Abstract Background Sepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis. Methods We created 72-h SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used dynamic time warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 h after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies. Results A total of 4678, 3665, 12,282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening ( n = 612, 13.1%), Delayed Worsening ( n = 960, 20.5%), Rapidly Improving ( n = 1932, 41.3%), and Delayed Improving ( n = 1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction, varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, P -value < 0.001), despite a lower SOFA (mean: 4.5) at ICU admission compared to Rapidly Improving (mortality:5.5%, mean SOFA: 5.5). An overall prediction accuracy of 0.78 (95% CI, [0.77, 0.8]) was obtained at 6 h after ICU admission, which increased to 0.87 (95% CI, [0.86, 0.88]) at 24 h. Similar subphenotypes were replicated in three validation cohorts. The majority of patients with sepsis have an improving phenotype with a lower mortality risk; however, they make up over 20% of all deaths due to their larger numbers. Conclusions Four novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Identifying trajectory-based subphenotypes has immediate implications for the powering and predictive enrichment of clinical trials. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets and identify more precise populations and endpoints for clinical trials.
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Early Prediction of Multiple Organ Dysfunction in the Pediatric Intensive Care Unit
Objective: The objective of the study is to build models for early prediction of risk for developing multiple organ dysfunction (MOD) in pediatric intensive care unit (PICU) patients. Design: The design of the study is a retrospective observational cohort study. Setting: The setting of the study is at a single academic PICU at the Johns Hopkins Hospital, Baltimore, MD. Patients: The patients included in the study were <18 years of age admitted to the PICU between July 2014 and October 2015. Measurements and main results: Organ dysfunction labels were generated every minute from preceding 24-h time windows using the International Pediatric Sepsis Consensus Conference (IPSCC) and Proulx et al. MOD criteria. Early MOD prediction models were built using four machine learning methods: random forest, XGBoost, GLMBoost, and Lasso-GLM. An optimal threshold learned from training data was used to detect high-risk alert events (HRAs). The early prediction models from all methods achieved an area under the receiver operating characteristics curve ≥0.91 for both IPSCC and Proulx criteria. The best performance in terms of maximum F1-score was achieved with random forest (sensitivity: 0.72, positive predictive value: 0.70, F1-score: 0.71) and XGBoost (sensitivity: 0.8, positive predictive value: 0.81, F1-score: 0.81) for IPSCC and Proulx criteria, respectively. The median early warning time was 22.7 h for random forest and 37 h for XGBoost models for IPSCC and Proulx criteria, respectively. Applying spectral clustering on risk-score trajectories over 24 h following early warning provided a high-risk group with ≥0.93 positive predictive value. Conclusions: Early predictions from risk-based patient monitoring could provide more than 22 h of lead time for MOD onset, with ≥0.93 positive predictive value for a high-risk group identified pre-MOD.
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- Award ID(s):
- 2031195
- NSF-PAR ID:
- 10301673
- Date Published:
- Journal Name:
- Frontiers in Pediatrics
- Volume:
- 9
- ISSN:
- 2296-2360
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Results We developed predictive models using four machine learning methods: logistic regression, supported vector machine, gradient boosted trees, and random forests. Hormone values (follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone binding globulin) were combined to create a multilayer perceptron score using a neural network classifier. Prediction of PCOS prior to clinical diagnosis in an out-of-sample test set of patients achieved an average AUC of 85%, 81%, 80%, and 82%, respectively in Models I, II, III and IV. Significant positive predictors of PCOS diagnosis across models included hormone levels and obesity; negative predictors included gravidity and positive bHCG.
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null (Ed.)Abstract Accurate prediction of suicide risk among children and adolescents within an actionable time frame is an important but challenging task. Very few studies have comprehensively considered the clinical risk factors available to produce quantifiable risk scores for estimation of short- and long-term suicide risk for pediatric population. In this paper, we built machine learning models for predicting suicidal behavior among children and adolescents based on their longitudinal clinical records, and determining short- and long-term risk factors. This retrospective study used deidentified structured electronic health records (EHR) from the Connecticut Children’s Medical Center covering the period from 1 October 2011 to 30 September 2016. Clinical records of 41,721 young patients (10–18 years old) were included for analysis. Candidate predictors included demographics, diagnosis, laboratory tests, and medications. Different prediction windows ranging from 0 to 365 days were adopted. For each prediction window, candidate predictors were first screened by univariate statistical tests, and then a predictive model was built via a sequential forward feature selection procedure. We grouped the selected predictors and estimated their contributions to risk prediction at different prediction window lengths. The developed predictive models predicted suicidal behavior across all prediction windows with AUCs varying from 0.81 to 0.86. For all prediction windows, the models detected 53–62% of suicide-positive subjects with 90% specificity. The models performed better with shorter prediction windows and predictor importance varied across prediction windows, illustrating short- and long-term risks. Our findings demonstrated that routinely collected EHRs can be used to create accurate predictive models for suicide risk among children and adolescents.more » « less
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Method Our methodology centers around building and training five different machine learning models followed by testing and tuning those models to find the best-suited predictor for each experiment with a dataset of 5,245 adult patients with neurological conditions taken from the eICU-CRD database.
Results The results of this study show XGBoost to be the most effective model for predicting between four common discharge outcomes of ‘home’, ‘nursing facility’, ‘rehab’, and ‘death’, with 71% average c-statistic. The XGBoost model was also the best-performer in the binary outcome experiment with a c-statistic of 76%. This article also explores the accuracy, reliability, and interpretability of the best performing models in each experiment by identifying and analyzing the features that are most impactful to the predictions.
Conclusions The acceptable accuracy and interpretability of the predictive models based on early admission data suggests that the models can be used in a suggestive context to help guide healthcare providers in efforts of planning effective and equitable discharge recommendations.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fped.2021.711104
