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Predicting and Preventing Poor Outcomes of Venous Thromboembolism in Children

预测和预防儿童静脉血栓栓塞的不良后果

基本信息

批准号：
9918437
负责人：
Ayesha Zia
金额：
$ 14.24万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9918437
关键词：
Accelerometer Acute Adherence Adult Adverse effects Affect Anticoagulation Assessment tool Biological Assay Biological Markers Biology Center for Translational Science Activities Child Childhood Chronic Chronic Disease Clinical Clinical Research Clinical Sciences Coagulation Process Complication Consent Cost of Illness Data Deep Vein Thrombosis Development Development Plans Diagnosis Disease Early Diagnosis Educational workshop Effectiveness Eligibility Determination Environment Epidemiology Event Exercise Family Physicians Fibrinolysis Force of Gravity Fostering Frequencies Funding Future Generations Goals Health Hemostatic function Hospitalized Child Incentives Individual Intervention Investigation Knowledge Lead Life Limb structure Longterm Follow-up Measures Medical center Mentors Muscle Cramp Oncologist Outcome Pain Patients Pediatric Hematologist Pediatric Hospitals Pharmacology Physical Function Physical activity Plasma Positioning Attribute Postphlebitic Syndrome Prevention Prevention strategy Preventive Prognostic Marker Prospective Studies Prospective cohort study Pulmonary Hypertension Quality of life Quality-of-Life Assessment Randomized Clinical Trials Randomized Controlled Trials Recurrence Regimen Research Research Design Research Personnel Research Training Resources Risk Signs and Symptoms Standardization Swelling Syndrome Testing Texas Therapeutic Thrombin Thrombophilia Thrombosis Time Training United States National Institutes of Health Universities Varicose Ulcer Varicosity Veins Work adverse outcome biomedical referral center care providers career career development chronic pain clinical care comparison group design effective therapy exercise program exercise regimen experience fitbit fitness group intervention high risk high risk population improved innovation novel strategies pediatric patients pediatrician predictive marker prevent primary outcome prospective public health relevance research study screening secondary outcome skills standard of care statistics symposium tool treatment strategy venous thromboembolism

项目摘要

DESCRIPTION (provided by applicant): There has been a dramatic increase in the rate of pediatric venous thromboembolism (VTE). The concept of VTE in children has now evolved from that of an acute event to one of chronic disease. VTE leads to tremendous burdens, especially on physical functioning, due either to antithrombotic therapy or the development of poor outcomes over time. The major poor outcomes after VTE include a chronic, life-long syndrome of pain, cramping and swelling of the affected extremity called the postthrombotic syndrome (PTS), recurrent VTE and other debilitating post thrombotic sequelae including, but not limited to pulmonary hypertension. Although early diagnosis of VTE complications can improve health outcomes, it is not known currently how to identify children at risk of these outcomes. The capacity of a given individual to generate thrombin called thrombin generation potential (TGP) and, dissolve the clot called fibrinolysis can be measured in plasma by global coagulation assays. Global coagulation assays capture coagulation in its entirety and provide information from clot initiation through clot dissolution. These assays may help identify children at risk of poor outcomes after VTE. Even if global coagulation assessment is more likely to identify those at risk of poor outcomes, it is unlikely that biomarker profiling or pharmacology alone will be sufficient to eradicate post VTE disease. Indeed, decreased exercise and activity levels are already known to contribute to the risk for PTS in adults. Maintaining adherence to a post VTE-activity regimen is likely to be a problem, though. Emerging technological tools might be leveraged to more carefully track activity and increase incentive for such activity in children. The paucity of data and the poor understanding of the biology behind these outcomes holds several important implications: 1) providers caring for pediatric patients with VTE (pediatric hematologists/oncologists) and those following them after diagnosis (pediatricians and family physicians) are poorly informed about the gravity of these complications; 2) standardized approaches to testing and long term follow-up are missing; and 3) expertise and/or resources to carry out well-conceived prospective studies to define robust, predictive biomarkers and effective treatment strategies are rare. This proposal describes a career development plan that will prepare the candidate to become a successful independent investigator and attain her long-term career goal of becoming a national leader in pediatric thrombosis. Her immediate goals include testing the conceptual innovation of looking at coagulation globally to predict poor VTE outcomes in children. She will also investigate the feasibility of using a fitness tracker to facilitate adherence to an activity regimen in children with deep venous thrombosis (DVT. To meet these goals, she has proposed a career development plan that integrates didactic coursework, participation in local and national conferences and workshops, and a progression of mentored research studies within the supportive research environment at University of Texas Southwestern Medical Center and Children's Hospital in Dallas, TX. This environment includes a NIH-funded CTSA and Clinical and Translational Research Center and a state- funded Hemostasis Thrombosis Center, an entity that is the only referral center for children with thrombosis in the entire North Texas. The research aims of this project are to: 1) To prospectively evaluate TGP and fibrinolysis, using global coagulation assays as biomarkers to identify children likely to develop adverse outcomes after an initial VTE and 2) demonstrate the feasibility and potential effectiveness of a personal "fitness tracker" to improve adherence to an activity regimen following an initial VTE in children. These research aims will serve as the platform for the career development plan and training aims which include: 1) training to enhance knowledge and understanding of clinical research, statistics and epidemiology by pursuing a Masters in Clinical Science; 2) develop and refine skills in clinical research design and implementation, and 3) transition into an independent investigator. Together, the research studies and training aims of the K23 proposal will provide the training, experience, and preliminary data for two R01 applications. One R01 will be a larger screening study to test and develop risk prediction tools for poor VTE outcomes incorporating conventional thrombophilia and the global coagulation biomarkers. The other R01 will be a fully powered, multisite RCT to determine efficacy of an activity/exercise regimen to prevent and treat PTS in high risk groups as identified from Aim 1. The proposed research and training aims will strategically position the PI to become a leader in pediatric thrombosis and its long-term outcomes. The innovative approach to study coagulation globally to predict poor outcomes and target the most frequent complication, PTS, as outlined in this K23 proposal has the potential for very high impact on clinical care for this very common, serious, and costly disease.

