中国10天或14天铋剂四联疗法根除幽门螺杆菌疗效的Meta分析

发布时间：2018-06-26 20:11

本文选题：幽门螺杆菌 + 铋剂四联疗法　；参考：《第三军医大学》2017年硕士论文

【摘要】：研究背景及目的幽门螺杆菌(Helicobacter pylori,H.pylori)是一种重要的人类病原菌,是许多消化道疾病及胃肠外疾病的常见致病因素,根除其可减少传染源、缓解或治愈相关疾病,减少其并发症的发生,因此有效根除H.pylori是非常必要的。然而抗生素耐药率的急剧增加、抑酸作用不足、根除方案的不合理使用使得H.pylori根除治疗面临新的困境,为评价铋剂四联疗法H.pylori的根除疗效,本研究含有中国10天或14天铋剂四联疗法与其他常见根除方案根除幽门螺杆菌的疗效进行了Meta分析。方法首先充分通过计算机检索以下数据库:Pubmed,EMBASE,the Cochrane Central Register of Controlled Trials、中国知网、中国生物医学文献数据库、维普等数据库,收集中国2005年至2016年11月期间所有包含10d或14d铋剂四联疗法根除幽门螺杆菌感染的随机对照试验,依照纳入排除标准,两位研究者独立行文献筛选、提取受试者的基本资料、观察指标(根除率及不良反应发生率)等相关数据、采用Jadad评分评价纳入研究质量,使用Rev Man5.3软件分析相关指标,计算RR及95%CI,使用漏斗图行发表偏倚评价。结果43项研究(共7686例患者)符合纳入标准。通过意向性分析(Intention-toTreat analysis,ITT分析),10天或14天铋剂四联疗法和三联疗法H.pylori根除率分别是88.96%(95%CI:87.73%~90.19%)和74.11%(95%CI:72.53%~75.69%),差异有统计学意义(RR=1.20,95%CI:1.16%~1.25%);10d或14d铋剂四联疗法和7d铋剂四联疗法H.pylori根除率分别是87.34%(95%CI:84.87%~89.80%)、81.65%(95%CI:78.76%~84.54%)(意向性分析),差异有统计学意义(RR=1.07,95%CI:1.02%~1.12%);10d或14d铋剂四联联疗法与序贯疗(RR=1.02,95%CI:0.97%~1.07%)、及与伴随疗法(RR=1.01,95%CI:0.95%~1.07%)差异无统计学意义。结论10d或14d铋剂四联疗法与序贯疗法及伴随疗法疗效相当,三联疗法及7d铋剂四联疗法不作为首选治疗方案。背景及目的与克拉霉素不同的是,幽门螺杆菌对阿莫西林的耐药率无论是原发性或继发性均很低。有研究报道表明根据阿莫西林的时间依赖性及PH值依赖性等特点结合大剂量的质子泵抑制剂组成的大剂量二联疗法可取得满意疗效。因此本研究探讨大剂量二联疗法在幽门螺杆菌(Helicobacter Pylori,Hp)根除治疗中的效果并与含铋剂的四联疗法疗效进行比较。方法收集263例幽门螺杆菌阳性初次治疗的患者(13C尿素呼气试验或14C尿素呼气试验或快速尿素酶法或幽门螺杆菌培养证实),按Excel设计的随机对照数字表分组,进行对应的治疗方案。A组:雷贝拉唑10mg及阿莫西林750 mg,均4次/日;B组:雷贝拉唑20mg及阿莫西林750mg,均4次/日;C组:雷贝拉唑20mg、枸橼酸铋钾220mg、阿莫西林1 000mg及克拉霉素500mg,均2次/日。上述方案疗程均14d。治疗结束4周后行13C或14C尿素呼气试验复查,呼气试验阳性表明根除失败,反之则成功。每位受试者在治疗前均应进行Hp的相关教育:根除Hp的必要性、正规治疗的重要性、治疗过程中可能出现的不良反应及必要时停药并告知医生、及时复查呼气试验等,正确填写病例报告调查表。结果据ITT分析及PP分析,A组的幽门螺杆菌的根除率分别是78.1%(95%CI,68.4%~86.8%)和79.1%(95%CI,70.5%~87.7%),B组的根除率是81.6%(95%CI,73.5%~89.7%)和83.5(95%CI,75.6%~91.4%),C组的根除率是84.3%(95%CI,76.7%~91.9%)和86.2%(95%CI,75.6%~91.4%),差异无统计学意义(P0.05)。3组总不良反应发生率分别是3.4%、5.7%、11.2%(P值:0.109),差异无统计学意义(P0.05)),但C组味觉异常(P=0.002)及牙龈发黑(P=0.002)等不良反应均较AB两组高,具有统计学差异。结论大剂量二联疗法在Hp根除治疗方面并不优于含铋剂的四联疗法。
[Abstract]:Background and objective Helicobacter pylori (H.pylori) is an important human pathogen, which is a common pathogenic factor of many digestive and gastrointestinal diseases. It is essential to eradicate H.pylori effectively by eradicating the source of infection, alleviating or curing the related diseases and reducing the incidence of its complications. The rapid increase of antibiotic resistance rate, insufficient acid suppressor effect and irrational use of the eradication regimen make H.pylori eradication treatment face new difficulties and to evaluate the eradication effect of bismuth quadruple therapy H.pylori. This study contains the efficacy of bismuth quadruple therapy with other common eradication regimens for eradicating Helicobacter pylori in 10 or 14 days of China. TA analysis. The method first fully retrieves the following database through the computer: Pubmed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese knowledge network, Chinese biomedical literature database, VP and other databases, all containing 10d or 14d bismuth therapy in the eradication of Helicobacter pylori from 2005 to November 2016. According to the exclusion criteria, two researchers were screened independently, the basic data of the subjects were extracted, the related data were extracted from the subjects, the indexes (the rate of eradication and the incidence of adverse reactions) were observed, the quality of the study was included by the Jadad score, and the related