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Association between Preoperative Glucose Dysregulation and Delirium after Non-Cardiac Surgery.

This study aimed to investigate the association between glucose dysregulation and delirium after non-cardiac surgery. Among a total of 203,787 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, we selected 61,805 with available preoperative blood glucose levels within 24 h before surgery. Patients experiencing glucose dysregulation were divided into three groups: hyperglycemia, hypoglycemia, and both. We compared the incidence of postoperative delirium within 30 days after surgery between exposed and unexposed patients according to the type of glucose dysregulation. The overall incidence of hyperglycemia, hypoglycemia, and both was 5851 (9.5%), 1452 (2.3%), and 145 (0.2%), respectively. The rate of delirium per 100 person-months of the exposed group was higher than that of the unexposed group in all types of glucose dysregulation. After adjustment, the hazard ratios of glucose dysregulation in the development of delirium were 1.35 (95% CI, 1.18-1.56) in hyperglycemia, 1.36 (95% CI, 1.06-1.75) in hypoglycemia, and 3.14 (95% CI, 1.27-7.77) in both. The subgroup analysis showed that exposure to hypoglycemia or both to hypo- and hyperglycemia was not associated with delirium in diabetic patients, but hyperglycemia was consistently associated with postoperative delirium regardless of the presence of diabetes. Preoperative glucose dysregulation was associated with increased risk of delirium after non-cardiac surgery. Our findings may be helpful for preventing postoperative delirium, and further investigations are required to verify the association and mechanisms for the effect we observed.

Towards global model generalizability: independent cross-site feature evaluation for patient-level risk prediction models using the OHDSI network.

BACKGROUND: Predictive models show promise in healthcare, but their successful deployment is challenging due to limited generalizability. Current external validation often focuses on model performance with restricted feature use from the original training data, lacking insights into their suitability at external sites. Our study introduces an innovative methodology for evaluating features during both the development phase and the validation, focusing on creating and validating predictive models for post-surgery patient outcomes with improved generalizability. METHODS: Electronic health records (EHRs) from 4 countries (United States, United Kingdom, Finland, and Korea) were mapped to the OMOP Common Data Model (CDM), 2008-2019. Machine learning (ML) models were developed to predict post-surgery prolonged opioid use (POU) risks using data collected 6 months before surgery. Both local and cross-site feature selection methods were applied in the development and external validation datasets. Models were developed using Observational Health Data Sciences and Informatics (OHDSI) tools and validated on separate patient cohorts. RESULTS: Model development included 41 929 patients, 14.6% with POU. The external validation included 31 932 (UK), 23 100 (US), 7295 (Korea), and 3934 (Finland) patients with POU of 44.2%, 22.0%, 15.8%, and 21.8%, respectively. The top-performing model, Lasso logistic regression, achieved an area under the receiver operating characteristic curve (AUROC) of 0.75 during local validation and 0.69 (SD = 0.02) (averaged) in external validation. Models trained with cross-site feature selection significantly outperformed those using only features from the development site through external validation (P < .05). CONCLUSIONS: Using EHRs across four countries mapped to the OMOP CDM, we developed generalizable predictive models for POU. Our approach demonstrates the significant impact of cross-site feature selection in improving model performance, underscoring the importance of incorporating diverse feature sets from various clinical settings to enhance the generalizability and utility of predictive healthcare models.

Applicable Machine Learning Model for Predicting Contrast-induced Nephropathy Based on Pre-catheterization Variables.

