Undiagnosed diseases network clinical site

未确诊的疾病和罕见疾病的发生与年龄、地理、社会经济地位或 教育水平。令人沮丧的是，它们很难科学地定义，也很难对需求进行分类， 在美国，有3000万人受到影响，未确诊的人数尚未计算在内。2016年人口普查发现42 2000万人居住在纽约/新泽西州/PA/DE中大西洋地区，占美国人口的13%。我们 根据人口和我们对>100名儿童和>100名成人的统计，我们认为需要一个UDN临床研究中心 每年都有未确诊的疾病出现在我们的机构。参考CHOP/UPENN反映了更大的 集水区而不仅仅是四个州的地区，并支持我们的关键论点，即区域需求很高， 我们准备提供专业知识、协调一致的护理和技术，使这些病人受益。现代 以医院为基础的诊断方法，其中个别临床团队提出并测试器官或系统- 具体的诊断概念，有几个局限性。它未能充分利用临床能力的一个 机构和有效地利用先进的测序，生物信息学战略，以及协同作用，从集体 思维UDN计划带来了一种合作的方法来解决未诊断的需求 患者群体，以减轻这些不足。我们建议以一种有利于 患者，同时尊重经济限制和临床医生的时间。本申请提出了一种临床 作为UDN的一部分运行的站点，利用现有UDN优化的工作流程， 可持续性的效率和战略，可能广泛有用。目标1描述了我们的组织， 患者流程包括文档管理和基础设施要素。在目标2中， 外显子组测序没有提供信息或怀疑非孟德尔遗传的患者 将对疾病进行具体评估。在目标3中，将试行可持续性战略，包括改进 患者评估期间的数据采集，环境暴露的生物信息学方法，“人类 敲除筛选核心”的方法和战略，为未来的诊断医生的教育。患者 将有一个短暂的停留，重点是教育和资源识别。最 患者将稳定，但缺乏诊断，并将有一个为期一周的评估住院，通常在我们的 临床和转化研究中心。在逗留期间，我们将进行额外的研究，并制定一个 后续计划。急性病患者、新生儿和胎儿可以使用稳定和 重症监护病房的管理。我们的建议与NIH的使命直接相关，因为它使用 在一个独特而脆弱的国家， 患者人群。拟议的临床研究中心具有宝贵的专业知识，丰富的合作经验， 网络，强有力的机构支持和创造性的解决方案， 未确诊的病人

Undiagnosed diseases and rare diseases occur without respect to age, geography, socioeconomic status or level of education. They are frustratingly hard to define scientifically and to classify needs, yet rare diseases affect 30 million people in the USA and the undiagnosed are as yet uncounted. The 2016 census found 42 million people living in the NY/NJ/PA/DE mid-Atlantic region, accounting for 13% of the USA population. We see a need for a UDN Clinical Site based on population and our accounting of >100 children and >100 adults who appear at our institutions yearly with undiagnosed conditions. Referrals to CHOP/UPENN reflect a larger catchment area than just the four-state area and support our pivotal thesis that the regional need is high and we are poised to deliver expertise, coordinated care, and technology to benefit these patients. The modern approach to hospital-based diagnosis, wherein individual clinical teams propose and test organ or system- specific diagnostic concepts, has several limitations. It fails to take advantage of the full clinical abilities of an institution and efficiently use advanced sequencing, bioinformatic strategies, and synergies from collective thinking. The UDN program has brought a collaborative approach to address the needs of the undiagnosed patient population and to mitigate these shortfalls. We propose to utilize technology in a manner that benefits the patient while being respectful of financial constraints and clinician time. This application proposes a Clinical Site operating as part of the UDN that utilizes work flows optimized by the existing UDN with potential efficiencies and strategies for sustainability that may be useful broadly. Aim 1 describes our organization and patient flow that incorporates document management and infrastructure elements. In Aim 2, the evaluation of patients with exome sequencing that has not been informative or who are suspected of a non-Mendelian disorder will be specifically assessed. In Aim 3, strategies for sustainability will be piloted including improved data capture during patient evaluations, a bioinformatic approach to environmental exposures, a “Human Knockout Screening Core” approach and strategies for the education of future diagnostic physicians. Patients with a recognized disease will have a short stay focused on education and resource identification. Most patients will be stable, but lack diagnosis, and will have a weeklong evaluative inpatient stay typically within our Clinical and Translational Research Center. During the stay, we will perform additional studies and develop a follow-up plan. Acutely ill patients, newborns, and fetuses can be evaluated using stabilization and management in an inpatient critical care unit. Our proposal is directly relevant to the NIH mission since it uses applied knowledge to enhance health, lengthen life and reduce illness and disability in a unique and vulnerable patient population. The proposed Clinical Site has valuable expertise, extensive experience with collaborative networks, strong institutional support and creative solutions to common challenges presented by the undiagnosed patient.