中医药防治慢性乙型肝炎循证医学工作平台的构建和应用研究

发布时间：2018-08-17 13:50

【摘要】：背景：循证医学是近20年来在临床医学实践中发展起来的一门新兴临床方法学,其研究的原则和方法日益受到人们的重视,广泛应用于临床医学研究。近年来的循证医学实践已改变了许多现代医学治疗疾病的用药原则和方法,使治疗方案更科学、更严谨,对现代医学的发展产生了巨大的影响。中医药学是中华民族的优秀文明成果,在理论和实践上有其独特的优势和鲜明的特色,将循证医学的方法用于中医药学的研究是近年来关心的热点,采用循证医学的原则和方法指导今后的中医药临床研究,改善研究方法,提高中医药临床研究质量,必将推动中医药学的发展。目前,尚缺乏成熟供临床科研广泛应用的专门用于中医药治疗慢性乙型肝炎的循证医学工作平台,为提高中医药防治和研究慢性乙型肝炎的能力和水平,构建中医药防治和研究慢性乙型肝炎循证医学工作平台显得十分必要和迫切。目的：为开展中医药防治慢性乙型肝炎的循证医学评价(评价和寻找已有的循证医学证据)、临床决策(指导临床运用循证医学证据)和临床研究(提供新的循证医学证据)提供中医临床循证医学信息化工作平台。方法：在中医基础理论和循证医学思想指导下,结合数理统计方法、计算机技术的全面应用,通过多学科整合,构建循证医学工作平台,全面收集慢性乙型肝炎临床诊疗数据,实现慢性乙型肝炎临床诊疗信息的规范化采集,构建慢性乙型肝炎病证信息数据库,为相关临床研究提供基础数据支撑。建立中医药治疗慢性乙型肝炎循证医学工作平台,为临床诊疗慢性乙型肝炎提供循证医学的证据资料和研究工具,采用循证医学方法评价中医药治疗慢性乙型肝炎的临床研究,完成中医药治疗慢性乙型肝炎临床观察文献质量评价。建立循证医学工作平台,回顾性收集慢性乙型肝炎病例资料,筛选慢性乙型肝炎发展为肝硬化、肝癌等严重临床结局的危险因素,初步确立慢性乙型肝炎预后评估指标。建立循证医学工作平台,对慢性乙型肝炎患者病证信息长期追踪随访,对其进行定期检测和综合评价,评估慢性乙型肝炎发展为肝硬化、肝癌等严重临床结局的危险性大小,建立慢性乙型肝炎病程进展监测体系。平台构建和设计首先必须准确了解与分析用户需求。需求分析是整个构建过程的基础,是最困难、最耗费时间的一步。作为“地基”的需求分析是否做得充分与准确,决定了在其上构建“大厦”的速度与质量。分析需求主要包括需求收集和需求分析两个阶段,需求收集可采用临床跟班、专人询问、设计调查表请临床医生填写等多种方式,以满足临床需求和突出中医药诊疗特色为需求分析的基本原则。为了保障平台构建方案的可行性,采取总体设计、分步实施的构建原则。第一步是构建慢性乙型肝炎临床病证信息采集系统,系统试运行稳定后,考虑纳入大样本、多中心病例；第二步是中医肝病文献管理系统的构建,在收集中医药治疗肝病文献基础上,分析研究全文检索的搜索引擎开源框架库lucene,改进lucene结果相关性排序算法；第三步是临床决策支持系统的筹建,以创建慢性乙型肝炎临床诊疗数据仓库为主要目标。由于中医临床研究的复杂性,致使其信息系统和信息处理技术要求高、难度大,故采取先易后难的方法。以前期相关课题为数据源基础,以慢乙肝病人临床病证数据库的构建为突破口,探索中医临床数据处理的有效方法,积累经验,最终满足中医临床研究需求。结果：慢性乙型肝炎病证采集系统的建立,为中医临床信息的采集和存贮提供规范和统一标准,有利于这些信息的有效利用,为日后实现大样本、多中心的临床研究提供了一个有效的工作平台,为构建海量中医临床病证信息仓库提供可靠的数据来源。中医肝病文献管理系统的建立,通过对海量文献信息的筛选、过滤和分类,为临床医生获取有价值的文献信息提供一个高效、专业的分类文献库,结合循证医学思想和方法实现对中医药治疗慢性肝病临床疗效的系统评价,为中医药疗效评价提供高级别的循证医学证据。根据本研究制定的纳入标准和排除标准,共检索出符合要求的中医药治疗慢性乙型肝炎临床研究文献281篇,根据循证医学评价标准,中医药治疗性的RCT文献数量呈逐年增多趋势,但总体研究质量还有待继续提高,应重视临床研究设计的方法学研究。本研究认为难以为建立中医药疗效评价体系提供科学、有效、真实的证据,缺乏大量可纳入循证医学评价的高质量临床研究。本研究全面检索中医药干预HBeAg阴性慢性乙型肝炎的临床观察文献,对最终符合纳入标准的24篇相关文献进行meta分析,分别比较中西医结合治疗组与单纯西医、单纯中医治疗的疗效差异,中西医结合治疗对改善肝功能,延缓病情发展确有一定优势,由于纳入文献数目偏少,文献质量偏低,有待后续研究进一步证实。经Logistic回归分析,本研究筛选出慢性乙型肝炎发生严重临床结局的独立危险因素包括ALP, GGT,年龄,TBIL, HBV-DNA,性别等。经Cox回归分析,年龄、ALB、性别、TBIL、HBV-DNA为慢性乙型肝炎发生肝硬化、肝癌等严重临床结局的独立影响因素。其中年龄、性别、HBV-DNA、TBIL同时进入两个多因素分析模型,年龄越长,性别为男性,HBV-DNA、TBIL水平升高,发生肝硬化、肝癌等严重临床结局的危险性越高。经判别分析,据判别分析结果,并结合临床应用的实用性和可行性,选择年龄、性别、总胆红素TBIL、口-谷氨酰转肽酶GGT、HBV-DNA等5个观察指标,构建分值在0-41分之间的慢性乙型肝炎临床预后评估模型。分值越高,发生严重临床结局的危险越高。根据预后评估模型研究结果,年龄在50岁以上,肝功能指标GGT55(u/l), TBIL18(umol/l),血清病毒学标志物HBV-DNA病毒载量105(copies/l)的慢性乙型肝炎男性患者为发生肝硬化＼肝癌等严重临床结局的高危人群。慢性乙型肝炎病证信息库的建立,通过对病例数据分布式网络化录入,实现慢性乙型肝炎病例资料结构化管理,大大提高了临床研究效率,对于发现病情进展影响因素,准确认识疾病发生发展过程也将会起到积极作用,为慢性乙型肝炎病程进展规律的深入研究,为后期临床监测体系的建立提供真实、可靠的数据源。该病证信息库收集了262例轻、中度慢性乙型肝炎患者病证资料,对年龄、性别、总胆红素TBIL、口-谷氨酰转肽酶GGT、HBV-DNA等5个观察指标重点监测,评估其发生肝硬化、肝癌等严重临床结局的危险性高低,构建可长期追踪随访的临床监测体系。结论：本研究综合集成了中医药学、循证医学、数理统计学和计算机技术与方法,为慢性乙型肝炎中医临床研究工作者开展循证医学实践提供规范化、信息化的工作平台,中医药治疗慢性乙型肝炎循证医学工作平台的建立与应用,为循证医学在中医临床研究中的推广应用提供一个示范性工作平台。
