基于调理脾胃法针药并用治疗女性混合性尿失禁的疗效评价研究

发布时间：2018-06-10 15:14

本文选题：混合性尿失禁 + 调理脾胃　；参考：《中国中医科学院》2016年博士论文

【摘要】：1.研究背景混合性尿失禁(MUI)是一种复杂的膀胱尿道功能障碍,同时具有压力性尿失禁(SUI)和急迫性尿失禁(UUI)的临床特征。对于此种疾病,现代医学目前尚无标准化的治疗手段。文献报道,无论是手术治疗还是药物治疗均存在有较高的治疗失败率。因此,探索一种确实、有效的治疗手段具有重要意义。中医学具有调节人体整体功能的作用,对很多慢性疾病具有独特的疗效。一些国内学者尝试采用中医药的方法治疗MUI取得一定疗效,但大部分报道均为个案报道和临床经验总结,有限的临床研究也都仅仅从患者症状改善的角度对疗效进行单一的主观评价,缺乏客观评价指标。因而无法提供有效的循证医学证据,限制了这些中医治疗手段在临床中的推广与应用。本课题组通过继承我院名老中医的学术思想,尝试应用调理脾胃法治疗MUI取得较好的疗效。本研究在前期研究的基础上,试图通过严谨的试验设计方案,采用国际公认的评价指标,评价基于调理脾胃法的针刺联合中药疗法对MUI的疗效。2.研究目的(1)评价基于调理脾胃法所组方的中药“益气缩泉汤”和针刺疗法对女性MUI的疗效。(2)探索“益气缩泉汤”和针刺疗法在治疗女性MUI方面是否存在增效作用。(3)探索针刺疗法与抗胆碱能西药在治疗女性MUI方面是否存在增效作用。3.研究方法本研究采用前瞻性、随机、多组平行对照的临床研究设计,使用QUID中文翻译版量表对女性MUI患者实现客观、量化诊断。在依据前期研究结果对研究所需的样本量进行估算后,将符合研究纳入标准的124例患者随机分为单纯针刺治疗组、单纯中药治疗组、针刺联合中药组和针刺联合西药治疗组。其中,单纯针刺治疗组采用针刺治疗,取穴包括双侧足三里、三阴交、次骼、会阳,其中次毼和会阳连接电针,采用疏密波(4/20hz)治疗30分钟,每周治疗3次；单纯中药组采用中药煎剂“益气缩泉汤”(炙黄芪30g,人参10g,当归10g,白术l0g,益智仁l0g,乌药6g,山药10g,陈皮10g,升麻l0g,柴胡l0g,覆盆子15g,炒莱菔子l0g)治疗,每次口服200ml,早晚分两次服用。针刺联合中药治疗组同时采用中药“益气缩泉汤”和针刺治疗;针刺治疗联合西药治疗组在针刺治疗的基础上,联合口服抗胆碱能药物酒石酸托特罗定缓释片4mg,每日1次。四组的治疗周期均为8周。研究的主要终点指标为通过24小时尿垫试验评价的患者每日漏尿量。次要终点指标包括：通过ICIQ-SF问卷评价的临床症状,72小时排尿日记评价的尿失禁(UI)发作频率,I-QOL问卷评价的患者生活质量和通过尿动力学检查评价的患者膀胱尿道功能。此外,研究过程中每组患者出现的不良事件以及不良事件的严重程度均被详细记录。对于主要终点指标的评价主要参考以下标准：①治愈：24小时尿垫试验转阴；②改善：24小时尿垫试验减低50%以上;③无效：24小时尿垫试验减低50%以下。研究中有效患者指治愈和改善患者的总和。研究结果的统计分析皆基于意向性分析(ITT)。对于定量资料的组间比较,当数据符合正态分布时4组间总体差异比较采用方差分析,非正态分布者采用Kruskal-Wallis H检验；对于定性资料的组间比较,4组间构成比的比较采用R×C表Chi-Square检验。当总体4组间存在显著性差异时,则进一步行任意两组间比较。定量资料当数据符合正态分布时采用两独立样本t检验,非正态分布者采用Wilcoxon秩和检验；对于定性资料构成比的比较采用Chi-Square检验或Fisher精确概率计算法,并采用Turky法调整检验水准。对于定量资料的组内比较,当数据符合正态分布时采用配对t检验,非正态分布者采用Wilcoxon符号秩和检验。对于定性资料组内构成比的比较采用McNemar检验。所有检验均为双侧检验,以P0.05作为统计学显著性差异指标。4.结果4.1一般情况本研究共纳入135名女性MUI患者,经筛查后剔除7例患者,研究过程中脱落4例患者,共124例患者至少完成一次以上的疗效评价,纳入最终结果分析。其中,年龄最小者为32岁,最大者为65岁,平均年龄为53.22±8.99岁。体重指数平均为22.69±2.79。患者入组时平均病程为4.5年,最少1年,最长为14年。四组患者在年龄、体重指数、病程和尿动力学指标等基线指标方面组间比较无显著差异(P0.05),提示四组患者资料具有良好的临床可比性(表1)。注：BMI：体重指数；Qmax:最大尿流率；PVR：膀胱残余尿量。a结果以x±s表示,组间比较采用方差分析;b结果以M(IQR)表示,组间比较采用Kruskal-Wallis H检验。4.2主要终点指标经过8周治疗,在不同治疗组中绝大多数患者均表现为改善和治愈,针刺联合中药治疗组的治愈率和有效率分别为29%和87.1%；单纯针刺治疗组的治愈率和有效率分别为16.1%和77.4%；单纯中药治疗组的治愈率和有效率分别为15.6%和75%；针刺治疗联合西药治疗组的治愈率和有效率分别为26.7%和83.3%。各治疗组在疾病的治愈率和有效率方面无显著性差异(P0.05)。就24小时尿垫试验所测量的患者每日漏尿量而言,各组患者的基线漏尿量无显著差异,表现为良好的临床可比性。8周后结果提示,各种治疗均能够显著降低患者的日漏尿量(表2)。其中,对比单纯针刺或中药治疗,针刺联合中药治疗能够更显著的降低患者的日漏尿量(P0.05)。虽然针刺联合西药治疗也表现出比单纯针刺或中药治疗更好的疗效,但却不具有统计学差异(P0.05)。4.3次要终点指标变化4.3.1临床症状评分变化治疗前各组患者ICIQ-SF问卷中各问题评分和总分均无显著性差异,提示各组患者基线症状的严重程度相似,具有良好的临床可比性。治疗8周后,各组患者的各项问题评分以及问卷总分均较基线值显著降低(表3),提示患者临床症状的改善。其中,针刺联合中药治疗组表现出最优的疗效,使患者中位ICIQ-SF总分由16分降至7分,但与其他治疗组相比无显著性差异(P0.05)。4.3.2 UI发作频率变化治疗前各组患者中位UI发作频率为4-5次/日,组间比较无显著性差异,具有良好的临床可比性。治疗8周后,各组患者UI日发作频率较基线水平均显著减少(表4),提示患者症状的改善。尽管针刺联合中药治疗更明显地降低了患者的U1日发作频率,由5次/日降为1次/日,但与其他治疗组相比无显著性差异(P0.05)。此外,8周治疗分别使83.9%(针刺联合中药组),74.2%(单纯针刺组),71.9%(单纯中药组)和83.3%(针刺联合西药组)的患者UI日发作频率降低50%以上,组间比较无显著性差异(P0.05)。4.3.3生活质量变化治疗前各组患者I-QOL问卷各方面评分和总分均无显著性差异,提示各组患者在基线具有相似的生活质量,具有良好的临床可比性。经过8周治疗,各组患者各方面生活质量均得到显著改善(表5)。其中,对比单纯针刺组,针刺联合中药组患者疗后具有更高的I-QOL总分,提示患者具有相对更高的生活质量。4.3.4膀胱尿道功能变化研究期间,共有43名MUI患者完成了基线和疗后的尿动力学评价。其中,针刺联合中药组12例,单纯针刺组13例,单纯中药组10例,针刺联合西药组8例。8周治疗后,各组患者的腹压漏尿点压力和尿道闭合压均得到显著增加(表6),组间比较无显著差异(P0.05)。其中,四组中各有41.7%,38.5%,40%和50%的患者腹压漏尿点压力恢复正常(150cmH2O)。然而,治疗后四组患者逼尿肌过度活动的发生率与基线相比无显著差异。4.3.5不良事件分析研究过程中共有11名患者报告了不良事件,但未发生严重不良事件。其中,针刺联合西药组具有更高的不良反应发生率(P0.05),共有7名患者出现口干,1名患者发生便秘。相比之下,其他治疗组仅有极少数患者报告不良事件。在针刺联合中药治疗组内1名患者描述一过性失眠；单纯针刺组有1名患者出现针刺部位淤血疼痛,经对症处理后症状消失；单纯中药治疗组内1名患者出现头晕,未经治疗自行缓解。5.结论(1)无论是基于调理脾胃法组方的益气缩泉汤还是针刺疗法都能够显著降低女性MUI患者的每日漏尿量,改善患者的临床症状,提高生活质量,并能够显著改善患者的膀胱尿道功能,具体表现为对腹压漏尿点压力和最大尿道闭合压力的提高。(2)益气缩泉汤与针刺疗法治疗MUI具有一定的协同增效作用,二者的联合治疗能够更有效地降低患者的每日漏尿量,提高患者的生活质量。(3)研究中未观察到针刺疗法与抗胆碱能西药联合治疗对女性MUI的协同治疗作用。
