Dataset Information

Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients.

ABSTRACT:

Purpose

Bayesian forecasting is crucial for model-based dose optimization based on therapeutic drug monitoring (TDM) data of vancomycin in intensive care (ICU) patients. We aimed to evaluate the performance of Bayesian forecasting using maximum a posteriori (MAP) estimation for model-based TDM.

Methods

We used a vancomycin TDM data set (n?=?408 patients). We compared standard MAP-based Bayesian forecasting with two alternative approaches: (i) adaptive MAP which handles data over multiple iterations, and (ii) weighted MAP which weights the likelihood contribution of data. We evaluated the percentage error (PE) for seven scenarios including historical TDM data from the preceding day up to seven days.

Results

The mean of median PEs of all scenarios for the standard MAP, adaptive MAP and weighted MAP method were?-?7.7%, -4.5% and?-?6.7%. The adaptive MAP also showed the narrowest inter-quartile range of PE. In addition, regardless of MAP method, including historical TDM data further in the past will increase prediction errors.

Conclusions

The proposed adaptive MAP method outperforms standard MAP in predictive performance and may be considered for improvement of model-based dose optimization. The inclusion of historical data beyond either one day (standard MAP and weighted MAP) or two days (adaptive MAP) reduces predictive performance.

SUBMITTER: Guo T

PROVIDER: S-EPMC7443423 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients.

Guo Tingjie T van Hest Reinier M RM Zwep Laura B LB Roggeveen Luca F LF Fleuren Lucas M LM Bosman Rob J RJ van der Voort Peter H J PHJ Girbes Armand R J ARJ Mathot Ron A A RAA Elbers Paul W G PWG van Hasselt Johan G C JGC

Pharmaceutical research 20200823 9

<h4>Purpose</h4>Bayesian forecasting is crucial for model-based dose optimization based on therapeutic drug monitoring (TDM) data of vancomycin in intensive care (ICU) patients. We aimed to evaluate the performance of Bayesian forecasting using maximum a posteriori (MAP) estimation for model-based TDM.<h4>Methods</h4>We used a vancomycin TDM data set (n = 408 patients). We compared standard MAP-based Bayesian forecasting with two alternative approaches: (i) adaptive MAP which handles data over m ...[more]

PMID: 32830297

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Project description:IntroductionThe pharmacokinetics of vancomycin are highly variable among neonates, which makes dosing challenging in this population. However, adequate drug exposure is critical, especially when treating methicillin-resistant Staphylococcus aureus (MRSA) infections. Utilization of population pharmacokinetic models and Bayesian methods offers the potential for developing individualized therapeutic approaches. To meet this need, a neonatal vancomycin population pharmacokinetic model was recently published. The current study sought to externally evaluate the predictive performance and generalizability of this model.MethodsA retrospective chart review of neonates who received vancomycin and had ≥1 peak and ≥1 trough concentrations at five Intermountain Healthcare neonatal intensive care units from 2006 to 2013 was performed and served as the external validation cohort. The published population pharmacokinetic model was implemented in NONMEM 7.2 with the structural and variance parameter values set equal to the estimates reported previously. The model was then used to predict the first peak and trough concentration for each neonate in the validation cohort and the model prediction error and absolute prediction error were calculated. Normalized prediction distribution errors (NPDE) were also evaluated.ResultsA total of 243 neonates were studied with a median postmenstrual age of 33 (range: 23-54) weeks and a median weight of 1.6 (range: 0.4-6.8) kg. The model predicted the observed vancomycin concentrations with reasonable precision. For all vancomycin concentrations, the median prediction error was -0.8 (95% CI: -1.4 to -0.4) mg/L and the median absolute prediction error was 3.0 (95% CI: 2.7-3.5) mg/L. No trends in NPDE across weight, postmenstrual age, serum creatinine, or time after dose were observed.ConclusionAn evaluation of a recently published neonatal vancomycin population pharmacokinetic model in a large external dataset supported the predictive performance and generalizability of the model. This model may be useful in evaluating neonatal vancomycin dosing regimens and estimating the extent of drug exposure.

Project description:IntroductionEffective planning of elective surgical procedures requiring postoperative intensive care is important in preventing cancellations and empty intensive care unit (ICU) beds. To improve planning, we constructed, validated and tested three models designed to predict length of stay (LOS) in the ICU in individual patients.MethodsRetrospective data were collected from 518 consecutive patients who underwent oesophagectomy with reconstruction for carcinoma between January 1997 and April 2005. Three multivariable linear regression models for LOS, namely preoperative, postoperative and intra-ICU, were constructed using these data. Internal validation was assessed using bootstrap sampling in order to obtain validated estimates of the explained variance (r2). To determine the potential gain of the best performing model in day-to-day clinical practice, prospective data from a second cohort of 65 consecutive patients undergoing oesophagectomy between May 2005 and April 2006 were used in the model, and the predictive performance of the model was compared with prediction based on mean LOS.ResultsThe intra-ICU model had an r2 of 45% after internal validation. Important prognostic variables for LOS included greater patient age, comorbidity, type of surgical approach, intraoperative respiratory minute volume and complications occurring within 72 hours in the ICU. The potential gain of the best model in day-to-day clinical practice was determined relative to mean LOS. Use of the model reduced the deficit number (underestimation) of ICU days by 65 and increased the excess number (overestimation) of ICU days by 23 for the cohort of 65 patients. A conservative analysis conducted in the second, prospective cohort of patients revealed that 7% more oesophagectomies could have been accommodated, and 15% of cancelled procedures could have been prevented.ConclusionPatient characteristics can be used to create models that will help in predicting LOS in the ICU. This will result in more efficient use of ICU beds and fewer cancellations.

Dataset Information

Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients.

Purpose

Methods

Results

Conclusions

Publications

Optimizing Predictive Performance of Bayesian Forecasting for Vancomycin Concentration in Intensive Care Patients.

Similar Datasets

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