针刺治疗中风血管性认知障的临床观察
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摘要
目的
通过随机对照的研究方法,采用多学科同步观察分析,在血管性认知障碍的概念范围内,客观观察评价针刺对治疗中风后遗症期血管性认知障碍的临床疗效及其安全性。方法
参照2006年美国神经疾病协会制订的标准(DSM-Ⅳ、美国国立神经与语言疾病及中风研究所(NINCDS)及美国痴呆和相关疾病协会(ADRDA)制订的血管性痴呆(vascular dementia, VD)诊断标准、加拿大卒中网联合颁布的血管性认知障碍统一标准和1990中国中医药学会年提出的《老年呆病的诊断、辨证分型及疗效评定标准》中医老年呆病的诊断标准筛选中风血管性障碍患者,根据临床需要设立的纳入标准和排除标准筛选适合入组研究的中风血管性障碍患者。临床研究设计采用随机对照的方法,将合格中风血管性障碍受试者以1：1的比例分配至治疗组和对照组。治疗组采用针刺疗法的同时给与常规康复锻炼和认知功能训练,对照组仅给与常规康复锻炼和认知功能训练。治疗组针刺穴位以百会、风池(双)、人中、神门(双)为主穴,根据临床中医辨证肾虚者配以肾俞、太溪,肝肾阴虚者配内关、三阴交,痰瘀者配丰隆、三阴交,气滞血瘀者配膈俞、悬钟。刺法上,百会需向前平刺、人中需向上斜刺、风池需向对侧鼻尖球方向斜刺、神门直刺,配穴按照常规刺法进行,得气后留针30分钟。隔日一次,10次为一疗程,观察1个疗程。
合格受试者入组后,详细记录其年龄、性别、婚姻状况、教育程度、重要疾病史、用药史、记忆病史和家族史等基本情况,记录包括髓海不足、气血亏虚、心脾两虚、肝肾不足、脾肾两虚证等主证以及有关兼证的症状项目,应用简短精神状态量表(MMSE)进行认知功能评价,应用画钟、人像辨认、物体记忆试验(FOM)、数字广度测试(DST)、词汇流畅性试验(RVR)和Boston命名试验(BNT)对患者的神经心理进行测试,应用日常生活能力(ADL)、社会活动功能(FAQ)量表对患者进行社会生活功能的评价,应用Hachinski缺血量表和CT或MRI结果进行VCI的鉴别诊断。在以上基线资料均说明两组具有可比性后,按照试验方案分别进行治疗。在治疗过程中,以就诊时、治疗后第一周末、第二周末、第三周末为观察点,详细记录主要效应指标CGIC (Clinical Global Impression of Change, Guy 1976)和包括认知与日常活动、社会功能等记分(MMSE总分、FAQ总分、ADL总分、画钟、FOM总分、RVR总分、DBT总分、BNT总分)的改变情况。用于观察安全性的包括血、尿、粪常规、GPT、BUN、血糖、血脂、心电图、CT或MRI等实验室检测项目分别在治疗前及治疗结束时各检测一次,如有特殊情况,如疑有不良反应时,应随时检测。研究中出现不良反应的症状均必须如实记录,并分析其出现的原因,症状的轻重程度、发生频率、持续时间等。
临床研究结束后,及时汇总临床资料,输入计算机,建立数据库,进行数据管理。对两组治疗后临床总疗效、临床症状、体征疗效等进行统计分析、比较,最后客观评价临床疗效及其安全性。根据数据资料及试验目的选择合适的统计方法：分类资料用χ2检验,等级资料用Ridit分析,两样本均数比较用t检验或Wilcoxon秩和检验,自身前后比较用配对t检验或Wilcoxon配对秩和检验,同时进行意图-治疗分析(intention-to-treat analyses, ITT)和依从方案受试者分析(per-protocol subjects analysis)。次要效应指标中单项指标数据缺失,以该组的均数代替。采用非参数统计方法进行认知与日常活动、社会功能等治疗前后的变化及组间的显著性检验。主要疗效分析采用协方差分析及重复测量分析方法,以终点值作为因变量,试验措施、年龄、性别、教育程度、疾病严重程度及合并用药情况等作为协变量,统计模型中检验各因子间的交互作用。
结果
本研究共有合格受试者120例,经过简单随机分组后,针刺治疗组60例；对照组60例,所有患者均为门诊病人。治疗前,治疗组和对照组在年龄、性别、痴呆类型、VCI严重程度构成、教育程度和既往病史分布、病程、CT检查结果、中医症状计分、治疗前合并用药情况、认知功能和社会、日常活动能力中医证候分布情况、和依从性比较上均没有差别,两组在基线水平上具有可比性。
治疗结束后,以综合疗效评价参考CGIC为主要效应指标进行分析发现：意图一治疗分析中两组CGIC平均分分别为3.38(95%CI：3.07-3.68)和3.25(95%CI：2.96～3.53),两组的差异无显著性意义；依从方案受试者分析表明,两组CGIC平均分分别为3.38(95%CI：3.06～3.70)和3.15(95%CI：2.84～3.45),两组的差异也无显著性意义,这说明两组患者完成全部规定疗程并有高依从性。以性别、年龄、教育程度和高血压病史为协变量,以组别为影响因素,分别对各个次要指标进行重复测量方差分析。结果显示,每4周两组MMSE均平均增加1分左右,但其他指标随时间的变化不显著,而且各个指标两组间差异均无显著性意义,协方差分析模型结果是：合并高血压与否=0.09,性别=1.7,年龄=76.3,教育程度分级=1.8。多元分析显示,MMSE、FAQ、CDT. RVR和DST的时间效应的Wilks X检验F值分别为6.8、2.9、3.9、2.9和5.3,对应的P值分别为0.00、0.04、0.01、0.04和0.002,其他指标Wilksλ检验的P值均>0.1,且各指标的组间差异的比较,P值也均>0.1。为明确两组比较出现假阴性可能性的大小,即了解统计检验发现两组所存在差异的能力,对综合疗效比较进行检验效能(Power)的计算。依从方案受试者分析中,对照组进展率Pc=(15+2)／60=0.283,针刺组进展率Pt=(9+1)／60=0.166。经计算,统计检验效能为0.19<0.8。
