敷脐疗法干预功能性便秘的系统评价及临床研究

发布时间：2018-05-29 06:37

本文选题：脐疗 + 功能性便秘　；参考：《中国中医科学院》2017年博士论文

【摘要】：功能性便秘(functional constipation,FC)是临床常见病证,属于功能性胃肠病,诊断主要依据患者的症状。临床表现个体差异大,既包括传统意义上的便次减少(3次/周),也涵盖更广义范畴的排便困难,包括各种伴随不适,罗马Ⅲ标准是目前全球用于FC诊断、治疗的共识性文件。FC发病与膳食、体力活动、生活习惯、精神心理问题及滥用泻剂等因素有关,其病生理机制尚不十分清楚,主要与胃肠排空转运时间延长、肛门括约肌或盆底肌功能缺失相关。随着饮食结构的改变和生活节奏加快,FC在中年、青年人中也日渐多见,60岁以上人群患病率更可达22%。目前西医处理功能性便秘主要采用处方或非处方药物,以各种泻剂为主,慢传输型便秘可配合泻剂使用促动力药物,而排便障碍型便秘药物治疗效果不佳,循证医学建议给予生物反馈治疗(Ⅰ级证据、A级推荐),国内未普遍开展。因此,西医治疗便秘的疗效和安全性都有待提升。中医认为便秘的形成主要在于脏腑功能失调,大肠传导糟粕和输布津液功能异常。其病位在大肠,与肺、脾、胃、肾、肝、小肠和魄门相关。中医治疗便秘有着丰富的治疗体系,关注证候特点加以施治,缓解排便困难的同时有效解决多脏腑的整体协调问题。“自古良工不废外治”,脐疗用于治疗便秘历史悠久、价廉易行,药物透皮吸收,避免有效成分被各种酶类及消化液分解破坏,同时,减轻了胃肠道负担。近现代有大量文献报道敷脐治疗便秘安全、有效,但临床未得到很好的推广。其中原因需要探讨,包括临床使用的可行性、与西医药治疗相比的优势与劣势,能否结合施治等等。为回答这些问题,本研究做了三方面的工作:1、查阅文献,完成功能性便秘发病机制和中西医治疗进展两篇综述,深入学习相关知识,了解目前中西医治疗便秘的现状和发展方向;2、完成中药敷脐干预功能性便秘:随机对照试验的系统综述,深入了解运用敷脐疗法治疗功能性便秘的临床科研现状,发现在治法治则、疗效评价等方面的问题;3、应用随机、双盲、安慰剂对照临床试验,以功能性便秘中的实秘患者为研究对象,观察大承气汤复方敷脐治疗实秘的疗效,以期为进一步研究奠定基础,也为临床使用提供思路和依据。一、系统综述目的:系统评价脐疗干预功能性便秘的有效性和安全性。方法依据 Cochrane 系统评价方法,检索 PubMed、Embase、The Cochrane Library、中国生物医学文献数据库、中国知网数据库、万方数据库、重庆维普数据库和相关文章的参考文献,纳入脐疗与安慰剂、空白和常规西药比较干预功能性便秘的随机对照试验。由两名研究者独立进行文献筛选、数据提取和纳入研究的质量评价。对同质性研究进行Meta分析,异质性较高的研究仅作定性分析。采用漏斗图检测可能的发表偏倚。应用GRADEpro软件对纳入研究的主要对照组中主要结局指标生成证据质量汇总表。结果:共纳入9项随机对照临床试验,包括945个患者。6项研究报告了随机化方法,1项研究使用了安慰剂,没有研究描述结局评价者盲法、样本量计算和意向性分析。由于异质性较高,仅3项研究纳入meta分析。结果发现,脐疗与常用西药(枸橼酸莫沙必利、大黄碳酸氢钠片、聚乙二醇4000散)比较,对于功能性便秘的总有效率作用相当(RR 1.10;95%CI 0.99 to 1.22;3 trials,n=120;I2 =37%)。多数研究支持脐疗联合基础治疗比单纯基础治疗可以更好地改善功能性便秘患者的主要症状积分。尚未发现脐疗干预功能性便秘患者存在严重不良反应。纳入研究的整体方法学质量较低且主要结局指标的证据质量仅为“中等水平”。结论:现有的临床证据表明,脐疗干预功能性便秘在总有效率和改善主要症状积分方面可能有益,且无严重不良反应。然而,由于纳入研究的数量和整体质量有限,且部分研究因异质性较高无法进行合并分析,脐疗干预功能性便秘的有效性和安全性尚不能得出肯定结论,还有待更多高质量的临床研究进行验证。二、临床研究目的:证实大承气汤复方敷脐联合西药治疗实秘的疗效优于单用西药。方法:以功能性便秘中的实秘患者为研究对象,疾病符合罗马Ⅲ诊断标准,证侯包括肠胃积热证和气机郁滞证。采用随机、双盲、安慰剂对照临床试验设计,根据既往研究计算样本量,募集患者,将符合试验条件的受试者随机分为试验组和对照组。试验组采用大承气汤(大黄:芒硝:厚朴:枳实为2:1:4:2)复方敷脐联合口服乳果糖治疗,对照组采用安慰剂敷脐联合口服乳果糖治疗,疗程14天。主要结局指标选用可量化的客观指标:排便频率和首次排便时间,次要指标涵盖主观、客观指标,分别是自评症状评分、生存质量满意度评分、结肠传输指标(72小时钡条存留部位与数量,结肠传输指数)、肛门直肠测压指标(感觉指标、动力指标)。所有受试者均签署知情同意书,分别接受培训,在治疗期与观察期内坚持填写治疗手册,每周随访一次。在治疗前依据证侯标准分出虚秘和实秘,实秘在治疗前、后及观察四周后共进行三次PRO量表评估,治疗前、后两次予以结肠传输试验和高分辨直肠肛管测压,采集数据,评估患者治疗前后排便频率、肠道传输功能、肛直肠动力及主观感受的变化,观察不良反应。临床试验按照CONSORT声明进行报告。严格执行随机化和随机方案的隐藏,试验过程中,对所有患者、药师、医生、护士、数据管理和统计分析人员实施盲法,使已知的偏倚达到最小。结果:(1)符合诊断的66位患者随机分为试验组和对照组,试验组脱落2人,31人纳入分析;对照组治疗期脱落3人,观察期剔除2人,30人纳入疗效分析,28人纳入远期疗效分析。(2)基线资料结果显示,试验组和对照组在人口特征数据和结局指标的基线资料方面差异均无统计学意义,具有可比性;(3)治疗后,试验组主要结局指标排便频率的改善优于对照组(t=-5.39,P0.001,95%CI:-2.28,-1.05);首次排便时间缩短,与对照组比较差异有统计学意义(卡方值=4.86,P=0.0285)。(4)治疗后,结局指标的主观指标得以改善。试验组排便困难积分和主诉症状积分的改善优于对照组(t=-4.26,P0.001;t=-2.36,P0.05)。生存质量总满意度积分优于对照组(t=-2.78,P0.05,95%CI:-2.22,-0.36)。(5)治疗后,结局指标的客观指标也得以改善,试验组72小时直肠、乙状结肠钡条存留数与对照组比较差异有统计学意义(差值:-1.63,95%CI:-3.07,-0.19,P0.05);治疗后,便秘的分型构成出现差异,以排便障碍型便秘改善最为明显。肛管直肠动力学感觉指标FSV、DSV、DTV、MTV在治疗后组间比较及治疗前后变化值在组间的比较均有显著差异(P0.001);动力指标中肛管静息压、模拟排便时肛门括约肌压力的变化在治疗后组间比较及治疗前后变化值在组间的比较差异均有统计学意义(P0.05),矛盾收缩得以缓解。(4)停药观察四周后,周排便次数组间差异有统计学意义(t=-5.15,P0.001,95%CI:-2.22,-0.98),排便困难积分、大便性状积分、主诉症状积分组间差异均有统计学意义(P0.001),试验组远期疗效好于对照组。(5)试验组不良反应发生率低,程度较轻。结论:(1)大承气汤复方敷脐联合西药治疗实秘临床疗效肯定,优于单用西药,能有效缓解排便困难,改善伴随症状,提高患者生存质量满意度。(2)该法对实秘患者中排便障碍型便秘的改善优于其它分型。(3)与西药乳果糖联合使用能增强疗效,减少副作用。(4)敷脐疗法干预功能性便秘,可以应用主观PRO量表与客观的便秘评价指标结合进行疗效评价。
[Abstract]:Functional constipation (functional constipation, FC) is a common clinical syndrome. It belongs to functional gastrointestinal disease. The diagnosis is based on the symptoms of the patients. The clinical manifestations are very different, including the traditional reduction (3 times per week), and the more broad category of defecation, including all kinds of discomfort. The Rome III standard is the present world. The common understanding document.FC for FC diagnosis is related to diet, physical activity, living habits, mental and psychological problems and abusing laxatives. The physiological