Division of Urology, McMaster University, Hamilton, ON, Canada; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; Department of Pediatrics, McMaster University, Hamilton, ON, Canada; McMaster Pediatric Surgery Research Collaborative, McMaster University, Hamilton, ON, Canada.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; McMaster Pediatric Surgery Research Collaborative, McMaster University, Hamilton, ON, Canada.
Front Pediatr. 2016 Mar 30;4:27. doi: 10.3389/fped.2016.00027. eCollection 2016.
Continuous antibiotic prophylaxis (CAP) use to prevent urinary tract infections (UTI) in infants with prenatal hydronephrosis (HN) remains controversial. Lack of consensus guidelines and diverse practice patterns for postnatal management of HN highlight the dire need for higher level of evidence studies. Herein, we aim to describe the steps from developing a well-defined research question to execute a multicentered randomized controlled trial (RCT) to address the issue of CAP use in patients with prenatal HN.
The steps involved were (1) choosing the proper research question, (2) survey of practice patterns and establishing clinical equipoise, (3) systematic review of the literature, (4) reviewing own practice, (5) longitudinal prospective study, (6) pilot study, (7) cost-utility analysis, and (8) definitive RCT (clinical trials registry number: NCT01140516). An update of our previous systematic review was conducted using two electronic databases and gray literature from 2010 to 2015. Eligibility criteria included studies of children <2 years old with postnatally confirmed prenatal HN, receiving CAP or not, and reporting on development of UTIs, capturing information on voiding cystourethrogram result and HN grade. Full-text screening was conducted by two independent reviewers. UTI rates in patients with high-grade HN were compared across different study designs. Finally, blinded comparative analysis of UTI rates between placebo and treatment groups was carried out using chi-square test.
UTI rates in patients with high-grade HN by their respective study design were: 25% for systematic review, 20% for retrospective study, 21% for prospective and pilot studies, and 13% for the definitive RCT thus far. Regardless of the type of study design, patients with hydroureteronephrosis had significantly higher (threefold to sixfold) UTI rates than those with isolated HN. Our updated systematic review yielded 486 citations, of which 9 (n = 1987 infants) observational studies met eligibility criteria.
UTI rates in patients with high-grade HN dropped from 25% in observational studies to 13% in our RCT. This decline in UTI rate demonstrates that study designs lacking strategies to minimize bias are more prone to overestimate treatment effects. These findings highlight the importance of conducting methodologically sound RCTs to answer clinically meaningful questions, such as the one presented here.
产前肾积水（HN）患儿连续使用抗生素预防（CAP）以预防尿路感染（UTI）的做法仍存在争议。对于 HN 的产后管理，缺乏共识指南和多样化的实践模式突出表明，迫切需要进行更高水平的证据研究。在此，我们旨在描述从提出明确的研究问题到执行多中心随机对照试验（RCT）的步骤，以解决产前 HN 患者使用 CAP 的问题。
所涉及的步骤包括：（1）选择适当的研究问题；（2）调查实践模式并建立临床平衡；（3）系统评价文献；（4）审查自身实践；（5）纵向前瞻性研究；（6）试点研究；（7）成本效益分析；（8）确定性 RCT（临床试验注册号：NCT01140516）。使用两个电子数据库和 2010 年至 2015 年的灰色文献对我们之前的系统评价进行了更新。纳入标准包括对接受或不接受 CAP 的 <2 岁的经证实存在产前 HN 的儿童进行的研究，并报告 UTI 的发生情况，收集有关排尿性膀胱尿道造影结果和 HN 分级的信息。由两名独立的审查员进行全文筛选。比较不同研究设计中高分级 HN 患者的 UTI 发生率。最后，使用卡方检验对安慰剂和治疗组之间的 UTI 发生率进行盲法比较分析。
按各自的研究设计，高分级 HN 患者的 UTI 发生率分别为：系统评价为 25%，回顾性研究为 20%，前瞻性和试点研究为 21%，确定性 RCT 为 13%。无论研究设计类型如何，患有肾积水的患者的 UTI 发生率都明显高于仅存在 HN 的患者（三倍至六倍）。我们的更新系统评价产生了 486 条引文，其中 9 项（n=1987 例婴儿）观察性研究符合入选标准。
高分级 HN 患者的 UTI 发生率从观察性研究的 25%降至我们 RCT 的 13%。UTI 发生率的下降表明，缺乏最小化偏倚策略的研究设计更容易高估治疗效果。这些发现强调了开展方法学上合理的 RCT 以回答临床有意义问题的重要性，例如这里提出的问题。
