WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Despite the frequent use of vancomycin in intensive care unit (ICU) patients, few studies aimed at characterizing vancomycin population pharmacokinetics have been performed in this critical population. • Population pharmacokinetics coupled with pharmacodynamic analysis, in order to optimize drug exposure and hence antibacterial effectiveness, has been little applied in these specific patients. WHAT THIS STUDY ADDS • Our population model characterized the pharmacokinetic profile of vancomycin in adult ICU patients, higher distribution volume values (V) being observed when the patient's serum creatinine (CrSe) was greater than 1 mg dl−1. • Age and creatinine clearance (CLcr) were identified as the main covariates explaining the pharmacokinetic variability in vancomycin CL. • Our pharmacokinetic/pharmacodynamic (PK/PD) simulation should aid clinicians to select initial vancomycin doses that will maximize the rate of response in the ICU setting, taking into account the patient's age and renal function as well as the susceptibility of Staphylococcus aureus. AIM To estimate the vancomycin pharmacokinetic profile in adult ICU patients and to assess vancomycin dosages for increasing the likelihood of optimal exposure. METHODS Five hundred and sixty‐nine concentration–time data from 191 patients were analysed using a population pharmacokinetic approach (NONMEN™). External model evaluation was made in 46 additional patients. The 24 h area under the concentration–time curve (AUC(0,24 h)) was derived from the final model. Minimum inhibitory concentration (MIC) values for S. aureus were obtained from the EUCAST database. AUC(0,24 h) : MIC ≥ 400 was considered as PK/PD efficacy index. The probability of different dosages attaining the target considering different strains of S. aureus and patient subgroups was estimated with Monte Carlo simulation. RESULTS Vancomycin CL showed a significant dependence on patient age and renal function whereas CrSe > 1 mg dl−1 increased V more than twofold. For our representative ICU patient, 61 years, 73 kg, CrSe= 1.4 mg dl−1, measured CLCr= 74.7 ml min−1, the estimated values were CL = 1.06 ml min−1 kg−1 and V= 2.04 l kg−1. The cumulative fraction of response for a standard vancomycin dose (2 g day−1) was less than 25% for VISA strains, and 33% to 95% for susceptible S. aureus, depending on patient characteristics. CONCLUSIONS Simulations provide useful information regarding the initial assessment of vancomycin dosing, the conventional dosing regimen probably being suboptimal in adult ICU patients. A graphic approach provides the recommended dose for any selected probability of attaining the PK/PD efficacy target or to evaluate the cumulative fraction of response for any dosing regimen in this population.
SummaryObjectives: This paper addresses the problem of decision-making in relation to the administration of noninvasive mechanical ventila tion (NIMV) in intensive care units. Methods: Data mining methods were employed to find out the factors influencing the success/failure of NIMV and to predict its results in future patients. These artificial intelligence-based methods have not been applied in this field in spite of the good results obtained in other medical areas.Results: Feature selection methods provided the most influential variables in the success/ failure of NIMV, such as NIMV hours, PaCO 2 at the start, PaO 2 / FiO 2 ratio at the start, hematocrit at the start or PaO 2 / FiO 2 ratio after two hours. These methods were also used in the preprocessing step with the aim of improving the results of the classifiers. The algorithms provided the best results when the dataset used as input was the one containing the attributes selected with the CFS method. Conclusions: Data mining methods can be successfully applied to determine the most influential factors in the success/failure of NIMV and also to predict NIMV results in future patients. The results provided by classifiers can be improved by preprocessing the data with feature selection techniques.
This paper presents an ensemble based classification proposal for predicting neurological outcome of severely traumatized patients. The study comprises both the whole group of patients and a subgroup containing those patients suffering traumatic brain injury (TBI). Data was gathered from patients hospitalized in the Intensive Care Unit (ICU) of the University Hospital in Salamanca. Predictive models were induced from both epidemiologic and clinical variables taken at the emergency room and along the stay in the ICU. The large number of variables leads to a low accuracy in the classifiers even when feature selection methods are used. In addition, the presence of a much larger number of instances of one of the classes in the subgroup of TBI patients produces a significantly lesser precision for the minority class. Usual ways of dealing with the last problem is to use undersampling and oversampling strategies, which can lead to the loss of valuable data and overfitting problems respectively. Our proposal for dealing with these problems is based in the use of ensemble multiclassifiers as well as in the use of an ensemble playing the role of base classifier in multiclassifiers. The proposed strategy gave the best values of the selected quality measures (accuracy, precision, sensitivity, specificity, F-measure and area under the Receiver Operator Characteristic curve) as well as the closest values of precision for the two classes under study in the case of the classification from imbalanced data.
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