A Method to Explore Variations of Ventilator-Associated Event Surveillance Definitions in Large Critical Care Databases in the United States.

The Centers for Disease Control has well-established surveillance programs to monitor preventable conditions in patients supported by mechanical ventilation (MV). The aim of the study was to develop a data-driven methodology to examine variations in the first tier of the ventilator-associated event surveillance definition, described as a ventilator-associated condition (VAC). Further, an interactive tool was designed to illustrate the effect of changes to the VAC surveillance definition, by applying different ventilator settings, time-intervals, demographics, and selected clinical criteria. DESIGN: Retrospective, multicenter, cross-sectional analysis. SETTING: Three hundred forty critical care units across 209 hospitals, comprising 261,910 patients in both the electronic Intensive Care Unit Clinical Research Database and Medical Information Mart for Intensive Care III databases. PATIENTS: A total of 14,517 patients undergoing MV for 4 or more days. MEASUREMENTS AND MAIN RESULTS: We designed a statistical analysis framework, complemented by a custom interactive data visualization tool to depict how changes to the VAC surveillance definition alter its prognostic performance, comparing patients with and without VAC. This methodology and tool enable comparison of three clinical outcomes (hospital mortality, hospital length-of-stay, and ICU length-of-stay) and provide the option to stratify patients by six criteria in two categories: patient population (dataset and ICU type) and clinical features (minimum Fio2, minimum positive end-expiratory pressure, early/late VAC, and worst first-day respiratory Sequential Organ Failure Assessment score). Patient population outcomes were depicted by heatmaps with mortality odds ratios. In parallel, outcomes from ventilation setting variations and clinical features were depicted with Kaplan-Meier survival curves. CONCLUSIONS: We developed a method to examine VAC using information extracted from large electronic health record databases. Building upon this framework, we developed an interactive tool to visualize and quantify the implications of variations in the VAC surveillance definition in different populations, across time and critical care settings. Data for patients with and without VAC was used to illustrate the effect of the application of this method and visualization tool.

Early Biomarker Signatures in Surgical Sepsis.

INTRODUCTION: Sepsis has complex, time-sensitive pathophysiology and important phenotypic subgroups. The objective of this study was to use machine learning analyses of blood and urine biomarker profiles to elucidate the pathophysiologic signatures of subgroups of surgical sepsis patients. METHODS: This prospective cohort study included 243 surgical sepsis patients admitted to a quaternary care center between January 2015 and June 2017. We applied hierarchical clustering to clinical variables and 42 blood and urine biomarkers to identify phenotypic subgroups in a development cohort. Clinical characteristics and short-term and long-term outcomes were compared between clusters. A naïve Bayes classifier predicted cluster labels in a validation cohort. RESULTS: The development cohort contained one cluster characterized by early organ dysfunction (cluster I, n = 18) and one cluster characterized by recovery (cluster II, n = 139). Cluster I was associated with higher Acute Physiologic Assessment and Chronic Health Evaluation II (30 versus 16, P < 0.001) and SOFA scores (13 versus 5, P < 0.001), greater prevalence of chronic cardiovascular and renal disease (P < 0.001) and septic shock (78% versus 17%, P < 0.001). Cluster I had higher mortality within 14 d of sepsis onset (11% versus 1.5%, P = 0.001) and within 1 y (44% versus 20%, P = 0.032), and higher incidence of chronic critical illness (61% versus 30%, P = 0.001). The Bayes classifier achieved 95% accuracy and identified two clusters that were similar to development cohort clusters. CONCLUSIONS: Machine learning analyses of clinical and biomarker variables identified an early organ dysfunction sepsis phenotype characterized by inflammation, renal dysfunction, endotheliopathy, and immunosuppression, as well as poor short-term and long-term clinical outcomes.

Systematic Review and Comparison of Publicly Available ICU Data Sets-A Decision Guide for Clinicians and Data Scientists.

