A Retrospective Within-Subjects Analysis of Vancomycin Bayesian Modeling With Pre-steady-State vs Steady-State Concentrations

采用预稳态浓度与稳态浓度对万古霉素贝叶斯模型进行回顾性受试者内分析

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Abstract

Background: Bayesian modeling of vancomycin can estimate 24-hour area under the curve (AUC(24)) using pre-steady-state concentrations. Limited literature exists comparing Bayesian AUC(24) calculations derived from steady-state versus pre-steady-state concentrations. Objective: To assess the agreement between vancomycin AUC(24) calculations using pre-steady-state versus steady-state concentrations, employing Bayesian modeling. Methods: This retrospective within-subjects cohort study included patients with at least 1 pre-steady-state and 1 steady-state vancomycin concentration. Patients with age >100 years, weight <40 kg, height <60 inches, or renal dysfunction were excluded. The steady-state AUC(24) from dosing software was documented with and without hiding steady-state levels from calculations. The primary outcome was agreement between AUC(24) without levels hidden compared with AUC(24) with steady-state levels hidden from analysis. Secondary outcomes included the agreement between AUC(24) with pre-steady-state levels hidden and the percentage of patients with matching AUC(24) categories. The AUC(24) agreement was evaluated via Bland-Altman plot and bias via linear regression. Statistical tests were performed using SPSS statistics software (IBM Corp). Results: A total of 93 patients were included. The mean difference in AUC(24) compared to AUC(24) with steady-state levels hidden was 8.8 mg*h/L, and with pre-steady-state levels hidden, it was -3.7 mg*h/L. Linear regression analysis indicated a proportional bias when steady-state levels were hidden (β = 0.22; P = 0.038) but not when pre-steady-state levels were hidden. Category mismatch occurred more often when steady-state levels were hidden vs when pre-steady-state levels were hidden (26% vs 8%; P < 0.001). Conclusion and Relevance: The study demonstrated overall agreement between AUC(24) compared to AUC(24) with steady-state levels hidden. The mean differences in AUC(24) estimates were small, no matter which level was hidden, although tighter limits of agreement were observed when steady-state levels were utilized in Bayesian calculations. Further research with larger sample sizes is necessary.

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