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      Interpretable Machine Learning for Early Prediction of Prognosis in Sepsis: A Discovery and Validation Study

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          Abstract

          Introduction

          This study aimed to develop and validate an interpretable machine-learning model based on clinical features for early predicting in-hospital mortality in critically ill patients with sepsis.

          Methods

          We enrolled all patients with sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV, v.1.0) database from 2008 to 2019. Lasso regression was used for feature selection. Seven machine-learning methods were applied to develop the models. The best model was selected based on its accuracy and area under curve (AUC) in the validation cohort. Furthermore, we employed the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model, and to analyze how the individual features affect the output of the model, and to visualize the Shapley value for a single individual.

          Results

          In total, 8,817 patients with sepsis were eligible for participation, the median age was 66.8 years (IQR, 55.9–77.1 years), and 3361 of 8817 participants (38.1%) were women. After selection, 25 of a total 57 clinical parameters collected on day 1 after ICU admission remained associated with prognosis and were used for developing the machine-learning models. Among seven constructed models, the eXtreme Gradient Boosting (XGBoost) model achieved the best performance with an AUC of 0.884 and an accuracy of 89.5% in the validation cohort. Feature importance analysis showed that Glasgow Coma Scale (GCS) score, blood urea nitrogen, respiratory rate, urine output, and age were the top 5 features of the XGBoost model with the greatest impact. Furthermore, SHAP force analysis illustrated how the constructed model visualized the individualized prediction of death.

          Conclusions

          We have demonstrated the potential of machine-learning approaches for predicting outcome early in patients with sepsis. The SHAP method could improve the interpretability of machine-learning models and help clinicians better understand the reasoning behind the outcome.

          Graphical abstract

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s40121-022-00628-6.

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          Most cited references28

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            MIMIC-III, a freely accessible critical care database

            MIMIC-III (‘Medical Information Mart for Intensive Care’) is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital. Data includes vital signs, medications, laboratory measurements, observations and notes charted by care providers, fluid balance, procedure codes, diagnostic codes, imaging reports, hospital length of stay, survival data, and more. The database supports applications including academic and industrial research, quality improvement initiatives, and higher education coursework.
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              The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.

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                Author and article information

                Contributors
                huchang@whu.edu.cn
                lulu189vip@163.com
                huang7@whu.edu.cn
                annie_wutong@foxmail.com
                qianchengxu@whu.edu.cn
                liujuan@whu.edu.cn
                hobbier1979@163.com
                Journal
                Infect Dis Ther
                Infect Dis Ther
                Infectious Diseases and Therapy
                Springer Healthcare (Cheshire )
                2193-8229
                2193-6382
                10 April 2022
                10 April 2022
                June 2022
                : 11
                : 3
                : 1117-1132
                Affiliations
                [1 ]GRID grid.413247.7, ISNI 0000 0004 1808 0969, Department of Critical Care Medicine, , Zhongnan Hospital of Wuhan University, ; Wuhan, 430071 Hubei China
                [2 ]Clinical Research Center of Hubei Critical Care Medicine, Wuhan, 430071 Hubei China
                [3 ]GRID grid.49470.3e, ISNI 0000 0001 2331 6153, School of Computer Science, , Wuhan University, ; Wuhan, 430072 Hubei China
                Article
                628
                10.1007/s40121-022-00628-6
                9124279
                35399146
                b9adf70d-c1d1-4977-a12c-16bb916f1da9
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 25 February 2022
                : 17 March 2022
                Funding
                Funded by: Chinese Medical Information and Big Data Association
                Award ID: Z-2019-1-003
                Award Recipient :
                Funded by: Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University
                Award ID: ZNJC202011
                Award Recipient :
                Categories
                Original Research
                Custom metadata
                © The Author(s) 2022

                machine learning,algorithm,sepsis,critically ill,mortality
                machine learning, algorithm, sepsis, critically ill, mortality

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