摘要
缺血性中风具有发病率高、致残率高、死亡率高的特点。随着中风发病的逐年增高,研究中风病的康复治疗已经成为医学界的热点。综合运用中药汤剂、静脉给药、外冼、药浴、针灸、按摩、精神调养等措施进行辨证治疗,做到康复治疗的个体化,同时重视早期康复是当前中风康复工作的重点。本课题组在前期工作的基础上广泛借鉴、吸收现代医学的研究成果,制定出综合多种中医药干预措施进行辨证治疗,体现个体化的缺血性中风早期康复中医方案。
自古以来,医学研究的最终目的就是探讨事物之间的因果关系。中医药临床疗效评价实际上是中医药干预措施与临床结局之间是否具有因果关系的研究。传统的统计方法往往得到的是相关关系,其适用于经典RCT的疗效评价。虚拟事实因果模型可以精确定义因果关系,其既可以用于RCT也可以用于观察性试验的疗效评价。实用性RCT更适合于以复杂干预为特点的中医方案的疗效评价,所以探索虚拟事实因果模型在实用性RCT中的应用。
1.研究目的
1.1主要研究目的
采用虚拟事实因果模型评价缺血性中风早期康复中医方案对缺血性中风患者神经功能缺损、运动功能损伤、痉挛程度的临床疗效。
1.2次要研究目的
1.2.1研究缺血性中风早期康复中医方案的有效治疗时间窗。
1.2.2研究缺血性中风早期康复中医方案的中医最佳适应证。
2.研究方法
采用实用性RCT,多中心合作,共纳入300例患者。通过中央随机系统将患者分为试验组200例,对照组100例。试验组采用缺血性中风早期康复中医方案,康复治疗模式为“内科基础治疗+中医综合康复技术”;对照组采用卒中单元模式指导下的西医康复方案,康复治疗模式为“内科基础治疗+现代康复技术”。疗效指标的评价,采用公认权威的脑血管病诊疗评价标准:美国国立卫生研究院卒中量表(NIHSS)评价患者神经功能缺损程度、运动功能评分法(Fugl-Meyer)评价运动功能、修改后的Ashworth痉挛评定量表评价痉挛程度。采用国家中医药管理局中风急症协作组制定的《中风病辨证诊断标准》进行中医证候的量化诊断;安全性指标为不良事件观察。两组观察疗程均为14天。
3.研究结果
3.1方案疗效评价结果
试验组改善运动功能积分比对照组好7.748分,且有统计学差异(P<0.05)。试验组改善神经功能积分比对照组好0.757分,改善痉挛积分比对照组好0.058分,但均无统计学差异(P均>0.05)。表明试验组在改善运动功能方面有疗效优势。
3.2方案有效时间窗研究结果
3.2.1方案改善神经功能缺损的有效治疗时间窗
研究结果显示:对照组在患者发病6小时内,改善神经功能积分比试验组好0.482分,但无统计学差异(P>0.05)。试验组在患者发病6小时～24小时,改善神经功能积分比对照组好0.230分,但无统计学差异(P>0.05);在患者发病24小时～14天时,改善神经功能积分比对照组好1.314分,且有统计学差异(P<0.05)。表明方案改善神经功能缺损的有效时间窗是发病24小时～14天。
3.2.2方案改善运动功能损伤的有效治疗时间窗
研究结果显示:试验组在患者发病6小时内改善运动功能的积分比对照组好6.248;在发病6小时～24小时内改善运动功能的积分比对照组好12.977分;在发病24小时～14天改善运动功能的积分比对照组好6.732分,但均无统计学差异(尸均>0.05)。表明方案改善运动功能缺损的有效时间窗可能是发病6小时～24小时。
3.2.3方案改善痉挛程度的有效治疗时间窗
研究结果显示:试验组在患者发病6小时内改善痉挛程度的积分比对照组好0.011分;在患者发病24小时～14天改善痉挛程度的积分比对照组好0.116分,但均无统计学差异(P均>0.05)。对照组改善痉挛程度的积分比试验组好0.112分,但无统计学差异(P>0.05)。表明方案改善痉挛程度缺损的有效时间窗可能是发病24小时～14天。
3.3方案最佳适应证研究结果
研究结果显示:试验组改善痰证的疗效比对照组好4.48分,且有统计学差异(P<0.05);试验组改善风证的疗效比对照组好1.76分,改善血瘀证的疗效比对照组好1.99分,但均无统计学差异(P均>0.05)。对照组改善火热证比试验组好0.42分,改善气虚证比试验组好1.00分,改善阴虚阳亢证比试验组好0.81分,但均无统计学差异(P均>0.05)。表明方案最佳适应证为证候要素辨证为痰证的患者。
3.4方案安全性分析结果
本研究未发现不良反应,表明缺血性中风早期康复中医方案相对安全。
4.研究结论
初步研究表明:(1)缺血性中风早期康复中医方案改善缺血性中风患者的运动功能缺损相对于西医康复方案有疗效优势,改善神经功能缺损和痉挛程度的疗效与西医康复方案相似。(2)缺血性中风早期康复中医方案改善神经功能缺损的有效治疗时间窗是发病24小时～14天,改善运动功能损伤能可能是发病6小时～24小时,改善痉挛程度的有效时间窗可能是发病24小时～14天。(3)缺血性中风早期康复中医方案的最佳适应证为证候要素为痰证的患者。(4)虚拟事实因果模型可以用于实用性RCT的中医临床疗效评价。
本研究为实用性RCT探索了一种新的疗效评价方法,为中医康复方案的临床疗效和可操作性提供了依据,有一定的创新性。
Ischemic stroke has the characteristics of high incidence,high disabilities and high mortality.With the stroke incidence increasing year by year,stroke rehabilitation has become a hot medical research.The important research of ischemic stroke rehabilitation focuses on integration of herbal decoction after syndrome differentiation, intravenous drip of herbal medical preparation,external wash,medicated bath, acupuncture,massage,spirit caring and other measures for differentiation therapy,and being attached much importance to early rehabilitation.Therefore,our team developed the TCM early rehabilitation project for ischemic stroke characterized with differentiation and individualized therapy on the basis of previous work and modern medical research in stroke.