mechanism of the disease is not very clear. It is mainly related to the prolongation of the transit time of gastrointestinal emptying, the loss of anal sphincter or pelvic floor muscle power, with the change of diet structure and the rhythm of life. Speed up, FC in middle age, young people are becoming more and more common, the prevalence rate of people over 60 years of age is up to 22%., the current western medical treatment for functional constipation mainly uses prescription or non prescription drugs, mainly with various laxatives, slow transmission constipation can be combined with laxatives for the use of stimulating drugs, and the effect of defecation type constipation is not effective, evidence-based medicine The effect and safety of Western medicine in the treatment of constipation need to be promoted. Therefore, the formation of constipation in western medicine is to be improved. The formation of constipation is mainly due to the dysfunction of the viscera, the large intestine conduction of dross and the transfer of body fluid. The disease is in the large intestine, the lung, spleen, stomach, kidney, liver, small intestine and soul. TCM treatment of constipation has a rich treatment system, pay attention to the syndrome characteristics to treat, alleviate the difficulty of defecation and solve the overall coordination problem of multiple viscera. "Ancient good workers do not waste external treatment". Umbilical therapy is used to treat constipation with a long history, cheap and easy to use, drug transdermal absorption, and avoid the effective components of various enzymes and digestive juice. There is a lot of literature reports on the safety and effectiveness of umbilicus in the treatment of constipation in recent modern times, but it has not been popularized well. The reasons need to be discussed, including the feasibility of clinical use, the advantages and disadvantages compared with the western medicine treatment, the combination of treatment and so on. To answer these questions, this study does this study. Three aspects of the work: 1, consult the literature, complete the pathogenesis of functional constipation and the progress of the treatment of Chinese and Western medicine two reviews, in-depth study of relevant knowledge, to understand the current situation and development direction of constipation in the treatment of Chinese and Western medicine; 2, complete Chinese medicine umbilical intervention functional constipation: a systematic review of randomized controlled trials and in-depth understanding of the application of the rule of law to the rule of law. The clinical research status of functional constipation, found in the treatment of the rule of law, the efficacy of evaluation and other aspects of the problems. 3, the application of random, double blind, placebo controlled clinical trials, functional constipation in the constipation patients as the research object, to observe the effect of Dachengqi Decoction compress umbilicus in the treatment of constipation, in order to lay the foundation for further study, and for clinical cause The purpose of this paper is to provide a systematic review for the purpose of systematic review: to systematically evaluate the effectiveness and safety of umbilical therapy in the intervention of functional constipation. Methods based on the Cochrane system evaluation method, PubMed, Embase, The Cochrane Library, Chinese biomedical literature database, Chinese knowledge network database, Wanfang database, Chongqing VIP database and related data are used. The reference of the article was included in the randomized controlled trial of umbilical therapy and placebo, blank and conventional western medicine to intervene in functional constipation. Two researchers were selected independently