Objective Contrast agents used for radiological examinations are an important cause of acute kidney injury (AKI). We developed and validated a machine learning and clinical scoring prediction model to stratify the risk of contrast-induced nephropathy, considering the limitations of current classical and machine learning models. Methods This retrospective study included 38,481 percutaneous coronary intervention cases from 23,703 patients in a tertiary hospital. We divided the cases into development and internal test sets (8:2). Using the development set, we trained a gradient boosting machine prediction model (complex model). We then developed a simple model using seven variables based on variable importance. We validated the performance of the models using an internal test set and tested them externally in two other hospitals. Results The complex model had the best area under the receiver operating characteristic (AUROC) curve at 0.885 [95% confidence interval (CI) 0.876-0.894] in the internal test set and 0.837 (95% CI 0.819-0.854) and 0.850 (95% CI 0.781-0.918) in two different external validation sets. The simple model showed an AUROC of 0.795 (95% CI 0.781-0.808) in the internal test set and 0.766 (95% CI 0.744-0.789) and 0.782 (95% CI 0.687-0.877) in the two different external validation sets. This was higher than the value in the well-known scoring system (Mehran criteria, AUROC=0.67). The seven precatheterization variables selected for the simple model were age, known chronic kidney disease, hematocrit, troponin I, blood urea nitrogen, base excess, and N-terminal pro-brain natriuretic peptide. The simple model is available at http://52.78.230.235:8081/Conclusions We developed an AKI prediction machine learning model with reliable performance. This can aid in bedside clinical decision making.

Perioperative adverse cardiac events and mortality after non-cardiac surgery: a multicenter study.

BACKGROUND: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. METHODS: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta­analysis. RESULTS: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta­analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). CONCLUSIONS: A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.

Effect of statin use on head and neck cancer prognosis in a multicenter study using a Common Data Model.

Few studies have found an association between statin use and head and neck cancer (HNC) outcomes. We examined the effect of statin use on HNC recurrence using the converted Observational Medical Outcome Partnership (OMOP) Common Data Model (CDM) in seven hospitals between 1986 and 2022. Among the 9,473,551 eligible patients, we identified 4669 patients with HNC, of whom 398 were included in the target cohort, and 4271 were included in the control cohort after propensity score matching. A Cox proportional regression model was used. Of the 4669 patients included, 398 (8.52%) previously received statin prescriptions. Statin use was associated with a reduced rate of 3- and 5-year HNC recurrence compared to propensity score-matched controls (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.61-1.03; and RR 0.89; 95% CI 0.70-1.12, respectively). Nevertheless, the association between statin use and HNC recurrence was not statistically significant. A meta-analysis of recurrence based on subgroups, including age subgroups, showed similar trends. The results of this propensity-matched cohort study may not provide a statistically significant association between statin use and a lower risk of HNC recurrence. Further retrospective studies using nationwide claims data and prospective studies are warranted.

Privacy-Preserving Federated Model Predicting Bipolar Transition in Patients With Depression: Prediction Model Development Study.

BACKGROUND: Mood disorder has emerged as a serious concern for public health; in particular, bipolar disorder has a less favorable prognosis than depression. Although prompt recognition of depression conversion to bipolar disorder is needed, early prediction is challenging due to overlapping symptoms. Recently, there have been attempts to develop a prediction model by using federated learning. Federated learning in medical fields is a method for training multi-institutional machine learning models without patient-level data sharing. OBJECTIVE: This study aims to develop and validate a federated, differentially private multi-institutional bipolar transition prediction model. METHODS: This retrospective study enrolled patients diagnosed with the first depressive episode at 5 tertiary hospitals in South Korea. We developed models for predicting bipolar transition by using data from 17,631 patients in 4 institutions. Further, we used data from 4541 patients for external validation from 1 institution. We created standardized pipelines to extract large-scale clinical features from the 4 institutions without any code modification. Moreover, we performed feature selection in a federated environment for computational efficiency and applied differential privacy to gradient updates. Finally, we compared the federated and the 4 local models developed with each hospital's data on internal and external validation data sets. RESULTS: In the internal data set, 279 out of 17,631 patients showed bipolar disorder transition. In the external data set, 39 out of 4541 patients showed bipolar disorder transition. The average performance of the federated model in the internal test (area under the curve [AUC] 0.726) and external validation (AUC 0.719) data sets was higher than that of the other locally developed models (AUC 0.642-0.707 and AUC 0.642-0.699, respectively). In the federated model, classifications were driven by several predictors such as the Charlson index (low scores were associated with bipolar transition, which may be due to younger age), severe depression, anxiolytics, young age, and visiting months (the bipolar transition was associated with seasonality, especially during the spring and summer months). CONCLUSIONS: We developed and validated a differentially private federated model by using distributed multi-institutional psychiatric data with standardized pipelines in a real-world environment. The federated model performed better than models using local data only.

