Glycemic Control Protocol Comparison using Virtual Trials

DTM2011 handbook/programme is given in files and also available as a hard copyBackground: Several accurate glycemic control (AGC) protocols for critical care patients exist but making comparisons is very hard. Objective: This study uses clinically validated virtual patient methods to compare safety and performance for several published AGC protocols. Method: Clinically validated virtual trials were run on 371 patients (39,481 hours, 26,646 measurements) created from the SPRINT AGC cohort. For protocols that do not modulate feed rates enteral nutrition was held at 100% of ACCP goal (25kcal/kg/day) when the patients were clinically fed, and parenteral nutrition rates were matched to clinical data. Performance was defined as %BG within glycemic bands and BG measurement frequency. Safety was defined as the incidence of severe (number patients with BG<40mg/dL) and moderate (%BG<72mg/dL) hypoglycemia. Clinical data from SPRINT is also compared. Results: Clinical SPRINT performance data matched re-simulated SPRINT with 86% vs. 86% BG in 80-145mg/dL, 2.00% vs. 2.07% BG above 180mg/dL and 7.83% vs. 7.29% BG below 72mg/dL, with 14 measurements (over 8 patients) of BG<40mg/dL. Yale results were 83.5%, 3.20%, 5.18%, with 6 severe hypoglycemic patients, using 37,961 measurements (23.0/day). Glucontrol had 75.2%, 3.70%, 9.45%, 52 cases and 26,199 measurements (15.8/day). Braithwaite had 84.2%, 3.00%, 4.22%, 19 cases and 24,396 measurements (14.8/day). The STAR (Stochastic TARgeted) model-based method had 90.6%, 1.67%, 1.33%, 5 cases and 20,591 measurements (12.3/day). Conclusions: Virtual trials provided an effective comparison across protocols with different target bands/values and different clinical cohorts. The model-based STAR protocol provided the best management of patient variability yielding the best performance and safety

Glucometer accuracy and implications for clinical studies

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Variability of insulin sensitivity during the first 4 days of critical illness

1-pageSafe, effective tight glycaemic control (TGC) can improve outcomes in critical care patients, but is difficult to achieve consistently. Insulin sensitivity defines the metabolic balance between insulin concentration and insulin mediated glucose disposal. Hence, variability of insulin sensitivity can cause variable glycaemia. This study investigates the daily evolution of model-based insulin sensitivity level and variability for critical care patients receiving TGC during the first four days of their ICU stay

The chemistry of vibrationally excited H2 in the interstellar medium

The internal energy available in vibrationally excited H2 molecules can be used to overcome or diminish the activation barrier of various chemical reactions of interest for molecular astrophysics. In this article we investigate in detail the impact on the chemical composition of interstellar clouds of the reactions of vibrationally excited H2 with C+, He+, O, OH, and CN, based on the available chemical kinetics data. It is found that the reaction of H2 (v>0) and C+ has a profound impact on the abundances of some molecules, especially CH+, which is a direct product and is readily formed in astronomical regions with fractional abundances of vibrationally excited H2, relative to ground state H2, in excess of 10^(-6), independently of whether the gas is hot or not. The effects of these reactions on the chemical composition of the diffuse clouds zeta Oph and HD 34078, the dense PDR Orion Bar, the planetary nebula NGC 7027, and the circumstellar disk around the B9 star HD 176386 are investigated through PDR models. We find that formation of CH+ is especially favored in dense and highly FUV illuminated regions such as the Orion Bar and the planetary nebula NGC 7027, where column densities in excess of 10^(13) cm^(-2) are predicted. In diffuse clouds, however, this mechanism is found to be not efficient enough to form CH+ with a column density close to the values derived from astronomical observations.Comment: accepted for publication in the Astrophysical Journal; 9 pages, 7 figure

Endogenous insulin secretion in critically ill patients

1-pageGlucose-insulin system models can be used for improved glycemic control of critically ill patients. A key component of glucose-insulin models is pancreatic insulin secretion. There is limited data in the literature quantifying insulin secretion in critically ill patients at physiologic levels. This study presents a model pancreatic insulin secretion in critically ill patients based on data from a critically ill population

Stacking order dynamic in the quasi-two-dimensional dichalcogenide 1T-TaS2_2 probed with MeV ultrafast electron diffraction

