Yuanfang Ren

Yingbo Ma, Yukyeong Song, Jeremy A. Balch et al.

As more clinical workflows continue to be augmented by artificial intelligence (AI), AI literacy among physicians will become a critical requirement for ensuring safe and ethical AI-enabled patient care. Despite the evolving importance of AI in healthcare, the extent to which it has been adopted into traditional and often-overloaded medical curricula is currently unknown. In a scoping review of 1,699 articles published between January 2016 and June 2024, we identified 18 studies which propose guiding frameworks, and 11 studies documenting real-world instruction, centered around the integration of AI into medical education. We found that comprehensive guidelines will require greater clinical relevance and personalization to suit medical student interests and career trajectories. Current efforts highlight discrepancies in the teaching guidelines, emphasizing AI evaluation and ethics over technical topics such as data science and coding. Additionally, we identified several challenges associated with integrating AI training into the medical education program, including a lack of guidelines to define medical students AI literacy, a perceived lack of proven clinical value, and a scarcity of qualified instructors. With this knowledge, we propose an AI literacy framework to define competencies for medical students. To prioritize relevant and personalized AI education, we categorize literacy into four dimensions: Foundational, Practical, Experimental, and Ethical, with tailored learning objectives to the pre-clinical, clinical, and clinical research stages of medical education. This review provides a road map for developing practical and relevant education strategies for building an AI-competent healthcare workforce.

Miguel Contreras, Brandon Silva, Benjamin Shickel et al.

The acuity state of patients in the intensive care unit (ICU) can quickly change from stable to unstable. Early detection of deteriorating conditions can result in providing timely interventions and improved survival rates. In this study, we propose APRICOT-M (Acuity Prediction in Intensive Care Unit-Mamba), a 150k-parameter state space-based neural network to predict acuity state, transitions, and the need for life-sustaining therapies in real-time in ICU patients. The model uses data obtained in the prior four hours in the ICU and patient information obtained at admission to predict the acuity outcomes in the next four hours. We validated APRICOT-M externally on data from hospitals not used in development (75,668 patients from 147 hospitals), temporally on data from a period not used in development (12,927 patients from one hospital from 2018-2019), and prospectively on data collected in real-time (215 patients from one hospital from 2021-2023) using three large datasets: the University of Florida Health (UFH) dataset, the electronic ICU Collaborative Research Database (eICU), and the Medical Information Mart for Intensive Care (MIMIC)-IV. The area under the receiver operating characteristic curve (AUROC) of APRICOT-M for mortality (external 0.94-0.95, temporal 0.97-0.98, prospective 0.96-1.00) and acuity (external 0.95-0.95, temporal 0.97-0.97, prospective 0.96-0.96) shows comparable results to state-of-the-art models. Furthermore, APRICOT-M can predict transitions to instability (external 0.81-0.82, temporal 0.77-0.78, prospective 0.68-0.75) and need for life-sustaining therapies, including mechanical ventilation (external 0.82-0.83, temporal 0.87-0.88, prospective 0.67-0.76), and vasopressors (external 0.81-0.82, temporal 0.73-0.75, prospective 0.66-0.74). This tool allows for real-time acuity monitoring in critically ill patients and can help clinicians make timely interventions.

Yuanfang Ren, Tyler J. Loftus, Ziyuan Guan et al.

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.

Subhash Nerella, Ziyuan Guan, Andrea Davidson et al.