for literature screening, data extraction and quality evaluation. Meta analysis of homogeneity study was carried out. The high heterogeneity study was only qualitative analysis. Funnel graph examination was used. The possible publication bias was measured. The GRADEpro software was used to generate the evidence quality summary of the main outcome indicators in the main control group. Results: 9 randomized controlled clinical trials were included in 945 patients, including the randomization method, 1 studies used comfortant, and no study described the outcome evaluator blindness. This quantity calculation and intentionality analysis. Due to high heterogeneity, only 3 studies were included in meta analysis. The results showed that umbilical therapy and common western medicine (mosapride citrate, rhubarb Sodium Bicarbonate Tablets, polyethylene glycol 4000 powder) were more effective for functional constipation (RR 1.10; 95%CI 0.99 to 1.22; 3 trials, n=120; I2 =37%). The conclusion is that umbilical therapy combined with basic therapy can better improve the main symptom score of patients with functional constipation. There is no serious adverse reaction in patients with functional constipation in umbilical therapy. The quality of the integrated methodology in the study is low and the quality of the main outcome indicators is only "moderate". Existing clinical evidence suggests that umbilical therapy intervention in functional constipation may be beneficial in terms of total efficiency and improvement of the main symptom score, and there is no serious adverse reaction. However, the effectiveness of umbilical therapy to interfere with functional constipation may be due to the limited number of studies and the limited overall quality of the study. The safety still can not draw the positive conclusion, still need more high quality clinical research to carry on the verification. Two, the clinical research aim: it is proved that the curative effect of Dachengqi Decoction compress the umbilicus combined with western medicine is superior to the western medicine alone. Method: the patients in the constipation of functional constipation are the research object, the disease conforms to the Rome III diagnostic standard, the syndrome includes the syndromes including A randomized, double blind, placebo controlled clinical trial was designed with a randomized, double-blind, placebo-controlled clinical trial. According to the previous study, the patients were collected and the subjects were randomly divided into the experimental group and the control group. The experimental group was treated with Dachengqi Decoction (rhubarb: Magnolia: Magnolia: Fructus aurantii 2:1:4:2) combined navel combined oral milk fruit. The control group was treated with a placebo and oral lactulose combined with oral lactulose for 14 days. The main outcome indexes were quantifiable objective indicators: the frequency of defecation and the first defecation time, the subjective index, the objective index, the self-evaluation symptom score, the quality of life satisfaction score, and the colon transmission index (72 hours barium strip retention). Position and quantity, colon transmission index), anorectal manometry index (sensory index, dynamic index). All subjects signed informed consent, received training separately, followed up the treatment manual during the treatment and observation period, followed up once a week. Before treatment, the constipation and constipation were divided according to the standard of syndrome. Before and after the treatment, the constipation was observed and observed. Three PRO scales were carried out after four weeks. Before and after treatment, the colonic transmission test and high resolution anorectal manometry were performed two times. The data were collected