Comparative Effectiveness of Vesicoureteral Reflux Treatments in Children

描述(由申请人提供)：膀胱输尿管反流(VUR)，即尿液从膀胱倒流到肾脏，是一种常见的儿科疾病，在美国高达10%的儿童中存在这种情况。在尿路感染的情况下，VUR可出现在高达50%的其他健康儿童中。在这些儿童中，VUR增加了肾脏疤痕、高血压、蛋白尿的风险，在极端情况下，还会增加终末期肾脏疾病的风险。虽然与VUR相关的长期肾脏问题显然对受影响的儿童有重大影响，但也有儿童没有遭受任何与VUR相关的后果。不幸的是，到目前为止，VUR研究一直无法确定哪些儿童最有可能受到VUR相关的肾脏损害。这种风险分层的缺乏导致了VUR管理的巨大差异：一些内科医生用手术治疗VUR，另一些内科医生用内窥镜检查，另一些医生用长期抗生素治疗。目前还不清楚这些方法中的哪种对哪些孩子最有效。我的长期职业目标是通过应用卫生服务研究方法来改善患有VUR和其他泌尿系统疾病的儿童的健康。作为一名儿科泌尿科医生和卫生服务研究人员，我正在卫生服务研究尚未充分发挥其潜力的领域建立独立的研究生涯。儿科泌尿科是临床研究方法正在发生根本性转变的一个子专业。我的前辈们主要基于他们个人的临床和手术经验为泌尿学研究奠定了基础；我的同行们已经开始转向基于大规模观察性研究和随机试验的研究。我计划通过在实地引入比较实效方法来促进这一转变。我的短期目标是：(1)利用观察和管理数据库等工具，进一步发展我对比较有效性研究的技术和方法的知识；(2)学习和应用决策分析技术，以指导VUR儿童的临床决策，并支持VUR治疗指南的制定；以及(3)为VUR未来的临床研究和这项研究未来的独立资金提案奠定基础。为了促进这些目标，我将利用比较有效性研究的优势来确定哪些VUR儿童将从哪种治疗中受益最大。在目标1a中，我们将使用一个国家数据库来定义关键临床结局的发生率，例如VUR治疗后的尿路感染发生率。在目标1b中，我们将在第二个国家数据库中验证这些发现，以确保我们的发现广泛适用于具有不同疾病严重程度和社会经济背景的儿童。在目标2中，我们将对社区成员进行调查，以确定患者和社区为基础的VUR治疗偏好。从长远来看，这些项目将为随后的以VUR为重点的R01应用奠定基础。在接下来的5年里，我将发展研究专业知识和基础设施，以支持积极的临床和卫生服务研究计划，我将把这些专业知识和基础设施重点放在儿科泌尿外科最常见和最具临床意义的疾病上。

DESCRIPTION (provided by applicant): Vesicoureteral reflux (VUR), or the reversed flow of urine from the bladder back up into the kidney, is a common pediatric condition, which is present in up to 10% of all children in the United States. In the setting of urinary tract infectio, VUR can be present in up to 50% of otherwise healthy children. In these children, VUR increases the risk of renal scarring, hypertension, proteinuria, and, in extreme cases, end-stage renal disease. Although it is clear that VUR-related, long-term renal problems have a significant impact on affected children, there are children who suffer no VUR-related consequences whatsoever. Unfortunately, VUR research has to date been unable to identify which children are most at risk of VUR-related renal damage. This lack of risk stratification has led to tremendous variation in VUR management: some physicians treat VUR with surgery, others with endoscopy, and others with long-term antibiotics. It remains unclear which of these approaches works best for which children. My long-term career goal is to improve the health of children with VUR and other urological conditions by the application of health services research methods. As a pediatric urologist and a health services researcher, I am in the process of establishing an independent research career in a field where health services research has not yet reached its full potential. Pediatric urology is a subspecialty in the midst of a fundamental shift in its approach to clinical research. My predecessors laid the foundations for urologic research based primarily on their personal clinical and surgical experience; my peers have begun to shift to research based on large-scale observational studies and randomized trials. I plan to contribute to this transformation by introducing comparative effectiveness methodology to the field. My short-term goals are: (1) To further develop my knowledge of techniques and methodologies for comparative-effectiveness research using tools such as observational and administrative databases; (2) to learn and apply the techniques of decision analysis in order to guide clinical decision-making in children with VUR and to support guideline development for VUR treatments; and (3) to develop the foundation for future clinical research of VUR and for future independent funding proposals for this research. To facilitate these goals, I will use the strengths of comparative-effectiveness research to determine which children with VUR will benefit most from which treatment. In Aim 1a, we will use a national database to define the incidence of critical clinical outcomes, such as the incidence of urinary infections after VUR treatment. In Aim 1b, we will validate those findings in a second national database to ensure that our findings are broadly applicable to children with varying disease severity and socioeconomic backgrounds. In Aim 2, we will survey community members to determine patient- and community-based VUR treatment preferences. In the long term, these projects will form the basis for a subsequent R01 application focused on VUR. In the next 5 years I will develop the research expertise and infrastructure to support an active clinical and health services research program, and I will focus that expertise and infrastructure on the most common and most clinically significant conditions in pediatric urology.