Intensive Care Units (ICU) provide close supervision and continuous care to patients with life-threatening conditions. However, continuous patient assessment in the ICU is still limited due to time constraints and the workload on healthcare providers. Existing patient assessments in the ICU such as pain or mobility assessment are mostly sporadic and administered manually, thus introducing the potential for human errors. Developing Artificial intelligence (AI) tools that can augment human assessments in the ICU can be beneficial for providing more objective and granular monitoring capabilities. For example, capturing the variations in a patient's facial cues related to pain or agitation can help in adjusting pain-related medications or detecting agitation-inducing conditions such as delirium. Additionally, subtle changes in visual cues during or prior to adverse clinical events could potentially aid in continuous patient monitoring when combined with high-resolution physiological signals and Electronic Health Record (EHR) data. In this paper, we examined the association between visual cues and patient condition including acuity status, acute brain dysfunction, and pain. We leveraged our AU-ICU dataset with 107,064 frames collected in the ICU annotated with facial action units (AUs) labels by trained annotators. We developed a new "masked loss computation" technique that addresses the data imbalance problem by maximizing data resource utilization. We trained the model using our AU-ICU dataset in conjunction with three external datasets to detect 18 AUs. The SWIN Transformer model achieved 0.57 mean F1-score and 0.89 mean accuracy on the test set. Additionally, we performed AU inference on 634,054 frames to evaluate the association between facial AUs and clinically important patient conditions such as acuity status, acute brain dysfunction, and pain.

Yuanfang Ren, Varun Sai Vemuri, Zhenhong Hu et al.

Background: This study aims to develop and validate federated learning models for predicting major postoperative complications and mortality using a large multicenter dataset from the OneFlorida Data Trust. We hypothesize that federated learning models will offer robust generalizability while preserving data privacy and security. Methods: This retrospective, longitudinal, multicenter cohort study included 358,644 adult patients admitted to five healthcare institutions, who underwent 494,163 inpatient major surgical procedures from 2012-2023. We developed and internally and externally validated federated learning models to predict the postoperative risk of intensive care unit (ICU) admission, mechanical ventilation (MV) therapy, acute kidney injury (AKI), and in-hospital mortality. These models were compared with local models trained on data from a single center and central models trained on a pooled dataset from all centers. Performance was primarily evaluated using area under the receiver operating characteristics curve (AUROC) and the area under the precision-recall curve (AUPRC) values. Results: Our federated learning models demonstrated strong predictive performance, with AUROC scores consistently comparable or superior performance in terms of AUROC and AUPRC across all outcomes and sites. Our federated learning models also demonstrated strong generalizability, with comparable or superior performance in terms of both AUROC and AUPRC compared to the best local learning model at each site. Conclusions: By leveraging multicenter data, we developed robust, generalizable, and privacy-preserving predictive models for major postoperative complications and mortality. These findings support the feasibility of federated learning in clinical decision support systems.

Yuanfang Ren, Yanjun Li, Tyler J. Loftus et al.

Initial hours of hospital admission impact clinical trajectory, but early clinical decisions often suffer due to data paucity. With clustering analysis for vital signs within six hours of admission, patient phenotypes with distinct pathophysiological signatures and outcomes may support early clinical decisions. We created a single-center, longitudinal EHR dataset for 75,762 adults admitted to a tertiary care center for 6+ hours. We proposed a deep temporal interpolation and clustering network to extract latent representations from sparse, irregularly sampled vital sign data and derived distinct patient phenotypes in a training cohort (n=41,502). Model and hyper-parameters were chosen based on a validation cohort (n=17,415). Test cohort (n=16,845) was used to analyze reproducibility and correlation with biomarkers. The training, validation, and testing cohorts had similar distributions of age (54-55 yrs), sex (55% female), race, comorbidities, and illness severity. Four clusters were identified. Phenotype A (18%) had most comorbid disease with higher rate of prolonged respiratory insufficiency, acute kidney injury, sepsis, and three-year mortality. Phenotypes B (33%) and C (31%) had diffuse patterns of mild organ dysfunction. Phenotype B had favorable short-term outcomes but second-highest three-year mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) had early/persistent hypotension, high rate of early surgery, and substantial biomarker rate of inflammation but second-lowest three-year mortality. After comparing phenotypes' SOFA scores, clustering results did not simply repeat other acuity assessments. In a heterogeneous cohort, four phenotypes with distinct categories of disease and outcomes were identified by a deep temporal interpolation and clustering network. This tool may impact triage decisions and clinical decision-support under time constraints.

Brandon Silva, Miguel Contreras, Tezcan Ozrazgat Baslanti et al.

