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      Exploiting Machine Learning Algorithms and Methods for the Prediction of Agitated Delirium After Cardiac Surgery: Models Development and Validation Study

      research-article
      , MD, MSc, CIP, FRCSC 1 , 2 , 3 , , , MD 4 , , MBBS, PhD 5 , , PhD 6
      (Reviewer), (Reviewer), (Reviewer), (Reviewer)
      JMIR Medical Informatics
      JMIR Publications
      delirium, cardiac surgery, machine learning, predictive modeling

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          Abstract

          Background

          Delirium is a temporary mental disorder that occasionally affects patients undergoing surgery, especially cardiac surgery. It is strongly associated with major adverse events, which in turn leads to increased cost and poor outcomes (eg, need for nursing home due to cognitive impairment, stroke, and death). The ability to foresee patients at risk of delirium will guide the timely initiation of multimodal preventive interventions, which will aid in reducing the burden and negative consequences associated with delirium. Several studies have focused on the prediction of delirium. However, the number of studies in cardiac surgical patients that have used machine learning methods is very limited.

          Objective

          This study aimed to explore the application of several machine learning predictive models that can pre-emptively predict delirium in patients undergoing cardiac surgery and compare their performance.

          Methods

          We investigated a number of machine learning methods to develop models that can predict delirium after cardiac surgery. A clinical dataset comprising over 5000 actual patients who underwent cardiac surgery in a single center was used to develop the models using logistic regression, artificial neural networks (ANN), support vector machines (SVM), Bayesian belief networks (BBN), naïve Bayesian, random forest, and decision trees.

          Results

          Only 507 out of 5584 patients (11.4%) developed delirium. We addressed the underlying class imbalance, using random undersampling, in the training dataset. The final prediction performance was validated on a separate test dataset. Owing to the target class imbalance, several measures were used to evaluate algorithm’s performance for the delirium class on the test dataset. Out of the selected algorithms, the SVM algorithm had the best F1 score for positive cases, kappa, and positive predictive value (40.2%, 29.3%, and 29.7%, respectively) with a P=.01, .03, .02, respectively. The ANN had the best receiver-operator area-under the curve (78.2%; P=.03). The BBN had the best precision-recall area-under the curve for detecting positive cases (30.4%; P=.03).

          Conclusions

          Although delirium is inherently complex, preventive measures to mitigate its negative effect can be applied proactively if patients at risk are prospectively identified. Our results highlight 2 important points: (1) addressing class imbalance on the training dataset will augment machine learning model’s performance in identifying patients likely to develop postoperative delirium, and (2) as the prediction of postoperative delirium is difficult because it is multifactorial and has complex pathophysiology, applying machine learning methods (complex or simple) may improve the prediction by revealing hidden patterns, which will lead to cost reduction by prevention of complications and will optimize patients’ outcomes.

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          Most cited references66

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          Logistic regression: a brief primer.

          Regression techniques are versatile in their application to medical research because they can measure associations, predict outcomes, and control for confounding variable effects. As one such technique, logistic regression is an efficient and powerful way to analyze the effect of a group of independent variables on a binary outcome by quantifying each independent variable's unique contribution. Using components of linear regression reflected in the logit scale, logistic regression iteratively identifies the strongest linear combination of variables with the greatest probability of detecting the observed outcome. Important considerations when conducting logistic regression include selecting independent variables, ensuring that relevant assumptions are met, and choosing an appropriate model building strategy. For independent variable selection, one should be guided by such factors as accepted theory, previous empirical investigations, clinical considerations, and univariate statistical analyses, with acknowledgement of potential confounding variables that should be accounted for. Basic assumptions that must be met for logistic regression include independence of errors, linearity in the logit for continuous variables, absence of multicollinearity, and lack of strongly influential outliers. Additionally, there should be an adequate number of events per independent variable to avoid an overfit model, with commonly recommended minimum "rules of thumb" ranging from 10 to 20 events per covariate. Regarding model building strategies, the three general types are direct/standard, sequential/hierarchical, and stepwise/statistical, with each having a different emphasis and purpose. Before reaching definitive conclusions from the results of any of these methods, one should formally quantify the model's internal validity (i.e., replicability within the same data set) and external validity (i.e., generalizability beyond the current sample). The resulting logistic regression model's overall fit to the sample data is assessed using various goodness-of-fit measures, with better fit characterized by a smaller difference between observed and model-predicted values. Use of diagnostic statistics is also recommended to further assess the adequacy of the model. Finally, results for independent variables are typically reported as odds ratios (ORs) with 95% confidence intervals (CIs). © 2011 by the Society for Academic Emergency Medicine.
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            Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability.

