Supplementary Material for: Does manual acupuncture improve gastro-esophageal reflux disease symptoms? A trial sequential meta-analysis

Introduction: The role of acupuncture in treating gastro-esophageal reflux disease (GERD) has been previously investigated; however, it’s unclear whether manual acupuncture is effective for treating GERD. This study aimed to evaluate the effectiveness and safety of manual acupuncture in treating GERD.
Methods: Potentially eligible studies were identified from PubMed, Embase, Cochrane Central Registry for Controlled Trials(CENTRAL), China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature database (Sinomed). Sensitivity analysis was conducted through excluding low-quality studies. Subgroup analysis was performed according to different proton pump inhibitors (PPIs) and treatment duration. Certainty of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
Results: Based on 504 records, 12 relevant studies was included in our meta-anaysis. Trial sequential analysis confirmed that manual acupuncture improved symptom scores (mean difference [MD]=-3.43, 95% CI=-5.14 to -1.73, I2=88%, P<0.001, very low evidence) and reduced recurrence rates (risk ratio [RR]=0.32, 95% confidence interval=0.16 to 0.64, I2=0%, P=0.001, very low evidence). Although meta-analysis showed no difference in adverse events between manual acupuncture and PPIs (RR=0.38, 95% CI=0.09 to 1.58, I2=0%, P=0.18, very low evidence), TSA revealed extremely insufficient statistical power. Furthermore, the global symptom improvement rate was lower with acupuncture compared to PPIs (RR=1.22, 95%CI=1.14 to 1.30, I2=18%, P<0.001, low evidence). Sensitivity analysis demonstrated the robustness of results. Subgroup analysis suggested the therapeutic effects of manual acupuncture alone irrespective of categories of PPIs and treatment duration.
Conclusion: Manual acupuncture has the potential to alleviate the severity of symptoms and decrease the recurrence rate in patients with GERD. However, considering the efficacy of PPI therapy in significantly improving overall symptoms, along with its established safety profile and extensive clinical utilization over the years, we do not recommend manual acupuncture alone as the primary treatment for patients with GERD.

引言：既往已有研究探讨针刺（acupuncture）治疗胃食管反流病（gastro-esophageal reflux disease, GERD）的作用，但目前尚不清楚手工针刺（manual acupuncture）是否对胃食管反流病具有治疗效果。本研究旨在评估手工针刺治疗胃食管反流病的有效性与安全性。
方法：从PubMed、Embase、考克兰对照试验中心注册库（Cochrane Central Registry for Controlled Trials, CENTRAL）、中国知网（China National Knowledge Infrastructure, CNKI）以及中国生物医学文献数据库（Chinese Biomedical Literature database, Sinomed）中检索潜在符合纳入标准的研究。通过排除低质量研究开展敏感性分析，依据不同质子泵抑制剂（proton pump inhibitors, PPIs）类别与治疗时长进行亚组分析。采用推荐分级、评估、制定与评价（Grading of Recommendations, Assessment, Development, and Evaluations, GRADE）框架对证据质量进行评级。
结果：共检索到504条记录，最终纳入12项相关研究进行Meta分析（meta-analysis）。试验序贯分析（trial sequential analysis, TSA）证实，手工针刺可改善症状评分（均数差（mean difference, MD）=-3.43，95%置信区间（confidence interval, CI）=-5.14~-1.73，I²=88%，P<0.001，证据质量极低），并降低复发率（相对危险度（risk ratio, RR）=0.32，95%置信区间=0.16~0.64，I²=0%，P=0.001，证据质量极低）。尽管Meta分析结果显示，手工针刺与质子泵抑制剂治疗的不良事件发生率无显著差异（相对危险度（risk ratio, RR）=0.38，95%置信区间=0.09~1.58，I²=0%，P=0.18，证据质量极低），但试验序贯分析显示统计效能严重不足。此外，与质子泵抑制剂治疗相比，针刺治疗的整体症状改善率更低（相对危险度（risk ratio, RR）=1.22，95%置信区间=1.14~1.30，I²=18%，P<0.001，证据质量低）。敏感性分析证实研究结果具有稳健性。亚组分析显示，无论质子泵抑制剂类别与治疗时长如何，单纯手工针刺均具有治疗效果。
结论：手工针刺有望缓解胃食管反流病患者的症状严重程度并降低复发率。然而，鉴于质子泵抑制剂治疗可显著改善整体症状，且其安全性已得到证实、临床应用多年且范围广泛，因此不推荐将单纯手工针刺作为胃食管反流病患者的首选治疗方案。