"Mount Sinai Regional Drug Induced Liver Injury Network Site"

“西奈山地区药物性肝损伤网络网站”

• 批准号: 8717659
• 负责人: Jawad Ahmad
• 金额: $ 32.21万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8717659
• 关键词: 2 year old; Acute Liver Failure; Adult; African American; Age; Algorithms; Ancillary Study; Antiviral Agents; Area; Asians; Biological Markers; Blood; Blood specimen; Caring; Categories; Child; Clinical; Clinical Data; Collaborations; Complementary and alternative medicine; Computerized Medical Record; DNA; Data; Databases; Diagnosis; Diagnostic; Disease; Early Diagnosis; Electronics; Eligibility Determination; Enrollment; Ensure; Epidemiology; Ethnic group; Etiology; Fatty Liver; Frequencies; Future; General Practitioners; Genomics; Geriatrics; Goals; HIV; HIV Infections; Hematologic Neoplasms; Hepatic; Hepatitis C virus; Hepatology; Hepatotoxicity; Hispanics; Home environment; Human Resources; Immunologic Deficiency Syndromes; Individual; Informed Consent; Infusion procedures; Injury; Injury to Liver; Institutes; Institution; International; Internist; Intervention; Investigation; Lead; Legal Guardians; Liver diseases; Measures; Medical center; Medicine; Minority; Minority Groups; Molecular; Monitor; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; New York; Oncologist; Outpatients; Parents; Pathogenesis; Patient Monitoring; Patients; Pharmaceutical Preparations; Pilot Projects; Population; Population Control; Preventive; Process; Provider; Qualifying; Reading; Recording of previous events; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Resources; Rights; Risk Factors; Sampling; Serum; Severities; Site; Source; Staging; System; Techniques; Underrepresented Minority; United States National Library of Medicine; Ursidae Family; Writing; acute drug induced liver toxicity; acute liver injury; age group; antiretroviral therapy; base; biobank; case control; chemotherapy; clinical practice; design; dietary supplements; genetic analysis; high risk; improved; innovation; insight; instrument; liver injury; meetings; member; metropolitan; mortality; older patient; patient population; prevent; programs; prospective; public health relevance; response; screening; success; tertiary care; tool; web site

DESCRIPTION (provided by applicant): Hepatotoxicity due to prescription medications and herbal supplements is increasingly recognized as a major cause of morbidity and mortality throughout the developed world. Due to its idiosyncratic nature, variable presentation, and the vast number of potential causative drugs as well as herbal and dietary supplements, drug-induced liver injury (DILI) is often diagnosed late in its course when patients present with severe liver disease. This makes diagnosis and characterization of the mechanisms involved in the pathogenesis of DILI, difficult and does not allow accurate assessment of the epidemiology and risk factors associated with DILI. Since one of the main concerns with the current DILIN is the late presentation of cases, future investigation should focus on accruing cases where the liver injury is detected early on. The aims of the Mount Sinai membership in the NIDDK DILI study are as follows: 1) To rapidly increase the number of enrolled adults and children with DILI, particularly among under-represented minority groups in the current DILIN prospective and retrospective databases; 2) To enroll patients early in the course of DILI by closely monitoring high risk groups; and 3) ultimately to investigate preventative measures to prevent DILI among high risk groups. The inclusion of Mount Sinai in the DILIN will lead to an increase in the number of DILI cases from Hispanic, Black and Asian patients. The significant number of Asian and Hispanic patients who will be recruited from the New York area may provide insights into the mechanism of liver injury related to the use of herbal and dietary supplements as these populations are known to be frequent users of these complementary and alternative medicines. A major component of the Mount Sinai DILIN will be focused on the recruitment of elderly patients with DILI, and importantly also on a control population taking these supplements, a population not well represented to date in the network. Similarly, Mount Sinai's large population of 4,000 HIV infected patients will provide cases and controls to represent the large population on antiretroviral therapy. The large number of patients undergoing chemotherapy treatment followed by the many Mount Sinai oncologists represents another ideal source of prospective DILI cases and controls. Mount Sinai is a member of eMERGE, a national consortium to develop, disseminate, and apply approaches using electronic medical records (EMR) systems to genomics research. A current projects in eMERGE is to develop an electronic algorithm to identify cases of DILI in EMR systems. If just 1 percent of the 100,000 eMERGE DNA samples have a history of DILI, then the DILIN could double its DNA sample database overnight. Investigators at Mount Sinai are well-qualified and poised to contribute to ancillary studies that arise from the wealth of available data and samples of the collective DILIN. Combined with outstanding infrastructure to collect detailed information through exploitation of the EMR and Data Warehouse, the partnership of the Personalized Medicine program, and involvement of a multi-disciplinary team across the institution and its affiliates, we bring tremendous manpower to bear upon this urgent problem.

描述（由申请人提供）：处方药和草药补充剂引起的肝毒性越来越被认为是发达国家发病率和死亡率的主要原因。由于药物性肝损伤（DILI）的特异质性质、多变的表现、大量的潜在致病药物以及草药和膳食补充剂，药物性肝损伤（DILI）通常在病程晚期诊断， 肝脏疾病这使得DILI发病机制的诊断和表征变得困难，并且无法准确评估与DILI相关的流行病学和风险因素。由于目前DILIN的主要问题之一是病例的晚期表现，未来的调查应集中在早期发现肝损伤的累积病例上。西奈山参加NIDDK DILI研究的目的如下：1）迅速增加DILI成人和儿童的登记人数，特别是在当前DILIN前瞻性和回顾性数据库中代表性不足的少数群体中; 2）通过密切监测高危群体在DILI过程中早期招募患者; 3）最终研究预防措施以预防高危人群中的DILI。将西奈山纳入DILIN将导致西班牙裔、黑人和亚洲患者的DILI病例数量增加。从纽约地区招募的大量亚洲和西班牙裔患者可能会深入了解与使用草药和膳食补充剂相关的肝损伤机制，因为已知这些人群经常使用这些补充和替代药物。西奈山DILIN的一个主要组成部分将侧重于招募老年DILI患者，重要的是还将侧重于服用这些补充剂的对照人群，这是一个迄今为止在网络中没有很好代表的人群。同样，西奈山4 000名艾滋病毒感染者的庞大人口将提供病例和对照，以代表接受抗逆转录病毒治疗的庞大人口。大量患者接受化疗治疗，随后由许多西奈山肿瘤学家代表了另一个理想的来源，前瞻性DILI病例和对照。西奈山是eMERGE的成员，eMERGE是一个国家联盟，旨在开发，传播和应用使用电子医疗记录（EMR）系统进行基因组学研究的方法。eMERGE目前的一个项目是开发一种电子算法，以识别EMR系统中的DILI病例。如果10万个eMERGE DNA样本中只有1%有DILI的历史，那么DILIN可以在一夜之间将其DNA样本数据库翻一番。西奈山的调查人员都是合格的，并准备为辅助研究，从丰富的可用数据和样本的集体DILIN产生贡献。结合优秀的基础设施，通过利用EMR和数据仓库收集详细信息，个性化医疗计划的合作伙伴关系，以及跨机构及其附属机构的多学科团队的参与，我们带来了巨大的人力资源来解决这个紧迫的问题。