Effective Treatment Recommendations for Type 2 Diabetes Management Using Reinforcement Learning: Treatment Recommendation Model Development and Validation.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and its related complications represent a growing economic burden for many countries and health systems. Diabetes complications can be prevented through better disease control, but there is a large gap between the recommended treatment and the treatment that patients actually receive. The treatment of T2DM can be challenging because of different comprehensive therapeutic targets and individual variability of the patients, leading to the need for precise, personalized treatment. OBJECTIVE: The aim of this study was to develop treatment recommendation models for T2DM based on deep reinforcement learning. A retrospective analysis was then performed to evaluate the reliability and effectiveness of the models. METHODS: The data used in our study were collected from the Singapore Health Services Diabetes Registry, encompassing 189,520 patients with T2DM, including 6,407,958 outpatient visits from 2013 to 2018. The treatment recommendation model was built based on 80% of the dataset and its effectiveness was evaluated with the remaining 20% of data. Three treatment recommendation models were developed for antiglycemic, antihypertensive, and lipid-lowering treatments by combining a knowledge-driven model and a data-driven model. The knowledge-driven model, based on clinical guidelines and expert experiences, was first applied to select the candidate medications. The data-driven model, based on deep reinforcement learning, was used to rank the candidates according to the expected clinical outcomes. To evaluate the models, short-term outcomes were compared between the model-concordant treatments and the model-nonconcordant treatments with confounder adjustment by stratification, propensity score weighting, and multivariate regression. For long-term outcomes, model-concordant rates were included as independent variables to evaluate if the combined antiglycemic, antihypertensive, and lipid-lowering treatments had a positive impact on reduction of long-term complication occurrence or death at the patient level via multivariate logistic regression. RESULTS: The test data consisted of 36,993 patients for evaluating the effectiveness of the three treatment recommendation models. In 43.3% of patient visits, the antiglycemic medications recommended by the model were concordant with the actual prescriptions of the physicians. The concordant rates for antihypertensive medications and lipid-lowering medications were 51.3% and 58.9%, respectively. The evaluation results also showed that model-concordant treatments were associated with better glycemic control (odds ratio [OR] 1.73, 95% CI 1.69-1.76), blood pressure control (OR 1.26, 95% CI, 1.23-1.29), and blood lipids control (OR 1.28, 95% CI 1.22-1.35). We also found that patients with more model-concordant treatments were associated with a lower risk of diabetes complications (including 3 macrovascular and 2 microvascular complications) and death, suggesting that the models have the potential of achieving better outcomes in the long term. CONCLUSIONS: Comprehensive management by combining knowledge-driven and data-driven models has good potential to help physicians improve the clinical outcomes of patients with T2DM; achieving good control on blood glucose, blood pressure, and blood lipids; and reducing the risk of diabetes complications in the long term.

Abnormality classification from electrocardiograms with various lead combinations.

Objective. As cardiovascular diseases are a leading cause of death, early and accurate diagnosis of cardiac abnormalities for a lower cost becomes particularly important. Given electrocardiogram (ECG) datasets from multiple sources, there exist many challenges to the development of generalized models that can identify multiple types of cardiac abnormalities from both 12-lead ECG signals and reduced-lead ECG signals. In this study, our objective is to build robust models that can accurately classify 30 types of abnormalities from various lead combinations of ECG signals.Approach. Given the challenges of this problem, we propose a framework for building robust models for ECG signal classification. Firstly, a preprocessing workflow is adopted for each ECG dataset to mitigate the problem of data divergence. Secondly, to capture the lead-wise relations, we use a squeeze-and-excitation deep residual network as our base model. Thirdly, we propose a cross-relabeling strategy and apply the sign-augmented loss function to tackle the corrupted labels in the data. Furthermore, we utilize a pos-if-any-pos ensemble strategy and a dataset-wise cross-evaluation strategy to handle the uncertainty of the data distribution in the application.Main results. In the Physionet/Computing in Cardiology Challenge 2021, our approach achieved the challenge metric scores of 0.57, 0.59, 0.59, 0.58, 0.57 on 12-, 6-, 4-, 3- and 2-lead versions and an averaged challenge metric score of 0.58 over all the lead versions.Significance. Using the proposed framework, we have developed the models from several large datasets with sufficiently labeled abnormalities. Our models are able to identify 30 ECG abnormalities accurately based on various lead combinations of ECG signals. The performance on hidden test data demonstrates the effectiveness of the proposed approaches.

