【摘要】 目的 探讨镇痛药物使用与艰难梭菌性肠炎（Clostridium difficile enteritis,CDE）发生的因果关联。方法 采用单变量和多变量孟德尔随机化（Mendelian randomization,MR）方法调查镇痛药物使用与CDE发生的潜在因果关系，以逆方差加权为主要分析方法。结果 单变量MR分析显示，非甾体抗炎药（nonsteroidal anti-inflammatory drug,NSAID）(OR=2.680,95%CI:1.689～4.252,P<0.001)和苯胺类药物（OR=2.521,95%CI:1.503～4.229,P<0.001）的使用增加CDE发病风险，而阿片类药物（OR=0.955,95%CI:0.818～1.114,P=0.556）和水杨酸类药物（OR=1.081,95%CI:0.820～1.425,P=0.579）的使用并不是CDE发生的危险因素。MR-Steiger检验未提示暴露与结局间存在反向因果关系。多变量MR调整后NSAID使用不再是CDE发生的危险因素（OR=1.709,95%CI:0.864～3.308,P=0.123），而苯胺类药物使用仍是CDE发生的危险因素（OR=2.147,95%CI:1.239～3.721,P=0.003）。敏感性分析均未见异质性、水平多效性、离群值，无单独单核苷酸多态性影响结果。结论 阿片类药物使用不增加CDE风险，NSAID使用与CDE的因果关系仍不明确，但NSAID分类下的苯胺类药物使用是CED发生的危险因素，水杨酸类药物使用不是CDE发生的危险因素。更多还原

【Abstract】 Objective To explore the causal relationship between use of analgesic drugs and incidence of Clostridium difficile enteritis(CDE). Methods Univariate and multivariate Mendelian randomization(MR) methods were employed to investigate the potential causal relationship between use of analgesic drugs and incidence of CDE, using inverse variance weighted as the primary analytical approach. Results Univariate MR analysis indicated that use of nonsteroidal anti-inflammatory drug(NSAID)(OR=2.680, 95%CI: 1.689-4.252, P<0.001) and aniline derivatives(OR=2.521, 95%CI: 1.503-4.229, P<0.001) increased the risk of CDE, whereas use of opioids(OR=0.955, 95%CI: 0.818-1.114, P=0.556) and salicylates(OR=1.081, 95%CI: 0.820-1.425, P=0.579) were not identified as risk factors for CDE. The MR-Steiger test did not suggest the presence of reverse causality between exposure and outcome. After adjustment in the multivariate MR analysis, the use of NSAID was no longer a risk factor for CDE(OR=1.709, 95%CI: 0.864-3.308, P=0.123), while use of aniline derivatives remained a risk factor(OR=2.147, 95%CI: 1.239-3.721, P=0.003). Sensitivity analyses showed no evidence of heterogeneity, horizontal pleiotropy, or outliers, and no single nucleotide polymorphisms independently influenced the results. Conclusion The use of opioids does not increase the risk of CDE infection. The causal relationship between NSAID use and CDE remains inconclusive. However, the use of aniline derivatives within the NSAID class is a risk factor for CDE, while use of salicylates is not a risk factor for CDE.更多还原