Acute brain dysfunctions (ABD), which include coma and delirium, are prevalent in the ICU, especially among older patients. The current approach in manual assessment of ABD by care providers may be sporadic and subjective. Hence, there exists a need for a data-driven robust system automating the assessment and prediction of ABD. In this work, we develop a machine learning system for real-time prediction of ADB using Electronic Health Record (HER) data. Our data processing pipeline enables integration of static and temporal data, and extraction of features relevant to ABD. We train several state-of-the-art transformer models and baseline machine learning models including CatBoost and XGB on the data that was collected from patients admitted to the ICU at UF Shands Hospital. We demonstrate the efficacy of our system for tasks related to acute brain dysfunction including binary classification of brain acuity and multi-class classification (i.e., coma, delirium, death, or normal), achieving a mean AUROC of 0.953 on our Long-former implementation. Our system can then be deployed for real-time prediction of ADB in ICUs to reduce the number of incidents caused by ABD. Moreover, the real-time system has the potential to reduce costs, duration of patients stays in the ICU, and mortality among those afflicted.

Esra Adiyeke, Yuanfang Ren, Ziyuan Guan et al.

Objectives: We aim to quantify longitudinal acute kidney injury (AKI) trajectories and to describe transitions through progressing and recovery states and outcomes among hospitalized patients using multistate models. Methods: In this large, longitudinal cohort study, 138,449 adult patients admitted to a quaternary care hospital between 2012 and 2019 were staged based on Kidney Disease: Improving Global Outcomes serum creatinine criteria for the first 14 days of their hospital stay. We fit multistate models to estimate probability of being in a certain clinical state at a given time after entering each one of the AKI stages. We investigated the effects of selected variables on transition rates via Cox proportional hazards regression models. Results: Twenty percent of hospitalized encounters (49,325/246,964) had AKI; among patients with AKI, 66% had Stage 1 AKI, 18% had Stage 2 AKI, and 17% had AKI Stage 3 with or without RRT. At seven days following Stage 1 AKI, 69% (95% confidence interval [CI]: 68.8%-70.5%) were either resolved to No AKI or discharged, while smaller proportions of recovery (26.8%, 95% CI: 26.1%-27.5%) and discharge (17.4%, 95% CI: 16.8%-18.0%) were observed following AKI Stage 2. At 14 days following Stage 1 AKI, patients with more frail conditions (Charlson comorbidity index greater than or equal to 3 and had prolonged ICU stay) had lower proportion of transitioning to No AKI or discharge states. Discussion: Multistate analyses showed that the majority of Stage 2 and higher severity AKI patients could not resolve within seven days; therefore, strategies preventing the persistence or progression of AKI would contribute to the patients' life quality. Conclusions: We demonstrate multistate modeling framework's utility as a mechanism for a better understanding of the clinical course of AKI with the potential to facilitate treatment and resource planning.

Miguel Contreras, Sumit Kapoor, Jiaqing Zhang et al.

Delirium is an acute confusional state that has been shown to affect up to 31% of patients in the intensive care unit (ICU). Early detection of this condition could lead to more timely interventions and improved health outcomes. While artificial intelligence (AI) models have shown great potential for ICU delirium prediction using structured electronic health records (EHR), most of them have not explored the use of state-of-the-art AI models, have been limited to single hospitals, or have been developed and validated on small cohorts. The use of large language models (LLM), models with hundreds of millions to billions of parameters, with structured EHR data could potentially lead to improved predictive performance. In this study, we propose DeLLiriuM, a novel LLM-based delirium prediction model using EHR data available in the first 24 hours of ICU admission to predict the probability of a patient developing delirium during the rest of their ICU admission. We develop and validate DeLLiriuM on ICU admissions from 104,303 patients pertaining to 195 hospitals across three large databases: the eICU Collaborative Research Database, the Medical Information Mart for Intensive Care (MIMIC)-IV, and the University of Florida Health's Integrated Data Repository. The performance measured by the area under the receiver operating characteristic curve (AUROC) showed that DeLLiriuM outperformed all baselines in two external validation sets, with 0.77 (95% confidence interval 0.76-0.78) and 0.84 (95% confidence interval 0.83-0.85) across 77,543 patients spanning 194 hospitals. To the best of our knowledge, DeLLiriuM is the first LLM-based delirium prediction tool for the ICU based on structured EHR data, outperforming deep learning baselines which employ structured features and can provide helpful information to clinicians for timely interventions.