Feasibility Study of Federated Learning on the Distributed Research Network of OMOP Common Data Model.

OBJECTIVES: Since protecting patients' privacy is a major concern in clinical research, there has been a growing need for privacy-preserving data analysis platforms. For this purpose, a federated learning (FL) method based on the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) was implemented, and its feasibility was demonstrated. METHODS: We implemented an FL platform on FeederNet, which is a distributed clinical data analysis platform based on the OMOP CDM in Korea. We trained it through an artificial neural network (ANN) using data from patients who received steroid prescriptions or injections, with the aim of predicting the occurrence of side effects depending on the prescribed dose. The ANN was trained using the FL platform with the OMOP CDMs of Kyung Hee University Medical Center (KHMC) and Ajou University Hospital (AUH). RESULTS: The area under the receiver operating characteristic curves (AUROCs) for predicting bone fracture, osteonecrosis, and osteoporosis using only data from each hospital were 0.8426, 0.6920, and 0.7727 for KHMC and 0.7891, 0.7049, and 0.7544 for AUH, respectively. In contrast, when using FL, the corresponding AUROCs were 0.8260, 0.7001, and 0.7928 for KHMC and 0.7912, 0.8076, and 0.7441 for AUH, respectively. In particular, FL led to a 14% improvement in performance for osteonecrosis at AUH. CONCLUSIONS: FL can be performed with the OMOP CDM, and FL often shows better performance than using only a single institution's data. Therefore, research using OMOP CDM has been expanded from statistical analysis to machine learning so that researchers can conduct more diverse research.

Machine learning-based prediction model for postoperative delirium in non-cardiac surgery.

BACKGROUND: Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium. METHODS: Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan-Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model. RESULTS: The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855-0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845-0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001). CONCLUSION: Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations. TRIAL REGISTRATION: KCT 0006363.

A Mechanistic Insight into the Oxygen Redox of Li-Rich Layered Cathodes and their Related Electronic/Atomic Behaviors Upon Cycling.

Li-rich cathodes are extensively investigated as their energy density is superior to Li stoichiometric cathode materials. In addition to the transition metal redox, this intriguing electrochemical performance originates from the redox reaction of the anionic sublattice. This new redox process, the so-called anionic redox or, more directly, oxygen redox in the case of oxides, almost doubles the energy density of Li-rich cathodes compared to conventional cathodes. Numerous theoretical and experimental investigations have thoroughly established the current understanding of the oxygen redox of Li-rich cathodes. However, different reports are occasionally contradictory, indicating that current knowledge remains incomplete. Moreover, several practical issues still hinder the real-world application of Li-rich cathodes. As these issues are related to phenomena resulting from the electronic to atomic evolution induced by unstable oxygen redox, a fundamental multiscale understanding is essential for solving the problem. In this review, the current mechanistic understanding of oxygen redox, the origin of the practical problems, and how current studies tackle the issues are summarized.

Prediction model for myocardial injury after non-cardiac surgery using machine learning.

Myocardial injury after non-cardiac surgery (MINS) is strongly associated with postoperative outcomes. We developed a prediction model for MINS and have provided it online. Between January 2010 and June 2019, a total of 6811 patients underwent non-cardiac surgery with normal preoperative level of cardiac troponin (cTn). We used machine learning techniques with an extreme gradient boosting algorithm to evaluate the effects of variables on MINS development. We generated two prediction models based on the top 12 and 6 variables. MINS was observed in 1499 (22.0%) patients. The top 12 variables in descending order according to the effects on MINS are preoperative cTn level, intraoperative inotropic drug infusion, operation duration, emergency operation, operation type, age, high-risk surgery, body mass index, chronic kidney disease, coronary artery disease, intraoperative red blood cell transfusion, and current alcoholic use. The prediction models are available at https://sjshin.shinyapps.io/mins_occur_prediction/ . The estimated thresholds were 0.47 in 12-variable models and 0.53 in 6-variable models. The areas under the receiver operating characteristic curves are 0.78 (95% confidence interval [CI] 0.77-0.78) and 0.77 (95% CI 0.77-0.78), respectively, with an accuracy of 0.97 for both models. Using machine learning techniques, we demonstrated prediction models for MINS. These models require further verification in other populations.

