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.
Glucose management in intensive care unit (ICU) patients has been a matter of debate for almost two decades. Compared to intermittent monitoring systems, continuous glucose monitoring (CGM) can offer ...benefit in the prevention of severe hyperglycemia and hypoglycemia by enabling insulin infusions to be adjusted more rapidly and potentially more accurately because trends in glucose concentrations can be more readily identified. Increasingly, it is apparent that a single glucose target/range may not be optimal for all patients at all times and, as with many other aspects of critical care patient management, a personalized approach to glucose control may be more appropriate. Here we consider some of the evidence supporting different glucose targets in various groups of patients, focusing on those with and without diabetes and neurological ICU patients. We also discuss some of the reasons why, despite evidence of benefit, CGM devices are still not widely employed in the ICU and propose areas of research needed to help move CGM from the research arena to routine clinical use.
•Proposing a new identifiable hysteretic model with explicit physical parameters determined by hysteresis loop.•Extracting dynamic features for training SVM model to identify unknown ...parameters.•Combining SHM and SVM to automatically create a nonlinear model for response prediction.•Validating the method against a full scale 3-story real-world building structure with realistic nonlinear seismic response.•Extending SHM from a retrospective monitoring tool to a prospective tool in earthquake response and recovery.
Structural health monitoring (SHM) is backwards analysis of past to current state of damage, but cannot create a structure-specific nonlinear model for forward analysis of future response and damage. This paper aims to develop an automated modelling approach to translate proven hysteresis loop analysis (HLA) SHM results into nonlinear foundation models for response forecasting in subsequent events, particularly for steel structures with post-yielding behaviors. Support vector machine (SVM) is employed to identify the proposed nonlinear baseline model. Stiffness features are extracted from HLA to train the SVM model incorporating the constraints of SHM identification.
A proof-of-concept case study validates the ability of the proposed method to accurately identify 12 model parameters with average error of 2.8% for a nonlinear numerical structure in the presence of 10% RMS measurement noise. Experimental validation from a full-scale 3-storey real building shows the predicted nonlinear responses match the measured response well with cross correlation coefficients Rcoeff = 0.94, 0.92 and 0.89 for the first, second and third floor, respectively. In addition, the predicted stiffness changes also match the SHM results very well with errors less than 2.1%. Finally, and most importantly, the identified model is able to predict the response of 2 further events with average of correlation coefficient Rcoeff = 0.91 and average error of 1.9% for stiffness changes across all cases. The overall results validate the ability of the created predictive model to accurately capture the essential dynamics and structural degradation, as well as predicting future possible response and risk.
Respiratory mechanics models can aid in optimising patient-specific mechanical ventilation (MV), but the applications are limited to fully sedated MV patients who have little or no spontaneously ...breathing efforts. This research presents a time-varying elastance (E(drs)) model that can be used in spontaneously breathing patients to determine their respiratory mechanics.
A time-varying respiratory elastance model is developed with a negative elastic component (E(demand)), to describe the driving pressure generated during a patient initiated breathing cycle. Data from 22 patients who are partially mechanically ventilated using Pressure Support (PS) and Neurally Adjusted Ventilatory Assist (NAVA) are used to investigate the physiology relevance of the time-varying elastance model and its clinical potential. E(drs) of every breathing cycle for each patient at different ventilation modes are presented for comparison.
At the start of every breathing cycle initiated by patient, E(drs) is < 0. This negativity is attributed from the E(demand) due to a positive lung volume intake at through negative pressure in the lung compartment. The mapping of E(drs) trajectories was able to give unique information to patients' breathing variability under different ventilation modes. The area under the curve of E(drs) (AUCE(drs)) for most patients is > 25 cmH2Os/l and thus can be used as an acute respiratory distress syndrome (ARDS) severity indicator.
The E(drs) model captures unique dynamic respiratory mechanics for spontaneously breathing patients with respiratory failure. The model is fully general and is applicable to both fully controlled and partially assisted MV modes.
Purpose
Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to ...describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3).
Patients and methods
All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine.
Results
Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 49–68 years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 61–80. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 6.8–17.7 mg/L).
Conclusion
The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.
Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited.
We performed a prospective cohort study involving 528 neonates ...with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function.
Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval CI, 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome.
In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
Untangling glycaemia and mortality in critical care Uyttendaele, Vincent; Dickson, Jennifer L; Shaw, Geoffrey M ...
Critical care (London, England),
06/2017, Letnik:
21, Številka:
1
Journal Article, Web Resource
Recenzirano
Odprti dostop
Hyperglycaemia is associated with adverse outcomes in the intensive care unit, and initial studies suggested outcome benefits of glycaemic control (GC). However, subsequent studies often failed to ...replicate these results, and they were often unable to achieve consistent, safe control, raising questions about the benefit or harm of GC as well as the nature of the association of glycaemia with mortality and clinical outcomes. In this study, we evaluated if non-survivors are harder to control than survivors and determined if glycaemic outcome is a function of patient condition and eventual outcome or of the glycaemic control provided.
Clinically validated, model-based, hour-to-hour insulin sensitivity (SI) and its hour-to-hour variability (%ΔSI) were identified over the first 72 h of therapy in 145 patients (119 survivors, 26 non-survivors). In hypothesis testing, we compared distributions of SI and %ΔSI in 6-hourly blocks for survivors and non-survivors. In equivalence testing, we assessed if differences in these distributions, based on blood glucose measurement error, were clinically significant.
