使用径向基函数伽辽金方法的个体化给药：慢性肾脏病贫血管理案例
Individualized drug dosing using RBF-Galerkin method: Case of anemia management in chronic kidney disease.
作者信息
Mirinejad Hossein, Gaweda Adam E, Brier Michael E, Zurada Jacek M, Inanc Tamer
机构信息
Electrical and Computer Engineering Department, University of Louisville, Louisville, KY, USA.
Department of Medicine, University of Louisville, Louisville, KY, USA.
出版信息
Comput Methods Programs Biomed. 2017 Sep;148:45-53. doi: 10.1016/j.cmpb.2017.06.008. Epub 2017 Jun 23.
BACKGROUND AND OBJECTIVE
Anemia 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.
METHODS
A 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.
RESULTS
Performance 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.
CONCLUSIONS
The proposed method is highly efficient for the control of hemoglobin level, yet provides accurate dosage adjustments in the treatment of CKD anemia.
背景与目的
贫血是慢性肾脏病（CKD）患者常见的合并症，常与生活质量的身体维度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群体的方法，采用一刀切的模式治疗个体患者。然而，美国食品药品监督管理局（FDA）的建议规定采用个体化贫血治疗，精确控制血红蛋白浓度并尽量减少药物使用。根据这些建议，本研究通过利用最优控制理论，提出了一种用于贫血管理的个体化给药方法。
方法
提出了一种基于径向基函数-伽辽金（RBF-Galerkin）优化方法的多步滚动时域控制（MRHC）方法，用于CKD患者的个体化贫血管理。作者最近开发的RBF-Galerkin方法使用径向基函数逼近以及伽辽金误差投影来数值求解约束最优控制问题。所提出的方法用于为个体患者生成最优给药建议。
结果
在两种情况下，即有无观测误差的血红蛋白测量，通过计算机模拟将所提出方法（MRHC）的性能与基于群体的贫血管理方案以及个体化多模型预测控制方法的性能进行比较。计算机模拟比较表明，在这些方法中，MRHC方法的血红蛋白浓度变化较小，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方法实现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，MRHC方法推荐的药物剂量更稳定、准确，达到稳态值的速度明显快于其他两种方法。
结论
所提出的方法在控制血红蛋白水平方面效率很高，同时在治疗CKD贫血时能提供准确的剂量调整。
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