Yingbo Ma, Suraj Kolla, Zhenhong Hu et al.

Modern electronic health records (EHRs) hold immense promise in tracking personalized patient health trajectories through sequential deep learning, owing to their extensive breadth, scale, and temporal granularity. Nonetheless, how to effectively leverage multiple modalities from EHRs poses significant challenges, given its complex characteristics such as high dimensionality, multimodality, sparsity, varied recording frequencies, and temporal irregularities. To this end, this paper introduces a novel multimodal contrastive learning framework, specifically focusing on medical time series and clinical notes. To tackle the challenge of sparsity and irregular time intervals in medical time series, the framework integrates temporal cross-attention transformers with a dynamic embedding and tokenization scheme for learning multimodal feature representations. To harness the interconnected relationships between medical time series and clinical notes, the framework equips a global contrastive loss, aligning a patient's multimodal feature representations with the corresponding discharge summaries. Since discharge summaries uniquely pertain to individual patients and represent a holistic view of the patient's hospital stay, machine learning models are led to learn discriminative multimodal features via global contrasting. Extensive experiments with a real-world EHR dataset demonstrated that our framework outperformed state-of-the-art approaches on the exemplar task of predicting the occurrence of nine postoperative complications for more than 120,000 major inpatient surgeries using multimodal data from UF health system split among three hospitals (UF Health Gainesville, UF Health Jacksonville, and UF Health Jacksonville-North).

Jiaqing Zhang, Miguel Contreras, Sabyasachi Bandyopadhyay et al.

Estimation of patient acuity in the Intensive Care Unit (ICU) is vital to ensure timely and appropriate interventions. Advances in artificial intelligence (AI) technologies have significantly improved the accuracy of acuity predictions. However, prior studies using machine learning for acuity prediction have predominantly relied on electronic health records (EHR) data, often overlooking other critical aspects of ICU stay, such as patient mobility, environmental factors, and facial cues indicating pain or agitation. To address this gap, we present MANGO: the Multimodal Acuity traNsformer for intelliGent ICU Outcomes, designed to enhance the prediction of patient acuity states, transitions, and the need for life-sustaining therapy. We collected a multimodal dataset ICU-Multimodal, incorporating four key modalities, EHR data, wearable sensor data, video of patient's facial cues, and ambient sensor data, which we utilized to train MANGO. The MANGO model employs a multimodal feature fusion network powered by Transformer masked self-attention method, enabling it to capture and learn complex interactions across these diverse data modalities even when some modalities are absent. Our results demonstrated that integrating multiple modalities significantly improved the model's ability to predict acuity status, transitions, and the need for life-sustaining therapy. The best-performing models achieved an area under the receiver operating characteristic curve (AUROC) of 0.76 (95% CI: 0.72-0.79) for predicting transitions in acuity status and the need for life-sustaining therapy, while 0.82 (95% CI: 0.69-0.89) for acuity status prediction...

Esra Adiyeke, Tianqi Liu, Venkata Sai Dheeraj Naganaboina et al.

