically stored in data silos, making traditional machine learning challenging. Federated learning can counteract those limitations by training machine learning models over data silos while keeping the sensitive data localized. This study proposes a federated learning workflow for ICU mortality prediction. Hereby, the applicability of federated learning as an alternative to centralized machine learning and local machine learning is investigated by introducing federated learning to the binary classification problem of predicting ICU mortality. We extract multivariate time series data from the MIMIC-III database (lab values and vital signs), and benchmark the predictive performance of four deep sequential classifiers (FRNN, LSTM, GRU, and 1DCNN) varying the patient history window lengths (8h, 16h, 24h, 48h) and the number of FL clients (2, 4, 8). The experiments demonstrate that both centralized machine learning and federated learning are comparable in terms of AUPRC and F1-score. Furthermore, the federated approach shows superior performance over local machine learning. Thus, the federated approach can be seen as a valid and privacy-preserving alternative to centralized machine learning for classifying ICU mortality when sharing sensitive patient data between hospitals is not possible.
The recent success of machine learning methods applied to time series collected from Intensive Care Units (ICU) exposes the lack of standardized machine learning benchmarks for developing and comparing such methods. While raw datasets, such as MIMIC-IV or eICU, can be freely accessed on Physionet, the choice of tasks and pre-processing is often chosen ad-hoc for each publication, limiting comparability across publications. In this work, we aim to improve this situation by providing a benchmark covering a large spectrum of ICU-related tasks. Using the HiRID dataset, we define multiple clinically relevant tasks in collaboration with clinicians. In addition, we provide a reproducible end-to-end pipeline to construct both data and labels. Finally, we provide an in-depth analysis of current state-of-the-art sequence modeling methods, highlighting some limitations of deep learning approaches for this type of data. With this benchmark, we hope to give the research community the possibility of a fair comparison of their work.
Electronic Health Record (EHR) systems provide critical, rich and valuable information at high frequency. One of the most exciting applications of EHR data is in developing a real-time mortality warning system with tools from survival analysis. However, most of the survival analysis methods used recently are based on (semi)parametric models using static covariates. These models do not take advantage of the information conveyed by the time-varying EHR data. In this work, we present an application of a highly scalable survival analysis method, BoXHED 2.0 to develop a real-time in-ICU mortality warning indicator based on the MIMIC IV data set. Importantly, BoXHED can incorporate time-dependent covariates in a fully nonparametric manner and is backed by theory. Our in-ICU mortality model achieves an AUC-PRC of 0.41 and AUC-ROC of 0.83 out of sample, demonstrating the benefit of real-time monitoring.
Complex deep learning models show high prediction tasks in various clinical prediction tasks but their inherent complexity makes it more challenging to explain model predictions for clinicians and healthcare providers. Existing research on explainability of deep learning models in healthcare have two major limitations: using post-hoc explanations and using raw clinical variables as units of explanation, both of which are often difficult for human interpretation. In this work, we designed a self-explaining deep learning framework using the expert-knowledge driven clinical concepts or intermediate features as units of explanation. The self-explaining nature of our proposed model comes from generating both explanations and predictions within the same architectural framework via joint training. We tested our proposed approach on a publicly available Electronic Health Records (EHR) dataset for predicting patient mortality in the ICU. In order to analyze the performance-interpretability trade-off, we compared our proposed model with a baseline having the same set-up but without the explanation components. Experimental results suggest that adding explainability components to a deep learning framework does not impact prediction performance and the explanations generated by the model can provide insights to the clinicians to understand the possible reasons behind patient mortality.
Respiratory failure is the one of major causes of death in critical care unit. During the outbreak of COVID-19, critical care units experienced an extreme shortage of mechanical ventilation because of respiratory failure related syndromes. To help this, the early mortality risk prediction in patients who suffer respiratory failure can provide timely support for clinical treatment and resource management. In the study, we propose a dynamic modeling approach for early mortality risk prediction of the respiratory failure patients based on the first 24 hours ICU physiological data. Our proposed model is validated on the eICU collaborate database. We achieved a high AUROC performance (80-83%) and significantly improved AUCPR 4% on Day 5 since ICU admission, compared to the state-of-art prediction models. In addition, we illustrated that the survival curve includes the time-varying information for the early ICU admission survival analysis.
Learning temporal patterns from multivariate longitudinal data is challenging especially in cases when data is sporadic, as often seen in, e.g., healthcare applications where the data can suffer from irregularity and asynchronicity as the time between consecutive data points can vary across features and samples, hindering the application of existing deep learning models that are constructed for complete, evenly spaced data with fixed sequence lengths. In this paper, a novel deep learning-based model is developed for modeling multiple temporal features in sporadic data using an integrated deep learning architecture based on a recurrent neural network (RNN) unit and a continuous-time autoregressive (CAR) model. The proposed model, called CARRNN, uses a generalized discrete-time autoregressive model that is trainable end-to-end using neural networks modulated by time lags to describe the changes caused by the irregularity and asynchronicity. It is applied to multivariate time-series regression tasks using data provided for Alzheimer's disease progression modeling and intensive care unit (ICU) mortality rate prediction, where the proposed model based on a gated recurrent unit (GRU) achieves the lowest prediction errors among the proposed RNN-based models and state-of-the-art methods using GRUs and long short-term memory (LSTM) networks in their architecture.
Interpretability of machine learning models is critical for data-driven precision medicine efforts. However, highly predictive models are generally complex and are difficult to interpret. Here using Model-Agnostic Explanations algorithm, we show that complex models such as random forest can be made interpretable. Using MIMIC-II dataset, we successfully predicted ICU mortality with 80% balanced accuracy and were also were able to interpret the relative effect of the features on prediction at individual level.
Accurate mortality prediction allows Intensive Care Units (ICUs) to adequately benchmark clinical practice and identify patients with unexpected outcomes. Traditionally, simple statistical models have been used to assess patient death risk, many times with sub-optimal performance. On the other hand deep learning holds promise to positively impact clinical practice by leveraging medical data to assist diagnosis and prediction, including mortality prediction. However, as the question of whether powerful Deep Learning models attend correlations backed by sound medical knowledge when generating predictions remains open, additional interpretability tools are needed to foster trust and encourage the use of AI by clinicians. In this work we show a Deep Learning model trained on MIMIC-III to predict mortality using raw nursing notes, together with visual explanations for word importance. Our model reaches a ROC of 0.8629 (+/-0.0058), outperforming the traditional SAPS-II score and providing enhanced interpretability when compared with similar Deep Learning approaches.
Intensive Care Unit Electronic Health Records (ICU EHRs) store multimodal data about patients including clinical notes, sparse and irregularly sampled physiological time series, lab results, and more. To date, most methods designed to learn predictive models from ICU EHR data have focused on a single modality. In this paper, we leverage the recently proposed interpolation-prediction deep learning architecture(Shukla and Marlin 2019) as a basis for exploring how physiological time series data and clinical notes can be integrated into a unified mortality prediction model. We study both early and late fusion approaches and demonstrate how the relative predictive value of clinical text and physiological data change over time. Our results show that a late fusion approach can provide a statistically significant improvement in mortality prediction performance over using individual modalities in isolation.