研究结果印证了该病病机及证候的有关认识。从表4、表5可见,以髓海不足、肾虚和以此为基础的复合证候的频数分布为66%(91／138),其次为心脾两虚(占18.84%)和气血两虚(占15.22%),兼证中则以瘀为主,其次为痰、火。
安全性检测和不良反应观察中,治疗前检测了血常规,肝功能,肾功能(BUN),心电图,其中治疗前正常心电图者治疗后复查,仍为正常。上述结果表明,治疗后患者血常规,肝功能、心电图未见异常改变。安全性的观察表明,本研究中大部分病例进行了治疗前后血常规、心电图、肝功能(ALT)、肾功能(BUN)检测,未观察到针刺对血常规,心电图有影响。研究过程中未观察到不良反应。
结论
在主要疗效和次要指标的比较上,尽管针刺治疗组对比于对照组的差异均无统计学意义,采用协方差模型的重复测量分析在控制了性别、年龄、教育程度等对疗效的影响后,也未发现各个效应指标的有意义的组间差异。但通过统计检验效能的计算,可知本研究中检验效能较低(0.19),尚不能有足够的把握排除结果的假阴性,提示本研究的阴性结果可能是由于样本含量不足所致。如扩大试验的样本量,将能发现有统计学意义的差异。综上所述,针刺治疗VCI其临床应用较为安全、临床疗效具有一定临床意义。
Objective
This randomized controlled clinical research adopts multi-disciplinary synchronic observation and analysis methods and objectively observe and evaluate the clinical effect and safety of needling therapy to treat post-stroke vascular cognitive impairment within the category of vascular cognitive impairment.
Methods
The case selection basis is listed as follows:DSM-Ⅳ; the diagnostic standards of vascular dementia issued by NINCDS and ADRDA; the standard of vascular cognitive impairment (VCI) issued by CSN; Diagnostic, Differentiation Types and Effect Evaluation Standards of Senile Dementia issued in 1990 by China Association for Traditional Chinese Medicine; the inclusion and exclusion criteria for clinical requirement. In this randomized controlled clinical trial, the qualified post-stroke vascular cognitive impairment subjects are divided into the Treatment Group and the Controlled Group at the rate of 1:1. The former adopts routine rehabilitation exercises and cognitive function training accompanied by needling therapy; the latter adopts only routine rehabilitation exercises and cognitive function training. The major acupoints selected in the Treatment Group are Baihui, Fengchi (double), Renzhong, and Shenmen (double). The supplementary acupoints are Kidney-shu and Taixi for kidney-deficiency type, Neiguan and Sanyinjiao for liver and kidney yin deficiency, Fenglong and Sanyinjiao for phlegm stagnation and Geshu and Xuanzhong for qi and blood stagnation. Needling methods:even forward needling for Baihui; upward oblique needling for Renzhong; oblique needling toward the opposite nasal tip for Fengchi; straight needling for Shenmen; routine needling for supplementary acupoints. Maintain the needle for 30 minutes after achieving qi. Treat every other day.10 times make a treatment course and observe 1 treatment course.