Traditional methods of surgical decision making heavily rely on human experience and prompt actions, which are variable. A data-driven system generating treatment recommendations based on patient states can be a substantial asset in perioperative decision-making, as in cases of intraoperative hypotension, for which suboptimal management is associated with acute kidney injury (AKI), a common and morbid postoperative complication. We developed a Reinforcement Learning (RL) model to recommend optimum dose of intravenous (IV) fluid and vasopressors during surgery to avoid intraoperative hypotension and postoperative AKI. We retrospectively analyzed 50,021 surgeries from 42,547 adult patients who underwent major surgery at a quaternary care hospital between June 2014 and September 2020. Of these, 34,186 surgeries were used for model training and 15,835 surgeries were reserved for testing. We developed a Deep Q-Networks based RL model using 16 variables including intraoperative physiologic time series, total dose of IV fluid and vasopressors extracted for every 15-minute epoch. The model replicated 69% of physician's decisions for the dosage of vasopressors and proposed higher or lower dosage of vasopressors than received in 10% and 21% of the treatments, respectively. In terms of IV fluids, the model's recommendations were within 0.05 ml/kg/15 min of the actual dose in 41% of the cases, with higher or lower doses recommended for 27% and 32% of the treatments, respectively. The model resulted in a higher estimated policy value compared to the physicians' actual treatments, as well as random and zero-drug policies. AKI prevalence was the lowest in patients receiving medication dosages that aligned with model's decisions. Our findings suggest that implementation of the model's policy has the potential to reduce postoperative AKI and improve other outcomes driven by intraoperative hypotension.

Jiaqing Zhang, Miguel Contreras, Jessica Sena et al.

Patient mobility monitoring in intensive care is critical for ensuring timely interventions and improving clinical outcomes. While accelerometry-based sensor data are widely adopted in training artificial intelligence models to estimate patient mobility, existing approaches face two key limitations highlighted in clinical practice: (1) modeling the long-term accelerometer data is challenging due to the high dimensionality, variability, and noise, and (2) the absence of efficient and robust methods for long-term mobility assessment. To overcome these challenges, we introduce MELON, a novel multimodal framework designed to predict 12-hour mobility status in the critical care setting. MELON leverages the power of a dual-branch network architecture, combining the strengths of spectrogram-based visual representations and sequential accelerometer statistical features. MELON effectively captures global and fine-grained mobility patterns by integrating a pre-trained image encoder for rich frequency-domain feature extraction and a Mixture-of-Experts encoder for sequence modeling. We trained and evaluated the MELON model on the multimodal dataset of 126 patients recruited from nine Intensive Care Units at the University of Florida Health Shands Hospital main campus in Gainesville, Florida. Experiments showed that MELON outperforms conventional approaches for 12-hour mobility status estimation with an overall area under the receiver operating characteristic curve (AUROC) of 0.82 (95\%, confidence interval 0.78-0.86). Notably, our experiments also revealed that accelerometer data collected from the wrist provides robust predictive performance compared with data from the ankle, suggesting a single-sensor solution that can reduce patient burden and lower deployment costs...

Miguel Contreras, Jessica Sena, Andrea Davidson et al.

Acute brain dysfunction (ABD) is a common, severe ICU complication, presenting as delirium or coma and leading to prolonged stays, increased mortality, and cognitive decline. Traditional screening tools like the Glasgow Coma Scale (GCS), Confusion Assessment Method (CAM), and Richmond Agitation-Sedation Scale (RASS) rely on intermittent assessments, causing delays and inconsistencies. In this study, we propose MANDARIN (Mixture-of-Experts Framework for Dynamic Delirium and Coma Prediction in ICU Patients), a 1.5M-parameter mixture-of-experts neural network to predict ABD in real-time among ICU patients. The model integrates temporal and static data from the ICU to predict the brain status in the next 12 to 72 hours, using a multi-branch approach to account for current brain status. The MANDARIN model was trained on data from 92,734 patients (132,997 ICU admissions) from 2 hospitals between 2008-2019 and validated externally on data from 11,719 patients (14,519 ICU admissions) from 15 hospitals and prospectively on data from 304 patients (503 ICU admissions) from one hospital in 2021-2024. Three datasets were used: the University of Florida Health (UFH) dataset, the electronic ICU Collaborative Research Database (eICU), and the Medical Information Mart for Intensive Care (MIMIC)-IV dataset. MANDARIN significantly outperforms the baseline neurological assessment scores (GCS, CAM, and RASS) for delirium prediction in both external (AUROC 75.5% CI: 74.2%-76.8% vs 68.3% CI: 66.9%-69.5%) and prospective (AUROC 82.0% CI: 74.8%-89.2% vs 72.7% CI: 65.5%-81.0%) cohorts, as well as for coma prediction (external AUROC 87.3% CI: 85.9%-89.0% vs 72.8% CI: 70.6%-74.9%, and prospective AUROC 93.4% CI: 88.5%-97.9% vs 67.7% CI: 57.7%-76.8%) with a 12-hour lead time. This tool has the potential to assist clinicians in decision-making by continuously monitoring the brain status of patients in the ICU.

