幽门螺旋杆菌一线治疗方案疗效和安全性：系统评价和网状meta分析

发布时间：2018-08-25 18:23

【摘要】：第一部分中国幽门螺旋杆菌一线治疗方案疗效和安全性:系统评价和网状meta分析幽门螺旋杆菌(Hpylori)感染是全球的巨大挑战之一,这种微生物感染了全球超过60%的自然人群,是慢性活动性胃炎、消化性溃疡病、胃粘膜相关淋巴组织淋巴瘤、胃癌的主要致病因素之一。对于幽门螺旋杆菌的根除方案的疗效和安全性,亚洲、欧洲及拉丁美洲的临床研究证据得出了不一致的结论。目的:比较我国临床常用的一线治疗方案的疗效和不良反应并基于概率进行排序,为临床幽门螺旋杆菌感染的治疗提供科学的参考依据。方法:系统检索电子数据库包括万方数据期刊论文资源、中国科学引文数据库、Web of Science、PubMed等,筛选2008年至2014年12月比较临床常用的一线幽门螺旋杆菌根除方案,包括标准的序贯治疗方案、新铋剂四联疗法、左氧氟沙星优化三联方案、7天和10天的标准三联疗法的随机对照试验。使用头对头的meta分析、网状meta分析和单组率的meta分析,定量综合这些一线治疗方案相对的和绝对的疗效和不良反应,并使用获益-风险分析方法评价各个方案的患者接受程度。采用Jadad评分评价随机对照试验的方法学质量,构建漏斗图定性测量发表偏倚,漏斗图的不对称性检验使用Egger线性回归法或者Begg秩相关法。结果:总共纳入了 45个初治幽门螺旋杆菌感染的随机对照试验,包括6148名接受根除治疗的感染者。网状meta分析显示:就幽门螺旋杆菌根除率而言,标准序贯治疗方案vs.10天标准三联方案的OR 2.90(95%CI 1.99,4.29);新铋剂四联疗法vs.10天标准三联方案的OR 2.85(95%CI 1.75,4.80);左氧氟沙星优化三联方案vs.10天标准三联方案的OR 2.37(95%CI 1.27,4.48),但是左氧氟沙星优化三联方案、标准序贯治疗方案、新铋剂四联疗法的两两比较却没有显示出统计学上的差异。标准序贯治疗方案有42%概率成为最高效的幽门螺旋杆菌根除方案;左氧氟沙星优化三联方案有80%可能性成为不良事件发生率最低的干预措施,而且这种方案有60%可能性成为患者接受度最高的干预措施。铋剂四联方案有55%的概率成为不良反应发生最高的根除方案。结论:在中国临床常用的5种一线幽门螺旋杆菌根除方案中,标准序贯治疗方案和左氧氟沙星优化三联方案优于其他的治疗选择。第二部分幽门螺旋杆菌细菌培养药敏试验指导的治疗方案和新一线四联方案:系统评价和网状meta分析在抗生素耐药时代,幽门螺旋杆菌(H.pylori)感染仍是全球的巨大公共卫生挑战,这种微生物感染是世界范围内最常见的传染病之一,幽门螺旋杆菌是慢性活动性胃炎、消化性溃疡病、胃粘膜相关淋巴组织淋巴瘤、胃癌的主要致病因素之一。针对日益升高的抗生素耐药开发的新的经验性一线四联方案的疗效和安全性,亚洲、欧洲及拉丁美洲的临床研究证据得出了颇有争议的结论,新开发的治疗策略包括伴同治疗方案、混合治疗方案、序贯治疗方案、新铋剂四联方案,在临床环境中的优劣仍然没有定论。目前尚缺乏多中心的随机对照试验比较这些一线根除方案和细菌培养药敏试验指导的根除方案的相对疗效。目的:比较基于细菌培养药敏试验指导的方案和新的四药方案的疗效和不良反应,并进行概率排序,为临床幽门螺旋杆菌的根除提供科学的参考依据。方法:系统检索电子数据库包括万方数据期刊论文资源、中国科学引文数据库、Web of Science、EMBASE、PubMed 等,筛选 2010 年到 2015 年 6 月比较基于细菌培养药敏试验指导的治疗方案和新的四药幽门螺旋杆菌根除方案,纳入分析的治疗方案包括药敏试验指导的方案、伴同治疗方案、混合治疗方案、序贯治疗方案、新铋剂四联方案的随机对照试验。通过传统的直接比较meta分析、网状meta分析和单组率的meta分析,定量综合这些方案的相对的和绝对的根除率和不良反应发生率,并使用获益-风险分析方法评价各个方案的患者接受程度。采用Jadad评分量表评价随机对照试验的方法学质量,构建漏斗图定性测量发表偏倚,漏斗图的不对称性检验使用Egger线性回归法或者Begg秩相关法。结果:总共纳入20个初治幽门螺旋杆菌感染的随机对照试验,包括6753名幽门螺旋杆菌感染者。对合格的随机对照试验数据进行的网状meta分析表明:就幽门螺旋杆菌根除率而言,伴同治疗方案vs.细菌培养药敏试验指导的治疗方案OR0.47(95%CI 0.24,0.84);新铋剂四联疗法vs.细菌培养药敏试验指导的治疗方案OR 0.43(95%CI 0.23,0.73);细菌培养药敏试验指导的治疗方案vs.混合治疗方案OR2.31(95%CI 1.11,4.40);细菌培养药敏试验指导的治疗方案v.序贯治疗方案OR4.06(95%CI 1.95,9.40);混合治疗方案vs.序贯治疗方案OR 1.93(95%CI 1.2,3.03)。细菌培养药敏试验指导的治疗方案有97%的概率成为幽门螺旋杆菌根除率最高的干预措施,该方案出现不良事件的概率最低,患者接受度的概率最高;伴同治疗方案虽然高效但是有79%概率成为最有可能出现不良反应的干预措施;混合治疗方案和新铋剂四联方案具有较高的疗效、较低的不良反应和良好的患者接受度。结论:对于成人幽门螺旋杆菌感染的根除,细菌培养药敏试验指导的治疗方案显著优于伴同方案、混合方案、新铋剂四联疗法和序贯治疗方案;在没有条件的医疗环境中可以采用混合治疗方案或者新铋剂四联疗法。
[Abstract]:Part I Efficacy and safety of first-line treatment for Helicobacter pylori in China: Systematic evaluation and reticular meta-analysis Helicobacter pylori (Hpylori) infection is one of the greatest global challenges. This microorganism infects more than 60% of the world's natural population and is a chronic active gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma Ba Tumor is one of the main pathogenic factors of gastric cancer. Clinical studies in Asia, Europe and Latin America have yielded inconsistent results on the efficacy and safety of eradication protocols for Helicobacter pylori. OBJECTIVE: To compare