My career goal is to improve health care for children with urological problems through research on effectiveness and health care delivery. As a pediatric urologist with a focus in health services research, I seek this Career Development Award so that I can establish an independent research career in a field where such research has not yet reached its full potential. Pediatric urology is a subspecialty in transition, moving from a field based primarily on personal surgical experience and case series, to one based on comprehensive longitudinal studies and randomized controlled trials. I seek to contribute to this transition process. In this application, I propose to investigate the clinical dilemma posed by siblings of children with vesicoureteral reflux (VUR). VUR is the retrograde flow of urine from the bladder into the ureter and kidney, and is associated with urinary tract infection (UTI) and renal injury. VUR is both common and familial, and asymptomatic siblings of children with VUR having high rates of VUR themselves. However, it is not known if screening of such siblings is beneficial. The natural history of unscreened siblings is also unknown. I plan to conduct a research study of sibling VUR, and leverage this research in three ways. First, the findings of the study will make a clinically useful contribution to our understanding of this controversial clinical condition. Second, I intend to use this research as the vehicle for a systematic expansion of my working knowledge of decision analysis as it applies to medical decision-making. Third, this research, and my educational development, will serve as a foundation for follow-up studies as I seek independent research funding in the future. My short term goals include the following: (1) To further develop my knowledge of techniques and methodologies for observational clinical studies, analysis of large administrative databases, and advanced statistical modeling techniques, (2) To learn and apply the techniques of decision analysis, to support guidelines for clinical decision-making regarding SCVUR, and to direct future directions for empiric studies of SCVUR;(3) To use health care claims data from a defined population to conduct a retrospective cohort study in order to (a) determine important clinical outcomes among SCVUR, both screened and unscreened, and (b) to determine practice patterns regarding SCVUR within the studied population;and (4) To lay the foundation for further clinical studies of SCVUR, and support applications for independent funding for this research. The research project will consist of a retrospective cohort study of siblings of children with VUR. These children will be identified via analysis of claims data within a large regional health insurance company. I will seek to characterize patterns of care for such siblings, and document specific clinical outcomes. Then, these findings will be applied to a decision analysis to determine whether screening of asymptomatic siblings for VUR is appropriate.
The research aims are complementary. The clinical study will determine critical clinical outcomes, such as the incidence of UTI among unscreened siblings. These data are simply not available in the current literature. These results, in turn, will facilitate the development of decision analysis models. Currently, such models are severely limited by the lack of data regarding outcomes among VUR siblings. More sophisticated models, incorporating the findings from this analysis, would be of great value as tools to help define the optimal management approach for sibling VUR. In addition to the research component of the proposal, I will obtain formal training in advanced clinical research techniques, decision analysis, and biostatistics. This coursework at the Harvard School of Public Health will extend my knowledge of research techniques, particularly in decision analysis methodology, beyond those acquired during my prior MPH curriculum. In these endeavors I will be supported by the extraordinary resources of Children's Hospital Boston and Harvard Medical School. I will be guided by my superior advisory team, led by my primary mentor Mark Schuster, MD, PhD, a highly accomplished pediatric health services researcher. In the long term, I anticipate that the activities described in this proposal will support and inform a subsequent application for R01 funding to study familial VUR. I hope to develop the expertise and infrastructure to support an active, multi-pronged clinical and health services research program, conducting simultaneous observational and interventional trials in key areas of pediatric urology, and focusing on common conditions affecting large numbers of children.

Public Health Relevance

This research project seeks learn more about the best way to manage vesicoureteral reflux (backwards flow of urine from the bladder up to the kidneys) among siblings of children with vesicoureteral reflux (VUR). VUR is quite common, and runs in families, so there are large numbers of siblings who might have VUR based on their family history. Although some people advocate testing these siblings for VUR even if they seem healthy, such """"""""screening"""""""" would subject large numbers of asymptomatic children to invasive tests with potentially adverse effects, long-term follow-up, prolonged antibiotic use, and possible surgery. Therefore, it is important that we learn more about VUR in these siblings in order to decide whether such screening makes sense.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Mentored Patient-Oriented Research Career Development Award (K23)
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Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Rankin, Tracy L
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Children's Hospital Boston
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Schaeffer, Anthony J; Greenfield, Saul P; Ivanova, Anastasia et al. (2017) Reliability of grading of vesicoureteral reflux and other findings on voiding cystourethrography. J Pediatr Urol 13:192-198
McQuaid, Joseph W; Kurtz, Michael P; Logvinenko, Tanya et al. (2017) Bladder debris on renal and bladder ultrasound: A significant predictor of positive urine culture. J Pediatr Urol 13:385.e1-385.e5
Nelson, Caleb P; Hoberman, Alejandro; Shaikh, Nader et al. (2016) Antimicrobial Resistance and Urinary Tract Infection Recurrence. Pediatrics 137:
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