Record the qualified subjects'age, gender, marriage status, education degree, important disease history, medication history, memory disorder history and family history. Record the major syndromes (marrow-reservoir deficiency, qi and blood deficiency, heart and spleen deficiency, liver and kidney deficiency and spleen and kidney deficiency, etc.) and the related accompanied symptoms and body signs. Conduct cognitive function evaluation with MMSE. Conduct the neuropsychological test with clock-drawing, figure identification test and FOM, DST, RVR and BNT. Conduct the social life function evaluation with ADL and FAQ. Conduct the diagnosis with Hachinski Ischemic Scale and CT or MR results. After the comparability of two groups is proved by the baseline material mentioned above, start the treatment according to the trial plan. During the treatment, observe at the time of clinic visit, and at the end of the first, second and third week after treatment. Record in detail the major effect indexes CGIC (Clinical Global Impression of Change, Guy 1976), the cognitive, daily activity and social function scores (MMSE score, FAQ score, ADL score, clock drawing score, FOM score, RVR score, DBT score, BNT score) and their changes. Examine once before and after treatment the lab examination items for safety, including blood, urine and stool routine tests, GPT, BUN, blood glucose, blood fat, electrocardiogram, CT and MRI tests. If special situation occurs or there's doubt about adverse reactions, conduct the examinations any time. Truthfully record the adverse reactions and analyze the possible causes, the severity degree of symptoms, the frequency and the lasting time, etc. If the symptoms are serious enough to stop medication, corresponding methods should be adopted immediately.
After the research, collect the clinical material and input to computer. Set up the database for data management. Analyze and compare the clinical total effective power, the clinical symptoms and the body sign curative effect of the two groups after treatment and finally evaluate the clinical effect and safety objectively. Suitable statistical methods are chosen according to the data and the trial objectives. For the classified material, take X2 test. For the ranked material, use Radit analysis. The averages of the two samples are compared with t test or Wilcoxon rank sum test. For self circa comparison, take the t pair test or Wilcoxon pair rank sum test. Conduct the intention-to-treat analysis and the per-protocol subjects analysis. For the absence of the single indexes of the secondary effect indexes, substitute with that group's average. For the changes before and after treatment in aspects of cognition, daily activity and social functions and the interclass significance test, adopt the nonparametric statistics methods. Adopt the covariance analysis and repeated measurement analysis methods to analyze the major curative effect. Take the point-value as dependent variable, take trial methods, age, gender, education degree and disease severity and medication as covariance and analyze the interaction effect of factors in the model.
Result
This research collects 142 case reports with 22 withdrawals midway or not included in the clinical research. According to the Chinese and Western Medicine standards and inclusion standards, there are 120 qualified subjects who are randomly classified into two groups with 60 in the Treatment Group and 60 in the Controlled Group. All are clinic patients. No difference is found in the comparison of two groups in aspects of age, gender, dementia types, VCI severity, education degree, disease history, disease course, CT results, Chinese Medicine symptoms scores, medication before treatment, cognition, social and daily activity ability and compliance which indicates there's comparability at baseline level.
After treatment, analysis with CGIC as the major effect index finds that in the intention-to-treat analysis, the two groups'CGIC averages are 3.38 (95%CI:3.07-3.68)和3.25 (95%CI:2.96-3.53) respectively and the difference has no significance; in the compliance analysis, the two groups'CGIC averages are 3.38 (95%CI:3.06-3.70) and 3.15 (95%CI:2.84-3.45) respectively and the difference has no significance which indicates the two groups'patients have high compliance to finish all the required courses. Take age, gender, and education degree and hypertension history as covariance and take groups as influencing factor, conduct the variance analysis of the repeated measurement of each secondary index. Result shows that the MMSE of two groups rise at 1 score every 4 weeks on average and the changes of the other indexes with time are not significant. The interclass difference of each index has no significance Covariance analysis results are:hypertension or not=0.09, gender=1.7, age=76.3, education degree level=1.8. Multivariate analysis shows the F value of Wilksλtest of the time effect of MMSE, FAQ, CDT, RVR and DST are 6.8,2.9,3.9,2.9 and 5.3 and the corresponding P value are 0.00, 0.04,0.01,0.04 and 0.002. The F value of Wilksλtest of the other indexes are all>0.1. The interclass comparison of each index shows the P value are all>0.1. In order to specify the possibility of false negative of two groups, that is to make clear the ability of statistics to find out the difference, conduct the calculation of Power of the comprehensive curative effect. In the analysis of compliance, Pc= (15+2)/60= 0.283 in the Controlled group and Pt= (9+1)/60= 0.166 in the Treatment Group. Statistical test power is 0.19<0.8.
