1,721,017 research outputs found
Approximate linear confidence and curvature of a kinetic model of dodecanedioic acid in humans
No full textDicarboxylic acids with an even number of carbon atoms have been proposed as an alternate energy substrate for enteral or parenteral nutrition in the acutely ill patient, due to their water solubility and their yielding TCA cycle intermediates upon beta-oxidation. In the present work, a nonlinear compartmental model of the kinetics of dodecanedioic acid is developed, and its parameters are estimated from time concentration experimental observations obtained from six healthy volunteers undergoing a per os administration of 3 g of the substance. Although the model is linear in the transfer of the free substance from plasma to the tissues, the exchange between gut and plasma compartments is represented as a saturable function. Albumin binding is then incorporated to obtain the final model in terms of the measured total concentrations. Estimates of the model's structural parameters were computed for each experimental subject, and the usual single-subject approximate confidence regions for the parameters were derived by inversion of the Hessian at the optimum. To verify the applicability of this approximation, the nonlinearity of the expectation surface at the optimum was measured by computing the normal (intrinsic) component of curvature. Because the model curvature was excessive in all subjects, the usual approximation could not be trusted to provide acceptable approximations to the parameter confidence regions. A suitable Monte Carlo simulation yielded empirical joint parameter distributions from which the approximate parameter variances could finally be obtaine
Consistency of compact and extended models of glucose-insulin homeostasis: The role of variable pancreatic reserve
Full text linkPublished compact and extended models of the glucose-insulin physiologic control system are compared, in order to understand why a specific functional form of the compact model proved to be necessary for a satisfactory representation of acute perturbation experiments such as the Intra Venous Glucose Tolerance Test (IVGTT). A spectrum of IVGTT’s of virtual subjects ranging from normal to IFG to IGT to frank T2DM were simulated using an extended model incorporating the population-of-controllers paradigm originally hypothesized by Grodsky, and proven to be able to capture a wide array of experimental results from heterogeneous perturbation procedures. The simulated IVGTT’s were then fitted with the Single-Delay Model (SDM), a compact model with only six free parameters, previously shown to be very effective in delivering precise estimates of insulin sensitivity and secretion during an IVGTT. Comparison of the generating, extended-model parameter values with the obtained compact model estimates shows that the functional form of the nonlinear insulin-secretion term, empirically found to be necessary for the compact model to satisfactorily fit clinical observations, captures the pancreatic reserve level of the simulated virtual patients. This result supports the validity of the compact model as a meaningful analysis tool for the clinical assessment of insulin sensitivity
Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test
Full text linkThe Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative
Empirical Modeling of Cerebral AutoRegulation
No full textMathematical models of the cardiovascular system and of Cerebral AutoRegulation have been employed for several years in order to describe the time course of pressures and flows changes subsequent to postural changes. The assessment of the degree of efficiency of Cerebral AutoRegulation has indeed importance in the prognosis of such conditions as cerebro-vascular accidents or Alzheimer. In the quest for a simple, but realistic mathematical description of cardiovascular control, which may be fitted onto noninvasive experimental observations after postural changes, the present work proposes a first version of a Stochastic Delay Differential Equations (SDDEs) model. The model consists of a total of four SDDEs and two ancillary algebraic equations, incorporates four distinct delayed controls from the brain onto different components of the circulation, and is able to accurately capture the time course of mean arterial pressure and cerebral blood flow velocity signals, reproducing observed auto-correlated error around the expected drift
A unifying organ model of pancreatic insulin secretion
Full text linkThe secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic β-cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 10 minutes) and low-frequency oscillations (period approx. 1.5 hours). Furthermore, characteristic insulin secretory response to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation; substantial insulin peaks following minimal glucose administration; progressively strengthened insulin secretion response after repeated administration of the same amount of glucose; insulin and glucose characteristic curves after Intra-Venous administration of glucose boli in healthy and prediabetic subjects as well as in Type 2 Diabetes Mellitus. Previous modeling of β-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Starting with the seminal work of Grodsky it was hypothesized that the population of pancreatic β-cells, possibly functionally aggregated in islets of Langerhans, could be viewed as a set of independent, similar, but not identical controllers (firing units) with distributed functional parameters. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters. The model's success in reproducing a diverse array of experiments implies that, in order to understand the macroscopic behaviour of the endocrine pancreas in regulating glycemia, there is no need to hypothesize intrapancreatic pacemakers, influences between different islets of Langerhans, glycolitic-induced oscillations or β-cell sensitivity to the rate of change of glycemia
Sampled-data Observer-based Glucose Control for the Artificial Pancreas
Full text linkArtificial Pancreas (AP) is an expression referred to a set of techniques for the closed-loop control of the plasma glucose concentration by means of exogenous insulin administration in diabetic patients. Diabetes comprises a group of metabolic disorders characterized by high blood sugar levels over a prolonged period, due to pancreas failure to produce enough insulin and/or insulin resistance, so that higher amounts of insulin are usually required in order to keep glycemia in a safe range. In this work, we face the problem of glucose control for a class of Type-2 diabetic patients, in the presence of sampled glucose measurements and without any information about the time course of insulinemia. A compact physiological model of the glucose-insulin system is reviewed, then an observer (based on this model) is designed to estimate the insulin trajectory from the glucose samples. Finally, a feedback control law (based on the reconstructed state) is designed to deliver exogenous intra-venous insulin to each individual. Simulations have been performed in-silico on models of virtual patients, whose parameters are tuned according to real data, and aim at validating the method in the presence of parameter variations and quantization errors
An economic evaluation of Clostridium difficile infection management in an Italian hospital environment
No full textClostridium difficile infection (CDI) accounts for the majority of nosocomial cases of diarrhea, and with recent upsurge of multidrug-resistant strains, morbidity and mortality have increased. Data on clinical impact of CDI come mostly from Anglo-Saxon countries, while in Italy only two studies address the issue and no economic data exist on costs of CDI in the in hospital setting. A retrospective cross-sectional study with pharmacoeconomic analysis was performed on the CDI series of the Policlinico Gemelli of Rome, a major 1400 bed Hospital
A geometrical approach to the PKPD modelling of inhaled bronchodilators
No full textThe present work introduces a new method to model the pharmacokinetics and pharmacodynamics (PKPD) of an inhaled dose of bronchodilator. This method provides an alternative approach to classic compartmental representations or computational fluid dynamics.
