Adaptive Personalized Prior-Knowledge-Informed Model Predictive Control for Type 1 Diabetes.

This work considers the problem of adaptive prior-informed model predictive control (MPC) formulations that explicitly incorporate prior knowledge in the model development and is robust to missing data in the output measurements. The proposed prediction model is based on a latent variables model to extract glycemic dynamics from highly-correlated data and incorporates prior knowledge of exponential stability to improve the prediction ability. Missing data structures are formulated to enable model predictions when output measurements are missing for short periods of time. Based on the latent variables model, the MPC strategy and adaptive rules are developed to automatically tune the aggressiveness of the MPC. The adaptive prior-knowledge-informed MPC is evaluated with computer simulations for the control of blood glucose concentrations in people with Type 1 diabetes (T1D) using simulated virtual patients. Due to the variability among people with T1D, the hyperparameters of the prior-knowledge-informed model are personalized to individual subjects. The percentage of time spent in the target range is 76.48% when there are no missing data and 76.52% when there are missing data episodes lasting up to 30 mins (6 samples). Incorporating the adaptive rules further improves the percentage of time in target range to 84.58% and 84.88% for cases with no missing data and missing data, respectively. The proposed adaptive prior-informed MPC formulation provides robust, effective, and safe regulation of glucose concentration in T1D despite disturbances and missing measurements.

Thought Believability and Anxious Feelings about COVID-19: A Case-Control Study in Northeastern Iran.

Background: Believability and thoughts are considered as the pillars of behaviors over time, and anxious feelings are a risk factor for mental disorders, especially during the coronavirus disease (COVID-19) pandemic. This study aimed to explore the thought believability and anxious feelings of COVID-19 among infected and healthy families. Methods: In this hospital-based matched case-control study, health surveillance files of COVID-19 patients were collected from January to June 2021 and were analyzed statistically. In this study, two questionnaires of demographic characteristics and the Believability of Anxious Feelings and Thoughts (BAFT) were used. Data were analyzed using the One-way ANOVA. Results: Of 600 participants, 300 (50%) were PCR-confirmed and 300 (50%) were non-infected. Overall, 163 (54.33%) of infected people were male, 146 (48.67%) single, and 156 (52.00%) government employees. The results showed that the mean scores of physical anxiety (PA) and negative evaluation (NE) in the case group is significantly higher than the control group (P = 0.001); while emotional regulation (ER) in the control group was significantly higher than the case group (P = 0.001). Conclusion: Having high believability to the risks of COVID-19 may be a predictor of preventive behaviors in individuals. Worrying about COVID-19 can increase the perceived risk of a pandemic in societies and consequence, increase the general public health.

Prior Informed Regularization of Recursively Updated Latent-Variables-Based Models with Missing Observations.

Many data-driven modeling techniques identify locally valid, linear representations of time-varying or nonlinear systems, and thus the model parameters must be adaptively updated as the operating conditions of the system vary, though the model identification typically does not consider prior knowledge. In this work, we propose a new regularized partial least squares (rPLS) algorithm that incorporates prior knowledge in the model identification and can handle missing data in the independent covariates. This latent variable (LV) based modeling technique consists of three steps. First, a LV-based model is developed on the historical time series data. In the second step, the missing observations in the new incomplete data sample are estimated. Finally, the future values of the outputs are predicted as a linear combination of estimated scores and loadings. The model is recursively updated as new data are obtained from the system. The performance of the proposed rPLS and rPLS with exogenous inputs (rPLSX) algorithms are evaluated by modeling variations in glucose concentration (GC) of people with Type 1 diabetes (T1D) in response to meals and physical activities for prediction windows up to one hour, or 12 sampling instances, into the future. The proposed rPLS family of GC prediction models are evaluated with both in-silico and clinical experiment data and compared with the performance of recursive time series and kernel-based models. The root mean squared error (RMSE) with simulated subjects in the multivariable T1D simulator where physical activity effects are incorporated in GC variations are 2.52 and 5.81 mg/dL for 30 and 60 mins ahead predictions (respectively) when information for all meals and physical activities are used, increasing to 2.70 and 6.54 mg/dL (respectively) when meals and activities occurred, but the information is with-held from the modeling algorithms. The RMSE is 10.45 and 14.48 mg/dL for clinical study with prediction horizons of 30 and 60 mins, respectively. The low RMSE values demonstrate the effectiveness of the proposed rPLS approach compared to the conventional recursive modeling algorithms.