[Abstract]:1. study background mixed urinary incontinence (MUI) is a complex bladder and urethral dysfunction, with clinical features of stress urinary incontinence (SUI) and urgent incontinence (UUI). There is no standardized treatment for modern medicine. Therefore, it is of great significance to explore a true and effective means of treatment. Traditional Chinese medicine has the role of regulating the overall function of the human body and has a unique effect on many chronic diseases. Some domestic scholars have tried to treat MUI with traditional Chinese medicine, but most of the reports are case reports and clinical classics. The limited clinical study is only a single subjective evaluation of the curative effect from the angle of symptom improvement and lack of objective evaluation index. Therefore, it is impossible to provide effective evidence-based medical evidence and restrict the popularization and application of these traditional Chinese medicine methods in clinical practice. Think, try to use the method of regulating spleen and stomach for the treatment of MUI. On the basis of the previous study, this study tried to evaluate the effect of acupuncture combined with traditional Chinese medicine therapy based on the method of regulating spleen and stomach on the effect of.2. study on the effect of MUI based on the rigorous experimental design scheme and the internationally recognized evaluation index (1) to evaluate the group based on the method of regulating spleen and stomach. The effect of "Yiqi shigu Quan Tang" and acupuncture therapy on female MUI. (2) explore the effect of "Yiqi Jin Quan Tang" and acupuncture therapy on the treatment of female MUI. (3) explore whether acupuncture therapy and anti cholinergic western medicine have synergistic effect in the treatment of female MUI by using.3. method, this study is prospective, random, and more Group parallel control clinical research design, using the QUID Chinese version of the scale to achieve objective and quantitative diagnosis of female MUI patients. After estimating the sample size required by the previous research results, 124 patients were randomly divided into simple acupuncture treatment group, simple Chinese medicine treatment group, acupuncture combined with traditional Chinese medicine. Group and acupuncture combined with western medicine treatment group. Among them, the acupuncture treatment group was treated with acupuncture only. The acupoints included bilateral Zusanli, Sanyinjiao, iliac, and Hui Yang, of which the secondary and Hui Yang were connected with electroacupuncture, the 4/20hz was used for 30 minutes and 3 times a week; the Dan Chunzhong medicine group was treated with Chinese medicine decoction "Yiqi Qi Quan Decoction" (Radix Astragali 30g, ginseng 1) 0g, Chinese angelica 10g, Atractylodes L0g, yizhi L0g, yam 6G, yam 10g, orange peel 10g, cohosh L0g, bupleurum L0g, raspberry 15g, and radish semen L0g) treatment, each time taking 200ml, two times in the morning and evening. The