indexes were analyzed with the Rev Man5.3 software, the RR and 95%CI were calculated and the funnel plot was used. Results 43 studies (7686 patients) were in conformity with the inclusion criteria. Through intentional analysis (Intention-toTreat analysis, ITT analysis), 10 or 14 days of bismuth quadruple therapy and triple therapy H.pylori eradication rates were 88.96% (95%CI:87.73%~90.19%) and 74.11% (95%CI:72.53%~75.69%), respectively, and the difference was statistically significant (RR=1.20,95% CI:1.16%~1.25%); the rate of H.pylori eradication was 87.34% (95%CI:84.87%~89.80%) and 81.65% (95%CI:78.76%~84.54%) (intentionality analysis) in the quadruple therapy of 10d or 14d bismuth and 7d bismuth, respectively. The difference was statistically significant (RR=1.07,95%CI:1.02%~1.12%); 10d or 14d bismuth combined therapy and sequential therapy (RR=1.02,95%CI:0.97%~1.07%), and associated with it. The treatment (RR=1.01,95%CI:0.95%~1.07%) difference was not statistically significant. Conclusion 10d or 14d Bi agent quadruple therapy is equivalent to sequential therapy and concomitant therapy. Triple therapy and 7d bismuth quadruple therapy are not the first choice. A large dose of two couplet therapy based on the time dependence of amoxicillin and the pH dependence of amoxicillin combined with large doses of proton pump inhibitors can achieve satisfactory results. Therefore, this study explored the treatment of Helicobacter Pylori (Hp) eradication with large dose of two couplet therapy. The effect was compared with the quadruple therapy with bismuth. Methods 263 patients with HP positive initial treatment (13C urea breath test or 14C urea breath test or rapid urease or Helicobacter pylori culture) were collected and grouped according to the random control digital table designed by Excel, and the corresponding treatment scheme.A group: rebebe 10mg and amoxicillin 750 mg were all 4 times per day; group B: 4 times / day for 20mg and amoxicillin 750mg; group C: Ray 20mg, bismuth potassium citrate 220mg, amoxicillin 1 000mg and clarithromycin 500mg, all 2 times / day. The course of treatment was 4 weeks after the end of 14D. treatment. The eradication failure and vice versa are successful. Every subject should have Hp related education before treatment: eradicating the necessity of Hp, the importance of regular treatment, the possible adverse reactions in the course of treatment and the necessary stopping of the drug when necessary and telling the doctor, rechecking the exhalation test in time, and correctly filling out the case report questionnaire. Results according to ITT analysis and PP analysis The eradication rates of Helicobacter pylori in group A were 78.1% (95%CI, 68.4%~86.8%) and 79.1% (95%CI, 70.5%~87.7%). The eradication rate of group B was 81.6% (95%CI, 73.5%~89.7%) and 83.5 (95%CI, 75.6%~91.4%). The eradication rate of C group was 84.3% (95%CI, 86.2%) and 86.2%. The difference was 3.4%, 5.7%, 11.2% (P value: 0.109), the difference was not statistically significant (P0.05), but the adverse reactions of C group (P=0.002) and gingival blackening (P=0.002) were higher than those of the AB two group, and there were statistical differences. Conclusion the high-dose two combination therapy in the eradication treatment of Hp is not better than the quadruplex therapy with bismuth.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R57

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