Yuanfang Ren, Chirayu Tripathi, Ziyuan Guan et al.

Given the sheer volume of surgical procedures and the significant rate of postoperative fatalities, assessing and managing surgical complications has become a critical public health concern. Existing artificial intelligence (AI) tools for risk surveillance and diagnosis often lack adequate interpretability, fairness, and reproducibility. To address this, we proposed an Explainable AI (XAI) framework designed to answer five critical questions: why, why not, how, what if, and what else, with the goal of enhancing the explainability and transparency of AI models. We incorporated various techniques such as Local Interpretable Model-agnostic Explanations (LIME), SHapley Additive exPlanations (SHAP), counterfactual explanations, model cards, an interactive feature manipulation interface, and the identification of similar patients to address these questions. We showcased an XAI interface prototype that adheres to this framework for predicting major postoperative complications. This initial implementation has provided valuable insights into the vast explanatory potential of our XAI framework and represents an initial step towards its clinical adoption.

Yonggi Park, Yuanfang Ren, Benjamin Shickel et al.

Background: The accurate prediction of postoperative complication risk using Electronic Health Records (EHR) and artificial intelligence shows great potential. Training a robust artificial intelligence model typically requires large-scale and diverse datasets. In reality, collecting medical data often encounters challenges surrounding privacy protection. Methods: This retrospective cohort study includes adult patients who were admitted to UFH Gainesville (GNV) (n = 79,850) and Jacksonville (JAX) (n = 28,636) for any type of inpatient surgical procedure. Using perioperative and intraoperative features, we developed federated learning models to predict nine major postoperative complications (i.e., prolonged intensive care unit stay and mechanical ventilation). We compared federated learning models with local learning models trained on a single site and central learning models trained on pooled dataset from two centers. Results: Our federated learning models achieved the area under the receiver operating characteristics curve (AUROC) values ranged from 0.81 for wound complications to 0.92 for prolonged ICU stay at UFH GNV center. At UFH JAX center, these values ranged from 0.73-0.74 for wound complications to 0.92-0.93 for hospital mortality. Federated learning models achieved comparable AUROC performance to central learning models, except for prolonged ICU stay, where the performance of federated learning models was slightly higher than central learning models at UFH GNV center, but slightly lower at UFH JAX center. In addition, our federated learning model obtained comparable performance to the best local learning model at each center, demonstrating strong generalizability. Conclusion: Federated learning is shown to be a useful tool to train robust and generalizable models from large scale data across multiple institutions where data protection barriers are high.

Brandon Silva, Miguel Contreras, Sabyasachi Bandyopadhyay et al.

Assessing acute brain dysfunction (ABD), including delirium and coma in the intensive care unit (ICU), is a critical challenge due to its prevalence and severe implications for patient outcomes. Current diagnostic methods rely on infrequent clinical observations, which can only determine a patient's ABD status after onset. Our research attempts to solve these problems by harnessing Electronic Health Records (EHR) data to develop automated methods for ABD prediction for patients in the ICU. Existing models solely predict a single state (e.g., either delirium or coma), require at least 24 hours of observation data to make predictions, do not dynamically predict fluctuating ABD conditions during ICU stay (typically a one-time prediction), and use small sample size, proprietary single-hospital datasets. Our research fills these gaps in the existing literature by dynamically predicting delirium, coma, and mortality for 12-hour intervals throughout an ICU stay and validating on two public datasets. Our research also introduces the concept of dynamically predicting critical transitions from non-ABD to ABD and between different ABD states in real time, which could be clinically more informative for the hospital staff. We compared the predictive performance of two state-of-the-art neural network models, the MAMBA selective state space model and the Longformer Transformer model. Using the MAMBA model, we achieved a mean area under the receiving operator characteristic curve (AUROC) of 0.95 on outcome prediction of ABD for 12-hour intervals. The model achieves a mean AUROC of 0.79 when predicting transitions between ABD states. Our study uses a curated dataset from the University of Florida Health Shands Hospital for internal validation and two publicly available datasets, MIMIC-IV and eICU, for external validation, demonstrating robustness across ICU stays from 203 hospitals and 140,945 patients.

