Multi-center Studies of Pediatric CSF Shunt Infections

描述(由申请者提供)：项目摘要：脑脊液分流感染极难治疗，导致长时间住院、反复分流手术，再感染率高达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。美国国立卫生研究院(NIH)最近的一次研讨会强调了优化脑脊液分流感染的治疗和预防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(儿科住院医生)，我经常照顾患有脑脊液分流感染、脑积水和其他神经发育障碍的儿童。这项建议的研究和职业发展目标将侧重于进行多中心纵向研究，这是产生足够样本量来研究患有神经发育障碍儿童的临床问题所必需的。拟议项目的核心是脑积水临床研究网络(HCRN)，这是四家儿科神经外科医院之间由慈善机构资助的中央协调研究工作。我与HCRN的关系提供了一个独特的机会，以足够的样本量对脑脊液分流感染治疗进行前瞻性的多中心研究。我的职业发展目标包括：1)扩展我现有的数据采集和管理技能，2)扩展我现有的研究设计、分析和结果解释技能，3)学习如何测量生活质量和心理计量学，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，以更好地了解新出现的基础神经科学发现，以及5)发展进行多中心研究的专业知识。这些施舍将促进我的首要职业目标--转变为一名独立的内科科学家，能够进行严格的多中心研究，以改善为患有神经发育障碍的儿童提供住院医疗服务的证据基础。拟议项目的中心假设是，治疗脑脊液分流感染的内科和外科决策的不同会导致不同的分流再感染率。具体目标包括：1)确定与脑脊液分流感染相关的患者危险因素；2)确定治疗脑脊液分流感染的静脉抗生素持续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。 公共卫生相关性：患有脑积水的儿童有一种神经发育障碍，其主要治疗方法是脑脊液(CSF)分流术。分流术通常需要手术修补，这增加了感染的风险。脑脊液分流感染导致住院时间延长、费用高昂、反复进行分流手术，以及高感染率的再感染。最近由美国国立卫生研究院赞助的一个研讨会呼吁对脑积水进行新的研究，包括需要优化脑脊液分流感染的治疗并防止脑脊液分流再感染。

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.