The research results confirm the knowledge about the etiology and syndromes of this disease. From Diagram 4 and 5, it can be found the frequency of marrow-reservoir deficiency, kidney deficiency and compound syndromes based on the former two types is 66%(91/138), the next are heart and spleen deficiency (18.84%) and qi and blood deficiency (15.22%). Stagnation is the major accompanied symptom and phlegm and fire follow it.
In the safety and adverse effect observation, blood routine test, liver function test, BUN and electrocardiogram test are undertaken before treatment and no abnormality is found in the electrocardiogram recheck of subjects whose electrocardiogram test result is normal. The results above show that no abnormal change is found in the blood routine test, liver function test and the electrocardiogram test of patients after treatment. The safety observation shows that most subjects have received the blood routine test, ALT, BUN and the electrocardiogram test before and after treatment and finds that needling has no detriment for blood routine test and electrocardiogram. No adverse effect is found in the treatment.
Conclusion
In the comparison of major curative effect and secondary indexes, the difference between the trial therapy and the controlted has no statistical significance. After controlling the effect of age, gender, education degree on curative effect with repeated measurement and analysis with covariance model, no significant interclass difference of each effect index is found. However with statistical test power calculation, it is found that the test power is low (0.19), so there is possibility of false negative which indicates that the negative result may be caused by inadequate number of samples. If sample number is enlarged, there's possibility of finding the statistical difference. To summarize, needling is a safe treatment method for VCI and its effect indicates the clinical significance.
通过随机对照的研究方法,采用多学科同步观察分析,在血管性认知障碍的概念范围内,客观观察评价针刺对治疗中风后遗症期血管性认知障碍的临床疗效及其安全性。方法
参照2006年美国神经疾病协会制订的标准(DSM-Ⅳ、美国国立神经与语言疾病及中风研究所(NINCDS)及美国痴呆和相关疾病协会(ADRDA)制订的血管性痴呆(vascular dementia, VD)诊断标准、加拿大卒中网联合颁布的血管性认知障碍统一标准和1990中国中医药学会年提出的《老年呆病的诊断、辨证分型及疗效评定标准》中医老年呆病的诊断标准筛选中风血管性障碍患者,根据临床需要设立的纳入标准和排除标准筛选适合入组研究的中风血管性障碍患者。临床研究设计采用随机对照的方法,将合格中风血管性障碍受试者以1：1的比例分配至治疗组和对照组。治疗组采用针刺疗法的同时给与常规康复锻炼和认知功能训练,对照组仅给与常规康复锻炼和认知功能训练。治疗组针刺穴位以百会、风池(双)、人中、神门(双)为主穴,根据临床中医辨证肾虚者配以肾俞、太溪,肝肾阴虚者配内关、三阴交,痰瘀者配丰隆、三阴交,气滞血瘀者配膈俞、悬钟。刺法上,百会需向前平刺、人中需向上斜刺、风池需向对侧鼻尖球方向斜刺、神门直刺,配穴按照常规刺法进行,得气后留针30分钟。隔日一次,10次为一疗程,观察1个疗程。