[Abstract]:BACKGROUND: Evidence-based medicine (EBM) is a new clinical methodology developed in clinical medicine practice in the past 20 years. Its research principles and methods have been paid more and more attention and widely used in clinical medicine research. The scheme is more scientific and rigorous, which has a tremendous impact on the development of modern medicine. Traditional Chinese medicine (TCM) is an excellent civilization achievement of the Chinese nation. It has its unique advantages and distinct characteristics in theory and practice. The application of evidence-based medicine (EBM) in the research of TCM is a hot topic in recent years. The principles and formulas of EBM are adopted. It will promote the development of traditional Chinese medicine to guide future clinical research of traditional Chinese medicine, improve research methods and improve the quality of clinical research of traditional Chinese medicine. It is necessary and urgent to construct an evidence-based medicine platform for the prevention and treatment of chronic hepatitis B.
OBJECTIVE: To provide information platform for clinical evidence-based medicine (EBM) of TCM in prevention and treatment of chronic hepatitis B (CHB), clinical decision-making (guiding clinical application of evidence-based medicine) and clinical research (providing new evidence-based medicine).
Methods: Under the guidance of the basic theory of traditional Chinese medicine and the thought of evidence-based medicine, combined with the comprehensive application of mathematical statistics and computer technology, the work platform of evidence-based medicine was constructed through multi-disciplinary integration, and the data of clinical diagnosis and treatment of chronic hepatitis B were collected comprehensively. The standardized collection of clinical diagnosis and treatment information of chronic hepatitis B was realized and the chronic hepatitis B was constructed. Establishing an evidence-based medicine platform for the treatment of chronic hepatitis B, providing evidence-based medicine and research tools for clinical diagnosis and treatment of chronic hepatitis B. Evidence-based medicine was used to evaluate the clinical research on the treatment of chronic hepatitis B. To evaluate the literature quality of clinical observation on chronic hepatitis B treated with traditional Chinese medicine, establish evidence-based medicine platform, retrospectively collect the data of chronic hepatitis B cases, screen the risk factors for the development of chronic hepatitis B into severe clinical outcomes such as cirrhosis and hepatocellular carcinoma, establish the prognostic evaluation index of chronic hepatitis B and establish evidence-based medicine. Learning platform, long-term follow-up of chronic hepatitis B patients'disease information, regular detection and comprehensive evaluation, evaluation of chronic hepatitis B to develop into cirrhosis, liver cancer and other serious clinical outcomes of the size of the risk, the establishment of chronic hepatitis B disease progression monitoring system.