Determining Physical Activity Characteristics from Wristband Data for Use in Automated Insulin Delivery Systems.

Algorithms that can determine the type of physical activity (PA) and quantify the intensity can allow precision medicine approaches, such as automated insulin delivery systems that modulate insulin administration in response to PA. In this work, data from a multi-sensor wristband is used to design classifiers to distinguish among five different physical states (PS) (resting, activities of daily living, running, biking, and resistance training), and to develop models to estimate the energy expenditure (EE) of the PA for diabetes therapy. The data collected are filtered, features are extracted from the reconciled signals, and the extracted features are used by machine learning algorithms, including deep-learning techniques, to obtain accurate PS classification and EE estimation. The various machine learning techniques have different success rates ranging from 75.7% to 94.8% in classifying the five different PS. The deep neural network model with long short-term memory has 94.8% classification accuracy. We achieved 0.5 MET (Metabolic Equivalent of Task) root-mean-square error for EE estimation accuracy, relative to indirect calorimetry with randomly selected testing data (10% of collected data). We also demonstrate a 5% improvement in PS classification accuracy and a 0.34 MET decrease in the mean absolute error when using multi-sensor approach relative to using only accelerometer data.

Modeling Metformin and Dapagliflozin Pharmacokinetics in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a complication of diabetes that affects circulating drug concentrations and elimination of drugs from the body. Multiple drugs may be prescribed for treatment of diabetes and co-morbidities, and CKD complicates the pharmacotherapy selection and dosing regimen. Characterizing variations in renal drug clearance using models requires large clinical datasets that are costly and time-consuming to collect. We propose a flexible approach to incorporate impaired renal clearance in pharmacokinetic (PK) models using descriptive statistics and secondary data with mechanistic models and PK first principles. Probability density functions were generated for various drug clearance mechanisms based on the degree of renal impairment and used to estimate the total clearance starting from glomerular filtration for metformin (MET) and dapagliflozin (DAPA). These estimates were integrated with PK models of MET and DAPA for simulations. MET renal clearance decreased proportionally with a reduction in estimated glomerular filtration rate (eGFR) and estimated net tubular transport rates. DAPA total clearance varied little with renal impairment and decreased proportionally to reported non-renal clearance rates. Net tubular transport rates were negative to partially account for low renal clearance compared with eGFR. The estimated clearance values and trends were consistent with MET and DAPA PK characteristics in the literature. Dose adjustment based on reduced clearance levels estimated correspondingly lower doses for MET and DAPA while maintaining desired dose exposure. Estimation of drug clearance rates using descriptive statistics and secondary data with mechanistic models and PK first principles improves modeling of CKD in diabetes and can guide treatment selection.

Multivariable Automated Insulin Delivery System for Handling Planned and Spontaneous Physical Activities.

BACKGROUND: Hybrid closed-loop control of glucose levels in people with type 1 diabetes mellitus (T1D) is limited by the requirements on users to manually announce physical activity (PA) and meals to the artificial pancreas system. Multivariable automated insulin delivery (mvAID) systems that can handle unannounced PAs and meals without any manual announcements by the user can improve glycemic control by modulating insulin dosing in response to the occurrence and intensity of spontaneous physical activities. METHODS: An mvAID system is developed to supplement the glucose measurements with additional physiological signals from a wristband device, with the signals analyzed using artificial intelligence algorithms to automatically detect the occurrence of PA and estimate its intensity. This additional information gained from the physiological signals enables more proactive insulin dosing adjustments in response to both planned exercise and spontaneous unanticipated physical activities. RESULTS: In silico studies of the mvAID illustrate the safety and efficacy of the system. The mvAID is translated to pilot clinical studies to assess its performance, and the clinical experiments demonstrate an increased time in range and reduced risk of hypoglycemia following unannounced PA and meals. CONCLUSIONS: The mvAID systems can increase the safety and efficacy of insulin delivery in the presence of unannounced physical activities and meals, leading to improved lives and less burden on people with T1D.