合格受试者入组后,详细记录其年龄、性别、婚姻状况、教育程度、重要疾病史、用药史、记忆病史和家族史等基本情况,记录包括髓海不足、气血亏虚、心脾两虚、肝肾不足、脾肾两虚证等主证以及有关兼证的症状项目,应用简短精神状态量表(MMSE)进行认知功能评价,应用画钟、人像辨认、物体记忆试验(FOM)、数字广度测试(DST)、词汇流畅性试验(RVR)和Boston命名试验(BNT)对患者的神经心理进行测试,应用日常生活能力(ADL)、社会活动功能(FAQ)量表对患者进行社会生活功能的评价,应用Hachinski缺血量表和CT或MRI结果进行VCI的鉴别诊断。在以上基线资料均说明两组具有可比性后,按照试验方案分别进行治疗。在治疗过程中,以就诊时、治疗后第一周末、第二周末、第三周末为观察点,详细记录主要效应指标CGIC (Clinical Global Impression of Change, Guy 1976)和包括认知与日常活动、社会功能等记分(MMSE总分、FAQ总分、ADL总分、画钟、FOM总分、RVR总分、DBT总分、BNT总分)的改变情况。用于观察安全性的包括血、尿、粪常规、GPT、BUN、血糖、血脂、心电图、CT或MRI等实验室检测项目分别在治疗前及治疗结束时各检测一次,如有特殊情况,如疑有不良反应时,应随时检测。研究中出现不良反应的症状均必须如实记录,并分析其出现的原因,症状的轻重程度、发生频率、持续时间等。
临床研究结束后,及时汇总临床资料,输入计算机,建立数据库,进行数据管理。对两组治疗后临床总疗效、临床症状、体征疗效等进行统计分析、比较,最后客观评价临床疗效及其安全性。根据数据资料及试验目的选择合适的统计方法：分类资料用χ2检验,等级资料用Ridit分析,两样本均数比较用t检验或Wilcoxon秩和检验,自身前后比较用配对t检验或Wilcoxon配对秩和检验,同时进行意图-治疗分析(intention-to-treat analyses, ITT)和依从方案受试者分析(per-protocol subjects analysis)。次要效应指标中单项指标数据缺失,以该组的均数代替。采用非参数统计方法进行认知与日常活动、社会功能等治疗前后的变化及组间的显著性检验。主要疗效分析采用协方差分析及重复测量分析方法,以终点值作为因变量,试验措施、年龄、性别、教育程度、疾病严重程度及合并用药情况等作为协变量,统计模型中检验各因子间的交互作用。
结果
本研究共有合格受试者120例,经过简单随机分组后,针刺治疗组60例；对照组60例,所有患者均为门诊病人。治疗前,治疗组和对照组在年龄、性别、痴呆类型、VCI严重程度构成、教育程度和既往病史分布、病程、CT检查结果、中医症状计分、治疗前合并用药情况、认知功能和社会、日常活动能力中医证候分布情况、和依从性比较上均没有差别,两组在基线水平上具有可比性。
治疗结束后,以综合疗效评价参考CGIC为主要效应指标进行分析发现：意图一治疗分析中两组CGIC平均分分别为3.38(95%CI：3.07-3.68)和3.25(95%CI：2.96～3.53),两组的差异无显著性意义；依从方案受试者分析表明,两组CGIC平均分分别为3.38(95%CI：3.06～3.70)和3.15(95%CI：2.84～3.45),两组的差异也无显著性意义,这说明两组患者完成全部规定疗程并有高依从性。以性别、年龄、教育程度和高血压病史为协变量,以组别为影响因素,分别对各个次要指标进行重复测量方差分析。结果显示,每4周两组MMSE均平均增加1分左右,但其他指标随时间的变化不显著,而且各个指标两组间差异均无显著性意义,协方差分析模型结果是：合并高血压与否=0.09,性别=1.7,年龄=76.3,教育程度分级=1.8。多元分析显示,MMSE、FAQ、CDT. RVR和DST的时间效应的Wilks X检验F值分别为6.8、2.9、3.9、2.9和5.3,对应的P值分别为0.00、0.04、0.01、0.04和0.002,其他指标Wilksλ检验的P值均>0.1,且各指标的组间差异的比较,P值也均>0.1。为明确两组比较出现假阴性可能性的大小,即了解统计检验发现两组所存在差异的能力,对综合疗效比较进行检验效能(Power)的计算。依从方案受试者分析中,对照组进展率Pc=(15+2)／60=0.283,针刺组进展率Pt=(9+1)／60=0.166。经计算,统计检验效能为0.19<0.8。
研究结果印证了该病病机及证候的有关认识。从表4、表5可见,以髓海不足、肾虚和以此为基础的复合证候的频数分布为66%(91／138),其次为心脾两虚(占18.84%)和气血两虚(占15.22%),兼证中则以瘀为主,其次为痰、火。
安全性检测和不良反应观察中,治疗前检测了血常规,肝功能,肾功能(BUN),心电图,其中治疗前正常心电图者治疗后复查,仍为正常。上述结果表明,治疗后患者血常规,肝功能、心电图未见异常改变。安全性的观察表明,本研究中大部分病例进行了治疗前后血常规、心电图、肝功能(ALT)、肾功能(BUN)检测,未观察到针刺对血常规,心电图有影响。研究过程中未观察到不良反应。
结论
在主要疗效和次要指标的比较上,尽管针刺治疗组对比于对照组的差异均无统计学意义,采用协方差模型的重复测量分析在控制了性别、年龄、教育程度等对疗效的影响后,也未发现各个效应指标的有意义的组间差异。但通过统计检验效能的计算,可知本研究中检验效能较低(0.19),尚不能有足够的把握排除结果的假阴性,提示本研究的阴性结果可能是由于样本含量不足所致。如扩大试验的样本量,将能发现有统计学意义的差异。综上所述,针刺治疗VCI其临床应用较为安全、临床疗效具有一定临床意义。
Objective
This randomized controlled clinical research adopts multi-disciplinary synchronic observation and analysis methods and objectively observe and evaluate the clinical effect and safety of needling therapy to treat post-stroke vascular cognitive impairment within the category of vascular cognitive impairment.