Yingbo Ma, Suraj Kolla, Dhruv Kaliraman et al.

The breadth, scale, and temporal granularity of modern electronic health records (EHR) systems offers great potential for estimating personalized and contextual patient health trajectories using sequential deep learning. However, learning useful representations of EHR data is challenging due to its high dimensionality, sparsity, multimodality, irregular and variable-specific recording frequency, and timestamp duplication when multiple measurements are recorded simultaneously. Although recent efforts to fuse structured EHR and unstructured clinical notes suggest the potential for more accurate prediction of clinical outcomes, less focus has been placed on EHR embedding approaches that directly address temporal EHR challenges by learning time-aware representations from multimodal patient time series. In this paper, we introduce a dynamic embedding and tokenization framework for precise representation of multimodal clinical time series that combines novel methods for encoding time and sequential position with temporal cross-attention. Our embedding and tokenization framework, when integrated into a multitask transformer classifier with sliding window attention, outperformed baseline approaches on the exemplar task of predicting the occurrence of nine postoperative complications of more than 120,000 major inpatient surgeries using multimodal data from three hospitals and two academic health centers in the United States.

Esra Adiyeke, Yuanfang Ren, Benjamin Shickel et al.

Background: Acute kidney injury (AKI), the decline of kidney excretory function, occurs in up to 18% of hospitalized admissions. Progression of AKI may lead to irreversible kidney damage. Methods: This retrospective cohort study includes adult patients admitted to a non-intensive care unit at the University of Pittsburgh Medical Center (UPMC) (n = 46,815) and University of Florida Health (UFH) (n = 127,202). We developed and compared deep learning and conventional machine learning models to predict progression to Stage 2 or higher AKI within the next 48 hours. We trained local models for each site (UFH Model trained on UFH, UPMC Model trained on UPMC) and a separate model with a development cohort of patients from both sites (UFH-UPMC Model). We internally and externally validated the models on each site and performed subgroup analyses across sex and race. Results: Stage 2 or higher AKI occurred in 3% (n=3,257) and 8% (n=2,296) of UFH and UPMC patients, respectively. Area under the receiver operating curve values (AUROC) for the UFH test cohort ranged between 0.77 (UPMC Model) and 0.81 (UFH Model), while AUROC values ranged between 0.79 (UFH Model) and 0.83 (UPMC Model) for the UPMC test cohort. UFH-UPMC Model achieved an AUROC of 0.81 (95% confidence interval [CI] [0.80, 0.83]) for UFH and 0.82 (95% CI [0.81,0.84]) for UPMC test cohorts; an area under the precision recall curve values (AUPRC) of 0.6 (95% CI, [0.05, 0.06]) for UFH and 0.13 (95% CI, [0.11,0.15]) for UPMC test cohorts. Kinetic estimated glomerular filtration rate, nephrotoxic drug burden and blood urea nitrogen remained the top three features with the highest influence across the models and health centers. Conclusion: Locally developed models displayed marginally reduced discrimination when tested on another institution, while the top set of influencing features remained the same across the models and sites.

Yuanfang Ren, Andrea E. Davidson, Jiaqing Zhang et al.