Transitions between different charge density wave (CDW) states in quasi-two-dimensional materials may be accompanied also by changes in the inter-layer stacking of the CDW. Using MeV ultrafast electron diffraction, the out-of-plane stacking order dynamics in the quasi-two-dimensional dichalcogenide 1T-TaS$_2$ is investigated for the first time. From the intensity of the CDW satellites aligned around the commensurate $l$ = 1/6 characteristic stacking order, it is found out that this phase disappears with a 0.5 ps time constant. Simultaneously, in the same experiment, the emergence of the incommensurate phase, with a slightly slower 2.0 ps time constant, is determined from the intensity of the CDW satellites aligned around the incommensurate $l$ = 1/3 characteristic stacking order. These results might be of relevance in understanding the metallic character of the laser-induced metastable "hidden" state recently discovered in this compound

Quantum Statistical Model of Nuclear Multifragmentation in the Canonical Ensemble Method

A quantum statistical model of nuclear multifragmentation is proposed. The recurrence equation method used within the canonical ensemble makes the model solvable and transparent to physical assumptions and allows to get results without involving the Monte Carlo technique. The model exhibits the first order phase transition. Quantum statistics effects are clearly seen on the microscopic level of occupation numbers but are almost washed out for global thermodynamic variables and the averaged observables studied. In the latter case, the recurrence relations for multiplicity distributions of both intermediate-mass and all fragments are derived and the specific changes in the shape of multiplicity distributions in the narrow region of the transition temperature is stressed. The temperature domain favorable to search for the HBT effect is noted.Comment: 38 pages, 11 figure

First pilot trial of the STAR-Liege protocol for tight glycemic control in critically ill patients

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Impact of calibration algorithms on hypoglycaemia detection in newborn infants using continuous glucose monitors

invited, 6-pagesNeonatal hypoglycaemia is a common condition that can cause seizures and serious brain injury in infants. It is diagnosed by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) devices can potentially improve hypoglycaemia detection, while reducing the number of BG measurements. Calibration algorithms convert the sensor signal into the CGM output. Thus, these algorithms can have a direct impact on measures used to quantify excursions from normal glycaemic levels. The aim of this study was to quantify the effects of calibration sensor error and non-linear filtering of CGM data on measures of hypoglycaemia (defined as BG < 2.6mmol/L) in neonates. CGM data was recalibrated using an algorithm that explicitly recognised the high accuracy of BG measurements available in this study. Median filtering was also implemented either before or after recalibration. Results for the entire cohort show an increase in the total number of hypoglycaemic events (161 to 193), duration of hypoglycaemia (2.2 to 2.6% of total data), and hypoglycaemic index (4.9 to 7.1µmol/L) after recalibration. With the addition of filtering, the number of hypoglycaemic events was reduced (193 to 131), with little or no change to the other metrics. These results show how reference sensor error and thus calibration algorithms play a significant role in quantifying hypoglycaemia. In particular, metrics such as counting the number of hypoglycaemic events were particularly sensitive to recalibration and filtering effects. While this conclusion might be expected, its potential impact is quantified here, in this case for at-risk neonates for whom hypoglycaemia carries potential long-term negative outcomes

Impact of glucocorticoids on insulin resistance in the critically ill

Glucocorticoids (GCs) have been shown to reduce insulin sensitivity in healthy individuals. Widely used in critical care to treat a variety of inflammatory and allergic disorders, they may inadvertently exacerbate stress-hyperglycaemia. This research uses model-based methods to quantify the reduction of insulin sensitivity from GCs in critically ill patients, and thus their impact on glycaemic control. A clinically validated model-based measure of insulin sensitivity (SI) was used to quantify changes between two matched cohorts of 40 intensive care unit (ICU) patients who received GCs and a control cohort who did not. All patients were admitted to the Christchurch hospital ICU between 2005 and 2007 and spent at least 24 hours on the SPRINT glycaemic control protocol. A 31% reduction in whole-cohort median insulin sensitivity was seen between the control cohort and patients receiving glucocorticoids with a median dose equivalent to 200mg/day of hydrocortisone per patient. Comparing percentile-patients as a surrogate for matched patients, reductions in median insulin sensitivity of 20, 25, and 21% were observed for the 25th, 50th and 75th-percentile patients. All these cohort and per-patient reductions are less than or equivalent to the 30-62% reductions reported in healthy subjects especially when considering the fact that the GC doses in this study are 1.3-4 times larger than those in studies of healthy subjects. This reduced suppression of insulin sensitivity in critically ill patients could be a result of saturation due to already increased levels of catecholamines and cortisol common in critically illness. Virtual trial simulation showed that reductions in insulin sensitivity of 20-30% associated with glucocorticoid treatment in the ICU have limited impact on glycaemic control levels within the context of the SPRINT protocol