Methods
The case selection basis is listed as follows:DSM-Ⅳ; the diagnostic standards of vascular dementia issued by NINCDS and ADRDA; the standard of vascular cognitive impairment (VCI) issued by CSN; Diagnostic, Differentiation Types and Effect Evaluation Standards of Senile Dementia issued in 1990 by China Association for Traditional Chinese Medicine; the inclusion and exclusion criteria for clinical requirement. In this randomized controlled clinical trial, the qualified post-stroke vascular cognitive impairment subjects are divided into the Treatment Group and the Controlled Group at the rate of 1:1. The former adopts routine rehabilitation exercises and cognitive function training accompanied by needling therapy; the latter adopts only routine rehabilitation exercises and cognitive function training. The major acupoints selected in the Treatment Group are Baihui, Fengchi (double), Renzhong, and Shenmen (double). The supplementary acupoints are Kidney-shu and Taixi for kidney-deficiency type, Neiguan and Sanyinjiao for liver and kidney yin deficiency, Fenglong and Sanyinjiao for phlegm stagnation and Geshu and Xuanzhong for qi and blood stagnation. Needling methods:even forward needling for Baihui; upward oblique needling for Renzhong; oblique needling toward the opposite nasal tip for Fengchi; straight needling for Shenmen; routine needling for supplementary acupoints. Maintain the needle for 30 minutes after achieving qi. Treat every other day.10 times make a treatment course and observe 1 treatment course.
Record the qualified subjects'age, gender, marriage status, education degree, important disease history, medication history, memory disorder history and family history. Record the major syndromes (marrow-reservoir deficiency, qi and blood deficiency, heart and spleen deficiency, liver and kidney deficiency and spleen and kidney deficiency, etc.) and the related accompanied symptoms and body signs. Conduct cognitive function evaluation with MMSE. Conduct the neuropsychological test with clock-drawing, figure identification test and FOM, DST, RVR and BNT. Conduct the social life function evaluation with ADL and FAQ. Conduct the diagnosis with Hachinski Ischemic Scale and CT or MR results. After the comparability of two groups is proved by the baseline material mentioned above, start the treatment according to the trial plan. During the treatment, observe at the time of clinic visit, and at the end of the first, second and third week after treatment. Record in detail the major effect indexes CGIC (Clinical Global Impression of Change, Guy 1976), the cognitive, daily activity and social function scores (MMSE score, FAQ score, ADL score, clock drawing score, FOM score, RVR score, DBT score, BNT score) and their changes. Examine once before and after treatment the lab examination items for safety, including blood, urine and stool routine tests, GPT, BUN, blood glucose, blood fat, electrocardiogram, CT and MRI tests. If special situation occurs or there's doubt about adverse reactions, conduct the examinations any time. Truthfully record the adverse reactions and analyze the possible causes, the severity degree of symptoms, the frequency and the lasting time, etc. If the symptoms are serious enough to stop medication, corresponding methods should be adopted immediately.
