References of "Pretty, Christopher G"
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See detailSurvey about diffusion and adoption of glycaemic controller in European intensive care units
Penning, Sophie ULg; Pironet, Antoine ULg; Chase, J. Geoffrey et al

Conference (2014, August)

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See detailDoes the achievement of an intermediate glycemic target reduce organ failure and mortality? A post-hoc analysis of the Glucontrol Trial
Penning, Sophie ULg; Chase, J. Geoffrey; Preiser, Jean-Charles et al

in Journal of Critical Care (2014)

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See detailReducing the impact of insulin sensitivity variability on glycaemic outcomes using separate stochastic models within the STAR glycaemic protocol.
Thomas, Felicity; Pretty, Christopher G.; Fisk, Liam et al

in Biomedical engineering online (2014), 13

BACKGROUND: The metabolism of critically ill patients evolves dynamically over time. Post critical insult, levels of counter-regulatory hormones are significantly elevated, but decrease rapidly over the ... [more ▼]

BACKGROUND: The metabolism of critically ill patients evolves dynamically over time. Post critical insult, levels of counter-regulatory hormones are significantly elevated, but decrease rapidly over the first 12-48 hours in the intensive care unit (ICU). These hormones have a direct physiological impact on insulin sensitivity (SI). Understanding the variability of SI is important for safely managing glycaemic levels and understanding the evolution of patient condition. The objective of this study is to assess the evolution of SI over the first two days of ICU stay, and using this data, propose a separate stochastic model to reduce the impact of SI variability during glycaemic control using the STAR glycaemic control protocol. METHODS: The value of SI was identified hourly for each patient using a validated physiological model. Variability of SI was then calculated as the hour-to-hour percentage change in SI. SI was examined using 6 hour blocks of SI to display trends while mitigating the effects of noise. To reduce the impact of SI variability on achieving glycaemic control a new stochastic model for the most variable period, 0-18 hours, was generated. Virtual simulations were conducted using an existing glycaemic control protocol (STAR) to investigate the clinical impact of using this separate stochastic model during this period of increased metabolic variability. RESULTS: For the first 18 hours, over 80% of all SI values were less than 0.5 x 10(-3) L/mU x min, compared to 65% for >18 hours. Using the new stochastic model for the first 18 hours of ICU stay reduced the number of hypoglycaemic measurements during virtual trials. For time spent below 4.4, 4.0, and 3.0 mmol/L absolute reductions of 1.1%, 0.8% and 0.1% were achieved, respectively. No severe hypoglycaemic events (BG < 2.2 mmol/L) occurred for either case. CONCLUSIONS: SI levels increase significantly, while variability decreases during the first 18 hours of a patients stay in ICU. Virtual trials, using a separate stochastic model for this period, demonstrated a reduction in variability and hypoglycaemia during the first 18 hours without adversely affecting the overall level of control. Thus, use of multiple models can reduce the impact of SI variability during model-based glycaemic control. [less ▲]

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See detailInterstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance
Pretty, Christopher G.; Le Compte, Aaron; Penning, Sophie ULg et al

in Computer Methods & Programs in Biomedicine (2014)

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See detailStochastic Targeted (STAR) Glycemic Control - Design, Safety and Performance
Evans, Alicia; Le Compte, Aaron; Tan, Chian-Siong et al

in Journal of Diabetes Science and Technology (2012)

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See detailEnhanced insulin sensitivity variability in the first 3 days of ICU stay: Implications for TGC
Chase, J. Geoffrey; Le Compte, Aaron; Penning, Sophie ULg et al

in Critical Care (2011, March)

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See detailValidation of a virtual patient and virtual trials method for accurate prediction of TGC protocol performance
Suhaimi, Fatanah; Le Compte, Aaron; Penning, Sophie ULg et al

in Critical Care (2011, March)

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See detailInsulin Sensitivity, Its Variability and Glycemic Outcome: A model-based analysis of the difficulty in achieving tight glycemic control in critical care
Chase, J. Geoffrey; Le Compte, Aaron J.; Preiser, Jean-Charles et al

in 18th World Congress of the International Federation of Automatic Control (IFAC) (2011)

Effective tight glycemic control (TGC) can improve outcomes in intensive care unit (ICU) <br />patients, but is difficult to achieve consistently. Glycemic level and variability, particularly early in a ... [more ▼]

