Optimization of identifying insulinaemic pharmacokinetic parameters using artificial neural network.

BACKGROUND AND OBJECTIVE: The identification of insulinaemic pharmacokinetic parameters using the least-squares criterion approach is easily influenced by outlying data due to its sensitivity. Furthermore, the least-squares criterion has a tendency to overfit and produce incorrect results. Hence, this research proposes an alternative approach using the artificial neural network (ANN) with two hidden layers to optimize the identifying of insulinaemic pharmacokinetic parameters. The ANN is selected for its ability to avoid overfitting parameters and its faster speed in processing data. METHODS: 18 voluntarily participants were recruited from the Canterbury and Otago region of New Zealand to take part in a Dynamic Insulin Sensitivity and Secretion Test (DISST) clinical trial. A total of 46 DISST data were collected. However, due to ambiguous and inconsistency, 4 data had to be removed. Analysis was done using MATLAB 2020a. RESULTS AND DISCUSSION: Results show that, with 42 gathered dataset, the ANN generates higher gains, ∅P = 20.73 [12.21, 28.57] mU·L·mmol-1·min-1 and ∅D = 60.42 [26.85, 131.38] mU·L·mmol-1 as compared to the linear least square method, ∅P = 19.67 [11.81, 28.02] mU·L·mmol-1 ·min-1 and ∅D = 46.21 [7.25, 116.71] mU·L·mmol-1. The average value of the insulin sensitivity (SI) of ANN is lower with, SI = 16 × 10-4 L·mU-1 ·min-1 than the linear least square, SI = 17 × 10-4 L·mU-1 ·min-1. CONCLUSION: Although the ANN analysis provided a lower SI value, the results were more dependable than the linear least square model because the ANN approach yielded a better model fitting accuracy than the linear least square method with a lower residual error of less than 5%. With the implementation of this ANN architecture, it shows that ANN able to produce minimal error during optimization process particularly when dealing with outlying data. The findings may provide extra information to clinicians, allowing them to gain a better knowledge of the heterogenous aetiology of diabetes and therapeutic intervention options.

Estimating the incidence of spontaneous breathing effort of mechanically ventilated patients using a non-linear auto regressive (NARX) model.

BACKGROUND AND OBJECTIVE: Mechanical ventilation (MV) provides breathing support for acute respiratory distress syndrome (ARDS) patients in the intensive care unit, but is difficult to optimize. Too much, or too little of pressure or volume support can cause further ventilator-induced lung injury, increasing length of MV, cost and mortality. Patient-specific respiratory mechanics can help optimize MV settings. However, model-based estimation of respiratory mechanics is less accurate when patient exhibit un-modeled spontaneous breathing (SB) efforts on top of ventilator support. This study aims to estimate and quantify SB efforts by reconstructing the unaltered passive mechanics airway pressure using NARX model. METHODS: Non-linear autoregressive (NARX) model is used to reconstruct missing airway pressure due to the presence of spontaneous breathing effort in mv patients. Then, the incidence of SB patients is estimated. The study uses a total of 10,000 breathing cycles collected from 10 ARDS patients from IIUM Hospital in Kuantan, Malaysia. In this study, there are 2 different ratios of training and validating methods. Firstly, the initial ratio used is 60:40 which indicates 600 breath cycles for training and remaining 400 breath cycles used for testing. Then, the ratio is varied using 70:30 ratio for training and testing data. RESULTS AND DISCUSSION: The mean residual error between original airway pressure and reconstructed airway pressure is denoted as the magnitude of effort. The median and interquartile range of mean residual error for both ratio are 0.0557 [0.0230 - 0.0874] and 0.0534 [0.0219 - 0.0870] respectively for all patients. The results also show that Patient 2 has the highest percentage of SB incidence and Patient 10 with the lowest percentage of SB incidence which proved that NARX model is able to perform for both higher incidence of SB effort or when there is a lack of SB effort. CONCLUSION: This model is able to produce the SB incidence rate based on 10% threshold. Hence, the proposed NARX model is potentially useful to estimate and identify patient-specific SB effort, which has the potential to further assist clinical decisions and optimize MV settings.

Assessing the Asynchrony Event Based on the Ventilation Mode for Mechanically Ventilated Patients in ICU.

Respiratory system modelling can assist clinicians in making clinical decisions during mechanical ventilation (MV) management in intensive care. However, there are some cases where the MV patients produce asynchronous breathing (asynchrony events) due to the spontaneous breathing (SB) effort even though they are fully sedated. Currently, most of the developed models are only suitable for fully sedated patients, which means they cannot be implemented for patients who produce asynchrony in their breathing. This leads to an incorrect measurement of the actual underlying mechanics in these patients. As a result, there is a need to develop a model that can detect asynchrony in real-time and at the bedside throughout the ventilated days. This paper demonstrates the asynchronous event detection of MV patients in the ICU of a hospital by applying a developed extended time-varying elastance model. Data from 10 mechanically ventilated respiratory failure patients admitted at the International Islamic University Malaysia (IIUM) Hospital were collected. The results showed that the model-based technique precisely detected asynchrony events (AEs) throughout the ventilation days. The patients showed an increase in AEs during the ventilation period within the same ventilation mode. SIMV mode produced much higher asynchrony compared to SPONT mode (p < 0.05). The link between AEs and the lung elastance (AUC Edrs) was also investigated. It was found that when the AEs increased, the AUC Edrs decreased and vice versa based on the results obtained in this research. The information of AEs and AUC Edrs provides the true underlying lung mechanics of the MV patients. Hence, this model-based method is capable of detecting the AEs in fully sedated MV patients and providing information that can potentially guide clinicians in selecting the optimal ventilation mode of MV, allowing for precise monitoring of respiratory mechanics in MV patients.