acupuncture combined with Chinese medicine treatment group and the Chinese medicine "Yiqi shigu Quan Decoction" and acupuncture treatment; acupuncture treatment group in the treatment group of Western medicine treatment group in the base of acupuncture treatment On the basis of the combined oral anticholinergic drug Tolterodine Tartrate Sustained Release Tablets 4mg, 1 times a day. The four groups were treated for 8 weeks. The main end point of the study was the daily leakage of urine in patients evaluated through the 24 hour urinary cushion test. Secondary end points included the clinical symptoms evaluated through the ICIQ-SF questionnaire and the 72 hour urination diary. Urinary incontinence (UI) attack frequency, I-QOL questionnaire evaluated the quality of life and urinary bladder urethral function evaluated by urodynamic examination. In addition, the adverse events and the severity of adverse events in each group were recorded in detail. The evaluation of the main final indicators was mainly referred to as following criteria: (1) Recovery: 24 hours of urine cushion test turned negative; (2) improvement: 24 hour urine cushion test decreased by more than 50%; 3. Invalid: 24 hour urine cushion test decreased by 50%. The effective patients in the study were the total of cured and improved patients. The statistical analysis of the results were based on the intentionality analysis (ITT). The total difference between the 4 groups was compared with the analysis of variance, and the non normal distribution used Kruskal-Wallis H test. For the comparison of the qualitative data, the comparison between the 4 groups was compared with the R x C Chi-Square test. When there was a significant difference between the 4 groups, the comparison between the two groups was further compared. Quantitative data was used as data Fu Hezheng The two independent sample t test is used in the state distribution, and the non normal distribution uses the Wilcoxon rank sum test. The comparison of the qualitative data composition ratio uses the Chi-Square test or the Fisher precision probability calculation method, and the Turky method is used to adjust the test level. For the quantitative data group comparison, when the data conforms to normal distribution, the paired t test is used. Wilcoxon sign rank sum test was used for non normal distribution. McNemar test was used to compare the constituent ratio of qualitative data group. All tests were bilateral test, and P0.05 was used as a statistical significant difference index of.4. results 4.1. A total of 135 female MUI patients were included in this study. 7 patients were removed after screening. In 4 patients, a total of 124 patients were evaluated at least one time and more. Among them, the youngest was 32 years old and the largest was 65 years old and the average age was 53.22 + 8.99 years. The average course of disease was 4.5 years, at least 1 years and the longest was 14 years when the body mass index was 22.69 + 2.79.. The four group was in age and weight. There were no significant differences in baseline indicators, such as index, course of disease and urodynamic indicators (P0.05), suggesting that four groups of patients had good clinical comparability (Table 1). Note: BMI: body mass index; Qmax: maximum urine flow rate; PVR:.A results