Detection of Meals and Physical Activity Events From Free-Living Data of People With Diabetes.

BACKGROUND: Predicting carbohydrate intake and physical activity in people with diabetes is crucial for improving blood glucose concentration regulation. Patterns of individual behavior can be detected from historical free-living data to predict meal and exercise times. Data collected in free-living may have missing values and forgotten manual entries. While machine learning (ML) can capture meal and exercise times, missing values, noise, and errors in data can reduce the accuracy of ML algorithms. METHODS: Two recurrent neural networks (RNNs) are developed with original and imputed data sets to assess detection accuracy of meal and exercise events. Continuous glucose monitoring (CGM) data, insulin infused from pump data, and manual meal and exercise entries from free-living data are used to predict meals, exercise, and their concurrent occurrence. They contain missing values of various lengths in time, noise, and outliers. RESULTS: The accuracy of RNN models range from 89.9% to 95.7% for identifying the state of event (meal, exercise, both, or neither) for various users. "No meal or exercise" state is determined with 94.58% accuracy by using the best RNN (long short-term memory [LSTM] with 1D Convolution). Detection accuracy with this RNN is 98.05% for meals, 93.42% for exercise, and 55.56% for concurrent meal-exercise events. CONCLUSIONS: The meal and exercise times detected by the RNN models can be used to warn people for entering meal and exercise information to hybrid closed-loop automated insulin delivery systems. Reliable accuracy for event detection necessitates powerful ML and large data sets. The use of additional sensors and algorithms for detecting these events and their characteristics provides a more accurate alternative.

Incorporating Prior Information in Adaptive Model Predictive Control for Multivariable Artificial Pancreas Systems.

BACKGROUND: Adaptive model predictive control (MPC) algorithms that recursively update the glucose prediction model are shown to be promising in the development of fully automated multivariable artificial pancreas systems. However, the recursively updated glycemic prediction models do not explicitly consider prior knowledge in the identification of the model parameters. Prior information of the glycemic effects of meals and physical activity can improve model accuracy and yield better glycemic control algorithms. METHODS: A glucose prediction model based on regularized partial least squares (rPLS) method where the prior information is encoded as the regularization term is developed to provide accurate predictions of the future glucose concentrations. An adaptive MPC is developed that incorporates dynamic trajectories for the glucose setpoint and insulin dosing constraints based on the estimated plasma insulin concentration (PIC). The proposed adaptive MPC algorithm is robust to disturbances caused by unannounced meals and physical activities even in cases with missing glucose measurements. The effectiveness of the proposed adaptive MPC based on rPLS is investigated with in silico subjects of the multivariable glucose-insulin-physiological variables simulator (mGIPsim). RESULTS: The efficacy of the proposed adaptive MPC strategy in regulating the blood glucose concentration (BGC) of people with T1DM is assessed using the average percent time in range (TIR) for glucose, defined as 70 to 180 mg/dL inclusive, and the average percent time in hypoglycemia (<70 and >54 mg/dL) and level 2 hypoglycemia (≤54 mg/dL). The TIR for a cohort of 20 virtual subjects of mGIPsim is 81.9% ± 7.4% (with no hypoglycemia or severe hypoglycemia) for the proposed MPC compared with 73.9% ± 7.6% (0.2% ± 0.1% in hypoglycemia and 0.1% ± 0.1% in level 2 hypoglycemia) for an MPC based on a recursive autoregressive exogenous (ARX) model. CONCLUSIONS: The adaptive MPC algorithm that incorporates prior knowledge in the recursive updating of the glucose prediction model can contribute to the development of fully automated artificial pancreas systems that can mitigate meal and physical activity disturbances.

