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Busulfan (Bu) is a bifunctional alkylating agent that is widely used prior to hematopoietic stem cell transplantation (HSCT), in combination with other chemotherapeutic drugs. As of 2020, there is no population pharmacokinetic (pop PK) model for Bu in Chinese pediatric patients. A systemic external evaluation of eleven published pop PK models was conducted in Chinese HSCT pediatric patients. Forty pediatric patients were enrolled in this study, with a total of 183 blood concentrations. The relative prediction error (PE%), median PE% (MDPE), median absolute PE%, and percentage of PE% within ±20% (F20 ) and ±30% (F30 ) were calculated in prediction-based diagnostics. Simulation-based diagnostics were conducted through a prediction- and variability-corrected visual predictive check (pvcVPC) and the normalized prediction distribution error (NPDE). The relative individual prediction error (IPE%) was calculated using Bayesian forecasting with 1-3 concentration points. The one-compartment open linear pop PK model, which was built by Su-jin Rhee et al. (model H), incorporating patient's body surface area, age, dosing day, and aspartate aminotransferase as significant covariates had preferable predictability than other pop PK models. In prediction-based diagnostics, the MDPE, F20 , and F30 of model H were 8.48%, 45.35%, and 59.56%, respectively. The NPDE of model H showed that it followed the normal distribution. Based on Bayesian forecasting, model H showed good predictive performance. Thus, model H was the most appropriate model, that can be used clinically for individualized dosage adjustments in Chinese pediatric HSCT patients. This article is protected by copyright. All rights reserved.

To investigate and rank the evidence for the efficacy of non-pharmacological interventions in relieving pain after cardiac surgery using comprehensive comparisons.Although several previous systematic reviews and meta-analyses showed that non-pharmacological interventions effectively control and reduce pain after cardiac surgery, none quantitatively compared the effect of these different types of interventions.Systematic review and Bayesian network meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analysis guidelines.Six databases were searched from inception to April 2021 to collect all published evidence from randomised clinical trials. One author extracted the relevant information from the eligible trials; a second author independently reviewed the data. Before analysing the extracted data, two investigators independently assessed the quality of the included studies. Conventional meta-analysis was conducted using either fixed- or random-effects models according to statistical heterogeneity. The Bayesian network meta-analysis was conducted using the consistency model.We identified 42 randomised clinical trials comparing 14 groups with 4253 patients. Transcutaneous electrical nerve stimulation, acupressure, music and massage were effective for pain relief, with transcutaneous electrical nerve stimulation being associated with the best probability of successful pain relief after cardiac surgery (cumulative ranking curve surface, 0.97; probability, 77.03%). Acupressure (cumulative ranking curve surface, 0.79; probability, 30.69%) was the second-best option. However, there was no evidence that any pair-up intervention significantly reduced opioid use or anxiety.These findings suggest that transcutaneous electrical nerve stimulation, acupressure, music and massage may effectively alleviate postoperative cardiac pain, with transcutaneous electrical nerve stimulation representing the best choice for pain relief.The results of this network meta-analysis can guide patients after cardiac surgery and healthcare providers to make optimal decisions in managing postoperative cardiac pain.PROSPERO CRD42021246183.