of urinary bladder residual urine.A were shown in X + s, and variance analysis was used in groups; B results were in M (IQR) table. Kruskal-Wallis H test was used to test the main end point of.4.2 for 8 weeks. Most of the patients in the different treatment groups were improved and cured. The cure rate and the effective rate of the acupuncture combined with Chinese medicine treatment group were 29% and 87.1%, respectively, and the cure rate and the effective rate of the simple acupuncture group were 16.1% and 77.4%, respectively. The cure rate and the effective rate of the pure Chinese medicine treatment group were 15.6% and 75% respectively. The cure rate and the effective rate of the acupuncture treatment group with the western medicine treatment group were 26.7% and 83.3%., respectively, and there was no significant difference in the cure rate and the efficiency of the disease in each treatment group (P0.05). In terms of the daily leakage of urine in the patients measured by the 24 hour urine cushion test, the patients in each group were in each group. There was no significant difference in the amount of baseline leaking urine. The results showed a good clinical comparability after.8 weeks. All kinds of treatments could significantly reduce the daily leakage of urine in patients (Table 2). In comparison with the treatment of pure acupuncture or traditional Chinese medicine, acupuncture combined with traditional Chinese medicine could significantly reduce the daily leakage of urine (P0.05) in the patients. It also showed better curative effect than pure acupuncture or traditional Chinese medicine treatment, but it did not have statistical difference (P0.05).4.3 secondary end point index change of 4.3.1 clinical symptom score. There was no significant difference in the score and total score of various problems in the ICIQ-SF questionnaire before treatment, suggesting that the severity of baseline symptoms in each group was similar, and it was good. 8 weeks after treatment, the scores of all the patients in each group and the total score of the questionnaire were significantly lower than the baseline (Table 3), indicating the improvement of the clinical symptoms of the patients. Among them, the acupuncture combined with Chinese medicine treatment group showed the best effect, which reduced the total score of ICIQ-SF from 16 to 7, but was not significant compared with the other treatment groups. There was no significant difference between the groups in each group before the treatment of the difference (P0.05).4.3.2 UI frequency change. There was no significant difference between the groups. There was a good clinical comparability between the groups. After 8 weeks of treatment, the frequency of UI day in each group was significantly less than that of the baseline (Table 4), indicating the improvement of the patient's symptoms. Although the acupuncture combined with Chinese medicine, the treatment was more effective. The frequency of U1 daily seizures was significantly reduced from 5 times to 1 times per day, but there was no significant difference compared with other treatment groups (P0.05). In addition, 8 weeks of treatment made 83.9% (acupuncture combined with Chinese medicine group), 74.2% (simple acupuncture group), 71.9% (pure Chinese medicine group) and 