Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes. Four distinct clusters were identified. Phenotype A (18%) had the greatest prevalence of comorbid disease with increased prevalence of prolonged respiratory insufficiency, acute kidney injury, sepsis, and long-term (3-year) mortality. Phenotypes B (33%) and C (31%) had a diffuse pattern of mild organ dysfunction. Phenotype B's favorable short-term clinical outcomes were tempered by the second highest rate of long-term mortality. Phenotype C had favorable clinical outcomes. Phenotype D (17%) exhibited early and persistent hypotension, high incidence of early surgery, and substantial biomarker incidence of inflammation. Despite early and severe illness, phenotype D had the second lowest long-term mortality. After comparing the sequential organ failure assessment scores, the clustering results did not simply provide a recapitulation of previous acuity assessments. This tool may impact triage decisions and have significant implications for clinical decision-support under time constraints and uncertainty.

Clinical courses of acute kidney injury in hospitalized patients: a multistate analysis.

Persistence of acute kidney injury (AKI) or insufficient recovery of renal function was associated with reduced long-term survival and life quality. We quantified AKI trajectories and describe transitions through progression and recovery among hospitalized patients. 245,663 encounters from 128,271 patients admitted to UF Health between 2012 and 2019 were retrospectively categorized according to the worst AKI stage experienced within 24-h periods. Multistate models were fit for describing characteristics influencing transitions towards progressed or regressed AKI, discharge, and death. Effects of age, sex, race, admission comorbidities, and prolonged intensive care unit stay (ICU) on transition rates were examined via Cox proportional hazards models. About 20% of encounters had AKI; where 66% of those with AKI had Stage 1 as their worst AKI severity during hospitalization, 18% had Stage 2, and 16% had Stage 3 AKI (12% with kidney replacement therapy (KRT) and 4% without KRT). At 3 days following Stage 1 AKI, 71.1% (70.5-71.6%) were either resolved to No AKI or discharged, while recovery proportion was 38% (37.4-38.6%) and discharge proportion was 7.1% (6.9-7.3%) following AKI Stage 2. At 14 days following Stage 1 AKI, patients with additional frail conditions stay had lower transition proportion towards No AKI or discharge states. Multistate modeling framework is a facilitating mechanism for understanding AKI clinical course and examining characteristics influencing disease process and transition rates.

Machine Learning-Enabled Clinical Information Systems Using Fast Healthcare Interoperability Resources Data Standards: Scoping Review.

Background: Machine learning-enabled clinical information systems (ML-CISs) have the potential to drive health care delivery and research. The Fast Healthcare Interoperability Resources (FHIR) data standard has been increasingly applied in developing these systems. However, methods for applying FHIR to ML-CISs are variable. Objective: This study evaluates and compares the functionalities, strengths, and weaknesses of existing systems and proposes guidelines for optimizing future work with ML-CISs. Methods: Embase, PubMed, and Web of Science were searched for articles describing machine learning systems that were used for clinical data analytics or decision support in compliance with FHIR standards. Information regarding each system's functionality, data sources, formats, security, performance, resource requirements, scalability, strengths, and limitations was compared across systems. Results: A total of 39 articles describing FHIR-based ML-CISs were divided into the following three categories according to their primary focus: clinical decision support systems (n=18), data management and analytic platforms (n=10), or auxiliary modules and application programming interfaces (n=11). Model strengths included novel use of cloud systems, Bayesian networks, visualization strategies, and techniques for translating unstructured or free-text data to FHIR frameworks. Many intelligent systems lacked electronic health record interoperability and externally validated evidence of clinical efficacy. Conclusions: Shortcomings in current ML-CISs can be addressed by incorporating modular and interoperable data management, analytic platforms, secure interinstitutional data exchange, and application programming interfaces with adequate scalability to support both real-time and prospective clinical applications that use electronic health record platforms with diverse implementations.

Clinical Courses of Acute Kidney Injury in Hospitalized Patients: A Multistate Analysis.

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.

Computable Phenotypes to Characterize Changing Patient Brain Dysfunction in the Intensive Care Unit.

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.

Diurnal Pain Classification in Critically Ill Patients using Machine Learning on Accelerometry and Analgesic Data.

