Comparative Effectiveness of Vesicoureteral Reflux Treatments in Children

描述（由申请人提供）：膀胱输尿管反流（VUR），或尿液从膀胱反流回肾脏，是一种常见的儿科疾病，在美国所有儿童中高达10%。在尿路感染的情况下，VUR可出现在高达50%的健康儿童中。在这些儿童中，VUR增加了肾瘢痕形成、高血压、蛋白尿的风险，在极端情况下，还会增加终末期肾病的风险。虽然很明显，与肾损伤相关的长期肾脏问题对受影响的儿童有重大影响，但也有儿童没有遭受肾损伤相关的任何后果。不幸的是，到目前为止，VUR研究还无法确定哪些儿童最容易发生与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：一些医生用手术治疗VUR，另一些用内窥镜检查，还有一些用长期抗生素。目前还不清楚哪种方法对哪些孩子最有效。我的长期职业目标是通过应用卫生服务研究方法来改善VUR和其他泌尿系统疾病儿童的健康状况。作为一名儿科泌尿科医生和卫生服务研究人员，我正在一个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。儿科泌尿外科是临床研究方法发生根本性转变的一个亚专科。我的前任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。我计划通过将比较有效性方法引入该领域来促进这种转变。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在比较有效性研究的技术和方法方面的知识；(2)学习和应用决策分析技术，以指导VUR患儿的临床决策，并支持VUR治疗指南的制定；(3)为未来VUR的临床研究和未来该研究的独立资助提案奠定基础。为了实现这些目标，我将利用比较有效性研究的优势来确定哪些患有VUR的儿童将从哪种治疗中获益最多。在Aim 1a中，我们将使用一个国家数据库来定义关键临床结果的发生率，例如VUR治疗后尿路感染的发生率。在Aim 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，我们将调查社区成员，以确定患者和社区的VUR治疗偏好。从长远来看，这些项目将构成后续R01应用程序的基础，重点是VUR。在接下来的5年里，我将发展研究专业知识和基础设施，以支持一个积极的临床和健康服务研究项目，我将把专业知识和基础设施集中在儿科泌尿科最常见和最重要的临床疾病上。

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.