描述（由申请人提供）：儿童静脉血栓栓塞 (VTE) 的发病率急剧增加。儿童 VTE 的概念现已从一种急性事件演变为一种慢性疾病。由于抗血栓治疗或随着时间的推移会出现不良结果，VTE 会带来巨大的负担，尤其是对身体功能的负担。 VTE 后的主要不良结局包括受累肢体疼痛、痉挛和肿胀的慢性终生综合征，称为血栓后综合征 (PTS)、复发性 VTE 和其他使人衰弱的血栓后后遗症，包括但不限于肺动脉高压。尽管 VTE 并发症的早期诊断可以改善健康结果，但目前尚不清楚如何识别有这些结果风险的儿童。特定个体产生凝血酶（称为凝血酶生成潜能 (TGP)）和溶解凝块（称为纤维蛋白溶解）的能力可以通过整体凝血测定在血浆中进行测量。整体凝血测定捕获完整的凝血过程，并提供从凝块形成到凝块溶解的信息。这些检测可能有助于识别 VTE 后有不良结局风险的儿童。即使整体凝血评估更有可能识别那些有不良结果风险的人，单靠生物标志物分析或药理学也不太可能足以根除 VTE 后疾病。事实上，众所周知，运动和活动水平的减少会增加成人患PTS的风险。然而，保持对 VTE 后活动方案的坚持可能是一个问题。可以利用新兴技术工具来更仔细地跟踪儿童的活动并增加对此类活动的激励。数据的匮乏以及对这些结果背后的生物学了解不足带来了几个重要的影响：1）护理 VTE 儿科患者的提供者（儿科血液学家/肿瘤学家）以及诊断后跟随他们的人（儿科医生和家庭医生）对这些并发症的严重性知之甚少； 2）缺乏标准化的测试方法和长期随访； 3) 开展周密的前瞻性研究来定义稳健的、预测性的生物标志物和有效的治疗策略的专业知识和/或资源很少。该提案描述了一个职业发展计划，该计划将使候选人做好成为一名成功的独立研究者的准备，并实现成为儿童血栓形成领域的全国领导者的长期职业目标。她的近期目标包括测试全球凝血的概念创新，以预测儿童静脉血栓栓塞的不良结果。她还将研究使用健身追踪器促进深静脉血栓 (DVT) 儿童坚持活动方案的可行性。为了实现这些目标，她提出了一项职业发展计划，其中包括教学课程、参加地方和国家会议和研讨会，以及在德克萨斯大学西南医学中心和德克萨斯州达拉斯儿童医院的支持性研究环境中进行一系列指导研究。这种环境包括 NIH 资助的 CTSA 和临床与转化研究中心以及国家资助的止血血栓中心，该实体是整个北德克萨斯州唯一的血栓儿童转诊中心。该项目的研究目的是：1) 前瞻性评估 TGP 和纤维蛋白溶解，使用整体凝血检测作为生物标志物来识别初次 VTE 后可能出现不良后果的儿童，2) 证明个人“健身追踪器”的可行性和潜在有效性，以提高儿童初次 VTE 后对活动方案的依从性。这些研究目标将作为职业发展计划和培训目标的平台，其中包括：1）通过攻读临床科学硕士学位来增强对临床研究、统计学和流行病学的知识和理解的培训； 2) 发展和完善临床研究设计和实施方面的技能，以及 3) 转变为独立研究者。 K23 提案的研究和培训目标将为两个 R01 应用提供培训、经验和初步数据。其中一个 R01 将是一项更大规模的筛查研究，旨在测试和开发针对不良 VTE 结果的风险预测工具，结合传统的血栓形成倾向和全球凝血生物标志物。另一个 R01 将是一项功能齐全的多部位随机对照试验，用于确定活动/运动方案预防和治疗目标 1 确定的高危人群 PTS 的有效性。拟议的研究和培训目标将从战略上将 PI 定位为儿科血栓形成及其长期结果的领导者。正如本 K23 提案中概述的那样，在全球范围内研究凝血以预测不良结果并针对最常见的并发症 PTS 的创新方法有可能对这种非常常见、严重且昂贵的疾病的临床护理产生非常大的影响。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Utility of a screening tool for haemostatic defects in a multicentre cohort of adolescents with heavy menstrual bleeding.

在月经出血过多的青少年多中心队列中使用一种筛查工具来筛查止血缺陷。

DOI：
10.1111/hae.13609
发表时间：
2018
期刊：
Haemophilia : the official journal of the World Federation of Hemophilia
影响因子：
0
作者：
Zia,Ayesha;Stanek,Joseph;Christian-Rancy,Myra;Ahuja,SanjayP;Savelli,Stephanie;O'Brien,SarahH
通讯作者：
O'Brien,SarahH

The gut microbiome and thromboembolism.