            To prospectively develop and validate a predictive model for delirium based on precipitating factors during hospitalization, and to examine the interrelationship of precipitating factors and baseline vulnerability. Two prospective cohort studies, in tandem. General medical wards, university teaching hospital. For the development cohort, 196 patients aged 70 years and older with no delirium at baseline, and for the validation cohort, 312 comparable patients. New-onset delirium by hospital day 9, defined by the Confusion Assessment Method diagnostic criteria. Delirium developed in 35 patients (18%) in the development cohort. Five independent precipitating factors for delirium were identified; use of physical restraints (adjusted relative risk [RR], 4.4; 95% confidence interval [CI], 2.5 to 7.9), malnutrition (RR, 4.0; 95% CI, 2.2 to 7.4), more than three medications added (RR, 2.9; 95% CI, 1.6 to 5.4), use of bladder catheter (RR, 2.4; 95% CI, 1.2 to 4.7), and any iatrogenic event (RR, 1.9; 95% CI, 1.1 to 3.2). Each precipitating factor preceded the onset of delirium by more than 24 hours. A risk stratification system was developed by adding 1 point for each factor present. Rates of delirium for low-risk (0 points), intermediate-risk (1 to 2 points), and high-risk groups (> or equal to 3 points) were 3%, 20%, and 59%, respectively (P < .001). The corresponding rates in the validation cohort, in which 47 patients (15%) developed delirium, were 4%, 20%, and 35%, respectively (P < .001). When precipitating and baseline factors were analyzed in cross-stratified format, delirium rates increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline and precipitating factors were documented to be independent and statistically significant. A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium. Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive, and cumulative ways.
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              A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics.

              To prospectively develop and validate a predictive model for the occurrence of new delirium in hospitalized elderly medical patients based on characteristics present at admission. Two prospective cohort studies done in tandem. University teaching hospital. The development cohort included 107 hospitalized general medical patients 70 years or older who did not have dementia or delirium at admission. The validation cohort included 174 comparable patients. Patients were assessed daily for delirium using a standardized, validated instrument. The predictive model developed in the initial cohort was then validated in a separate cohort of patients. Delirium developed in 27 of 107 patients (25%) in the development cohort. Four independent baseline risk factors for delirium were identified using proportional hazards analysis: These included vision impairment (adjusted relative risk, 3.5; 95% Cl, 1.2 to 10.7); severe illness (relative risk, 3.5; Cl, 1.5 to 8.2); cognitive impairment (relative risk, 2.8; Cl, 1.2 to 6.7); and a high blood urea nitrogen/creatinine ratio (relative risk, 2.0; Cl, 0.9 to 4.6). A risk stratification system was developed by assigning 1 point for each risk factor present. Rates of delirium for low- (0 points), intermediate- (1 to 2 points), and high-risk (3 to 4 points) groups were 9%, 23%, and 83% (P < 0.0001), respectively. The corresponding rates in the validation cohort, in which 29 of 174 patients (17%) developed delirium, were 3%, 16%, and 32% (P < 0.002). The rates of death or nursing home placement, outcomes potentially related to delirium, were 9%, 16%, and 42% (P = 0.02) in the development cohort and 3%, 14%, and 26% (P = 0.007) in the validation cohort. Delirium among elderly hospitalized patients is common, and a simple predictive model based on four risk factors can be used at admission to identify elderly persons at the greatest risk.
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                Author and article information

                Contributors
                Journal
                JMIR Med Inform
                JMIR Med Inform
                JMI
                JMIR Medical Informatics
                JMIR Publications (Toronto, Canada )
                2291-9694
                Oct-Dec 2019
                23 October 2019
                : 7
                : 4
                : e14993
                Affiliations
                [1 ] Division of Cardiac Surgery, Department of Cardiac Sciences, King Faisal Cardiac Center King Abdulaziz Medical City Ministry of National Guard Health Affairs - Western Region Jeddah Saudi Arabia
                [2 ] College of Medicine-Jeddah King Saud bin Abdulaziz University for Health Ministry of National Guard Health Affairs Jeddah Saudi Arabia
                [3 ] King Abdullah International Medical Research Center Jeddah Saudi Arabia
                [4 ] Department of Surgery Faculty of Medicine Dalhousie University Halifax, NS Canada
                [5 ] Department of Community Health and Epidemiology Faculty of Medicine Dalhousie University Halifax, NS Canada
                [6 ] kNowledge Intensive Computing for Healthcare Enterprise Research Group Faculty of Computer Science Dalhousie University Halifax, NS Canada
                Author notes
                Corresponding Author: Hani Nabeel N Mufti muftihn@ 123456ngha.med.sa
                Author information
                https://orcid.org/0000-0002-0471-5738
                https://orcid.org/0000-0001-6924-0625
                https://orcid.org/0000-0002-7805-6122
                https://orcid.org/0000-0003-3075-7736
                Article
                v7i4e14993
                10.2196/14993
                6913743
                31558433
                d59734ee-07b4-47b1-b118-7e7221eef879
                ©Hani Nabeel N Mufti, Gregory Marshal Hirsch, Samina Raza Abidi, Syed Sibte Raza Abidi. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 23.10.2019.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Medical Informatics, is properly cited. The complete bibliographic information, a link to the original publication on http://medinform.jmir.org/, as well as this copyright and license information must be included.

                History
                : 11 June 2019
                : 9 July 2019
                : 2 September 2019
                : 24 September 2019
                Categories
                Original Paper
                Original Paper

                delirium,cardiac surgery,machine learning,predictive modeling

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