Since ancient times,the ultimate goal of medical research is to explore the causal relationship between things.The clinical effectiveness evaluation of TCM in nature is to study the causal relationship between TCM measures and the corresponding clinical outcomes.Traditional statistical methods can usually get correlation,while counterfactual model can define a causal relationship precisely.Therefore,we explore the TCM project effectiveness evaluation methodology based on counterfactual model.
1.Objectives
The primary objective is to study the clinical effectiveness evaluation of TCM stroke early rehabilitation project on neurological deficit,motor function impairment and convulsion degree based on counterfactual model.
Secondary objective is to study the effective time window and the best target syndrome of TCM stroke early rehabilitation project.
2.Methods
Depending on Multi-center collaboration and online randomized system,300 patients were randomly divided into two groups:the treatment group with 200 cases and the control group with 100 cases.The treatment group was treated with the TCM rehabilitation project which integrates the basic treatment of internal medicine,TCM comprehensive rehabilitation technology.The control group was treated with the western medicine rehabilitation project consisting of the basic treatment of internal medicine and the modern rehabilitation technology.The clinical effectiveness evaluation indexes refer to the recognized criterion of diagnosis and treatment of cerebrovascular diseases.The indexes include NIHSS used for evaluating the neurological deficit degree,the motor function score(Fugl-Meyer) for evaluating motor function and the modified Ashworth convulsion rating scale for evaluating the convulsion degree.The literature "Differentiation diagnosis standard of stroke" compiled by the stroke emergency collaboration group of state administration of TCM is utilized for quantized diagnosis of TCM syndromes.The safety index is defined by adverse observation event.The treatment course is 14 days.
3.Results
3.1 Therapeutic evaluation
Amelioration motor function's score in the treatment group was better than that in the control group,and there was statistical difference between two groups(P<0.05). Amelioration neural function's score and convulsion's score in the treatment group were both better than those in the control group,but there were no statistical difference between these two groups(P>0.05).The results indicated that the treatment group has the therapeutic strength in improving the motor function.
3.2 Effective time window
3.2.1 Effective time window in improving the neurological function deficit
The improvement of the neurological function deficit in the control group was superior to the treatment group within 6 hours,but there was no statistical difference between two groups(P>0.05).The improvement of the neurological function deficit in the treatment group was superior to the control group between 6-hour disease course and 24-hour disease course,but there was no statistical difference between two groups(P>0.05).The improvement of the neurological function deficit in the treatment group was superior to the control group between 24-hour disease course and 14-day disease course and there was statistical difference between two groups (P<0.05).The results showed that effective time widow in improving the neurological function deficit of TCM rehabilitation project maybe is disease course between 24-hour and 14-day.
3.2.2 Effective time widow in improving motor function impairment
Amelioration motor function's score in the treatment group were better than those in the control group within 6-hour disease course,between 6-hour and 24-hour, between 24-hour and 14-day respectively,but there were no statistical differences between two groups(P>0.05).The results showed that effective time widow in improving motor function impairment of TCM rehabilitation project maybe is disease course between 6-hour and 24-hour.
3.2.3 Effective time widow in improving convulsion degree
The score of improving the convulsion degree in the treatment group was better than that in the control group within 6-hour disease course,between 24-hour and 14-day disease course respectively,but there were both no statistical difference between two groups.The score of improving the convulsion degree in the control group was better than that in the treatment group,but there is no statistical difference between two groups.The results showed that the effective time widow in improving convulsion degree of TCM Ischemic stroke rehabilitation project maybe between 24-hour and 14-day disease course.
3.3 Best target syndrome
The improvement of phlegm syndrome in the treatment group was better than that in the control group,and there was statistical difference between two groups (P<0.05).The improvement scores of wind syndrome and blood stasis in the treatment group were better than those in the control group respectively,but there were no differences between two groups(P>0.05).The improvement scores of fire-heat syndrome and of qi-deficiency syndrome,hyperactivity of yang due to yin-deficiency in the control group were better than those in the treatment group respectively,but there were no statistical differences between two groups(P>0.05). Therefore,the TCM best target syndrome in the treatment group is phlegm syndrome.
3.4 Safety analysis
There was no adverse event related to the TCM rehabilitation project of ischemic stroke found in the study,which indicateed that the TCM project was safety.
4.Conclusions
We can draw some primary conclusions:(1)TCM rehabilitation project of ischemic stroke showed some superiority to western medicine rehabilitation program on improving the motor function,while both groups can improve neural function, spasmodical degree and there are no differences between them.(2) For TCM early rehabilitation project,the effective time window of disease course on improving the neurological deficit,the motor function and the limb spasticity maybe are from 24 hours to 14 days,6 hours to 24 hours,24 hours to 14 days respectively.(3)The target population of TCM rehabilitation project for Ischemic stroke is patients with phlegm syndrome.(4)Counterfactual model can evaluate the clinical efficacy of Pagmatic randomized controlled trial..
The study explored a new method for clinical effectiveness evaluation of Pragmatic randomized controlled trial and provide scientific evidence for clinical effectiveness and operability of TCM Ischemic stroke early rehabilitation project,which has certain innovative.
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