Quantifying pain in patients admitted to intensive care units (ICUs) is challenging due to the increased prevalence of communication barriers in this patient population. Previous research has posited a positive correlation between pain and physical activity in critically ill patients. In this study, we advance this hypothesis by building machine learning classifiers to examine the ability of accelerometer data collected from daily wearables to predict self-reported pain levels experienced by patients in the ICU. We trained multiple Machine Learning (ML) models, including Logistic Regression, CatBoost, and XG-Boost, on statistical features extracted from the accelerometer data combined with previous pain measurements and patient demographics. Following previous studies that showed a change in pain sensitivity in ICU patients at night, we performed the task of pain classification separately for daytime and nighttime pain reports. In the pain versus no-pain classification setting, logistic regression gave the best classifier in daytime (AUC: 0.72, F1-score: 0.72), and CatBoost gave the best classifier at nighttime (AUC: 0.82, F1-score: 0.82). Performance of logistic regression dropped to 0.61 AUC, 0.62 F1-score (mild vs. moderate pain, nighttime), and CatBoost's performance was similarly affected with 0.61 AUC, 0.60 F1-score (moderate vs. severe pain, daytime). The inclusion of analgesic information benefited the classification between moderate and severe pain. SHAP analysis was conducted to find the most significant features in each setting. It assigned the highest importance to accelerometer-related features on all evaluated settings but also showed the contribution of the other features such as age and medications in specific contexts. In conclusion, accelerometer data combined with patient demographics and previous pain measurements can be used to screen painful from painless episodes in the ICU and can be combined with analgesic information to provide moderate classification between painful episodes of different severities.

Dynamic Delirium Prediction in the Intensive Care Unit using Machine Learning on Electronic Health Records.

Delirium is a syndrome of acute brain failure which is prevalent amongst older adults in the Intensive Care Unit (ICU). Incidence of delirium can significantly worsen prognosis and increase mortality, therefore necessitating its rapid and continual assessment in the ICU. Currently, the common approach for delirium assessment is manual and sporadic. Hence, there exists a critical need for a robust and automated system for predicting delirium in the ICU. In this work, we develop a machine learning (ML) system for real-time prediction of delirium using Electronic Health Record (EHR) data. Unlike prior approaches which provide one delirium prediction label per entire ICU stay, our approach provides predictions every 12 hours. We use the latest 12 hours of ICU data, along with patient demographic and medical history data, to predict delirium risk in the next 12-hour window. This enables delirium risk prediction as soon as 12 hours after ICU admission. We train and test four ML classification algorithms on longitudinal EHR data pertaining to 16,327 ICU stays of 13,395 patients covering a total of 56,297 12-hour windows in the ICU to predict the dynamic incidence of delirium. The best performing algorithm was Categorical Boosting which achieved an area under receiver operating characteristic curve (AUROC) of 0.87 (95% Confidence Interval; C.I, 0.86-0.87). The deployment of this ML system in ICUs can enable early identification of delirium, thereby reducing its deleterious impact on long-term adverse outcomes, such as ICU cost, length of stay and mortality.

Multi-dimensional patient acuity estimation with longitudinal EHR tokenization and flexible transformer networks.

Transformer model architectures have revolutionized the natural language processing (NLP) domain and continue to produce state-of-the-art results in text-based applications. Prior to the emergence of transformers, traditional NLP models such as recurrent and convolutional neural networks demonstrated promising utility for patient-level predictions and health forecasting from longitudinal datasets. However, to our knowledge only few studies have explored transformers for predicting clinical outcomes from electronic health record (EHR) data, and in our estimation, none have adequately derived a health-specific tokenization scheme to fully capture the heterogeneity of EHR systems. In this study, we propose a dynamic method for tokenizing both discrete and continuous patient data, and present a transformer-based classifier utilizing a joint embedding space for integrating disparate temporal patient measurements. We demonstrate the feasibility of our clinical AI framework through multi-task ICU patient acuity estimation, where we simultaneously predict six mortality and readmission outcomes. Our longitudinal EHR tokenization and transformer modeling approaches resulted in more accurate predictions compared with baseline machine learning models, which suggest opportunities for future multimodal data integrations and algorithmic support tools using clinical transformer networks.

Performance of a Machine Learning Algorithm Using Electronic Health Record Data to Predict Postoperative Complications and Report on a Mobile Platform.