Establishment of an International Evidence Sharing Network Through Common Data Model for Cardiovascular Research.

A retrospective observational study is one of the most widely used research methods in medicine. However, evidence postulated from a single data source likely contains biases such as selection bias, information bias, and confounding bias. Acquiring enough data from multiple institutions is one of the most effective methods to overcome the limitations. However, acquiring data from multiple institutions from many countries requires enormous effort because of financial, technical, ethical, and legal issues as well as standardization of data structure and semantics. The Observational Health Data Sciences and Informatics (OHDSI) research network standardized 928 million unique records or 12% of the world's population into a common structure and meaning and established a research network of 453 data partners from 41 countries around the world. OHDSI is a distributed research network wherein researchers do not own or directly share data but only analyzed results. However, sharing evidence without sharing data is difficult to understand. In this review, we will look at the basic principles of OHDSI, common data model, distributed research networks, and some representative studies in the cardiovascular field using the network. This paper also briefly introduces a Korean distributed research network named FeederNet.

Prediction Model for 30-Day Mortality after Non-Cardiac Surgery Using Machine-Learning Techniques Based on Preoperative Evaluation of Electronic Medical Records.

BACKGROUND: Machine-learning techniques are useful for creating prediction models in clinical practice. This study aimed to construct a prediction model of postoperative 30-day mortality based on an automatically extracted electronic preoperative evaluation sheet. METHODS: We used data from 276,341 consecutive adult patients who underwent non-cardiac surgery between January 2011 and December 2020 at a tertiary center for model development and internal validation, and another dataset from 63,384 patients between January 2011 and October 2021 at another center for external validation. Postoperative 30-day mortality was 0.16%. We developed an extreme gradient boosting (XGB) prediction model using only variables from preoperative evaluation sheets. RESULTS: The model yielded an area under the curve of 0.960 and an area under the precision and recall curve of 0.216, which were 0.932 and 0.122, respectively, in the external validation set. The optimal threshold calculated by Youden's J statistic had a sensitivity of 0.885 and specificity of 0.914. In an additional analysis with balanced distribution, the model showed a similar predictive value. CONCLUSION: We presented a machine-learning prediction model for 30-day mortality after non-cardiac surgery using preoperative variables automatically extracted from electronic medical records and validated the model in a multi-center setting. Our model may help clinicians predict postoperative outcomes.

An artificial intelligence electrocardiogram analysis for detecting cardiomyopathy in the peripartum period.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a fatal maternal complication, with left ventricular systolic dysfunction (LVSD; Left ventricular ejection fraction 45% or less) occurring at the end of pregnancy or in the months following delivery. The scarcity of screening tools for PPCM leads to a delayed diagnosis and increases its mortality and morbidity. We aim to evaluate an electrocardiogram (ECG)-deep learning model (DLM) for detecting cardiomyopathy in the peripartum period. METHODS: For the DLM development and internal performance test for detecting LVSD, we obtained a dataset of 122,733 ECG-echocardiography pairs from 58,530 male and female patients from two community hospitals. For the DLM external validation, this study included 271 ECG-echocardiography pairs (157 unique pregnant and postpartum period women) examined in the Ajou University Medical Center (AUMC) between January 2007 and May 2020. All included cases underwent an ECG within two weeks before or after the day of transthoracic echocardiography, which was performed within a month before delivery, or within five months after delivery. Based on the diagnostic criteria of PPCM, we analyzed the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to evaluate the model effectiveness. RESULTS: The ECG-based DLM detected PPCM with an AUROC of 0.877. Moreover, its sensitivity, specificity, PPV, and NPV for the detection of PPCM were 0.877, 0.833, 0.809, 0.352, and 0.975, respectively. CONCLUSIONS: An ECG-based DLM non-invasively and effectively detects cardiomyopathies occurring in the peripartum period and could be an ideal screening tool for PPCM.