Identification of 27 abnormalities from multi-lead ECG signals: an ensembled SE_ResNet framework with Sign Loss function.

Objective. Cardiovascular disease is a major threat to health and one of the primary causes of death globally. The 12-lead ECG is a cheap and commonly accessible tool to identify cardiac abnormalities. Early and accurate diagnosis will allow early treatment and intervention to prevent severe complications of cardiovascular disease. Our objective is to develop an algorithm that automatically identifies 27 ECG abnormalities from 12-lead ECG databases.Approach. Firstly, a series of pre-processing methods were proposed and applied on various data sources in order to mitigate the problem of data divergence. Secondly, we ensembled two SE_ResNet models and one rule-based model to enhance the performance of various ECG abnormalities' classification. Thirdly, we introduce a Sign Loss to tackle the problem of class imbalance, and thus improve the model's generalizability.Main results. In the PhysioNet/Computing in Cardiology Challenge (2020), our proposed approach achieved a challenge validation score of 0.682, and a full test score of 0.514, placed us 3rd out of 40 in the official ranking.Significance. We proposed an accurate and robust predictive framework that combines deep neural networks and clinical knowledge to automatically classify multiple ECG abnormalities. Our framework is able to identify 27 ECG abnormalities from multi-lead ECG signals regardless of discrepancies in data sources and the imbalance of data labeling. We trained our framework on five datasets and validated it on six datasets from various countries. The outstanding performance demonstrate the effectiveness of our proposed framework.

Influence of guideline adherence and parameter control on the clinical outcomes in patients with diabetic nephropathy.

INTRODUCTION: We assessed the association between guideline adherence and outcomes of clinical parameter control and end-stage kidney disease (ESKD), and further studied the effect of parameter control on ESKD for Chinese patients with diabetic nephropathy (DN). RESEARCH DESIGN AND METHODS: In this retrospective study, 1128 patients with DN (15,374 patient-visit samples) diagnosed by renal biopsy were enrolled. Samples were classified as adherence and nonadherence based on whether prescribed drugs conformed to medication regimen and drug contraindication recommended by guidelines, including American Diabetes Association (ADA) and Chinese guidelines. Guideline adherence rate was calculated on all samples for antihyperglycemic, antihypertensive and lipid-lowering treatments. Clinical parameter control was compared after 3-6 months' therapy between two groups by generalized estimating equation models. Time-dependent Cox models were applied to evaluate the influence of guideline adherence on ESKD. Latent class mixed model was used to identify distinct trajectories for parameters and their ESKD risks were compared using Cox proportional-hazards models. RESULTS: Guideline adherence rate of antihyperglycemic therapy was the highest, with 72.87% and 68.15% of samples meeting ADA and Chinese guidelines, respectively. Adherence was more likely to have good glycated hemoglobin A1c (HbA1c) control (ADA: OR 1.46, 95% CI 1.12 to 1.88; Chinese guideline: OR 1.42, 95% CI 1.09 to 1.85) and good blood pressure control (ADA: OR 1.35, 95% CI 1.03 to 1.78; Chinese guideline: OR 1.39, 95% CI 1.08 to 1.79) compared with nonadherence. The improvement of patient's adherence showed the potential to reduce ESKD risk. For proteinuria, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure and uric acid, patients in higher-value trajectory group had higher ESKD risk. Proteinuria and LDL-C trajectories were most closely related to ESKD risk, while the risk was not significantly different in HbA1c trajectories. CONCLUSIONS: Guideline adherence and good control of proteinuria and LDL-C in clinical practice are important and in need for improving clinical outcomes in patients with DN.

Integrating Clinical Knowledge and Real-World Evidence for Type 2 Diabetes Treatment.

Clinical decision support system (CDSS) plays a significant role nowadays and it assists physicians in making decisions for treatment. Generally based on clinical guideline, the principles of the recommendation are provided and may suggest several candidate medications for similar patient group with certain clinical conditions. However, it is challenging to prioritize these candidates and even refine the guideline to a finer level for patient-specific recommendation. Here we propose a method and system to integrate the clinical knowledge and real-world evidence (RWE) for type 2 diabetes treatment, to enable both standardized and personalized medication recommendation. The RWE is generated by medication effectiveness analysis and subgroup analysis. The knowledge model has been verified by clinical experts from the advanced hospitals. The data verification results show that the medications that are consistent with the method recommendation can lead to better clinical outcome in terms of glycemic control, compared to those inconsistent.