Meal and Physical Activity Detection from Free-living Data for Discovering Disturbance Patterns to Glucose Levels in People with Diabetes.

Objective: Interpretation of time series data collected in free-living has gained importance in chronic disease management. Some data are collected objectively from sensors and some are estimated and entered by the individual. In type 1 diabetes (T1D), blood glucose concentration (BGC) data measured by continuous glucose monitoring (CGM) systems and insulin doses administered can be used to detect the occurrences of meals and physical activities and generate the personal daily living patterns for use in automated insulin delivery (AID). Methods: Two challenges in time-series data collected in daily living are addressed: data quality improvement and detection of unannounced disturbances to BGC. CGM data have missing values for varying periods of time and outliers. People may neglect reporting their meal and physical activity information. In this work, novel methods for preprocessing real-world data collected from people with T1D and detection of meal and exercise events are presented. Four recurrent neural network (RNN) models are investigated to detect the occurrences of meals and physical activities disjointly or concurrently. Results: RNNs with long short-term memory (LSTM) with 1D convolution layers and bidirectional LSTM with 1D convolution layers have average accuracy scores of 92.32% and 92.29%, and outper-form other RNN models. The F1 scores for each individual range from 96.06% to 91.41% for these two RNNs. Conclusions: RNNs with LSTM and 1D convolution layers and bidirectional LSTM with 1D convolution layers provide accurate personalized information about the daily routines of individuals. Significance: Capturing daily behavior patterns enables more accurate future BGC predictions in AID systems and improves BGC regulation.

A physical activity-intensity driven glycemic model for type 1 diabetes.

BACKGROUND AND OBJECTIVE: The glucose response to physical activity for a person with type 1 diabetes (T1D) depends upon the intensity and duration of the physical activity, plasma insulin concentrations, and the individual physical fitness level. To accurately model the glycemic response to physical activity, these factors must be considered. METHODS: Several physiological models describing the glycemic response to physical activity are proposed by incorporating model terms proportional to the physical activity intensity and duration describing endogenous glucose production (EGP), glucose utilization, and glucose transfer from the plasma to tissues. Leveraging clinical data of T1D during physical activity, each model fit is assessed. RESULTS: The proposed model with terms accommodating EGP, glucose transfer, and insulin-independent glucose utilization allow for an improved simulation of physical activity glycemic responses with the greatest reduction in model error (mean absolute percentage error: 16.11 ± 4.82 vs. 19.49 ± 5.87, p = 0.002). CONCLUSIONS: The development of a physiologically plausible model with model terms representing each major contributor to glucose metabolism during physical activity can outperform traditional models with physical activity described through glucose utilization alone. This model accurately describes the relation of plasma insulin and physical activity intensity on glucose production and glucose utilization to generate the appropriately increasing, decreasing or stable glucose response for each physical activity condition. The proposed model will enable the in silico evaluation of automated insulin dosing algorithms designed to mitigate the effects of physical activity with the appropriate relationship between the reduction in basal insulin and the corresponding glycemic excursion.

Potato Consumption and Risk of Site-Specific Cancers in Adults: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