Effective tight glycemic control (TGC) can improve outcomes in intensive care unit (ICU) <br />patients, but is difficult to achieve consistently. Glycemic level and variability, particularly early in a <br />patient’s stay, are a function of variability in insulin sensitivity/resistance resulting from the level and <br />evolution of stress response, and are independently associated with mortality. This study examines the <br />daily evolution of variability of insulin sensitivity in ICU patients using patient data (N = 394 patients, <br />54019 hours) from the SPRINT TGC study. Model-based insulin sensitivity (SI) was identified each hour <br />and hour-to-hour percent changes in SI were assessed for Days 1-3 individually and Day 4 Onward, as <br />well as over all days. Cumulative distribution functions (CDFs), median values, and inter-quartile points <br />(25th and 75th percentiles) are used to assess differences between groups and their evolution over time. <br />Compared to the overall (all days) distributions, ICU patients are more variable on Days 1 and 2 (p < <br />0.0001), and less variable on Days 4 Onward (p < 0.0001). Day 3 is similar to the overall cohort (p = 0.74). <br />Absolute values of SI start lower and rise for Days 1 and 2, compared to the overall cohort (all days), (p < <br />0.0001), are similar on Day 3 (p = .72) and are higher on Days 4 Onward (p < 0.0001). ICU patients have <br />lower insulin sensitivity (greater insulin resistance) and it is more variable on Days 1 and 2, compared to <br />an overall cohort on all days. This is the first such model-based analysis of its kind. Greater variability <br />with lower SI early in a patient’s stay greatly increases the difficulty in achieving and safely maintaining <br />glycemic control, reducing potential positive outcomes. Clinically, the results imply that TGC patients will <br />require greater measurement frequency, reduced reliance on insulin, and more explicit specification of <br />carbohydrate nutrition in Days 1-3 to safely minimise glycemic variability for best outcome. [less ▲]

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See detailVariability of insulin sensitivity for diabetics and non-diabetics during the first 3 days of ICU stay
Pretty, Christopher G.; Le Compte, Aaron; Preiser, Jean-Charles et al

in Intensive Care Medicine (2011), 37 (Suppl 1)

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See detailVariability of insulin sensitivity for diabetics and non-diabetics during the first 3 days of ICU stay
Pretty, Christopher G.; Le Compte, Aaron; Preiser, Jean-Charles et al

Poster (2011)

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See detailSafety and Performance of Stochastic Targeted (STAR) Glycemic Control of Insulin and Nutrition - First Pilot Results
Shaw, Geoffrey M.; Le Compte, Aaron; Evans, Alicia et al

Poster (2011)

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See detailSafety and Performance of Stochastic Targeted (STAR) Glycemic Control of Insulin and Nutrition – First Pilot Results
Shaw, Geoffrey M.; Le Compte, Aaron; Evans, Alicia et al

in Intensive Care Medicine (2011)

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See detailPilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control.
Evans, Alicia; Shaw, Geoffrey M; Le Compte, Aaron et al

in Annals of intensive care (2011), 1

ABSTRACT: INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly ... [more ▼]

ABSTRACT: INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials. METHODS: Seven patients covering 660 hours. Insulin and nutrition interventions are given 1-3 hourly as chosen by the nurse to allow them to manage workload. Interventions are calculated by using clinically validated computer models of human metabolism and its variability in critical illness to maximize the overlap of the model-predicted (5-95th percentile) range of BG outcomes with the 4.0-6.5 mmol/L band while ensuring a maximum 5% risk of BG < 4.0 mmol/L. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of SCCM/ACCP goal (25 kg/kcal/h). Maximum insulin doses and dose changes were limited for safety. Measurements were made with glucometers. Results are compared to those for the SPRINT study, which reduced mortality 25-40% for length of stay >/=3 days. Written informed consent was obtained for all patients, and approval was granted by the NZ Upper South A Regional Ethics Committee. RESULTS: A total of 402 measurements were taken over 660 hours (~14/day), because nurses showed a preference for 2-hourly measurements. Median [interquartile range, (IQR)] cohort BG was 5.9 mmol/L [5.2-6.8]. Overall, 63.2%, 75.9%, and 89.8% of measurements were in the 4.0-6.5, 4.0-7.0, and 4.0-8.0 mmol/L bands. There were no hypoglycemic events (BG < 2.2 mmol/L), and the minimum BG was 3.5 mmol/L with 4.5% < 4.4 mmol/L. Per patient, the median [IQR] hours of TGC was 92 h [29-113] using 53 [19-62] measurements (median, ~13/day). Median [IQR] results: BG, 5.9 mmol/L [5.8-6.3]; carbohydrate nutrition, 6.8 g/h [5.5-8.7] (~70% goal feed median); insulin, 2.5 U/h [0.1-5.1]. All patients achieved BG < 6.1 mmol/L. These results match or exceed SPRINT and clinical workload is reduced more than 20%. CONCLUSIONS: STAR TGC modulating insulin and nutrition inputs provided very tight control with minimal variability by managing intra- and inter- patient variability. Performance and safety exceed that of SPRINT, which reduced mortality and cost in the Christchurch ICU. The use of glucometers did not appear to impact the quality of TGC. Finally, clinical workload was self-managed and reduced 20% compared with SPRINT. [less ▲]