the efficacy and adverse reactions of first-line therapies commonly used in China and rank them based on probability for clinical pylori. Methods: Systematic search of electronic databases including Wanfang data Journal papers, China Science Citation Database, Web of Science, PubMed, etc. was conducted to screen the first-line Helicobacter pylori eradication protocols commonly used in clinic from 2008 to December 2014, including standard sequential treatment protocols. Randomized controlled trials of new bismuth quadruple therapy, levofloxacin optimized triple therapy, and standard triple therapy for 7 and 10 days. Relative and absolute efficacy and adverse reactions of these first-line therapies were quantitatively synthesized using head-to-head meta-analysis, mesh meta-analysis, and meta-analysis of single-group rates, and evaluated using benefit-risk analysis. The Jadad score was used to evaluate the methodological quality of randomized controlled trials, constructed funnel plot qualitative measurement publication bias, and used Egger linear regression or Begg rank correlation to test asymmetry of funnel plot. Reticular meta-analysis showed that the OR 2.90 (95% CI 1.99, 4.29) of standard sequential therapy vs. 10-day standard triple therapy vs. 10-day standard triple therapy vs. 2.85 (95% CI 1.75, 4.80) of new bismuth tetralogy vs. 10-day standard triple therapy vs. 10-day standard triple therapy vs. levofloxacin optimized triple therapy vs. 10-day standard therapy OR 2.37 (95% CI 1.27, 4.48) of the quasi-triple regimen, but there was no statistical difference between the levofloxacin-optimized triple regimen, the standard sequential regimen, and the new bismuth quadruple regimen. Bismuth quadruple regimen has a 55% probability of the highest incidence of adverse reactions. Conclusion: Among the five first-line Helicobacter pylori eradication regimens commonly used in China, Bismuth quadruple regimen has the highest probability of occurrence of adverse reactions. Standard sequential therapy regimens and levofloxacin optimized triple regimens are superior to other treatment options. Part II Therapeutic regimens guided by antibiotic susceptibility tests for Helicobacter pylori and a new quadruple regimen: Systematic evaluation and reticular meta-analysis. In an era of antibiotic resistance, Helicobacter pylori infection remains a huge global problem. Public health challenges. This microbial infection is one of the most common infectious diseases worldwide. Helicobacter pylori is one of the leading causes of chronic active gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. New empirical quadruple-drug-resistant first-line protocols are being developed Evidence from clinical studies in Asia, Europe, and Latin America has led to controversial conclusions. New therapeutic strategies, including peer therapy, combination therapy, sequential therapy, and new bismuth quadruple therapy, are not yet conclusive