A five compartment lung model comprising the upper airways, bronchial tree mucosa, bronchial muscles, alveoli and plasma has been modified to take into account anatomical, geometrical features such as bronchial branching and smooth muscle distribution. Many anatomical and physiological features of the bronchial tree depend, as a first approximation, on bronchial generation or on mean distance from the larynx. Among these are diameters, resistances, and receptor density, which work together in determining the local response to the inhaled dose; integrating these local responses over the whole bronchial tree allows an approximation of total broncodilator response, particularly with respect to airflow resistance.
While the PK part of the model reflects classical compartmental assumptions, the PD part substitutes a simplified geometrical and functional description of the bronchial tree for the typical PD models of effect, leading to the direct computation of the approximate FEV1.
In the present work the construction of the model is detailed, and literature data are used to derive the anatomical approximations used. Simulation of two asthmatic subjects is employed to illustrate the behaviour of the model in representing the evolution over time of the distribution and effect of an inhaled dose of bronchodilator. The relevance of formulation diffusivity on therapeutic efficacy is discussed and conclusions regarding the applicability of the model in interpreting single-subject and population experiments are drawn
Observational study on preoperative surgical field disinfection: Povidone-iodine and Chlorhexidine-alcohol.
No full textAbstract
BACKGROUND AND OBJECTIVES:
Surgical site infection (SSI) rate is reported to range around 16%. Preoperative skin disinfection is keystone for SSI reduction. Chlorhexidine-alcohol has been reported to be more effective than Povidone-iodine (PVI). However, in many countries established habits and the inferior costs of PVI restrain the employment of chlorhexidine disinfection kits (ChloraPrep®) for the preparation of the surgical field.
MATERIALS AND METHODS:
The costs of surgical field preparation in clean-contaminated surgery utilizing PVI (Betadine) and chlorhexidine alcohol and the evaluation of surgeon compliance and satisfaction, were studied by a observational study on 50 surgical operations in which surgical field was prepared with PVI checking established guidelines, and on 50 surgical operations in which chlorhexidine-alcohol (ChloraPrep) was employed. The use of auxiliary material was tabulated as well as the timing of the phases of disinfection and the surgeon's opinions.
RESULTS:
The use of auxiliary material (gloves, gauzes, paper towels, surgical instruments, small swabs for umbilical cleaning) is associated with the type of disinfectant, with major use of auxiliary materials recorded in PVI disinfection. PVI disinfection does not follow stringent guidelines, in particular waiting for the disinfectant to dry. PVI guidelines are more demanding than those relative to ChloraPrep. The time necessary for the preparation of the field is significantly longer for PVI. Auxiliary material and guideline compliance must be taken into account when calculating costs; the former are direct costs (even though marginal) and the latter can determine major infective risk.
CONCLUSIONS:
Chlorhexidine in kits is easier and faster to use than PVI, requires less auxiliary material and has been shown previously to reduce SSI in clean contaminated surger
Simulation of Trauma Incidents: Modelling the Evolution of Patients and Resources
No full textMathematical modeling and simulation with medical applications has gained much interest in the last few years, mainly due to the widespread availability of low-cost technology and computational power. This paper presents an integrated platform for the in-silico simulation of trauma incidents, based on a suite of interacting mathematical models. The models cover the generation of a scenario for an incident, a model of physiological evolution of the affected individuals, including the possible effect of the treatment, and a model of evolution in time of the required medical resources. The problem of optimal resource allocation is also investigated. Model parameters have been identified according to the expertise of medical doctors and by reviewing some related literature. The models have been implemented and exposed as web services, while some software clients have been built for the purpose of testing. Due to its extendability, our integrated platform highlights the potential of model-based simulation in different health-related fields, such as emergency medicine and personal health systems. Modifications of the models are already being used in the context of two funded projects, aiming at evaluating the response of health systems to major incidents with and without model-based decision support
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