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See detailOrgan failure and tight glycemic control in the SPRINT study.
Chase, J Geoffrey; Pretty, Christopher G; Pfeifer, Leesa et al

in Critical Care (2010), 14(4), 154

INTRODUCTION: Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful ... [more ▼]

INTRODUCTION: Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality. METHODS: A retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA </=5 each day and its trends over time and cohort/group. Organ-failure free days (all SOFA components </=2) and number of organ failures (SOFA components >2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB >/=0.5) to SOFA </=5 using conditional and joint probabilities. RESULTS: Admission and maximum SOFA scores were similar (P = 0.20; P = 0.76), with similar time to maximum (median: one day; IQR: 13 days; P = 0.99). Median length of stay was similar (4.1 days SPRINT and 3.8 days Pre-SPRINT; P = 0.94). The percentage of patients with SOFA </=5 is different over the first 14 days (P = 0.016), rising to approximately 75% for Pre-SPRINT and approximately 85% for SPRINT, with clear separation after two days. Organ-failure-free days were different (SPRINT = 41.6%; Pre-SPRINT = 36.5%; P < 0.0001) as were the percent of total possible organ failures (SPRINT = 16.0%; Pre-SPRINT = 19.0%; P < 0.0001). By Day 3 over 90% of SPRINT patients had cTIB >/=0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB >/=0.5) increased the likelihood SOFA </=5. CONCLUSIONS: SPRINT TGC resolved organ failure faster, and for more patients, from similar admission and maximum SOFA scores, than conventional control. These reductions mirror the reduced mortality with SPRINT. The cTIB >/=0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials. [less ▲]

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See detailWhat makes tight glycemic control tight? The impact of variability and nutrition in two clinical studies.
Suhaimi, Fatanah; Le Compte, Aaron; Preiser, Jean-Charles ULg et al

in Journal of Diabetes Science and Technology (2010), 4(2), 284-98

INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of ... [more ▼]

