Multi-center Studies of Pediatric CSF Shunt Infections

项目概述：脑脊液分流感染极难治疗，导致住院时间延长，反复进行分流翻修手术，再感染发生率高达25%。我们对脑脊液分流感染的适当治疗的理解是有限的，因此，管理是高度可变的。最近美国国立卫生研究院（NIH）的一次研讨会强调了优化脑脊液分流感染治疗和防止脑脊液分流再感染的必要性。作为一名在住院环境中照顾儿童的儿科医生（儿科住院医师），我经常照顾脑脊液分流感染、脑积水等神经发育障碍的儿童。本提案的研究和职业发展目标将集中于开展多中心纵向研究，这对于产生足够的样本量来研究神经发育障碍儿童的临床问题是必要的。拟议项目的核心是脑积水临床研究网络（HCRN），这是一项由慈善机构资助的、由四家儿科神经外科医院集中协调的研究工作。我与HCRN的合作关系为脑脊液分流感染治疗的前瞻性多中心研究提供了一个独特的机会。我的职业发展目标包括：1)扩展我在数据采集和管理方面的现有技能，2)扩展我在研究设计，分析和结果解释方面的现有技能，3)学习如何测量生活质量和心理测量学以评估神经发育障碍儿童的长期结果，4)学习神经生物学方法以更好地理解新兴的基本神经科学发现，5)发展进行多中心研究的专业知识。这些捐款将促进我的总体职业目标——成为一名独立的内科医生兼科学家，能够进行严格的多中心研究，以改善为神经发育障碍儿童提供住院医疗保健的证据基础。提出的项目的中心假设是，治疗脑脊液分流感染的医疗和手术决策的差异导致了不同的分流再感染率。具体目的包括：1)确定与脑脊液分流感染相关的患者危险因素；2)确定脑脊液分流感染的静脉抗生素治疗时间与脑脊液分流再感染的关系；3)设计一项治疗HCRN脑脊液分流感染的多中心随机对照试验。

DESCRIPTION (provided by applicant): Project Summary: CSF shunt infections are extremely difficult to treat, resulting in prolonged hospitalizations, repeated shunt revision surgeries, and re-infection at rates as high as 25 percent. Our understanding of appropriate treatment of CSF shunt infection is limited and, as a result, management is highly variable. A recent National Institutes of Health (NIH) workshop highlighted a need to optimize treatment of CSF shunt infection and prevent CSF shunt re-Infection. As a pediatrician who cares for children in the inpatient setting (pediatric hospitalist), I frequently care for children with CSF shunt infection, hydrocephalus and other neurodevelopmental disorders. The research and career development aims of this proposal will focus on the conduct of multicenter longitudinal studies, which are necessary to generate adequate sample sizes to study clinical problems in children with neurodevelopmental disorders. Central to the proposed project is the Hydrocephalus Clinical Research Network (HCRN), a philanthropically-funded, centrally coordinated research effort between four pediatric neurosurgical hospitals. My affiliation with the HCRN offers a unique opportunity for a prospective, multicenter study of CSF shunt Infection treatment with adequate sample sizes. My career development aims Include the following: 1) expand my existing skills in data acquisition and management, 2) expand my existing skills In study design, analysis, and interpretation of results, 3) learn how to measure quality of life and psychometrics to assess long-term outcomes for children with neurodevelopmental disorders, 4) learn neurobiology methodologies to better understand emerging basic neuroscience findings, and 5) develop expertise In conducting multicenter studies. These alms will facilitate my overarching career goal- to transition to an independent physician-scientist capable of performing rigorous multicenter studies needed to improve the evidence base of Inpatient health care delivered to children with neurodevelopmental disorders. The central hypothesis of the proposed project is that variation in medical and surgical decision-making in the treatment of CSF shunt infection results in different rates of shunt re-infections. Specific Aims include: 1) Identify patient risk factors associated with CSF shunt infection, and 2) determine the association of intravenous antibiotic duration for treatment of CSF shunt infection with CSF shunt re-infection and 3) design a multicenter randomized controlled trial for the treatment of CSF shunt infection in the HCRN. Public Health Relevance: Children with hydrocephalus have a neurodevelopmental disorder whose principal treatment is cerebrospinal fluid (CSF) shunt placement. Shunts often require surgical revision which increases the risk of infection. CSF shunt infections lead to prolonged hospitalizations, high expenditures, repeated shunt revision surgeries, and re-infection at high rates. A recent NIH-sponsored workshop called for renewed research in hydrocephalus, including a need to optimize treatment of CSF shunt infection and prevent CSF shunt re-infection.