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      A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study

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          Abstract

          Background

          Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes.

          Methods and findings

          We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation.

          Conclusions

          Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.

          Abstract

          Using nearly 1.5 million health records from >350,000 older adults with diabetes in Hong Kong, Elaine Chow and colleagues investigate a novel machine learning model to predict risk of severe hypoglycaemia.

          Author summary

          Why was this study done?
          • Older adults with diabetes are at high risk of severe hypoglycemia (SH) requiring hospitalization.

          • Existing machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall.

          • A simple tool to identify those at risk for developing SH in T2D is needed.

          What did the researchers do and find?
          • We included 1,456,618 records of 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance in 2013 to 2018.

          • We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months.

          • Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit.

          • The XGBoost model yielded the best performance, superior to an 11-variable conventional logistic-regression model.

          What do these findings mean?
          • Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization.

          • This may be integrated into electronic health record (EHR) decision support systems for preemptive intervention in older adults at highest risk.

          • A limitation of this study is the lack of model validation in independent cohorts outside Hong Kong.

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          Most cited references37

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          The Precision-Recall Plot Is More Informative than the ROC Plot When Evaluating Binary Classifiers on Imbalanced Datasets

          Binary classifiers are routinely evaluated with performance measures such as sensitivity and specificity, and performance is frequently illustrated with Receiver Operating Characteristics (ROC) plots. Alternative measures such as positive predictive value (PPV) and the associated Precision/Recall (PRC) plots are used less frequently. Many bioinformatics studies develop and evaluate classifiers that are to be applied to strongly imbalanced datasets in which the number of negatives outweighs the number of positives significantly. While ROC plots are visually appealing and provide an overview of a classifier's performance across a wide range of specificities, one can ask whether ROC plots could be misleading when applied in imbalanced classification scenarios. We show here that the visual interpretability of ROC plots in the context of imbalanced datasets can be deceptive with respect to conclusions about the reliability of classification performance, owing to an intuitive but wrong interpretation of specificity. PRC plots, on the other hand, can provide the viewer with an accurate prediction of future classification performance due to the fact that they evaluate the fraction of true positives among positive predictions. Our findings have potential implications for the interpretation of a large number of studies that use ROC plots on imbalanced datasets.
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            External validation of prognostic models: what, why, how, when and where?

            Abstract Prognostic models that aim to improve the prediction of clinical events, individualized treatment and decision-making are increasingly being developed and published. However, relatively few models are externally validated and validation by independent researchers is rare. External validation is necessary to determine a prediction model’s reproducibility and generalizability to new and different patients. Various methodological considerations are important when assessing or designing an external validation study. In this article, an overview is provided of these considerations, starting with what external validation is, what types of external validation can be distinguished and why such studies are a crucial step towards the clinical implementation of accurate prediction models. Statistical analyses and interpretation of external validation results are reviewed in an intuitive manner and considerations for selecting an appropriate existing prediction model and external validation population are discussed. This study enables clinicians and researchers to gain a deeper understanding of how to interpret model validation results and how to translate these results to their own patient population.
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              Non-communicable disease syndemics: poverty, depression, and diabetes among low-income populations.

              The co-occurrence of health burdens in transitioning populations, particularly in specific socioeconomic and cultural contexts, calls for conceptual frameworks to improve understanding of risk factors, so as to better design and implement prevention and intervention programmes to address comorbidities. The concept of a syndemic, developed by medical anthropologists, provides such a framework for preventing and treating comorbidities. The term syndemic refers to synergistic health problems that affect the health of a population within the context of persistent social and economic inequalities. Until now, syndemic theory has been applied to comorbid health problems in poor immigrant communities in high-income countries with limited translation, and in low-income or middle-income countries. In this Series paper, we examine the application of syndemic theory to comorbidities and multimorbidities in low-income and middle-income countries. We employ diabetes as an exemplar and discuss its comorbidity with HIV in Kenya, tuberculosis in India, and depression in South Africa. Using a model of syndemics that addresses transactional pathophysiology, socioeconomic conditions, health system structures, and cultural context, we illustrate the different syndemics across these countries and the potential benefit of syndemic care to patients. We conclude with recommendations for research and systems of care to address syndemics in low-income and middle-income country settings.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Journal
                PLoS Med
                PLoS Med
                plos
                PLOS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                12 April 2024
                April 2024
                : 21
                : 4
                : e1004369
                Affiliations
                [1 ] Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                [2 ] Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                [3 ] Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                [4 ] Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
                Author notes

                JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Novo-Nordisk, Pfizer and Sanofi. APSK has received honoraria for consultancy or giving lectures from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli-Lilly, Kyowa Kirin, Merck Serono, Merck Sharp & Dohme, Nestle, Novo-Nordisk, Pfizer and Sanofi. RCWM has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Boehringer Ingelheim, Bayer, Kyowa Kirin, Merck, Novo Nordisk, Pfizer, Roche Diagnostics and Tricida Inc. The proceeds have been donated to the Chinese University of Hong Kong, American Diabetes Association and other charity organizations to support diabetes research and education. RCWM is an Academic Editor on PLOS Medicine’s editorial board. Other authors declared no conflict of interests with this work.

                Author information
                https://orcid.org/0000-0002-2798-3268
                https://orcid.org/0000-0003-2968-1762
                https://orcid.org/0000-0003-1581-5643
                https://orcid.org/0000-0002-5244-6069
                https://orcid.org/0000-0001-8927-6764
                https://orcid.org/0000-0003-1325-1194
                https://orcid.org/0000-0002-4147-3387
                Article
                PMEDICINE-D-23-03065
                10.1371/journal.pmed.1004369
                11014435
                38607977
                40dd75cd-51c2-4bce-b2d9-7bcf08098acf
                © 2024 Shi 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
                : 19 October 2023
                : 29 February 2024
                Page count
                Figures: 2, Tables: 2, Pages: 16
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100004853, Chinese University of Hong Kong;
                Award ID: IRF2022
                Award Recipient :
                This work was supported by the Chinese University of Hong Kong (Impact Research Fellowship Scheme, IRF2022 to AY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                People and Places
                Population Groupings
                Age Groups
                Adults
                Elderly
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Forecasting
                Physical Sciences
                Mathematics
                Statistics
                Statistical Methods
                Forecasting
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Hypoglycemia
                Medicine and Health Sciences
                Health Care
                Health Information Technology
                Electronic Medical Records
                Computer and Information Sciences
                Information Technology
                Health Information Technology
                Electronic Medical Records
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Insulin
                Biology and Life Sciences
                Biochemistry
                Hormones
                Insulin
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Type 2 Diabetes
                Type 2 Diabetes Risk
                Medicine and Health Sciences
                Medical Conditions
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes
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                Custom metadata
                Data cannot be shared publicly because the raw data is confidential and not available for sharing in accordance with the policy of the Hong Kong Hospital Authority Data Collaboration Lab (HADCL). For inquiries regarding data access, please reach out to HADCL through their website at https://www3.ha.org.hk/data/DCL/.

                Medicine
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