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复合益生菌治疗胃肠炎患儿的多中心试验
Multicenter Trial of Combination Probiotics for Children with Gastroenteritis


Stephen B. Freedman ... 妇产科和儿科 • 2018.11.22
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益生菌治疗胃肠炎患儿
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两项临床试验未显示所用益生菌对儿童急性胃肠炎有效

 

夏璐†,杨云生‡*

†上海嘉会国际医院消化科;‡中国人民解放军总医院消化科

*通讯作者

 

2018年11月22日两篇关于益生菌治疗的研究发表于NEJM,提出益生菌治疗并不能使急性胃肠炎患儿获益,这一研究再次引起对益生菌作用的新的质疑和波澜1,2。近期不少学者讨论、发表看法,“益生菌神话已经破灭”等评论也见诸报道。如何看待这两项重要的临床研究成果呢?

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摘要


背景

在美国每年的儿科急诊(ED)就诊量中,胃肠炎约占170万人次。目前缺乏可确定益生菌能否改善这些患儿结局的数据。

 

方法

我们开展了一项随机、双盲试验,纳入了在加拿大6家儿科ED就诊的886例3~48月龄的胃肠炎患儿。参与者接受含鼠李糖乳杆菌(Lactobacillus rhamnosus,菌株号R0011)和瑞士乳杆菌(L. helveticus,菌株号R0052)的复合益生菌产品(剂量为每日2次、每次4.0×109菌落形成单位)或安慰剂治疗5日。主要结局为中至重度胃肠炎(定义为纳入后改良Vesikari量表症状评分≥9分[评分范围为0~20分,较高的评分表示较严重的疾病])。次要结局包括腹泻和呕吐的持续时间、有计划外访视的患儿百分比以及是否有不良事件。

 

结果

益生菌组414例参与者中的108例(26.1%)、安慰剂组413例参与者中的102例(24.7%)在纳入研究后14日内出现了中至重度胃肠炎(比值比,1.06;95%置信区间[CI],0.77~1.46;P=0.72)。在用研究中心、年龄、粪便中轮状病毒检出情况以及纳入研究前的腹泻和呕吐频率校正后,试验分组不能预测中至重度的胃肠炎(比值比,1.06;95% CI,0.76~1.49;P=0.74)。在腹泻(分别为52.5小时[四分位距,18.3~95.8]和55.5小时[四分位距,20.2~102.3];P=0.31)或呕吐(分别为17.7小时[四分位距,0~58.6]和18.7小时[四分位距,0~51.6];P=0.18)的中位持续时间、有计划外访视的参与者百分比(30.2%和26.6%;比值比,1.19;95% CI,0.87~1.62;P=0.27)和报告不良事件的参与者百分比(34.8%和38.7%;比值比,0.83;95% CI,0.62~1.11;P=0.21)方面,益生菌组和安慰剂组无显著差异。

 

结论

在到急诊就诊的胃肠炎患儿中,每日2次给予鼠李糖乳杆菌-瑞士乳杆菌复合益生菌未能预防纳入研究后14日内中至重度胃肠炎的发生(由加拿大卫生研究院[Canadian Institutes of Health Research]等资助;PROGUT在ClinicalTrials.gov注册号为NCT01853124)。





作者信息

Stephen B. Freedman, M.D.C.M., Sarah Williamson-Urquhart, B.Sc.Kin., Ken J. Farion, M.D., Serge Gouin, M.D.C.M., Andrew R. Willan, Ph.D., Naveen Poonai, M.D., Katrina Hurley, M.D., Philip M. Sherman, M.D., Yaron Finkelstein, M.D., Bonita E. Lee, M.D., Xiao-Li Pang, Ph.D., Linda Chui, Ph.D., David Schnadower, M.D., M.P.H., Jianling Xie, M.D., M.P.H., Marc Gorelick, M.D., and Suzanne Schuh, M.D. for the PERC PROGUT Trial Group*
From the Sections of Pediatric Emergency Medicine and Gastroenterology, Alberta Children’s Hospital, Alberta Children’s Hospital Research Institute (S.B.F.), and the Section of Pediatric Emergency Medicine, Alberta Children’s Hospital (S.W.-U., J.X.), Cumming School of Medicine, University of Calgary, Calgary, the Departments of Pediatrics and Emergency Medicine, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa (K.J.F.), the Division of Pediatric Emergency Medicine, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal (S.G.), Ontario Child Health Support Unit, SickKids Research Institute, the Division of Biostatistics, Dalla Lana School of Public Health (A.R.W.), the Division of Gastroenterology, Hepatology, and Nutrition (P.M.S.), the Divisions of Pediatric Emergency Medicine and Clinical Pharmacology and Toxicology (Y.F.), and the Division of Pediatric Emergency Medicine and Research Institute (S.S.), Hospital for Sick Children, University of Toronto, Toronto, the Division of Emergency Medicine, London Health Sciences Centre, Department of Pediatrics, Schulich School of Medicine and Dentistry, Western University, London, ON (N.P.), the Division of Pediatric Emergency Medicine, IWK Health Centre, Halifax, NS (K.H.), the Department of Pediatrics, Faculty of Medicine and Dentistry, Women and Children’s Health Research Institute (B.E.L.) and the Provincial Laboratory for Public Health–Alberta Public Laboratories and Department of Laboratory Medicine and Pathology (X.-L.P., L.C.), University of Alberta, Edmonton — all in Canada; the Division of Pediatric Emergency Medicine, Washington University School of Medicine, St. Louis (D.S.); and Children’s Minnesota and Department of Pediatrics, University of Minnesota Medical School, Minneapolis (M.G.). Address reprint requests to Dr. Freedman at the Sections of Emergency Medicine and Gastroenterology, Department of Pediatrics, Alberta Children’s Hospital and Research Institute, University of Calgary, 2888 Shaganappi Trail NW, Calgary, AB T3B 6A8, Canada, or at stephen.freedman@albertahealthservices.ca. *A complete list of the members of the PERC PROGUT Trial Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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