83.3% (acupuncture combined western medicine group) decreased more than 50% of UI day attack frequency. There was no significant difference between the groups (P0.05) and there was no significant difference in the score and total score of the I-QOL questionnaire in each group before the treatment of.4.3.3. It suggested that the patients in each group had a similar quality of life in the baseline and had a good clinical comparability. After 8 weeks of treatment, the quality of life in each group had been significantly improved. Table 5). Among them, compared with the simple acupuncture group, the patients with acupuncture combined with Chinese medicine group had a higher total score of I-QOL after treatment, suggesting that during the study of a relatively high quality of life of the patients with a higher quality of life.4.3.4, a total of 43 MUI patients completed the baseline and postoperative urodynamic evaluation. Among them, 12 cases were combined with acupuncture combined with traditional Chinese medicine group and 1 of pure acupuncture group. 3 cases, pure Chinese medicine group 10 cases, acupuncture combined with Western Medicine Group 8 cases of.8 weeks after treatment, all groups of abdominal pressure leakage urine point pressure and urethral closure pressure were significantly increased (Table 6), there was no significant difference between groups (P0.05). Among the four groups, 41.7%, 38.5%, 40% and 50% of the patients with abdominal pressure leak pressure recovered normal (150cmH2O). However, four after treatment, four There was no significant difference in the incidence of detrusor overactivity in the group of patients compared with the baseline. 11 patients reported adverse events in the.4.3.5 adverse event analysis, but there were no serious adverse events. Among them, acupuncture combined with western medicine group had a higher incidence of adverse reactions (P0.05), a total of 7 patients had a dry mouth and 1 patients occurred. Constipation. In comparison, only a few patients in other treatment groups reported adverse events. 1 patients in the acupuncture combined with Chinese medicine treatment group described a sexual insomnia; in the simple acupuncture group, 1 patients had pain in the acupuncture site and the symptoms disappeared after the treatment, and 1 patients in the treatment group were dizzy and untreated themselves. The relieving.5. conclusion (1) whether it is based on the prescription of regulating spleen and stomach and the acupuncture therapy can significantly reduce the daily leakage of urine in women's MUI patients, improve the clinical symptoms and improve the quality of life, and can significantly improve the bladder urethral function of the patients, specifically for the pressure of abdominal pressure leakage and the maximum urethral closure. 2. (2) Yiqi Quan Tang and acupuncture therapy have a certain synergistic effect on the treatment of MUI. The combined treatment of the two can effectively reduce the daily leakage of urine and improve the quality of life of the patients. (3) no observation of the synergistic effect of acupuncture therapy and anti cholinergic western medicine on female MUI.
【学位授予单位】：中国中医科学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R711.59

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