The Need to Calculate Target Glucose Levels When Measuring Changes in Insulin Sensitivity During Interventions for Individuals With Type 2 Diabetes.

BACKGROUND: Physiological models that are used with dynamic test data to assess insulin sensitivity (SI) assume that the metabolic target glucose concentration ( GTARGET) is equal to fasting glucose concentration ( G0). However, recent research has implied that irregularities in G0 in diabetes may cause erroneous SI values. This study quantifies the magnitude of these errors. METHODS: A clinically validated insulin/glucose model was used to calculate SI with the standard fasting assumption (SFA) G0 = GTARGET. Then GTARGET was treated as a variable in a second analysis (VGT). The outcomes were contrasted across twelve participants with established type 2 diabetes mellitus that were recruited to take part in a 24-week dietary intervention. Participants underwent three insulin-modified intravenous glucose tolerance tests (IM-IVGTT) at 0, 12, and 24 weeks. RESULTS: SIVGT had a median value of 3.36×10-4 L·mU-1·min-1 (IQR: 2.30 - 4.95×10-4) and were significantly lower ( P < .05) than the median SISFA (6.38×10-4 L·mU-1·min-1, IQR: 4.87 - 9.39×10-4). The VGT approach generally yielded lower SI values in line with expected participant physiology and more effectively tracked changes in participant state over the 24-week trial. Calculated GTARGET values were significantly lower than G0 values (median GTARGET = 5.48 vs G0 = 7.16 mmol·L-1 P < .001) and were notably higher in individuals with longer term diabetes. CONCLUSIONS: Typical modeling approaches can overestimate SI when GTARGET does not equal G0. Hence, calculating GTARGET may enable more precise SI measurements in individuals with type 2 diabetes, and could imply a dysfunction in diabetic metabolism.

Assessing respiratory mechanics using pressure reconstruction method in mechanically ventilated spontaneous breathing patient.

BACKGROUND: Respiratory system modelling can aid clinical decision making during mechanical ventilation (MV) in intensive care. However, spontaneous breathing (SB) efforts can produce entrained "M-wave" airway pressure waveforms that inhibit identification of accurate values for respiratory system elastance and airway resistance. A pressure wave reconstruction method is proposed to accurately identify respiratory mechanics, assess the level of SB effort, and quantify the incidence of SB effort without uncommon measuring devices or interruption to care. METHODS: Data from 275 breaths aggregated from all mechanically ventilated patients at Christchurch Hospital were used in this study. The breath specific respiratory elastance is calculated using a time-varying elastance model. A pressure reconstruction method is proposed to reconstruct pressure waves identified as being affected by SB effort. The area under the curve of the time-varying respiratory elastance (AUC Edrs) are calculated and compared, where unreconstructed waves yield lower AUC Edrs. The difference between the reconstructed and unreconstructed pressure is denoted as a surrogate measure of SB effort. RESULTS: The pressure reconstruction method yielded a median AUC Edrs of 19.21 [IQR: 16.30-22.47]cmH2Os/l. In contrast, the median AUC Edrs for unreconstructed M-wave data was 20.41 [IQR: 16.68-22.81]cmH2Os/l. The pressure reconstruction method had the least variability in AUC Edrs assessed by the robust coefficient of variation (RCV)=0.04 versus 0.05 for unreconstructed data. Each patient exhibited different levels of SB effort, independent from MV setting, indicating the need for non-invasive, real time assessment of SB effort. CONCLUSION: A simple reconstruction method enables more consistent real-time estimation of the true, underlying respiratory system mechanics of a SB patient and provides the surrogate of SB effort, which may be clinically useful for clinicians in determining optimal ventilator settings to improve patient care.

The necessity of identifying the basal glucose set-point in the IVGTT for patients with Type 2 Diabetes.

BACKGROUND: The model-based dynamic insulin sensitivity and secretion test (DISST) uses fasting glucose (G 0 ) as the basal glucose (G B ) concentration when assessing insulin sensitivity (SI). However, this model was developed in a healthy, normoglycaemic cohort. We sought to determine the suitability the DISST model has for individuals with established type 2 diabetes (T2D). METHODS: 14 participants with established T2D were recruited to take part in a dietary intervention study. Insulin-modified intravenous glucose tolerance tests (IM-IVGTT) were undertaken at week 0, 12 and 24 and were used with DISST model to identify G B . A total of 36 tests were conducted across 12 participants throughout the study. Measured G 0 and identified G B values were compared using a Kolmogorov-Smirnov (KS) and signed rank (RS) test for the cohort. RESULTS: There were significant differences between the G 0 and identified G B values in this cohort (prs and pks < 0.0001), although both values were well correlated (R = 0.70). The residual plot demonstrates that the modified model captures the behaviour of the participants more accurately than the original model. CONCLUSIONS: This analysis has shown that G B is an important variable for modelling the glycaemic behaviour in T2D. These findings suggest that the original DISST model, while appropriate for normoglycaemic cohorts, needs to model basal glucose level as a variable for assessing individuals with established T2D.