Eunice Kennedy Shriver NICHD Cooperative Multicenter Neonatal Research Network

 描述(由申请者提供)：杜克大学医学院新生儿学部热情地提交这份续签申请，这是杜克大学连续第四个周期参加由尤尼斯·肯尼迪·施莱弗NICHD赞助的多中心合作新生儿研究网络(NRN)。NRN的目的是对新生儿进行干预性和观察性临床研究，特别是那些低出生体重或妊娠的新生儿，以改善医学和神经发育结果。杜克大学支持NRN的目标是：1)优先处理和实施批准的NRN方案，同时保持90%的随访率；2)带来创新的、协作的多学科研究机会 给NRN；3)向NRN介绍年轻教师的指导机会，以培养新的想法，并确保在新生儿重症监护方面不断取得进展。为了支持这些目标，杜克大学增加了两个卫星站点。2009年1月，当北卡罗来纳大学教堂山分校(UNC)加入杜克大学时，杜克大学成为第一个增加独立学术机构的网络网站。WakeMed医疗中心成立于2014年7月。UNC和WakeMed的加入扩大了研究人群，并增强了该网站的临床试验专业知识。它还增加了NRN研究对我们地区和州新生儿保健的影响。杜克大学的网站(杜克大学、北卡罗来纳大学、WakeMed大学)在NRN Inositol III期试验中名列前茅，是TH网络的通用数据库和早产儿输血研究中注册人数最多的网站之一。杜克大学、北卡罗来纳州大学和WakeMed大学维持着多学科的随访诊所，这些诊所保持着90%的临床试验和队列研究的随访率。杜克大学领导着两个主要的网络项目，“新生儿念珠菌病早期诊断”和“匿名DNA银行”，这两个项目结合了杜克大学在传染病、医学真菌学、生物医学工程、遗传流行病学和分子方法学方面的专业知识。念珠菌试验材料仍在继续分析，并提供了可能有助于减少念珠菌病的信息。DNA库样本和相关的临床数据已被用来确定磷酸化酶途径基因变异与BPD风险之间的关联，以及BDNF基因变异与严重视网膜病变之间的关联。今年，在PAS NRN上，研究人员报告了8号染色体上一个基因内区的变异与严重的NEC之间的关联，这种关联达到了全基因组的意义。世行的数据也被用作其他由美国国立卫生研究院资助的基因与早产儿发病率相关研究的验证队列。除了这两项研究产生的资源仍被来自多个地点的研究人员使用外，杜克大学还让NRN的初级教员和实习生参与进来。八个不同的杜克大学网站调查人员在上一个周期发表了38篇NRN论文(8篇第一作者论文)。杜克大学、北卡罗来纳大学和WakeMed将继续努力，最大限度地扩大招生人数，并对队列研究和临床试验保持90%的后续行动。NRN已经审查了脑损伤的细胞疗法和动脉导管未闭(PDA试验)管理策略的创新研究，并可能在2016-2021年周期开始。PDA方案由劳顿博士(北卡罗来纳大学)领导。新生儿脑病自体脐血研究(Cotten)于2015年1月作为NRN概念提出，并被批准开发为NRN考虑的完整方案。杜克大学的网站将继续这些努力，并为临床试验带来更多的新概念。杜克大学、北卡罗来纳州大学和WAKEMED儿科部门以及卫生系统完全支持我们对NRN的持续合作承诺，因为我们坚信，我们与NRN的互动已经直接影响和改善了我们三家机构和整个州的婴儿护理。

 DESCRIPTION (provided by applicant): The Duke University School of Medicine, Division of Neonatology enthusiastically submits this renewal application for a fourth consecutive cycle of participation in the Eunice Kennedy Shriver NICHD-sponsored Cooperative Multicenter Neonatal Research Network (NRN). The NRN's purpose is to perform interventional and observational clinical studies in newborn infants, particularly those of low birth weight or gestation, that lead to improved medical and neurodevelopmental outcomes. Duke's aims in support of the NRN are to: 1) prioritize and conduct approved NRN protocols while maintaining a > 90% follow-up rate; 2) bring innovative, collaborative multidisciplinary research opportunities to the NRN; 3) introduce young faculty to NRN mentoring opportunities to foster new ideas and ensure ongoing progress in Neonatal Intensive Care. In support of these aims Duke added two satellite sites. In January 2009, Duke was the first Network site to add an independent academic institution when the University of North Carolina at Chapel Hill (UNC) joined Duke. WakeMed Medical Center was added in July 2014. The addition of UNC and WakeMed expands the study population and enhances the Site's clinical trial expertise. It also increases the impact of NRN studies on neonatal health care in our region and State. The Duke Site (Duke, UNC, WakeMed) leads enrollment in the NRN Inositol phase III trial and is among the highest enrolling sites in th Network's Generic Database and Transfusion for Prematures studies. Duke, UNC, and WakeMed maintain multidisciplinary follow-up clinics which maintain follow-up rates for clinical trials and cohort studies > 90%. Duke leads two major Network projects, "Early Diagnosis of Neonatal Candidiasis" and the "Anonymized DNA Bank", that combined Duke' expertise in Infectious Diseases, Medical Mycology, Biomedical Engineering, Genetic Epidemiology and Molecular Methodologies. Candida trial materials continue to be analyzed and have provided information that has likely contributed to the decrease in Candidiasis. The DNA bank samples and linked clinical data have been used to identify associations between variants in phosphorylase pathway genes and BPD risk, and variants in the BDNF gene and severe retinopathy. This year at PAS NRN investigators reported associations between variants in an intragenic region on chromosome 8 and severe NEC that reached genome wide significance. The Bank's data has also been used as a validation cohort for other NIH-funded investigations of genetic associations with morbidities of prematurity. In addition to these two studies which have produced resources still being used by investigators from multiple sites, Duke has made involvement of junior faculty and trainees in the NRN. Eight different Duke Site investigators have co-authored 38 NRN papers published in the last cycle (8 first-author papers). Duke, UNC, and WakeMed will continue efforts to maximize enrollment and maintain follow-up for cohort studies and clinical trials > 90%. Innovative studies of cell therapy for brain injury and management strategies for Patent Ductus Arteriosus (PDA trial) have been reviewed by the NRN and are likely to begin in the 2016 - 2021 cycle. The PDA protocol is led by Dr. Laughton (UNC). The autologous cord blood study for infants with neonatal encephalopathy (Cotten) was presented as an NRN concept in January 2015, and approved to be developed into a full protocol for NRN consideration. The Duke Site will continue these efforts plus bring additional novel concepts for clinical trials. The Duke, UNC, and WakeMed Departments of Pediatrics, and the Health Systems fully support our ongoing collaborative commitment to the NRN, as we firmly believe that our interactions with the NRN have directly affected and improved the care of infants in our three institutions and throughout our State.