in clinical settings. There is a lack of multicenter randomized controlled trials. OBJECTIVE: To compare the efficacy and adverse reactions of the first-line eradication scheme and the bacterial culture susceptibility test guided eradication scheme. The unified retrieval electronic database includes Wanfang data journal paper resources, China Science Citation Database, Web of Science, EMBASE, PubMed and so on. The therapeutic schemes based on the guidance of bacterial culture drug susceptibility test and the new eradication schemes of four drugs of Helicobacter pylori were screened from 2010 to June 2015. The therapeutic schemes included in the analysis included drug susceptibility. Randomized controlled trials of trial-guided regimens, concomitant regimens, mixed regimens, sequential regimens, and new bismuth quadruple regimens. The relative and absolute eradication rates and adverse reaction rates of these regimens were quantitatively synthesized by traditional direct comparative meta-analysis, reticular meta-analysis, and meta-analysis of single-group rates, and the benefits of use were obtained. Risk analysis was used to assess the acceptability of patients for each protocol. The Jadad scale was used to evaluate the methodological quality of randomized controlled trials, and a funnel plot was constructed for qualitative measurement of publication bias. A randomized controlled trial involving 6,753 patients with Helicobacter pylori infection was conducted. Mesh-based meta-analysis of eligible randomized controlled trial data showed that in terms of eradication rates of Helicobacter pylori, the concomitant treatment regimen vs. the regimen OR0.47 (95% CI 0.24, 0.84) guided by the bacterial culture susceptibility test; the new bismuth quadruple therapy vs. the bacterial culture drug Sensitivity test guided regimen OR 0.43 (95% CI 0.23, 0.73); bacterial culture guided regimen vs. mixed regimen OR 2.31 (95% CI 1.11, 4.40); bacterial culture guided regimen V. sequential regimen OR 4.06 (95% CI 1.95, 9.40); mixed regimen vs. sequential regimen OR 1.93 (95% CI 1.2, 3.03). Bacterial culture drug susceptibility test guided treatment program has a 97% probability of the highest eradication rate of Helicobacter pylori intervention, the program has the lowest probability of adverse events, the highest probability of patient acceptance; concomitant treatment program although efficient, but 79% probability of adverse reactions is the most likely intervention; Conclusion: For the eradication of adult Helicobacter pylori infection, the therapeutic regimen guided by bacterial culture susceptibility test is significantly superior to the companion regimen, the mixed regimen, the new bismuth regimen and the sequential regimen. Mixed therapy or new bismuth quadruple therapy can be used in the medical environment.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R573

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