The etiology of cancer type may vary significantly due to anatomy, embryology, and physiology of the cancer site. Although the association between potato consumption and colorectal cancer (CRC) was summarized in a 2018 meta-analysis of 5 cohort studies, to the best of our knowledge, no meta-analysis has evaluated potato consumption in relation to multiple cancer sites in adults. Medline/PubMed, ISI Web of Knowledge, Scopus, and the Cochrane Database of Systematic Reviews were searched for relevant publications through August 2020. We selected cohort or case-control studies conducted in adults that reported risk estimates (relative risk [RRs], HRs, and ORs) of potato intake for any cancer type. Random effects meta-analyses compared high and low intake categories. Twenty prospective cohort studies (total n = 785,348) including 19,882 incident cases, and 36 case-control studies (21,822 cases; 66,502 controls) were included. Among cohort studies, we did not find an association between high versus low intake of total potato (white and yellow) consumption and overall cancers: 1.04 (95% CI: 0.96, 1.11; tau2 = 0.005, n = 18). We found no relation between total potato consumption (high compared with low intake) and risk of CRC, pancreatic cancer, colon, gastric, breast, prostate, kidney, lung, or bladder cancer in cohort or case-control studies. We did not find an association between high versus low consumption of potato preparations (boiled/fried/mashed/roasted/baked) and risk of gastrointestinal-, sex-hormone-, or urinary-related cancers in cohort or case-control studies. Certainty of the evidence was low for total cancer, CRC, colon, rectal, renal, pancreatic, breast, prostate, and lung cancer and very low for gastric and bladder cancer. In conclusion, potato intake or potato preparations were not associated with multiple cancer sites when comparing high and low intake categories. This finding was consistent with the findings from the 2018 meta-analysis regarding potato intake and risk of CRC.

Discrimination of simultaneous psychological and physical stressors using wristband biosignals.

BACKGROUND AND OBJECTIVE: In this work, we address the problem of detecting and discriminating acute psychological stress (APS) in the presence of concurrent physical activity (PA) using wristband biosignals. We focused on signals available from wearable devices that can be worn in daily life because the ultimate objective of this work is to provide APS and PA information in real-time management of chronic conditions such as diabetes by automated personalized insulin delivery. Monitoring APS noninvasively throughout free-living conditions remains challenging because the responses to APS and PA of many physiological variables measured by wearable devices are similar. METHODS: Various classification algorithms are compared to simultaneously detect and discriminate the PA (sedentary state, treadmill running, and stationary bike) and the type of APS (non-stress state, mental stress, and emotional anxiety). The impact of APS inducements is verified with commonly used self-reported questionnaires (The State-Trait Anxiety Inventory (STAI)). To aid the classification algorithms, novel features are generated from the physiological variables reported by a wristband device during 117 hours of experiments involving simultaneous APS inducement and PA. We also translate the APS assessment into a quantitative metric for use in predicting the adverse outcomes. RESULTS: An accurate classification of the concurrent PA and APS states is achieved with an overall classification accuracy of 99% for PA and 92% for APS. The average accuracy of APS detection during sedentary state, treadmill running, and stationary bike is 97.3, 94.1, and 84.5%, respectively. CONCLUSIONS: The simultaneous assessment of APS and PA throughout free-living conditions from a convenient wristband device is useful for monitoring the factors contributing to an elevated risk of acute events in people with chronic diseases like cardiovascular complications and diabetes.

Controlling the AP Controller: Controller Performance Assessment and Modification.

BACKGROUND: Despite recent advances in closed-loop control of blood glucose concentration (BGC) in people with type 1 diabetes (T1D), online performance assessment and modification of artificial pancreas (AP) control systems remain a challenge as the metabolic characteristics of users change over time. METHODS: A controller performance assessment and modification system (CPAMS) analyzes the glucose concentration variations and controller behavior, and modifies the parameters of the control system used in the multivariable AP system. Various indices are defined to quantitatively evaluate the controller performance in real time. Controller performance assessment and modification system also incorporates online learning from historical data to anticipate impending disturbances and proactively counteract their effects. RESULTS: Using a multivariable simulation platform for T1D, the CPAMS is used to enhance the BGC regulation in people with T1D by means of automated insulin delivery with an adaptive learning predictive controller. Controller performance assessment and modification system increases the percentage of time in the target range (70-180) mg/dL by 52.3% without causing any hypoglycemia and hyperglycemia events. CONCLUSIONS: The results demonstrate a significant improvement in the multivariable AP controller performance by using CPAMS.