Importance: Predicting postoperative complications has the potential to inform shared decisions regarding the appropriateness of surgical procedures, targeted risk-reduction strategies, and postoperative resource use. Realizing these advantages requires that accurate real-time predictions be integrated with clinical and digital workflows; artificial intelligence predictive analytic platforms using automated electronic health record (EHR) data inputs offer an intriguing possibility for achieving this, but there is a lack of high-level evidence from prospective studies supporting their use. Objective: To examine whether the MySurgeryRisk artificial intelligence system has stable predictive performance between development and prospective validation phases and whether it is feasible to provide automated outputs directly to surgeons' mobile devices. Design, Setting, and Participants: In this prognostic study, the platform used automated EHR data inputs and machine learning algorithms to predict postoperative complications and provide predictions to surgeons, previously through a web portal and currently through a mobile device application. All patients 18 years or older who were admitted for any type of inpatient surgical procedure (74 417 total procedures involving 58 236 patients) between June 1, 2014, and September 20, 2020, were included. Models were developed using retrospective data from 52 117 inpatient surgical procedures performed between June 1, 2014, and November 27, 2018. Validation was performed using data from 22 300 inpatient surgical procedures collected prospectively from November 28, 2018, to September 20, 2020. Main Outcomes and Measures: Algorithms for generalized additive models and random forest models were developed and validated using real-time EHR data. Model predictive performance was evaluated primarily using area under the receiver operating characteristic curve (AUROC) values. Results: Among 58 236 total adult patients who received 74 417 major inpatient surgical procedures, the mean (SD) age was 57 (17) years; 29 226 patients (50.2%) were male. Results reported in this article focus primarily on the validation cohort. The validation cohort included 22 300 inpatient surgical procedures involving 19 132 patients (mean [SD] age, 58 [17] years; 9672 [50.6%] male). A total of 2765 patients (14.5%) were Black or African American, 14 777 (77.2%) were White, 1235 (6.5%) were of other races (including American Indian or Alaska Native, Asian, Native Hawaiian or Pacific Islander, and multiracial), and 355 (1.9%) were of unknown race because of missing data; 979 patients (5.1%) were Hispanic, 17 663 (92.3%) were non-Hispanic, and 490 (2.6%) were of unknown ethnicity because of missing data. A greater number of input features was associated with stable or improved model performance. For example, the random forest model trained with 135 input features had the highest AUROC values for predicting acute kidney injury (0.82; 95% CI, 0.82-0.83); cardiovascular complications (0.81; 95% CI, 0.81-0.82); neurological complications, including delirium (0.87; 95% CI, 0.87-0.88); prolonged intensive care unit stay (0.89; 95% CI, 0.88-0.89); prolonged mechanical ventilation (0.91; 95% CI, 0.90-0.91); sepsis (0.86; 95% CI, 0.85-0.87); venous thromboembolism (0.82; 95% CI, 0.81-0.83); wound complications (0.78; 95% CI, 0.78-0.79); 30-day mortality (0.84; 95% CI, 0.82-0.86); and 90-day mortality (0.84; 95% CI, 0.82-0.85), with accuracy similar to surgeons' predictions. Compared with the original web portal, the mobile device application allowed efficient fingerprint login access and loaded data approximately 10 times faster. The application output displayed patient information, risk of postoperative complications, top 3 risk factors for each complication, and patterns of complications for individual surgeons compared with their colleagues. Conclusions and Relevance: In this study, automated real-time predictions of postoperative complications with mobile device outputs had good performance in clinical settings with prospective validation, matching surgeons' predictive accuracy.

Physiologic signatures within six hours of hospitalization identify acute illness phenotypes.

During the early stages of hospital admission, clinicians use limited information to make decisions as patient acuity evolves. We hypothesized that clustering analysis of vital signs measured within six hours of hospital admission would reveal distinct patient phenotypes with unique pathophysiological signatures and clinical outcomes. We created a longitudinal electronic health record dataset for 75,762 adult patient admissions to a tertiary care center in 2014-2016 lasting six hours or longer. Physiotypes were derived via unsupervised machine learning in a training cohort of 41,502 patients applying consensus k-means clustering to six vital signs measured within six hours of admission. Reproducibility and correlation with clinical biomarkers and outcomes were assessed in validation cohort of 17,415 patients and testing cohort of 16,845 patients. Training, validation, and testing cohorts had similar age (54-55 years) and sex (55% female), distributions. There were four distinct clusters. Physiotype A had physiologic signals consistent with early vasoplegia, hypothermia, and low-grade inflammation and favorable short-and long-term clinical outcomes despite early, severe illness. Physiotype B exhibited early tachycardia, tachypnea, and hypoxemia followed by the highest incidence of prolonged respiratory insufficiency, sepsis, acute kidney injury, and short- and long-term mortality. Physiotype C had minimal early physiological derangement and favorable clinical outcomes. Physiotype D had the greatest prevalence of chronic cardiovascular and kidney disease, presented with severely elevated blood pressure, and had good short-term outcomes but suffered increased 3-year mortality. Comparing sequential organ failure assessment (SOFA) scores across physiotypes demonstrated that clustering did not simply recapitulate previously established acuity assessments. In a heterogeneous cohort of hospitalized patients, unsupervised machine learning techniques applied to routine, early vital sign data identified physiotypes with unique disease categories and distinct clinical outcomes. This approach has the potential to augment understanding of pathophysiology by distilling thousands of disease states into a few physiological signatures.