Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Korea.
Clin Transl Sci. 2021 Sep;14(5):1988-1996. doi: 10.1111/cts.13056. Epub 2021 May 31.
Disability in patients with acute stroke varies over time, with the prediction of outcomes being critical for proper management. This study aimed to develop a model to predict the cumulative probability of each modified Rankin Scale (mRS) score over time with inclusion of significant covariates. Longitudinal data obtained from 193 patients, 1-24 months after onset of acute ischemic stroke, were included for a modeling analysis using nonlinear mixed-effect modeling (NONMEM). After selecting a model that best described the time course of the probability of different mRS scores, potential covariates were tested. Visual predicted check plots, parameter estimates, and decreases in minimum objective function values were used for model evaluation. The inclusion of disease progression (DP) in the baseline proportional odds cumulative logit model significantly improved the model compared to the baseline model without DP. An inhibitory maximum effect (E ) model was determined to be the best DP model for describing the probability of specific mRS scores over time. In the final model, DP was multiplied with the baseline cumulative logit probability with a baseline adjustment. In addition to differences in lesion volume (DLV), the final model included comorbid diabetes mellitus (DM) and baseline National Institutes of Health Stroke Scale (NIHSS) scores on E as statistically significant covariates. This study developed a model including DLV, NIHSS score, and comorbid DM for predicting the disability time course in patients with acute ischemic stroke. This model may help to predict disease outcomes and to develop more appropriate management plans for patients with acute stroke.
患者在急性脑卒中后的残疾状况随时间而变化,因此对结局进行预测对于恰当的管理至关重要。本研究旨在开发一种模型,以预测包括重要协变量在内的各改良 Rankin 量表(mRS)评分的累积概率。使用非线性混合效应模型(NONMEM)对 193 例发病后 1-24 个月的急性缺血性脑卒中患者的纵向数据进行建模分析。在选择最能描述不同 mRS 评分概率时间进程的模型后,对潜在协变量进行了检验。使用视觉预测检查图、参数估计和最小目标函数值的降低来评估模型。在基线比例优势累积对数模型中纳入疾病进展(DP),与不包括 DP 的基线模型相比,显著改善了模型。确定抑制最大效应(E)模型是描述特定 mRS 评分随时间变化的概率的最佳 DP 模型。在最终模型中,DP 与基线累积对数概率相乘,并对基线进行调整。除了病变体积(DLV)的差异外,最终模型还包括合并的糖尿病(DM)和基线国立卫生研究院卒中量表(NIHSS)评分对 E 的影响,这些均为统计学显著的协变量。本研究开发了一种包括 DLV、NIHSS 评分和合并 DM 的模型,用于预测急性缺血性脑卒中患者的残疾时间进程。该模型有助于预测疾病结局,并为急性脑卒中患者制定更恰当的管理计划。