Martin Alice E, Newlove-Delgado Tamsin V, Abbott Rebecca A, Bethel Alison, Thompson-Coon Joanna, Whear Rebecca, Logan Stuart
Paediatrics, Royal Devon and Exeter Hospital, Barrack Road, Exeter, England, UK, EX2 5DW.
NIHR CLAHRC South West Peninsula (PenCLAHRC), University of Exeter Medical School, St Luke's Campus, Exeter, England, UK, EX1 2LU.
Cochrane Database Syst Rev. 2017 Mar 6;3(3):CD010973. doi: 10.1002/14651858.CD010973.pub2.
BACKGROUND: Between 4% and 25% of school-aged children at some stage complain of recurrent abdominal pain (RAP) of sufficient severity to interfere with their daily lives. When no clear organic cause is found, the children are managed with reassurance and simple measures; a large range of pharmacological interventions have been recommended for use in these children. OBJECTIVES: To determine the effectiveness of pharmacological interventions for RAP in children of school age. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and eight other electronic databases up to June 2016. We also searched two trials registers and contacted researchers of published studies. SELECTION CRITERIA: Randomised controlled trials involving children aged five to 18 years old with RAP or an abdominal pain-related functional gastrointestinal disorder, as defined by the Rome III criteria (Rasquin 2006). The interventions were any pharmacological intervention compared to placebo, no treatment, waiting list, or standard care. The primary outcome measures were pain intensity, pain duration or pain frequency, and improvement in pain. The secondary outcome measures were school performance, social or psychological functioning, and quality of daily life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts, and potentially relevant full-text reports for eligible studies. Two review authors extracted data and performed a 'Risk of bias' assessment. We used the GRADE approach to rate the overall quality of the evidence. We deemed a meta-analysis to be not appropriate as the studies were significantly heterogeneous. We have consequently provided a narrative summary of the results. MAIN RESULTS: This review included 16 studies with a total of 1024 participants aged between five and 18 years, all of whom were recruited from paediatric outpatient clinics. Studies were conducted in seven countries: seven in the USA, four in Iran, and one each in the UK, Switzerland, Turkey, Sri Lanka, and India. Follow-up ranged from two weeks to four months. The studies examined the following interventions to treat RAP: tricyclic antidepressants, antibiotics, 5-HT4 receptor agonists, antispasmodics, antihistamines, H2 receptor antagonists, serotonin antagonists, selective serotonin re-uptake inhibitors, a dopamine receptor antagonist, and a hormone. Although some single studies reported that treatments were effective, all of these studies were either small or had key methodological weaknesses with a substantial risk of bias. None of these 'positive' results have been reproduced in subsequent studies. We judged the evidence of effectiveness to be of low quality. No adverse effects were reported in these studies. AUTHORS' CONCLUSIONS: There is currently no convincing evidence to support the use of drugs to treat RAP in children. Well-conducted clinical trials are needed to evaluate any possible benefits and risks of pharmacological interventions. In practice, if a clinician chooses to use a drug as a 'therapeutic trial', they and the patient need to be aware that RAP is a fluctuating condition and any 'response' may reflect the natural history of the condition or a placebo effect, rather than drug efficacy.
背景:在某些阶段,4%至25%的学龄儿童会抱怨反复出现腹痛(RAP),其严重程度足以干扰他们的日常生活。当未发现明确的器质性病因时,会对这些儿童进行安抚并采取简单措施;已推荐了多种药物干预措施用于这些儿童。 目的:确定药物干预对学龄儿童RAP的有效性。 检索方法:我们检索了截至2016年6月的Cochrane对照试验中央注册库(CENTRAL)、Ovid MEDLINE、Embase以及其他八个电子数据库。我们还检索了两个试验注册库并联系了已发表研究的研究者。 入选标准:涉及5至18岁患有RAP或符合罗马III标准(Rasquin 2006)定义的腹痛相关功能性胃肠疾病的儿童的随机对照试验。干预措施为与安慰剂、不治疗、等待名单或标准护理相比的任何药物干预。主要结局指标为疼痛强度、疼痛持续时间或疼痛频率以及疼痛改善情况。次要结局指标为学业成绩、社会或心理功能以及日常生活质量。 数据收集与分析:两位综述作者独立筛选标题、摘要以及可能相关的全文报告以寻找符合条件的研究。两位综述作者提取数据并进行“偏倚风险”评估。我们使用GRADE方法对证据的总体质量进行评级。由于研究存在显著异质性,我们认为不适合进行荟萃分析。因此,我们提供了结果的叙述性总结。 主要结果:本综述纳入了16项研究,共有1024名年龄在5至18岁之间的参与者,所有参与者均来自儿科门诊。研究在七个国家进行:美国七项,伊朗四项,英国、瑞士、土耳其、斯里兰卡和印度各一项。随访时间从两周到四个月不等。这些研究考察了以下治疗RAP的干预措施:三环类抗抑郁药、抗生素、5-HT4受体激动剂、解痉药、抗组胺药、H2受体拮抗剂、5-羟色胺拮抗剂、选择性5-羟色胺再摄取抑制剂、多巴胺受体拮抗剂和一种激素。尽管一些单项研究报告称治疗有效,但所有这些研究要么规模较小,要么存在关键的方法学弱点且存在重大偏倚风险。这些“阳性”结果在后续研究中均未得到重现。我们判断有效性证据质量较低。这些研究中未报告不良反应。 作者结论:目前没有令人信服的证据支持使用药物治疗儿童RAP。需要进行良好设计的临床试验来评估药物干预的任何可能益处和风险。在实践中,如果临床医生选择使用药物进行“治疗试验”,他们和患者需要意识到RAP是一种波动的病症,任何“反应”可能反映的是该病症的自然病程或安慰剂效应,而非药物疗效。
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