Model-Based Prediction of the Patient-Specific Response to Adrenaline

A model for the cardiovascular and circulatory systems has previously been validated in simulated cardiac and circulatory disease states. It has also been shown to accurately capture the main hemodynamic trends in porcine models of pulmonary embolism and PEEP (positive end-expiratory pressure) titrations at different volemic levels. In this research, the existing model and parameter identification process are used to study the effect of different adrenaline doses in healthy and critically ill patient populations, and to develop a means of predicting the hemodynamic response to adrenaline. The hemodynamic effects on arterial blood pressures and stroke volume (cardiac index) are simulated in the model and adrenaline-specific parameters are identified. The dose dependent changes in these parameters are then related to adrenaline dose using data from studies published in the literature. These relationships are then used to predict the future, patient-specific response to a change in dose or over time periods from 1-12 hours. The results are compared to data from 3 published adrenaline dosing studies comprising a total of 37 data sets. Absolute percentage errors for the identified model are within 10% when re-simulated and compared to clinical data for all cases. All identified parameter trends match clinically expected changes. Absolute percentage errors for the predicted hemodynamic responses (N=15) are also within 10% when re-simulated and compared to clinical data. Clinically accurate prediction of the effect of inotropic circulatory support drugs, such as adrenaline, offers significant potential for this type of model-based application. Overall, this work represents a further clinical, proof of concept, of the underlying fundamental mathematical model, methods and approach, as well as providing a template for using the model in clinical titration of adrenaline in a decision support role in critical care. They are thus a further justification in support of upcoming human clinical trials to validate this model

Pilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control

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) /=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

Evaluation of a Model-Based Hemodynamic Monitoring Method in a Porcine Study of Septic Shock

Introduction. The accuracy and clinical applicability of an improved model-based system for tracking hemodynamic changes is assessed in an animal study on septic shock. Methods. This study used cardiovascular measurements recorded during a porcine trial studying the efficacy of large-pore hemofiltration for treating septic shock. Four Pietrain pigs were instrumented and induced with septic shock. A subset of the measured data, representing clinically available measurements, was used to identify subjectspecific cardiovascular models. These models were then validated against the remaining measurements. Results. The system accurately matched independent measures of left and right ventricle end diastolic volumes and maximum left and right ventricular pressures to percentage errors less than 20% (except for the 95th percentile error in maximum right ventricular pressure) and all 2 &gt; 0.76. An average decrease of 42% in systemic resistance, a main cardiovascular consequence of septic shock, was observed 120 minutes after the infusion of the endotoxin, consistent with experimentally measured trends. Moreover, modelled temporal trends in right ventricular end systolic elastance and afterload tracked changes in corresponding experimentally derived metrics. Conclusions. These results demonstrate that this model-based method can monitor disease-dependent changes in preload, afterload, and contractility in porcine study of septic shock

Evaluation of a Model-Based Hemodynamic Monitoring Method in a Porcine Study of Septic Shock

Introduction. The accuracy and clinical applicability of an improved model-based system for tracking hemodynamic changes is assessed in an animal study on septic shock. Methods. This study used cardiovascular measurements recorded during a porcine trial studying the efficacy of large-pore hemofiltration for treating septic shock. Four Pietrain pigs were instrumented and induced with septic shock. A subset of the measured data, representing clinically available measurements, was used to identify subjectspecific cardiovascular models. These models were then validated against the remaining measurements. Results. The system accurately matched independent measures of left and right ventricle end diastolic volumes and maximum left and right ventricular pressures to percentage errors less than 20% (except for the 95th percentile error in maximum right ventricular pressure) and all 2 &gt; 0.76. An average decrease of 42% in systemic resistance, a main cardiovascular consequence of septic shock, was observed 120 minutes after the infusion of the endotoxin, consistent with experimentally measured trends. Moreover, modelled temporal trends in right ventricular end systolic elastance and afterload tracked changes in corresponding experimentally derived metrics. Conclusions. These results demonstrate that this model-based method can monitor disease-dependent changes in preload, afterload, and contractility in porcine study of septic shock

Model-based glycemic control in a Malaysian intensive care unit: performance and safety study

Background: Stress-induced hyperglycemia is common in critically ill patients. A few forms of model-based glycemic control have been introduced to reduce this phenomena and among them is the automated STAR protocol which has been used in the Christchurch and Gyulá hospitals’ intensive care units (ICUs) since 2010. Methods: This article presents the pilot trial assessment of STAR protocol which has been implemented in the International Islamic University Malaysia Medical Centre (IIUMMC) Hospital ICU since December 2017. One hundred and forty-two patients who received STAR treatment for more than 20 hours were used in the assessment. The initial results are presented to discuss the ability to adopt and adapt the model-based control framework in a Malaysian environment by analyzing its performance and safety. Results: Overall, 60.7% of blood glucose measurements were in the target band. Only 0.78% and 0.02% of cohort measurements were below 4.0 mmol/L and 2.2 mmol/L (the limitsfor mild and severe hypoglycemia, respectively). Treatment preference-wise, the clinical staff were favorable of longer intervention options when available. However, 1 hourly treatments were still used in 73.7% of cases. Conclusion: The protocol succeeded in achieving patient-specific glycemic control while maintaining safety and was trusted by nurses to reduce workload. Its lower performance results, however, give the indication for modification in some of the control settings to better fit the Malaysian environment. © 2019 Abu-Samah et al

Proceedings of the Sixth International Workshop on Web Caching and Content Distribution

OVERVIEW The International Web Content Caching and Distribution Workshop (WCW) is a premiere technical meeting for researchers and practitioners interested in all aspects of content caching, distribution and delivery on the Internet. The 2001 WCW meeting was held on the Boston University Campus. Building on the successes of the five previous WCW meetings, WCW01 featured a strong technical program and record participation from leading researchers and practitioners in the field. This report includes all the technical papers presented at WCW'01. Note: Proceedings of WCW'01 are published by Elsevier. Hardcopies of these proceedings can be purchased through the workshop organizers. As a service to the community, electronic copies of all WCW'01 papers are accessible through Technical Report BUCS‐TR‐2001‐017, available from the Boston University Computer Science Technical Report Archives at http://www.cs.bu.edu/techreps. [Ed.note: URL outdated. Use http://www.bu.edu/cs/research/technical-reports/ or http://hdl.handle.net/2144/1455 in this repository to access the reports.]Cisco Systems; InfoLibria; Measurement Factory Inc; Voler

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements