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      Application of explainable ensemble artificial intelligence model to categorization of hemodialysis-patient and treatment using nationwide-real-world data in Japan

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          Abstract

          Background

          Although dialysis patients are at a high risk of death, it is difficult for medical practitioners to simultaneously evaluate many inter-related risk factors. In this study, we evaluated the characteristics of hemodialysis patients using machine learning model, and its usefulness for screening hemodialysis patients at a high risk of one-year death using the nation-wide database of the Japanese Society for Dialysis Therapy.

          Materials and methods

          The patients were separated into two datasets (n = 39,930, 39,930, respectively). We categorized hemodialysis patients in Japan into new clusters generated by the K-means clustering method using the development dataset. The association between a cluster and the risk of death was evaluated using multivariate Cox proportional hazards models. Then, we developed an ensemble model composed of the clusters and support vector machine models in the model development phase, and compared the accuracy of the prediction of mortality between the machine learning models in the model validation phase.

          Results

          Average age of the subjects was 65.7±12.2 years; 32.7% had diabetes mellitus. The five clusters clearly distinguished the groups on the basis of their characteristics: Cluster 1, young male, and chronic glomerulonephritis; Cluster 2, female, and chronic glomerulonephritis; Cluster 3, diabetes mellitus; Cluster 4, elderly and nephrosclerosis; Cluster 5, elderly and protein energy wasting. These clusters were associated with the risk of death; Cluster 5 compared with Cluster 1, hazard ratio 8.86 (95% CI 7.68, 10.21). The accuracy of the ensemble model for the prediction of 1-year death was 0.948 and higher than those of logistic regression model (0.938), support vector machine model (0.937), and deep learning model (0.936).

          Conclusions

          The clusters clearly categorized patient on their characteristics, and reflected their prognosis. Our real-world-data-based machine learning system is applicable to identifying high-risk hemodialysis patients in clinical settings, and has a strong potential to guide treatments and improve their prognosis.

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          Most cited references12

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          Cardiovascular disease in dialysis patients

          Abstract Cardiovascular disease (CVD) is a highly common complication and the first cause of death in patients with end-stage renal disease (ESRD) on haemodialysis (HD). In this population, mortality due to CVD is 20 times higher than in the general population and the majority of maintenance HD patients have CVD. This is likely due to ventricular hypertrophy as well as non-traditional risk factors, such as chronic volume overload, anaemia, inflammation, oxidative stress, chronic kidney disease–mineral bone disorder and other aspects of the ‘uraemic milieu’. Better understanding the impact of these numerous factors on CVD would be an important step for prevention and treatment. In this review we focus non-traditional CVD risk factors in HD patients.
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            Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

            Mortality risk among hemodialysis (HD) patients may be highest soon after initiation of HD. A period of elevated mortality risk was identified among US incident HD patients, and which patient characteristics predict death during this period and throughout the first year was examined using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS; 1996 through 2004). A retrospective cohort study design was used to identify mortality risk factors. All patient information was collected at enrollment. Life-table analyses and discrete logistic regression were used to identify a period of elevated mortality risk. Cox regression was used to estimate adjusted hazard ratios (HR) measuring associations between patient characteristics and mortality and to examine whether these associations changed during the first year of HD. Among 4802 incident patients, risk for death was elevated during the first 120 d compared with 121 to 365 d (27.5 versus 21.9 deaths per 100 person-years; P = 0.002). Cause-specific mortality rates were higher in the first 120 d than in the subsequent 121 to 365 d for nearly all causes, with the greatest difference being for cardiovascular-related deaths. In addition, 20% of all deaths in the first 120 d occurred subsequent to withdrawal from dialysis. Most covariates were found to have consistent effects during the first year of HD: Older age, catheter vascular access, albumin <3.5, phosphorus <3.5, cancer, and congestive heart failure all were associated with elevated mortality. Pre-ESRD nephrology care was associated with a significantly lower risk for death before 120 d (HR 0.65; 95% confidence interval 0.51 to 0.83) but not in the subsequent 121- to 365-d period (HR 1.03; 95% confidence interval 0.83 to 1.27). This care was related to approximately 50% lower rates of both cardiac deaths and withdrawal from dialysis during the first 120 d. Mortality risk was highest in the first 120 d after HD initiation. Inadequate predialysis nephrology care was strongly associated with mortality during this period, highlighting the potential benefits of contact with a nephrologist at least 1 mo before HD initiation.
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              Risk factors for mortality in patients undergoing hemodialysis: A systematic review and meta-analysis.

              No consensus exists regarding the factors influencing mortality in patients undergoing hemodialysis (HD). This meta-analysis aimed to evaluate the impact of various patient characteristics on the risk of mortality in such patients.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: Project administrationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 May 2020
                2020
                : 15
                : 5
                : e0233491
                Affiliations
                [1 ] Medical Science, Kawasaki Medical School, Kurashiki, Okayama, Japan
                [2 ] College of Engineering, University of Michigan, Ann Arbor, Michigan, United States of America
                [3 ] Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo, Kyoto, Japan
                [4 ] Tsuruta Itabashi Clinic, Itabashi, Tokyo, Japan
                [5 ] Shimoochiai Clinic, Shinjuku, Tokyo, Japan
                [6 ] Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Okayama, Japan
                [7 ] Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi, Tokyo, Japan
                [8 ] Department of Nephrology, Yabuki Hospital, Yamagata, Yamagata, Japan
                [9 ] Department of Nephrology, Tokyo Women’s Medical University, Shinjuku, Tokyo, Japan
                Tokushima University Graduate school, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0676-096X
                http://orcid.org/0000-0002-9156-5415
                Article
                PONE-D-20-09660
                10.1371/journal.pone.0233491
                7259704
                32469924
                e7efe959-7ba3-494b-b073-4993f370cb5d
                © 2020 Kanda et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 3 April 2020
                : 6 May 2020
                Page count
                Figures: 12, Tables: 6, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: KAKENHI Grant Number JP 19K08740
                Award Recipient :
                This work was supported by Japan Society for the Promotion of Science (KAKENHI Grant Number JP 19K08740) to EK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Support Vector Machines
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Deep Learning
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Medicine and Health Sciences
                Diagnostic Medicine
                Prognosis
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Nephrology
                Chronic Kidney Disease
                Custom metadata
                Data cannot be made publicly available by the authors, as they are owned by the Japanese Society for Dialysis Therapy. Interested readers may request the data at the following URL: http://www.jsdt.or.jp/jsdt/1761.html.

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