Undiagnosed diseases network clinical site

未确诊疾病网络临床网站

• 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
• 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

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.

未诊断的疾病和罕见疾病不尊重年龄，地理，社会经济地位或 教育水平。他们很难科学地定义和分类需求，但罕见的疾病很难定义 在美国影响3000万人，而未诊所的人尚未受到影响。 2016年人口普查发现42 居住在纽约州/NJ/PA/de中大西洋地区的百万人占美国人口的13％。我们 根据人口和我们对100名儿童和> 100名成年人的会计，请参见UDN临床网站的需求 他们每年都以未诊断的条件出现在我们的机构中​​。转介到砍/upenn反射较大的 集水区不仅是四州区域，还支持我们的关键论点，即区域需求很高，并且 我们被毒死了，以提供专业知识，协调的护理和技术，以使这些患者受益。现代 基于医院的诊断方法，个人临床团队提案和测试器官或系统 - 特定的诊断概念有几个局限性。它无法利用 机构并有效地使用高级测序，生物信息学策略和集体协同作用 思维。 UDN计划带来了一种协作方法来满足未诊断的需求 患者人数并减轻这些缺口。我们建议以有益的方式利用技术 患者尊重财务限制和临床时间。该申请提出临床 作为使用现有UDN优化的工作流的UDN的一部分，该站点具有潜力 效率和可持续性策略可能广泛有用。 AIM 1描述了我们的组织， 结合文档管理和基础设施元素的患者流量。在AIM 2中，评估 尚未提供信息或怀疑非​​孟德尔人的外显子测序患者 疾病将被专门评估。在AIM 3中，将实行可持续性策略，包括改进 患者评估期间的数据捕获，一种生物信息学的环境暴露方法，“人类 淘汰筛查核心的方法和对未来诊断医生教育的策略。 有公认的疾病将短暂关注教育和资源识别。最多 患者将是稳定的，但缺乏诊断性，并且通常会在我们的住院期间进行一周的评估。 临床和转化研究中心。在逗留期间，我们将进行其他研究，并开发 后续计划。急性病患者，新生儿和胎儿可以使用稳定和 在住院重症监护病房中的管理。我们的建议与NIH任务直接相关，因为它使用 应用知识以增强健康，延长寿命并减少独特而脆弱的疾病和残疾 患者人数。拟议的临床网站在协作中具有宝贵的专业知识，丰富的经验 网络，强大的机构支持以及针对由此提出的共同挑战的创造性解决方案 未经诊断的患者。

项目成果

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

• DOI: 10.1097/aci.0000000000000484
• 发表时间: 2018-12
• 期刊: Current opinion in allergy and clinical immunology
• 影响因子: 2.8

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

• DOI: 10.1038/s41525-023-00386-5
• 发表时间: 2024-01-09
• 期刊: NPJ GENOMIC MEDICINE
• 影响因子: 5.3
• 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.

• DOI: 10.1038/s41525-023-00389-2
• 发表时间: 2024-01-11
• 期刊: NPJ GENOMIC MEDICINE
• 影响因子: 5.3
• 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.