[关键词]
[摘要]
目的 系统归纳、分析儿童环境性肠道功能障碍(EED)临床试验的设计和评价的主要技术要素,通过标准化试验设计,为不同试验结果的比较提供一定的可行性。方法 采用文献研究的方法,通过系统检索2000-2020年发表在PubMed、Cochrane以及EMBASE数据库,由2位研究者独立按照文献纳入与排除标准筛选儿童EED的临床随机对照试验文献,对纳入文献的试验设计与评价技术要素进行提取。结果 检索出文献634篇,最终纳入16项研究。(1)试验目的:以改善肠道功能障碍的生物标志物为主14篇(87.5%),其中6篇(37.5%)同时评价了改善生长发育迟缓效果。(2)试验设计:全部文献均采用了随机对照试验(RCT)的设计方法,其中3篇(18.75%)为整群随机对照试验;选择安慰剂对照9篇(56.25%),双盲试验12篇(75.0%)。(3)受试人群:一般为生活在资源匮乏地区,长期暴露于卫生条件不足和营养缺乏环境中的儿童。(4)干预措施:主要是药物类(乳酸杆菌GG、利福昔明、美沙拉嗪、锌、阿苯达唑、阿奇霉素、多种微量元素)9篇(56.25%),其次食物类(菜豆、黑眼豆、米糠)和环境卫生条件干预各3篇(18.75%)。(5)疗程:3 d~36个月。(6)有效性评价指标:主要是EED生物标志物14篇(87.5%)和生长发育指标6篇(37.5%)。其中,生物标志物主要包括尿乳果糖与甘露醇比值变化(L:M)9篇(56.25%),尿乳果糖的排泄率6篇(37.5%);粪便髓过氧化物酶5篇(31.25%),粪便α-1抗胰蛋白酶、粪便新蝶呤各4篇(25.0%),粪便钙卫蛋白3篇(18.75%),粪便再生基因1β2篇(12.5%)。生长发育指标包括年龄别身长/身高的Z评分、身长/身高、体质量各5篇(31.25%),年龄别体质量2篇(12.5%)等。(7)试验的质量控制:以EED生物标志物为评价指标的研究,均在中心实验室进行统一检测。结论 纳入的文献信息完善、质量较高,结果涵盖了儿童EED临床研究设计与评价的基本技术要素,对于EED临床试验设计与实施,具有重要的借鉴与参考价值。
[Key word]
[Abstract]
Objective To systematically evaluate the design points of clinical trials of children with Environmental Enteric Dysfunction(EED), and to provide certain feasibility for comparison with different trail results through standardized trail design. Methods By using the method of literature research, PubMed, Cochrane and EMBASE databases from 2000 to 2020 were searched systematically. Two researchers independently screened the clinical randomized controlled trials (RCTs) of children's EED according to the inclusion and exclusion criteria, and extracted the elements of experimental design and evaluation of the included articles. Results A total of 634 literatures were retrieved and 16 studies were included. (1) The main purpose of the study was to improve the biomarkers of intestinal dysfunction in 14 articles (87.5%), of which 6 (37.5%) evaluated the effect of improving growth retardation. (2) Design randomized controlled trials were used in all the studies, including 3 cluster-randomized controlled trial (18.75%), 9 placebo-controlled trials (56.25%) and 12 double-blind trials (75.0%). (3) The subjects were generally children living in resource deficient areas and exposed to inadequate sanitation and nutrition for a long time. (4) The main intervention measures were drugs (Lactobacillus GG, rifaximin, mesalazine, zinc, albendazole, azithromycin, multiple micronutrients) in 9 articles (56.25%), followed by food (cowpea, Common Bean, rice bran) and environmental hygiene condition intervention (18.75%). (5) The course of treatment was 3 days to 36 months. (6) The main efficacy indicators of 14 studies (87.5%) were EED biomarkers and 6 (37.5%) were linear growth. Among them, 9 articles (56.25%) of urinary lactulose/mannitol ratio change (L:M), 6 (37.5%) of urinary lactulose excretion rate, 5 (31.25%) of fecal myeloperoxidase, 4 (25.0%) of fecal α-1 antitrypsin and 4 (25.0%) of fecal neopterin, 3 (18.75%) of fecal calprotectin and 2 (12.5%) of fecal regeneration gene were used to evaluate EED biomarkers. The evaluation of linear growth includes 5 articles (31.25%) used length for age z-scores, length/height, weight, and 2 articles (12.5%) used weight for age zscores. (7) The quality control of the experiment and the study of EED biomarkers as the evaluation index were all tested in the central laboratory. Conclusion The included literature information is perfect and of high quality. The results cover the basic elements of the design and evaluation of pediatric EED clinical research, which has important reference value for the design and implementation of EED clinical trials.
[中图分类号]
R969.4;R985
[基金项目]