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（由适用提供）：小儿静脉血栓主义（VTE）的速度急剧增加。现在，儿童中VTE的概念已经从急性事件的概念演变为一种慢性疾病。 VTE会导致巨大的伯内斯，尤其是在身体功能方面，这是由于抗血栓疗法或随着时间的推移而发展不良的结果。 VTE之后的主要较差结果包括慢性，终身疼痛的综合征，被影响的肢体的痉挛和肿胀，称为癌后综合征（PTS），复发性VTE和其他令人衰弱的血栓性后遗症，包括，包括但不限于肺部高血压。尽管对VTE并发症的早期诊断可以改善健康结果，但目前尚不知道如何识别有这些结果风险的儿童。给定个体产生称为凝血酶产生电位（TGP）的凝血酶和溶解称为纤维蛋白溶解的凝血酶的能力可以通过全局凝血测定在等离子体中测量。全球凝血测定法捕获完整的凝血，并通过凝块溶解提供来自凝块启动的信息。这些测定可能有助于确定VTE后有不良预后的儿童。即使全球凝血评估更有可能识别出患有不良预后的风险的评估，也不太可能仅生物标志物分析或药理学就足以足以进行VTE后的VTE疾病。实际上，已经知道运动水平降低和活动水平会导致成人PT的风险。但是，保持遵守VTE活性方案的依从性可能是一个问题。新兴的技术工具可能会被利用，以更仔细地跟踪活动并增加对儿童活动的激励。这些结果背后的数据的匮乏和对生物学背后的生物学的不良理解具有几种重要含义：1）携带VTE儿科患者（儿科医生和家庭医生）的提供者对这些并发症的重力得知； 3）很少有专业知识和/或资源进行构思良好的前瞻性研究，以定义强大的，预测性的生物标志物和有效的治疗策略。该提案描述了一项职业发展计划，该计划将使候选人成为成功的独立调查员，并实现她成为小儿血栓形成的国家领导者的长期职业目标。她的直接目标包括测试全球凝结凝血以预测儿童的VTE结果不佳的概念创新。 She will also investigate the feasibility of using a fitness tracker to support 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 supported research environment at University of Texas Southwestern Medical Center and Children's Hospital in Dallas, TX. environment includes a NIH资助的CTSA，临床和转化研究中心以及国家资助的止血性血栓形成中心，该实体是整个北德克萨斯州唯一的转诊儿童转诊中心，该项目的目标是：1）前瞻性评估TGP和纤维溶液，使用全球辅助分析供应型生物凝聚力。个人“健身追踪器”的可行性和潜在有效性，以提高儿童初始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）培训，通过追求临床科学硕士学位，以增强对临床研究，统计和流行病学的了解和理解； 2）在临床研究设计和实施方面发展和完善技能，以及3）过渡到独立研究者。 K23提案的研究和培训目标共同为两个R01应用程序提供培训，经验和初步数据。一项R01将是一项更大的筛查研究，用于测试和开发融合常规血栓形成和全球凝血生物标志物的VTE结果的风险预测工具。另一个R01将是一个完全动力的多站点RCT，以确定活动/运动方案的效率，以预防和治疗AIM 1中确定的高风险组中的PT。拟议的研究和培训目标将在战略上将PI策略性地定位为PI，使PI成为小儿血栓形成的领导者。全球研究凝血的创新方法，以预测不良的结果并针对最常见的并发症，PTS（如该K23提案中概述）可能对这种非常常见，严重且昂贵的疾病对临床护理产生很大的影响。

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.