INTRODUCTION: Tight glycemic control (TGC) remains controversial while successful, consistent, and effective protocols remain elusive. This research analyzes data from two TGC trials for root causes of the differences achieved in control and thus potentially in glycemic and other outcomes. The goal is to uncover aspects of successful TGC and delineate the impact of differences in cohorts. METHODS: A retrospective analysis was conducted using records from a 211-patient subset of the GluControl trial taken in Liege, Belgium, and 393 patients from Specialized Relative Insulin Nutrition Titration (SPRINT) in New Zealand. Specialized Relative Insulin Nutrition Titration targeted 4.0-6.0 mmol/liter, similar to the GluControl A (N = 142) target of 4.4-6.1 mmol/liter. The GluControl B (N = 69) target was 7.8-10.0 mmol/liter. Cohorts were matched by Acute Physiology and Chronic Health Evaluation II score and percentage males (p > .35); however, the GluControl cohort was slightly older (p = .011). Overall cohort and per-patient comparisons (median, interquartile range) are shown for (a) glycemic levels achieved, (b) nutrition from carbohydrate (all sources), and (c) insulin dosing for this analysis. Intra- and interpatient variability were examined using clinically validated model-based insulin sensitivity metric and its hour-to-hour variation. RESULTS: Cohort blood glucose were as follows: SPRINT, 5.7 (5.0-6.6) mmol/liter; GluControl A, 6.3 (5.3-7.6) mmol/liter; and GluControl B, 8.2 (6.9-9.4) mmol/liter. Insulin dosing was 3.0 (1.0-3.0), 1.5 (0.5-3), and 0.7 (0.0-1.7) U/h, respectively. Nutrition from carbohydrate (all sources) was 435.5 (259.2-539.1), 311.0 (0.0-933.1), and 622.1 (103.7-1036.8) kcal/day, respectively. Median per-patient results for blood glucose were 5.8 (5.3-6.4), 6.4 (5.9-6.9), and 8.3 (7.6-8.8) mmol/liter. Insulin doses were 3.0 (2.0-3.0), 1.5 (0.8-2.0), and 0.5 (0.0-1.0) U/h. Carbohydrate administration was 383.6 (207.4-497.7), 103.7 (0.0-829.4), and 207.4 (0.0-725.8) kcal/day. Overall, SPRINT gave approximately 2x more insulin with a 3-4x narrower, but generally non-zero, range of nutritional input to achieve equally TGC with less hypoglycemia. Specialized Relative Insulin Nutrition Titration had much less hypoglycemia (<2.2 mmol/liter), with 2% of patients, compared to GluControl A (7.7%) and GluControl B (2.9%), indicating much lower variability, with similar results for glucose levels <3.0 mmol/liter. Specialized Relative Insulin Nutrition Titration also had less hyperglycemia (>8.0 mmol/liter) than groups A and B. GluControl patients (A+B) had a approximately 2x wider range of insulin sensitivity than SPRINT. Hour-to-hour variation was similar. Hence GluControl had greater interpatient variability but similar intrapatient variability. CONCLUSION: Protocols that dose insulin blind to carbohydrate administration can suffer greater outcome glycemic variability, even if average cohort glycemic targets are met. While the cohorts varied significantly in model-assessed insulin resistance, their variability was similar. Such significant intra- and interpatient variability is a further significant cause and marker of glycemic variability in TGC. The results strongly recommended that TGC protocols be explicitly designed to account for significant intra- and interpatient variability in insulin resistance, as well as specifying or having knowledge of carbohydrate administration to minimize variability in glycemic outcomes across diverse cohorts and/or centers. [less ▲]

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See detailValidation of a model-based virtual trials method for tight glycemic control in intensive care.
Chase, J Geoffrey; Suhaimi, Fatanah; Penning, Sophie ULg et al

in BioMedical Engineering OnLine (2010), 9

BACKGROUND: In-silico virtual patients and trials offer significant advantages in cost, time and safety for designing effective tight glycemic control (TGC) protocols. However, no such method has fully ... [more ▼]

BACKGROUND: In-silico virtual patients and trials offer significant advantages in cost, time and safety for designing effective tight glycemic control (TGC) protocols. However, no such method has fully validated the independence of virtual patients (or resulting clinical trial predictions) from the data used to create them. This study uses matched cohorts from a TGC clinical trial to validate virtual patients and in-silico virtual trial models and methods. METHODS: Data from a 211 patient subset of the Glucontrol trial in Liege, Belgium. Glucontrol-A (N = 142) targeted 4.4-6.1 mmol/L and Glucontrol-B (N = 69) targeted 7.8-10.0 mmol/L. Cohorts were matched by APACHE II score, initial BG, age, weight, BMI and sex (p > 0.25). Virtual patients are created by fitting a clinically validated model to clinical data, yielding time varying insulin sensitivity profiles (SI(t)) that drives in-silico patients.Model fit and intra-patient (forward) prediction errors are used to validate individual in-silico virtual patients. Self-validation (tests A protocol on Group-A virtual patients; and B protocol on B virtual patients) and cross-validation (tests A protocol on Group-B virtual patients; and B protocol on A virtual patients) are used in comparison to clinical data to assess ability to predict clinical trial results. RESULTS: Model fit errors were small (<0.25%) for all patients, indicating model fitness. Median forward prediction errors were: 4.3, 2.8 and 3.5% for Group-A, Group-B and Overall (A+B), indicating individual virtual patients were accurate representations of real patients. SI and its variability were similar between cohorts indicating they were metabolically similar.Self and cross validation results were within 1-10% of the clinical data for both Group-A and Group-B. Self-validation indicated clinically insignificant errors due to model and/or clinical compliance. Cross-validation clearly showed that virtual patients enabled by identified patient-specific SI(t) profiles can accurately predict the performance of independent and different TGC protocols. CONCLUSIONS: This study fully validates these virtual patients and in silico virtual trial methods, and clearly shows they can accurately simulate, in advance, the clinical results of a TGC protocol, enabling rapid in silico protocol design and optimization. These outcomes provide the first rigorous validation of a virtual in-silico patient and virtual trials methodology. [less ▲]

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