Electrocardiographic biomarker based on machine learning for detecting overt hyperthyroidism.

Aims: Although overt hyperthyroidism adversely affects a patient's prognosis, thyroid function tests (TFTs) are not routinely conducted. Furthermore, vague symptoms of hyperthyroidism often lead to hyperthyroidism being overlooked. An electrocardiogram (ECG) is a commonly used screening test, and the association between thyroid function and ECG is well known. However, it is difficult for clinicians to detect hyperthyroidism through subtle ECG changes. For early detection of hyperthyroidism, we aimed to develop and validate an electrocardiographic biomarker based on a deep learning model (DLM) for detecting hyperthyroidism. Methods and results: This multicentre retrospective cohort study included patients who underwent ECG and TFTs within 24 h. For model development and internal validation, we obtained 174 331 ECGs from 113 194 patients. We extracted 48 648 ECGs from 33 478 patients from another hospital for external validation. Using 500 Hz raw ECG, we developed a DLM with 12-lead, 6-lead (limb leads, precordial leads), and single-lead (lead I) ECGs to detect overt hyperthyroidism. We calculated the model's performance on the internal and external validation sets using the area under the receiver operating characteristic curve (AUC). The AUC of the DLM using a 12-lead ECG was 0.926 (0.913-0.94) for internal validation and 0.883(0.855-0.911) for external validation. The AUC of DLMs using six and a single-lead were in the range of 0.889-0.906 for internal validation and 0.847-0.882 for external validation. Conclusion: We developed a DLM using ECG for non-invasive screening of overt hyperthyroidism. We expect this model to contribute to the early diagnosis of diseases and improve patient prognosis.

Prediction model for postoperative atrial fibrillation in non-cardiac surgery using machine learning.

Some patients with postoperative atrial fibrillation (POAF) after non-cardiac surgery need treatment, and a predictive model for these patients is clinically useful. Here, we developed a predictive model for POAF in non-cardiac surgery based on machine learning techniques. In a total of 201,864 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, 5,725 (2.8%) were treated for POAF. We used machine learning with an extreme gradient boosting algorithm to evaluate the effects of variables on POAF. Using the top five variables from this algorithm, we generated a predictive model for POAF and conducted an external validation. The top five variables selected for the POAF model were age, lung operation, operation duration, history of coronary artery disease, and hypertension. The optimal threshold of probability in this model was estimated to be 0.1, and the area under the receiver operating characteristic (AUROC) curve was 0.80 with a 95% confidence interval of 0.78-0.81. Accuracy of the model using the estimated threshold was 0.95, with sensitivity and specificity values of 0.28 and 0.97, respectively. In an external validation, the AUROC was 0.80 (0.78-0.81). The working predictive model for POAF requiring treatment in non-cardiac surgery based on machine learning techniques is provided online (https://sjshin.shinyapps.io/afib_predictor_0913/). The model needs further verification among other populations.

Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage (p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

l-Tryptophan: Antioxidant as a Film-Forming Additive for a High-Voltage Cathode.

l-tryptophan (TrP) was investigated as a functional film-forming additive on a lithium-rich layered oxide cathode because it has a much lower oxidation potential than other common carbonate-based electrolytes. Owing to its prior oxidation to a base electrolyte, an artificial cathode-electrolyte interphase (CEI) was formed on the cathode surface, which could be confirmed via X-ray photoelectron spectroscopy and scanning electron microscopy and verified through density functional theory calculations. The functional film formed on the cathode surface suppressed the side reactions between the cathode and electrolyte during cell cycling. As a result, the film prevented CEI thickening and performance deterioration. The optimum weight of TrP was determined to be 0.4 wt % for obtaining the best performance.