OBJECTIVE: As data science and artificial intelligence continue to rapidly gain traction, the publication of freely available ICU datasets has become invaluable to propel data-driven clinical research. In this guide for clinicians and researchers, we aim to: 1) systematically search and identify all publicly available adult clinical ICU datasets, 2) compare their characteristics, data quality, and richness and critically appraise their strengths and weaknesses, and 3) provide researchers with suggestions, which datasets are appropriate for answering their clinical question. DATA SOURCES: A systematic search was performed in Pubmed, ArXiv, MedRxiv, and BioRxiv. STUDY SELECTION: We selected all studies that reported on publicly available adult patient-level intensive care datasets. DATA EXTRACTION: A total of four publicly available, adult, critical care, patient-level databases were included (Amsterdam University Medical Center data base [AmsterdamUMCdb], eICU Collaborative Research Database eICU CRD], High time-resolution intensive care unit dataset [HiRID], and Medical Information Mart for Intensive Care-IV). Databases were compared using a priori defined categories, including demographics, patient characteristics, and data richness. The study protocol and search strategy were prospectively registered. DATA SYNTHESIS: Four ICU databases fulfilled all criteria for inclusion and were queried using SQL (PostgreSQL version 12; PostgreSQL Global Development Group) and analyzed using R (R Foundation for Statistical Computing, Vienna, Austria). The number of unique patient admissions varied between 23,106 (AmsterdamUMCdb) and 200,859 (eICU-CRD). Frequency of laboratory values and vital signs was highest in HiRID, for example, 5.2 (±3.4) lactate values per day and 29.7 (±10.2) systolic blood pressure values per hour. Treatment intensity varied with vasopressor and ventilatory support in 69.0% and 83.0% of patients in AmsterdamUMCdb versus 12.0% and 21.0% in eICU-CRD, respectively. ICU mortality ranged from 5.5% in eICU-CRD to 9.9% in AmsterdamUMCdb. CONCLUSIONS: We identified four publicly available adult clinical ICU datasets. Sample size, severity of illness, treatment intensity, and frequency of reported parameters differ markedly between the databases. This should guide clinicians and researchers which databases to best answer their clinical questions.

Analysis of Discrepancies Between Pulse Oximetry and Arterial Oxygen Saturation Measurements by Race and Ethnicity and Association With Organ Dysfunction and Mortality.

Importance: Discrepancies in oxygen saturation measured by pulse oximetry (Spo2), when compared with arterial oxygen saturation (Sao2) measured by arterial blood gas (ABG), may differentially affect patients according to race and ethnicity. However, the association of these disparities with health outcomes is unknown. Objective: To examine racial and ethnic discrepancies between Sao2 and Spo2 measures and their associations with clinical outcomes. Design, Setting, and Participants: This multicenter, retrospective, cross-sectional study included 3 publicly available electronic health record (EHR) databases (ie, the Electronic Intensive Care Unit-Clinical Research Database and Medical Information Mart for Intensive Care III and IV) as well as Emory Healthcare (2014-2021) and Grady Memorial (2014-2020) databases, spanning 215 hospitals and 382 ICUs. From 141 600 hospital encounters with recorded ABG measurements, 87 971 participants with first ABG measurements and an Spo2 of at least 88% within 5 minutes before the ABG test were included. Exposures: Patients with hidden hypoxemia (ie, Spo2 ≥88% but Sao2 <88%). Main Outcomes and Measures: Outcomes, stratified by race and ethnicity, were Sao2 for each Spo2, hidden hypoxemia prevalence, initial demographic characteristics (age, sex), clinical outcomes (in-hospital mortality, length of stay), organ dysfunction by scores (Sequential Organ Failure Assessment [SOFA]), and laboratory values (lactate and creatinine levels) before and 24 hours after the ABG measurement. Results: The first Spo2-Sao2 pairs from 87 971 patient encounters (27 713 [42.9%] women; mean [SE] age, 62.2 [17.0] years; 1919 [2.3%] Asian patients; 26 032 [29.6%] Black patients; 2397 [2.7%] Hispanic patients, and 57 632 [65.5%] White patients) were analyzed, with 4859 (5.5%) having hidden hypoxemia. Hidden hypoxemia was observed in all subgroups with varying incidence (Black: 1785 [6.8%]; Hispanic: 160 [6.0%]; Asian: 92 [4.8%]; White: 2822 [4.9%]) and was associated with greater organ dysfunction 24 hours after the ABG measurement, as evidenced by higher mean (SE) SOFA scores (7.2 [0.1] vs 6.29 [0.02]) and higher in-hospital mortality (eg, among Black patients: 369 [21.1%] vs 3557 [15.0%]; P < .001). Furthermore, patients with hidden hypoxemia had higher mean (SE) lactate levels before (3.15 [0.09] mg/dL vs 2.66 [0.02] mg/dL) and 24 hours after (2.83 [0.14] mg/dL vs 2.27 [0.02] mg/dL) the ABG test, with less lactate clearance (-0.54 [0.12] mg/dL vs -0.79 [0.03] mg/dL). Conclusions and Relevance: In this study, there was greater variability in oxygen saturation levels for a given Spo2 level in patients who self-identified as Black, followed by Hispanic, Asian, and White. Patients with and without hidden hypoxemia were demographically and clinically similar at baseline ABG measurement by SOFA scores, but those with hidden hypoxemia subsequently experienced higher organ dysfunction scores and higher in-hospital mortality.

Discovery and Validation of Urinary Molecular Signature of Early Sepsis.

