Undiagnosed diseases network clinical site

未确诊疾病网络临床网站

基本信息

批准号：
10600336
负责人：
Daniel James Rader
金额：
$ 64.44万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-02 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10600336
关键词：
Accounting Acute Address Administrative Supplement Admission activity Adult Affect Age Area Bioinformatics Catchment Area Categories Censuses Center for Translational Science Activities Child Clinical Clinical Research Consultations Critical Care Data Data Analyses Diagnosis Diagnostic Disease Education Educational Background Elements Ensure Environmental Exposure Epigenetic Process Evaluation Fetus Foundations Funding Future Geography Health Home Hospitalization Hospitals Human Immune Individual Infrastructure Inpatients Institution Knock-out Knowledge Life Mediating Medical Mid-Atlantic Region Mission Mitochondrial Diseases Modeling Modernization Newborn Infant Organ Patients Pediatric Hospitals Pennsylvania Persons Phenotype Philadelphia Physicians Population Program Sustainability Rare Diseases Resources Sampling Services Site Socioeconomic Status Somatic Mutation Speed System Technology Testing Thinking Time Translating United States National Institutes of Health University Hospitals Untranslated RNA Validation Variant Vertebral column Work base care coordination clinical research site collaborative approach data integration disability education resources exome sequencing experience follow-up genetic disorder diagnosis genome sequencing human disease imaging facilities improved innovation interdisciplinary approach laboratory facility metabolomics patient population programs research clinical testing screening synergism transcriptome sequencing whole genome

项目摘要

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.

未确诊疾病和罕见疾病的发生与年龄、地理位置、社会经济地位或令人沮丧的是，很难对罕见疾病进行科学定义和分类。 2016 年人口普查发现，美国有 3000 万人受到感染，而尚未确诊的人数尚未统计到 42 人。百万人口居住在纽约州/新泽西州/宾夕法尼亚州/德国大西洋中部地区，占美国人口的 13%。根据人口和我们对超过 100 名儿童和超过 100 名成人的统计，认为需要建立一个 UDN 临床站点每年到我们机构就诊但病情未确诊的患者，转诊至 CHOP/UPENN 的比例更大。集水区不仅仅是四个州的地区，并支持我们的关键论点，即区域需求很高并且我们准备提供专业知识、协调护理和技术来造福这些现代患者。基于医院的诊断方法，各个临床团队提出并测试器官或系统- 特定的诊断概念有一些局限性，它无法充分利用患者的临床能力。机构并有效地利用先进的测序、生物信息学策略和集体的协同作用 UDN 计划带来了一种协作方法来满足未确诊患者的需求。我们建议以有益的方式利用技术。该应用程序提出了一种临床方案，同时尊重患者的财务限制和临床医生的时间。站点作为 UDN 的一部分运行，利用由现有 UDN 优化的工作流程，具有潜力目标 1 描述了我们的组织和可能广泛有用的可持续发展的效率和战略。目标 2 中包含文档管理和基础设施要素的患者流程。外显子组测序未提供信息或怀疑患有非孟德尔遗传的患者在目标 3 中，将对可持续性战略进行试点，包括改进。患者评估期间的数据采集、环境暴露的生物信息方法、“人类淘汰筛选核心”用于教育未来诊断医生的方法和策略。患有已知疾病的患者将短暂停留，重点关注教育和资源识别。患者将稳定，但缺乏诊断，并且通常会在我们的治疗范围内进行为期一周的评估住院治疗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开发一个可以使用稳定和评估急性病患者、新生儿和胎儿的随访计划。我们的建议与 NIH 的使命直接相关，因为它使用了住院重症监护病房的管理。应用知识来增强独特和弱势群体的健康、延长寿命并减少疾病和残疾拟议的临床中心拥有宝贵的专业知识和丰富的协作经验。网络、强大的机构支持和针对共同挑战的创造性解决方案未确诊的患者。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterizing the pathogenicity of genetic variants: the consequences of context.

表征遗传变异的致病性：背景的后果。

DOI：
发表时间：
2024-01-09
期刊：
影响因子：
0
作者：
Ciesielski, Timothy H;Sirugo, Giorgio;Iyengar, Sudha K;Williams, Scott M
通讯作者：
Williams, Scott M

Kagami Ogata syndrome: a small deletion refines critical region for imprinting.

Kagami Ogata 综合征：一个小的缺失改善了印记的关键区域。

DOI：
发表时间：
2024-01-11
期刊：
影响因子：
0
作者：
Kilich, Gonench;Hassey, Kelly;Behrens, Edward M;Falk, Marni;Vanderver, Adeline;Rader, Daniel J;Cahill, Patrick J;Raper, Anna;Zhang, Zhe;Westerfer, Dawn;Jadhav, Tanaya;Conlin, Laura;Izumi, Kosuke;Rajagopalan, Ramakrishnan;Sullivan, Kathleen E
通讯作者：
Sullivan, Kathleen E

Very early-onset inflammatory bowel disease: an integrated approach.

极早发性炎症性肠病：综合方法。