After the research, collect the clinical material and input to computer. Set up the database for data management. Analyze and compare the clinical total effective power, the clinical symptoms and the body sign curative effect of the two groups after treatment and finally evaluate the clinical effect and safety objectively. Suitable statistical methods are chosen according to the data and the trial objectives. For the classified material, take X2 test. For the ranked material, use Radit analysis. The averages of the two samples are compared with t test or Wilcoxon rank sum test. For self circa comparison, take the t pair test or Wilcoxon pair rank sum test. Conduct the intention-to-treat analysis and the per-protocol subjects analysis. For the absence of the single indexes of the secondary effect indexes, substitute with that group's average. For the changes before and after treatment in aspects of cognition, daily activity and social functions and the interclass significance test, adopt the nonparametric statistics methods. Adopt the covariance analysis and repeated measurement analysis methods to analyze the major curative effect. Take the point-value as dependent variable, take trial methods, age, gender, education degree and disease severity and medication as covariance and analyze the interaction effect of factors in the model.
Result
This research collects 142 case reports with 22 withdrawals midway or not included in the clinical research. According to the Chinese and Western Medicine standards and inclusion standards, there are 120 qualified subjects who are randomly classified into two groups with 60 in the Treatment Group and 60 in the Controlled Group. All are clinic patients. No difference is found in the comparison of two groups in aspects of age, gender, dementia types, VCI severity, education degree, disease history, disease course, CT results, Chinese Medicine symptoms scores, medication before treatment, cognition, social and daily activity ability and compliance which indicates there's comparability at baseline level.
After treatment, analysis with CGIC as the major effect index finds that in the intention-to-treat analysis, the two groups'CGIC averages are 3.38 (95%CI:3.07-3.68)和3.25 (95%CI:2.96-3.53) respectively and the difference has no significance; in the compliance analysis, the two groups'CGIC averages are 3.38 (95%CI:3.06-3.70) and 3.15 (95%CI:2.84-3.45) respectively and the difference has no significance which indicates the two groups'patients have high compliance to finish all the required courses. Take age, gender, and education degree and hypertension history as covariance and take groups as influencing factor, conduct the variance analysis of the repeated measurement of each secondary index. Result shows that the MMSE of two groups rise at 1 score every 4 weeks on average and the changes of the other indexes with time are not significant. The interclass difference of each index has no significance Covariance analysis results are:hypertension or not=0.09, gender=1.7, age=76.3, education degree level=1.8. Multivariate analysis shows the F value of Wilksλtest of the time effect of MMSE, FAQ, CDT, RVR and DST are 6.8,2.9,3.9,2.9 and 5.3 and the corresponding P value are 0.00, 0.04,0.01,0.04 and 0.002. The F value of Wilksλtest of the other indexes are all>0.1. The interclass comparison of each index shows the P value are all>0.1. In order to specify the possibility of false negative of two groups, that is to make clear the ability of statistics to find out the difference, conduct the calculation of Power of the comprehensive curative effect. In the analysis of compliance, Pc= (15+2)/60= 0.283 in the Controlled group and Pt= (9+1)/60= 0.166 in the Treatment Group. Statistical test power is 0.19<0.8.
The research results confirm the knowledge about the etiology and syndromes of this disease. From Diagram 4 and 5, it can be found the frequency of marrow-reservoir deficiency, kidney deficiency and compound syndromes based on the former two types is 66%(91/138), the next are heart and spleen deficiency (18.84%) and qi and blood deficiency (15.22%). Stagnation is the major accompanied symptom and phlegm and fire follow it.
In the safety and adverse effect observation, blood routine test, liver function test, BUN and electrocardiogram test are undertaken before treatment and no abnormality is found in the electrocardiogram recheck of subjects whose electrocardiogram test result is normal. The results above show that no abnormal change is found in the blood routine test, liver function test and the electrocardiogram test of patients after treatment. The safety observation shows that most subjects have received the blood routine test, ALT, BUN and the electrocardiogram test before and after treatment and finds that needling has no detriment for blood routine test and electrocardiogram. No adverse effect is found in the treatment.
Conclusion
In the comparison of major curative effect and secondary indexes, the difference between the trial therapy and the controlted has no statistical significance. After controlling the effect of age, gender, education degree on curative effect with repeated measurement and analysis with covariance model, no significant interclass difference of each effect index is found. However with statistical test power calculation, it is found that the test power is low (0.19), so there is possibility of false negative which indicates that the negative result may be caused by inadequate number of samples. If sample number is enlarged, there's possibility of finding the statistical difference. To summarize, needling is a safe treatment method for VCI and its effect indicates the clinical significance.
引文
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