Identify alterations in gene expression unique to systemic and kidney-specific pathophysiologic processes using whole-genome analyses of RNA isolated from the urinary cells of sepsis patients. DESIGN: Prospective cohort study. SETTING: Quaternary care academic hospital. PATIENTS: A total of 266 sepsis and 82 control patients enrolled between January 2015 and February 2018. INTERVENTIONS: Whole-genome transcriptomic analysis of messenger RNA isolated from the urinary cells of sepsis patients within 12 hours of sepsis onset and from control subjects. MEASUREMENTS AND MAIN RESULTS: The differentially expressed probes that map to known genes were subjected to feature selection using multiple machine learning techniques to find the best subset of probes that differentiates sepsis from control subjects. Using differential expression augmented with machine learning ensembles, we identified a set of 239 genes in urine, which show excellent effectiveness in classifying septic patients from those with chronic systemic disease in both internal and independent external validation cohorts. Functional analysis indexes disrupted biological pathways in early sepsis and reveal key molecular networks driving its pathogenesis. CONCLUSIONS: We identified unique urinary gene expression profile in early sepsis. Future studies need to confirm whether this approach can complement blood transcriptomic approaches for sepsis diagnosis and prognostication.

Improved predictive models for acute kidney injury with IDEA: Intraoperative Data Embedded Analytics.

BACKGROUND: Acute kidney injury (AKI) is a common complication after surgery that is associated with increased morbidity and mortality. The majority of existing perioperative AKI risk prediction models are limited in their generalizability and do not fully utilize intraoperative physiological time-series data. Thus, there is a need for intelligent, accurate, and robust systems to leverage new information as it becomes available to predict the risk of developing postoperative AKI. METHODS: A retrospective single-center cohort of 2,911 adults who underwent surgery at the University of Florida Health between 2000 and 2010 was utilized for this study. Machine learning and statistical analysis techniques were used to develop perioperative models to predict the risk of developing AKI during the first three days after surgery, first seven days after surgery, and overall (after surgery during the index hospitalization). The improvement in risk prediction was examined by incorporating intraoperative physiological time-series variables. Our proposed model enriched a preoperative model that produced a probabilistic AKI risk score by integrating intraoperative statistical features through a machine learning stacking approach inside a random forest classifier. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, and Net Reclassification Improvement (NRI). RESULTS: The predictive performance of the proposed model is better than the preoperative data only model. The proposed model had an AUC of 0.86 (accuracy of 0.78) for the seven-day AKI outcome, while the preoperative model had an AUC of 0.84 (accuracy of 0.76). Furthermore, by integrating intraoperative features, the algorithm was able to reclassify 40% of the false negative patients from the preoperative model. The NRI for each outcome was AKI at three days (8%), seven days (7%), and overall (4%). CONCLUSIONS: Postoperative AKI prediction was improved with high sensitivity and specificity through a machine learning approach that dynamically incorporated intraoperative data.

DeepSOFA: A Continuous Acuity Score for Critically Ill Patients using Clinically Interpretable Deep Learning.

Traditional methods for assessing illness severity and predicting in-hospital mortality among critically ill patients require time-consuming, error-prone calculations using static variable thresholds. These methods do not capitalize on the emerging availability of streaming electronic health record data or capture time-sensitive individual physiological patterns, a critical task in the intensive care unit. We propose a novel acuity score framework (DeepSOFA) that leverages temporal measurements and interpretable deep learning models to assess illness severity at any point during an ICU stay. We compare DeepSOFA with SOFA (Sequential Organ Failure Assessment) baseline models using the same model inputs and find that at any point during an ICU admission, DeepSOFA yields significantly more accurate predictions of in-hospital mortality. A DeepSOFA model developed in a public database and validated in a single institutional cohort had a mean AUC for the entire ICU stay of 0.90 (95% CI 0.90-0.91) compared with baseline SOFA models with mean AUC 0.79 (95% CI 0.79-0.80) and 0.85 (95% CI 0.85-0.86). Deep models are well-suited to identify ICU patients in need of life-saving interventions prior to the occurrence of an unexpected adverse event and inform shared decision-making processes among patients, providers, and families regarding goals of care and optimal resource utilization.

Constrained variant detection with SPaRC: Sparsity, parental relatedness, and coverage.

Structural variants (SVs) are rearrangements of DNA sequences such as inversions, deletions, insertions and translocations. The common method for detecting SVs has been to sequence data from a test genome and map it to a reference genome. More recently, DNA sequencing studies may consist of hundreds, or even thousands of individuals, some of which may be related. In order to improve our ability to identify SVs, we boost the true SV signals by simultaneously analyzing parent and child genomes. Our algorithmic formulation - SPaRC - employs realistic criteria such as sparsity of SVs, relatedness between individuals and variable sequencing coverage throughout the genome.