Background: Circadian desynchrony characterized by the misalignment between an individual's internal biological rhythms and external environmental cues, significantly affects various physiological processes and health outcomes. Quantifying circadian desynchrony often requires prolonged and frequent monitoring, and currently, an easy tool for this purpose is missing. Additionally, its association with the incidence of delirium has not been clearly explored. Methods: A prospective observational study was carried out in intensive care units (ICU) of a tertiary hospital. Circadian transcriptomics of blood monocytes from 86 individuals were collected on two consecutive days, although a second sample could not be obtained from all participants. Using two public datasets comprised of healthy volunteers, we replicated a model for determining internal circadian time. We developed an approach to quantify circadian desynchrony by comparing internal circadian time and external blood collection time. We applied the model and quantified circadian desynchrony index among ICU patients, and investigated its association with the incidence of delirium. Results: The replicated model for determining internal circadian time achieved comparable high accuracy. The quantified circadian desynchrony index was significantly higher among critically ill ICU patients compared to healthy subjects, with values of 10.03 hours vs 2.50-2.95 hours (p < 0.001). Most ICU patients had a circadian desynchrony index greater than 9 hours. Additionally, the index was lower in patients whose blood samples were drawn after 3pm, with values of 5.00 hours compared to 10.01-10.90 hours in other groups (p < 0.001)...

Yanjun Li, Yuanfang Ren, Tyler J. Loftus et al.

Background: During the early stages of hospital admission, clinicians must use limited information to make diagnostic and treatment decisions as patient acuity evolves. However, it is common that the time series vital sign information from patients to be both sparse and irregularly collected, which poses a significant challenge for machine / deep learning techniques to analyze and facilitate the clinicians to improve the human health outcome. To deal with this problem, We propose a novel deep interpolation network to extract latent representations from sparse and irregularly sampled time-series vital signs measured within six hours of hospital admission. Methods: We created a single-center longitudinal dataset of electronic health record data for all (n=75,762) adult patient admissions to a tertiary care center lasting six hours or longer, using 55% of the dataset for training, 23% for validation, and 22% for testing. All raw time series within six hours of hospital admission were extracted for six vital signs (systolic blood pressure, diastolic blood pressure, heart rate, temperature, blood oxygen saturation, and respiratory rate). A deep interpolation network is proposed to learn from such irregular and sparse multivariate time series data to extract the fixed low-dimensional latent patterns. We use k-means clustering algorithm to clusters the patient admissions resulting into 7 clusters. Findings: Training, validation, and testing cohorts had similar age (55-57 years), sex (55% female), and admission vital signs. Seven distinct clusters were identified. M Interpretation: In a heterogeneous cohort of hospitalized patients, a deep interpolation network extracted representations from vital sign data measured within six hours of hospital admission. This approach may have important implications for clinical decision-support under time constraints and uncertainty.

Yuanfang Ren, Jeremy Balch, Kenneth L. Abbott et al.

Continuous monitoring and patient acuity assessments are key aspects of Intensive Care Unit (ICU) practice, but both are limited by time constraints imposed on healthcare providers. Moreover, anticipating clinical trajectories remains imprecise. The objectives of this study are to (1) develop an electronic phenotype of acuity using automated variable retrieval within the electronic health records and (2) describe transitions between acuity states that illustrate the clinical trajectories of ICU patients. We gathered two single-center, longitudinal electronic health record datasets for 51,372 adult ICU patients admitted to the University of Florida Health (UFH) Gainesville (GNV) and Jacksonville (JAX). We developed algorithms to quantify acuity status at four-hour intervals for each ICU admission and identify acuity phenotypes using continuous acuity status and k-means clustering approach. 51,073 admissions for 38,749 patients in the UFH GNV dataset and 22,219 admissions for 12,623 patients in the UFH JAX dataset had at least one ICU stay lasting more than four hours. There were three phenotypes: persistently stable, persistently unstable, and transitioning from unstable to stable. For stable patients, approximately 0.7%-1.7% would transition to unstable, 0.02%-0.1% would expire, 1.2%-3.4% would be discharged, and the remaining 96%-97% would remain stable in the ICU every four hours. For unstable patients, approximately 6%-10% would transition to stable, 0.4%-0.5% would expire, and the remaining 89%-93% would remain unstable in the ICU in the next four hours. We developed phenotyping algorithms for patient acuity status every four hours while admitted to the ICU. This approach may be useful in developing prognostic and clinical decision-support tools to aid patients, caregivers, and providers in shared decision-making processes regarding escalation of care and patient values.