Requirement analysis is the foundation of the whole construction process, the most difficult and time-consuming step. The adequacy and accuracy of requirement analysis as a "foundation" determines the speed and quality of building a "building" on it. Set and demand analysis are two stages. Needs can be collected by clinical attendants, special inquiries, questionnaires designed for clinicians to fill in and other ways to meet clinical needs and highlight the characteristics of traditional Chinese medicine diagnosis and treatment as the basic principles of demand analysis. The first step is to build a chronic hepatitis B clinical syndrome information acquisition system, the system trial run stable, consider into large samples, multi-center cases; the second step is the construction of traditional Chinese medicine liver disease literature management system, based on the collection of traditional Chinese medicine treatment of liver disease literature, research and analysis of full-text search engine open source framework library lucene, change The third step is the preparation of the clinical decision support system to create a clinical diagnosis and treatment data warehouse of chronic hepatitis B as the main goal. The subject is based on the data source, taking the construction of the clinical syndrome database of patients with chronic hepatitis B as a breakthrough point, to explore the effective methods of clinical data processing of traditional Chinese medicine, accumulate experience, and ultimately meet the needs of clinical research of traditional Chinese medicine.
Results: The establishment of the collection system of chronic hepatitis B syndromes provides a standard and unified standard for the collection and storage of clinical information of TCM, which is conducive to the effective utilization of this information, provides an effective working platform for the future large sample and multi-center clinical research, and provides a platform for the construction of a large amount of information warehouse of TCM clinical syndromes. The establishment of a literature management system for liver diseases of traditional Chinese medicine provides an efficient and professional classification literature base for clinicians to obtain valuable literature information by screening, filtering and classifying massive literature information. It provides high-level evidence-based medical evidence for the evaluation of TCM efficacy.
According to the inclusion criteria and exclusion criteria formulated by this study, 281 clinical research literatures on chronic hepatitis B treated by traditional Chinese medicine were retrieved. According to the evaluation criteria of evidence-based medicine, the number of therapeutic RCT literatures of traditional Chinese medicine increased year by year, but the overall research quality still needs to be improved. The clinical research design should be emphasized. Methodological research. This study considers that it is difficult to provide scientific, effective and real evidence for the establishment of a therapeutic evaluation system of traditional Chinese medicine, and lacks a large number of high-quality clinical studies that can be included in the evaluation of evidence-based medicine. The meta-analysis of the relevant literature, respectively, compares the curative effect difference between the treatment group of integrated Chinese and Western medicine and the treatment group of Western medicine alone. The treatment of integrated Chinese and Western medicine has certain advantages in improving liver function and delaying the development of the disease.
Logistic regression analysis showed that the independent risk factors for severe clinical outcomes of chronic hepatitis B were ALP, GGT, age, TBIL, HBV-DNA, sex, etc. Cox regression analysis showed that age, ALB, sex, TBIL, HBV-DNA were independent risk factors for severe clinical outcomes of chronic hepatitis B, such as cirrhosis and liver cancer. Gender, HBV-DNA and TBIL entered two multivariate analysis models at the same time. The older the age, the male, the higher the level of HBV-DNA and TBIL, the higher the risk of severe clinical outcomes such as cirrhosis and liver cancer. The higher the score, the higher the risk of serious clinical outcomes. According to the results of the prognostic evaluation model, the age above 50 years old, liver function indicators GGT55 (u/l), TBIL18 (umol/l), serum virological markers. Male chronic hepatitis B patients with HBV-DNA viral load 105 (copies/l) were at high risk for severe clinical outcomes such as cirrhosis and liver cancer.
The establishment of chronic hepatitis B syndrome information database can realize the structured management of chronic hepatitis B case data through distributed and network input of case data. It can greatly improve the efficiency of clinical research. It will also play a positive role in finding out the influencing factors of disease progress and accurately understanding the process of disease occurrence and development. The data of 262 patients with mild to moderate chronic hepatitis B were collected from the disease information bank. The five indexes, including age, sex, total bilirubin TBIL, oral-glutamyl transpeptidase GGT, HBV-DNA, were monitored to evaluate the occurrence of liver disease. The risk of severe clinical outcomes such as cirrhosis and hepatocellular carcinoma is high or low.
Conclusion: This study integrates the traditional Chinese medicine, evidence-based medicine, mathematical statistics and computer technology and methods to provide a standardized and informationized platform for the clinical research workers of chronic hepatitis B to carry out evidence-based medicine practice. The establishment and application of evidence-based medicine platform of traditional Chinese medicine for the treatment of chronic hepatitis B are also discussed. The application of syndrome medicine in clinical research of traditional Chinese medicine provides an exemplary work platform.
【学位授予单位】：湖北中医药大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R259

【参考文献】