Matthew M. Ruppert

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.

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.

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.

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.

Benjamin Shickel, Tyler J. Loftus, Matthew Ruppert et al.

Accurate prediction of postoperative complications can inform shared decisions regarding prognosis, preoperative risk-reduction, and postoperative resource use. We hypothesized that multi-task deep learning models would outperform random forest models in predicting postoperative complications, and that integrating high-resolution intraoperative physiological time series would result in more granular and personalized health representations that would improve prognostication compared to preoperative predictions. In a longitudinal cohort study of 56,242 patients undergoing 67,481 inpatient surgical procedures at a university medical center, we compared deep learning models with random forests for predicting nine common postoperative complications using preoperative, intraoperative, and perioperative patient data. Our study indicated several significant results across experimental settings that suggest the utility of deep learning for capturing more precise representations of patient health for augmented surgical decision support. Multi-task learning improved efficiency by reducing computational resources without compromising predictive performance. Integrated gradients interpretability mechanisms identified potentially modifiable risk factors for each complication. Monte Carlo dropout methods provided a quantitative measure of prediction uncertainty that has the potential to enhance clinical trust. Multi-task learning, interpretability mechanisms, and uncertainty metrics demonstrated potential to facilitate effective clinical implementation.

Triton Ong, Matthew Ruppert, Parisa Rashidi et al.

Purpose: Preliminarily evaluate the feasibility and efficacy of using meditative virtual reality (VR) to improve the hospital experience of intensive care unit (ICU) patients. Methods: Effects of VR were examined in a non-randomized, single-center cohort. Fifty-nine patients admitted to the surgical or trauma ICU of the University of Florida Health Shands Hospital participated. A Google Daydream headset was used to expose ICU patients to commercially available VR applications focused on calmness and relaxation (Google Spotlight Stories and RelaxVR). Sessions were conducted once daily for up to seven days. Outcome measures included pain level, anxiety, depression, medication administration, sleep quality, heart rate, respiratory rate, blood pressure, delirium status, and patient ratings of the VR system. Comparisons were made using paired t-tests and mixed models where appropriate. Results: The VR meditative intervention was found to improve patients' ICU experience with reduced levels of anxiety and depression; however, there was no evidence suggesting that VR had any significant effects on physiological measures, pain, or sleep. Conclusion: The use of VR technology in the ICU was shown to be easily implemented and well-received by patients.

Lasith Adhikari, Tezcan Ozrazgat-Baslanti, Paul Thottakkara et al.

Acute kidney injury (AKI) is a common and serious complication after a surgery which is associated with morbidity and mortality. The majority of existing perioperative AKI risk score prediction models are limited in their generalizability and do not fully utilize the physiological intraoperative time-series data. Thus, there is a need for intelligent, accurate, and robust systems, able to leverage information from large-scale data to predict patient's risk of developing postoperative AKI. A retrospective single-center cohort of 2,911 adult patients who underwent surgery at the University of Florida Health has been used for this study. We used machine learning and statistical analysis techniques to develop perioperative models to predict the risk of AKI (risk during the first 3 days, 7 days, and until the discharge day) before and after the surgery. In particular, we examined the improvement in risk prediction by incorporating three intraoperative physiologic time series data, i.e., mean arterial blood pressure, minimum alveolar concentration, and heart rate. For an individual patient, the preoperative model produces a probabilistic AKI risk score, which will be enriched by integrating intraoperative statistical features through a machine learning stacking approach inside a random forest classifier. We compared the performance of our model based on the area under the receiver operating characteristics curve (AUROC), accuracy and net reclassification improvement (NRI). The predictive performance of the proposed model is better than the preoperative data only model. For AKI-7day outcome: The AUC was 0.86 (accuracy was 0.78) in the proposed model, while the preoperative AUC was 0.84 (accuracy 0.76). Furthermore, with the integration of intraoperative features, we were able to classify patients who were misclassified in the preoperative model.

Anis Davoudi, Kumar Rohit Malhotra, Benjamin Shickel et al.

Currently, many critical care indices are repetitively assessed and recorded by overburdened nurses, e.g. physical function or facial pain expressions of nonverbal patients. In addition, many essential information on patients and their environment are not captured at all, or are captured in a non-granular manner, e.g. sleep disturbance factors such as bright light, loud background noise, or excessive visitations. In this pilot study, we examined the feasibility of using pervasive sensing technology and artificial intelligence for autonomous and granular monitoring of critically ill patients and their environment in the Intensive Care Unit (ICU). As an exemplar prevalent condition, we also characterized delirious and non-delirious patients and their environment. We used wearable sensors, light and sound sensors, and a high-resolution camera to collected data on patients and their environment. We analyzed collected data using deep learning and statistical analysis. Our system performed face detection, face recognition, facial action unit detection, head pose detection, facial expression recognition, posture recognition, actigraphy analysis, sound pressure and light level detection, and visitation frequency detection. We were able to detect patient's face (Mean average precision (mAP)=0.94), recognize patient's face (mAP=0.80), and their postures (F1=0.94). We also found that all facial expressions, 11 activity features, visitation frequency during the day, visitation frequency during the night, light levels, and sound pressure levels during the night were significantly different between delirious and non-delirious patients (p-value<0.05). In summary, we showed that granular and autonomous monitoring of critically ill patients and their environment is feasible and can be used for characterizing critical care conditions and related environment factors.

Meghan Brennan, Sahil Puri, Tezcan Ozrazgat-Baslanti et al.

Background: Major postoperative complications are associated with increased short and long-term mortality, increased healthcare cost, and adverse long-term consequences. The large amount of data contained in the electronic health record (EHR) creates barriers for physicians to recognize patients most at risk. We hypothesize, if presented in an optimal format, information from data-driven predictive risk algorithms for postoperative complications can improve physician risk assessment. Methods: Prospective, non-randomized, interventional pilot study of twenty perioperative physicians at a quarterly academic medical center. Using 150 clinical cases we compared physicians' risk assessment before and after interaction with MySurgeryRisk, a validated machine-learning algorithm predicting preoperative risk for six major postoperative complications using EHR data. Results: The area under the curve (AUC) of MySurgeryRisk algorithm ranged between 0.73 and 0.85 and was significantly higher than physicians' risk assessments (AUC between 0.47 and 0.69) for all postoperative complications except cardiovascular complications. The AUC for repeated physician's risk assessment improved by 2% to 5% for all complications with the exception of thirty-day mortality. Physicians' risk assessment for acute kidney injury and intensive care unit admission longer than 48 hours significantly improved after knowledge exchange, resulting in net reclassification improvement of 12.4% and 16%, respectively. Conclusions: The validated MySurgeryRisk algorithm predicted postoperative complications with equal or higher accuracy than pilot cohort of physicians using available clinical preoperative data. The interaction with algorithm significantly improved physicians' risk assessment.