SI level was never equivalent between survivors and non-survivors (95% CI of percentage difference in medians outside ±12%). Non-survivors had higher SI, ranging from 9% to 47% higher overall in 6-h blocks, and this difference became statistically significant as glycaemic control progressed. %ΔSI was equivalent between survivors and non-survivors for all 6-hourly blocks (95% CI of difference in medians within ±12%) and decreased in general over time as glycaemic control progressed.
Whereas non-survivors had higher SI levels, variability was equivalent to that of survivors over the first 72 h. These results indicate survivors and non-survivors are equally controllable, given an effective glycaemic control protocol, suggesting that glycaemia level and variability, and thus the association between glycaemia and outcome, are essentially determined by the control provided rather than by underlying patient or metabolic condition.
Summary Background Neonatal hypoglycaemia is common, and a preventable cause of brain damage. Dextrose gel is used to reverse hypoglycaemia in individuals with diabetes; however, little evidence ...exists for its use in babies. We aimed to assess whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. Methods We undertook a randomised, double-blind, placebo-controlled trial at a tertiary centre in New Zealand between Dec 1, 2008, and Nov 31, 2010. Babies aged 35–42 weeks' gestation, younger than 48-h-old, and at risk of hypoglycaemia were randomly assigned (1:1), via computer-generated blocked randomisation, to 40% dextrose gel 200 mg/kg or placebo gel. Randomisation was stratified by maternal diabetes and birthweight. Group allocation was concealed from clinicians, families, and all study investigators. The primary outcome was treatment failure, defined as a blood glucose concentration of less than 2·6 mmol/L after two treatment attempts. Analysis was by intention to treat. The trial is registered with Australian New Zealand Clinical Trials Registry, number ACTRN12608000623392. Findings Of 514 enrolled babies, 242 (47%) became hypoglycaemic and were randomised. Five babies were randomised in error, leaving 237 for analysis: 118 (50%) in the dextrose group and 119 (50%) in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (16 14% vs 29 24%; relative risk 0·57, 95% CI 0·33–0·98; p=0·04). We noted no serious adverse events. Three (3%) babies in the placebo group each had one blood glucose concentration of 0·9 mmol/L. No other adverse events took place. Interpretation Treatment with dextrose gel is inexpensive and simple to administer. Dextrose gel should be considered for first-line treatment to manage hypoglycaemia in late preterm and term babies in the first 48 h after birth. Funding Waikato Medical Research Foundation, the Auckland Medical Research Foundation, the Maurice and Phyllis Paykel Trust, the Health Research Council of New Zealand, and the Rebecca Roberts Scholarship.
Abstract Intensive insulin therapy (IIT) and tight glycaemic control (TGC), particularly in intensive care unit (ICU), are the subjects of increasing and controversial debate in recent years. ...Model-based TGC has shown potential in delivering safe and tight glycaemic management, all the while limiting hypoglycaemia. A comprehensive, more physiologically relevant Intensive Control Insulin-Nutrition-Glucose (ICING) model is presented and validated using data from critically ill patients. Two existing glucose–insulin models are reviewed and formed the basis for the ICING model. Model limitations are discussed with respect to relevant physiology, pharmacodynamics and TGC practicality. Model identifiability issues are carefully considered for clinical settings. This article also contains significant reference to relevant physiology and clinical literature, as well as some references to the modeling efforts in this field. Identification of critical constant population parameters was performed in two stages, thus addressing model identifiability issues. Model predictive performance is the primary factor for optimizing population parameter values. The use of population values are necessary due to the limited clinical data available at the bedside in the clinical control scenario. Insulin sensitivity, S I , the only dynamic, time-varying parameter, is identified hourly for each individual. All population parameters are justified physiologically and with respect to values reported in the clinical literature. A parameter sensitivity study confirms the validity of limiting time-varying parameters to S I only, as well as the choices for the population parameters. The ICING model achieves median fitting error of <1% over data from 173 patients ( N = 42,941 h in total) who received insulin while in the ICU and stayed for ≥72 h. Most importantly, the median per-patient 1-h ahead prediction error is a very low 2.80% IQR 1.18, 6.41%. It is significant that the 75th percentile prediction error is within the lower bound of typical glucometer measurement errors of 7–12%. These results confirm that the ICING model is suitable for developing model-based insulin therapies, and capable of delivering real-time model-based TGC with a very tight prediction error range. Finally, the detailed examination and discussion of issues surrounding model-based TGC and existing glucose–insulin models render this article a mini-review of the state of model-based TGC in critical care.
Patient-specific spontaneous breathing effort (SB) is common in invasively mechanically ventilated (MV) adult patients, and especially common in preterm neonates who are not typically sedated. ...However, there is no proven, ethically feasible and non-invasive method to quantify SB effort in neonates, creating the potential for model-based measures. Lung mechanics and SB effort are segregated using a basis function model to identify passive lung mechanics, and an additional time-varying elastance model to identify patient-specific SB effort and asynchrony as negative and positive added elastances, respectively. Data from ten preterm neonates on standard MV care in the neonatal intensive care unit (NICU) are used to assess this model-based approach, using area under the curve (AUC) for positive (asynchrony) and negative (SB effort) time-varying elastance. Median interquartile-range (IQR) of passive pulmonary lung elastance was 3.82 2.09—5.80 cmH
2
O/ml. Median IQR AUC quantified SB effort was -0.32 -0.43—-0.12cmH
2
O/ml. AUC quantified asynchrony was 0.00 0.00—0.01cmH
2
O/ml, and affected 28% of the 25,287 total breaths. This proof of concept model-based approach provides a non-invasive, computationally straightforward, and thus clinically feasible means to quantify patient-specific spontaneous breathing effort and asynchrony.
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