Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.
Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.
复制标题
使用 RBF-Galerkin 方法进行个体化药物剂量：慢性肾病贫血管理案例。
DOI：
10.1016/j.cmpb.2017.06.008
复制
发表时间：
2017
影响因子：
6.1
通讯作者：
Inanc,Tamer
中科院分区：
文献类型：
--
作者：
Mirinejad,Hossein;Gaweda,AdamE;Brier,MichaelE;Zurada,JacekM;Inanc,Tamer
贫血是慢性肾脏病（CKD）患者常见的合并症，通常与生活质量的身体部分下降以及不良心血管事件相关。目前肾性贫血的治疗方法大多是基于人群的方法，采用一刀切的模式治疗个体患者。然而，FDA的建议规定了个性化的贫血治疗，精确控制血红蛋白浓度和最小的药物使用。根据这些建议，这项工作提出了一个个性化的药物给药的方法，贫血管理，利用理论的最佳control.MethodsA多滚动时域控制（MRHC）的RBF-Galerkin优化方法的基础上提出了个性化的贫血管理CKD患者。径向基函数-伽辽金方法是作者最近发展起来的一种数值方法，它利用径向基函数逼近沿着伽辽金误差投影来求解约束最优控制问题。所提出的方法被施加到产生最佳剂量的建议为个别patient.ResultsPerformance的所提出的方法（MRHC）进行了比较，在硅片上的人口为基础的贫血管理协议和个性化的多模型预测控制方法的两种情况下的情况下：血红蛋白测量和没有观测误差。计算机模拟比较表明，采用MRHC方法的血红蛋白浓度在方法之间的差异较小，尤其是在存在测量误差的情况下。此外，根据方差分析（ANOVA）统计检验，MRHC获得的平均血红蛋白水平比其他两种方法更接近目标血红蛋白水平。此外，药物剂量推荐的MRHC更稳定，准确，达到稳态值显着更快比其他两种methods.ConclusionsThe所提出的方法产生的血红蛋白水平的控制是非常有效的，但在治疗CKD贫血提供准确的剂量调整。
Background and ObjectiveAnemia is a common comorbidity in patients with chronic kidney disease (CKD) and is frequently associated with decreased physical component of quality of life, as well as adverse cardiovascular events. Current treatment methods for renal anemia are mostly population-based approaches treating individual patients with a one-size-fits-all model. However, FDA recommendations stipulate individualized anemia treatment with precise control of the hemoglobin concentration and minimal drug utilization. In accordance with these recommendations, this work presents an individualized drug dosing approach to anemia management by leveraging the theory of optimal control.MethodsA Multiple Receding Horizon Control (MRHC) approach based on the RBF-Galerkin optimization method is proposed for individualized anemia management in CKD patients. Recently developed by the authors, the RBF-Galerkin method uses the radial basis function approximation along with the Galerkin error projection to solve constrained optimal control problems numerically. The proposed approach is applied to generate optimal dosing recommendations for individual patients.ResultsPerformance of the proposed approach (MRHC) is compared in silico to that of a population-based anemia management protocol and an individualized multiple model predictive control method for two case scenarios: hemoglobin measurement with and without observational errors. In silico comparison indicates that hemoglobin concentration with MRHC method has less variation among the methods, especially in presence of measurement errors. In addition, the average achieved hemoglobin level from the MRHC is significantly closer to the target hemoglobin than that of the other two methods, according to the analysis of variance (ANOVA) statistical test. Furthermore, drug dosages recommended by the MRHC are more stable and accurate and reach the steady-state value notably faster than those generated by the other two methods.ConclusionsThe proposed method is highly efficient for the control of hemoglobin level, yet provides accurate dosage adjustments in the treatment of CKD anemia.