Glucometer accuracy and implications for clinical studies

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Validation of a virtual patient and virtual trials method for accurate prediction of tight glycemic control protocol performance

Peer reviewe

Enhanced insulin sensitivity variability in the first 3 days of ICU stay: implications for tight glycemic control

Effective tight glycemic control (TGC) can improve outcomes, particularly in cardiovascular surgery, but is difficult to achieve. Variability in insulin sensitivity/resistance resulting from the level and evolution of stress response, particularly early in a patient’s stay, can lead to hyperglycemia and variability, which are associated with mortality. This study quantifies the daily evolution of the variability of insulin sensitivity for cardiovascular surgical and all other ICU patients

Pulse Wave Velocity Measurement in the Carotid Artery Using an LED-LED Array Pulse Oximeter

Pulse wave velocity (PWV) is frequently used as an early indicator of risk of cardiovascular disease. Conventional methods of PWV measurement are invasive and measure the regional PWV, introducing errors from unknown measurement distance to masking local changes in compliance. This paper describes the development and testing of a non-invasive PWV sensor using photoplethysmograph signals. The sensor measures the pulse in the carotid artery with three sensor arrays spaced at 20 mm, 30 mm and 50 mm spacing. Each array of 20 LED-LED sensors are placed at 5 mm to get the largest amplitude pulse across the neck, and to allow for inaccurate sensor placement. LEDs are used as light emitters and the inherent capacitance of reverse biased LEDs measure the reflected light. The foot-foot and phase difference methods were used to calculate the PWV at each measurement distance. The foot-foot method was more reliable than the phase difference at all distances with a PWV of 5.26 m s−1 in a single-subject trial. The sample rate of 570 Hz was deemed too slow as one sample difference resulted in a PWV change of 1.5ms−1. The developed sensor measured the local PWV within the expected physiological range around 6 m s−1. All future measurements will be measured at 1 kHz and an increased LED output intensity

Endogenous insulin secretion and suppression during and after sepsis in critically ill patients: implications for tight glycemic control protocols

Introduction: Insulin infusions over 2 U/hr can suppress endogenous insulin secretion in healthy subjects 30-45% [1]. Virtually all tight glycaemic control (TGC) protocols deliver insulin via infusion. This study examines the impact of bolus delivery of insulin in TGC on the endogenous insulin secretion of critically ill patients. Methods: 18 patients from the Christchurch Hospital ICU enrolled in a prospective clinical trial studying sepsis each had two sets of blood samples assayed for insulin and C-peptide. The first set was taken at the commencement of the SPRINT TGC protocol for patients with suspected sepsis. The second set was taken when their SIRS score was consistently below 2. Each set had 4 samples taken at: -1, 10, 40 and 60 min following bolus delivery of insulin as required by SPRINT to capture endogenous insulin secretion during the bolus profile. Bolus size was dictated by the protocol, but was in the range 2-6 units. Model-based methods [2] were used to calculate the endogenous insulin secretion rate for each set of samples. The level of suppression was calculated as the ratio of the secretion rate between 5-15 mins (just after peak plasma insulin) and average of the 0-5 min (basal) and 15-60 min (return to basal) secretion rates identified

Brain mass estimation by head circumference and body mass methods in neonatal glycaemic modelling and control

Introduction: Hyperglycaemia is a common complication of stress and prematurity in extremely low-birth-weight infants. Model-based insulin therapy protocols have the ability to safely improve glycaemic control for this group. Estimating non-insulin-mediated brain glucose uptake by the central nervous system in these models is typically done using population-based body weight models, which may not be ideal. Method: A head circumference-based model that separately treats small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants is compared to a body weight model in a retrospective analysis of 48 patients with a median birth weight of 750g and median gestational age of 25 weeks. Estimated brain mass, model-based insulin sensitivity (SI) profiles, and projected glycaemic control outcomes are investigated. SGA infants (5) are also analyzed as a separate cohort. Results: Across the entire cohort, estimated brain mass deviated by a median 10% between models, with a per-patient median difference in SI of 3.5%. For the SGA group, brain mass deviation was 42%, and per-patient SI deviation 13.7%. In virtual trials, 87-93% of recommended insulin rates were equal or slightly reduced (δ<0.16mU/h) under the head circumference method, while glycaemic control outcomes showed little change. Conclusion: The results suggest that body weight methods are not as accurate as head circumference methods. Head circumference-based estimates may offer improved modelling accuracy and a small reduction in insulin administration, particularly for SGA infants. © 2014 Elsevier Ireland Ltd