to assess the frequency of defecation, intestinal transmission function, anorectal motility and subjective feelings before and after treatment. The clinical trials were reported in accordance with the CONSORT statement. In the course of randomization and randomization, all patients, pharmacists, doctors, nurses, data management and statistical analysts were carried out blind method to minimize the known bias. Results: (1) the 66 patients who were diagnosed were randomly divided into the experimental group and the control group, the test group dropped 2 people, 31 people were analyzed, and the control group dropped 3 during the treatment period. In the observation period, 2 people were eliminated, 30 were included in the curative effect analysis, and 28 people were included in the long-term effect analysis. (2) the baseline data showed that there was no statistical difference between the experimental group and the control group in the baseline data of the demographic data and the outcome indicators. (3) the improvement of the frequency of the defecation of the main outcome indicators of the experimental group was better than that of the control group after treatment. Group (t=-5.39, P0.001,95%CI:-2.28, -1.05), the first defecation time shortened, compared with the control group, the difference was statistically significant (chi square value =4.86, P=0.0285). (4) after treatment, the subjective indicators of the outcome index were improved. The improvement of the difficulty score of the test group and the symptom score of the main complaint was better than that of the control group (t=-4.26, P0.001; t=-2.36, P0.05). The total satisfaction score was better than that of the control group (t=-2.78, P0.05,95%CI:-2.22, -0.36). (5) the objective index of the outcome index was also improved after treatment. The 72 hour rectum in the test group and the barium strip in the sigmoid colon were significantly different from the control group (the difference: -1.63,95%CI:-3.07, -0.19, P0.05). After treatment, the subtypes of constipation were poor. The anorectal motility index FSV, DSV, DTV, and MTV were significantly different between groups after treatment and before and after treatment (P0.001); the dynamic index of anal canal resting pressure and the changes of anal sphincter pressure during the simulated defecation were compared and treated after treatment. There were statistically significant differences between the pre and post changes in the group (P0.05), and the contractions were relieved. (4) there were statistical significance (t=-5.15, P0.001,95%CI:-2.22, -0.98), the integral of defecation difficulties, the integral of stool characters, and the statistical significance (P0.001). The long-term effect of the test group was better than that of the control group. (5) the incidence of adverse reactions in the experimental group was low and the degree was lighter. Conclusion: (1) the clinical efficacy of Dachengqi decoction combined with the combination of umbilical cord and Western medicine in the treatment of constipation is affirmative, which is superior to the western medicine alone. It can effectively relieve the difficulty of defecation, improve the accompanying symptoms and improve the satisfaction of the patient's quality of life. (2) the method has a barrier of defecation in the patients with constipation. The improvement of hinder constipation is better than that of other types. (3) combined use of lactulose with western medicine can enhance the curative effect and reduce side effects. (4) applying umbilical therapy to intervene functional constipation, we can use the subjective PRO scale and objective constipation evaluation index to evaluate the curative effect.
【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】：2017
【分类号】：R246.1

【参考文献】