References of "Penning, Sophie"
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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

Poster (2011, March)

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

Poster (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 detailSafety and Performance of Stochastic Targeted (STAR) TGC of Insulin and Nutrition
Shaw, GM; Le Compte, Aaron; Evans, A et al

in Proceedings of SQAO 2011 (2011)

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See detailPilot Trials of STAR Target to Range Glycemic Control
Penning, Sophie ULg; Le Compte, Aaron; Massion, Paul 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

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 Trials of STAR Target to Range Glycemic Control
Penning, Sophie ULg; Le Compte, Aaron; Massion, Paul et al

Poster (2011)

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See detailGlycemic Variability, Hypoglycemia and Organ Failure in the Glucontrol Study
Penning, Sophie ULg; Le Compte, Aaron J.; Preiser, Jean-Charles et al

in 10th Belgian Day on Biomedical Engineering (2011)

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See detailTight Glycemic Control in Intensive Care: From engineering to clinical practice change
Chase, J. G.; Le Compte, A. J.; Evans, A. et al

in 5th European Conference of the International Federation for Medical and Biological Engineering (2011)

Tight glycemic control (TGC) is prevalent in critical care. Providing safe, effective TGC has proven very difficult to achieve with clinically derived protocols. The prob-lem is exacerbated by extreme ... [more ▼]

Tight glycemic control (TGC) is prevalent in critical care. Providing safe, effective TGC has proven very difficult to achieve with clinically derived protocols. The prob-lem is exacerbated by extreme patient variability and the need to minimize clinical effort and burden. These ingredients make an ideal scenario for model-based methods to provide opti-mised solutions. This paper presents the development, clinical-ly validated virtual trials optimisation, and initial clinical implementation of a stochastic targeted (STAR) TGC method and framework. It is compared to a prior successful, model-derived, less flexible and dynamic TGC protocol (SPRINT). The use of stochastic models to safely forecast a range of glu-cose outcomes over 1-3 hours ensures better performance, more dynamic use of the range of insulin and nutrition inputs and thus better glycemic performance and safety from hypo-glycemia, the latter of which was reduced by 3.0x times. Hence, the paper presents an overall engineering approach to TGC from engineering models to clinical implementation and ongo-ing clinical practice change. [less ▲]

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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 detailFirst pilot trial of the STAR-Liege protocol for tight glycemic control in critically ill patients
Penning, Sophie ULg; Le Compte, Aaron J.; Moorhead, Katherine T. et al

in Computer Methods & Programs in Biomedicine (2011)

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See detailPhysiological modeling, tight glycemic control, and the ICU clinician: what are models and how can they affect practice?
Chase, J. Geoffrey; Le Compte, Aaron J.; Preiser, Jean-Charles et al

in Annals of Intensive Care (2011), 1:11

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See detailTight Glycemic Control Models for Critically Ill Patients in Intensive Care Units
Penning, Sophie ULg; Le Compte, Aaron; Desaive, Thomas ULg et al

Poster (2010, November 26)

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See detailTight Glycemic Control Models for Critically Ill Patients in Intensive Care Units
Penning, Sophie ULg; Le Compte, Aaron; Moorhead, Katherine ULg et al

in 9th Belgian Day on Biomedical Engineering, "Bridging the gap between medicine and engineering', Friday November 26th 2010 in the Academy Palace, Hertogstraat 1, 1000 Brussels (2010, November 26)

Critically ill patients often present stress-induced hyperglycemia and low insulin sensitivity. Recent studies have shown that high blood glucose (BG) levels are linked to worsened patient outcomes and ... [more ▼]

Critically ill patients often present stress-induced hyperglycemia and low insulin sensitivity. Recent studies have shown that high blood glucose (BG) levels are linked to worsened patient outcomes and increased mortality. Tight glycemic control (TGC) aims at reducing BG levels taking into account inter-patient variability, evolving physiological patient conditions and minimizing hypoglycemic risks. Clinical protocols are used to specify insulin and nutrition rates and BG measurement time interval during control. This research compares different protocols to determine the best one to use at the CHU of Liege. [less ▲]

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See detailPilot Trials of the STAR TGC Protocol in a Cardiac Surgery ICU
LeCompte, Aaron J.; Penning, Sophie ULg; Moorhead, Katherine ULg et al

in Proceedings of the 10th Annual Diabetes Technology Meeting (2010, November)

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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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