Electrocardiogram R-wave is an Unreliable Indicator of Pulse Wave Initialization

Pulse wave velocity (PWV) measurements are commonly used to evaluate a patient’s arterial stiffness, an indicator of cardiovascular dysfunction. PWV is usually calculated by measuring the pulse transit time (PTT) over a known distance through the arteries. In an experimental study on animals, it is straight forward to measure the PTT using two pressure catheters a known distance apart in the central arteries. However, in a clinical setting it is uncommon for such a direct invasive method to be used. This study aims to identify whether a surrogate measure of PTT could be found without the need for an external device and without being additionally invasive. The aim is to use the time between the R-wave of an electrocardiogram (ECG), and the pulse wave passing one pressure catheter (rPTT), both of which are common in critical care. The analysis was performed using data from four porcine experiments (Pietrain Pigs, 20-29kg) in which ECG, aortic arch pressure and abdominal aortic pressure were measured simultaneously over a range of induced hemodynamic conditions including recruitment manoeuvres (RM), fluid admission and dobutamine admission. From the measured data, the correlation of rPTT and PTT was calculated for each pig and condition. The overall results showed varied correlations across the pigs (r2 = 0.07 to 0.79). The variability is suspected to be due to two main causes, the first being pig specific response to the interventions. The second cause leading to poor correlation is suspected to be the pre-ejection period (PEP), the time following the ECG R-wave but before ejection of blood from the ventricle. The analysis showed that rPTT was an unreliable measure of PTT and a poor surrogate

Spontaneous coronary artery dissection in a young man - Case report

A 31 year old man with a 17-year-history of drug abuse (heroine and cannabis) was admitted with recurrent chest pain over a period of about three weeks. Chest discomfort severely worsened during the 5 hours before hospital admission. Electrocardiography revealed poor R-wave progression and non specific repolarization abnormalities. Echocardiography showed extensive left ventricular anterior and apical wall motion abnormalities and a ventricular thrombus located at the apex of the left ventricle was present. Subsequently, a diagnosis of acute coronary syndrome was made. Coronary angiography revealed spontaneous coronary artery dissection of the left anterior descending (LAD) artery with Thrombolysis In Myocardial Infarction (TIMI) flow 2 to 3. We managed the patient conservatively. The clinical course was uneventful and repeated angiography on day 4 demonstrated spontaneous healing of large parts of the dissection with TIMI 3 flow in the LAD

Model-based insulin-nutrition administration for glycemic control in Malaysian critical care: First pilot trial

© 2018, Springer Science+Business Media Singapore. Stress-induced hyperglycemia is prevalent in critical care, even in patients with no history of diabetes. Control of blood glucose level with tight insulin therapy has been shown to reduce incidences of hyperglycemia leading to reduced mortality and improved clinical outcomes. STAR is a tablet-based glucose control protocol with a specialized user interface into which insulin and nutrition information can be entered and predicted. This research describes the first clinical pilot trial of STAR approach in International Islamic University Hospital, Kuantan, Malaysia. The clinically specified target for blood glucose level is between 4.4 and 8.0 mmol/L. Seven episodes (of 359 h) were recruited based on the need for glucose control. Overall, 43.93% of measurement are in the range of 4.4–8.0 mmol/L band. The blood glucose median is 8.30 [6.32–10.00] mmol/L with only 1 patient having below than 2.22 mmol/L which is the guaranteed minimum risk level. This pilot study shows that STAR protocol is a patient specific approach that provides a good glycemic control in critically ill patients. Nevertheless, its implementation in Malaysian intensive care environments requires modifications and improvements in certain areas

Next-generation, personalised, model-based critical care medicine : a state-of-the art review of in silico virtual patient models, methods, and cohorts, and how to validation them

© 2018 The Author(s). Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care