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代谢组学生物标志物预测酒精依赖患者对安非他酮治疗的反应。

Metabolomics biomarkers to predict acamprosate treatment response in alcohol-dependent subjects.

机构信息

Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905, USA.

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota, 55905, USA.

出版信息

Sci Rep. 2017 May 31;7(1):2496. doi: 10.1038/s41598-017-02442-4.

Abstract

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD.

摘要

精准医学治疗酒精使用障碍(AUD)可以使合适的患者在合适的时间接受合适的药物治疗。在这里,我们构建了包含临床信息和血清代谢物水平的多变量模型,以预测乙酰谷酰胺治疗反应。120 名患者的样本被随机分为训练集(n=80)和测试集(n=40),共进行了五次独立的划分。治疗反应定义为完全戒酒(在乙酰谷酰胺治疗的 3 个月内不饮酒),而无反应则定义为在此期间任何饮酒。在每次的五次训练集中,我们都使用最小绝对收缩和选择算子(LASSO)惩罚选择方法构建预测模型,然后在相应的测试集中评估每个模型的预测性能。模型在测试集中预测乙酰谷酰胺治疗反应的平均敏感性和特异性分别为 0.83 和 0.31,这表明我们的模型在预测应答者方面表现良好,但在预测非应答者方面表现不佳(即许多非应答者被预测为应答者)。具有更大样本量和额外生物标志物的研究将扩大预测算法在 AUD 药物反应中的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8cf/5451388/545535321793/41598_2017_2442_Fig1_HTML.jpg

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