New Investigation Initiatives for the Prevention of Complications of Thalassemia

描述（由申请人提供）：这是波士顿儿童医院（CHB）的一个综合性地中海贫血护理中心的新申请，与亚特兰大儿童医院的地中海贫血项目进行场外合作。这两个组织都以分包商的身份参与了疾病预防控制中心领导的地中海贫血项目的头五年。本建议的目的是对地中海贫血并发症进行评估、预防和管理。目标人群包括新英格兰和亚特兰大地区的个体，他们患有输血依赖性β地中海贫血（Thal）、α地中海贫血（纯合子和血红蛋白H病）、地中海贫血中间体和相关疾病。Thal的疾病负担很高。没有任何一组人在一生中接受的新鲜红细胞输注次数能与输血依赖性Thal患者相比（基本上是终生每月输注一次）。因此，血液传播疾病的筛查是管理的重要组成部分。此外，输血会导致强制性铁超载，与铁有关的心脏病、肝病和内分泌疾病是这类患者发病和死亡的主要原因。口服铁螯合剂的良好依从性与生存率的提高高度相关，但即使是表面上螯合良好的患者，加上未输血的Thal intermedia患者，也可能在数十年内出现危及生命的铁相关并发症，包括心力衰竭、心律失常、肝硬化、糖尿病以及不孕症和其他生殖内分泌紊乱。面对这些挑战，管理、监测和预防并发症的关键包括定期到专家中心进行全面检查，由熟练掌握Thal护理的专家进行检查，持续进行血液安全监测和铁及其后遗症检测，以及社区外展、与患者支持团体合作、家庭和患者教育，以及持续的心理社会评估和支持。CHB的地中海贫血项目已经活跃了40多年，并引领了该领域的许多发展，特别是在螯合治疗方面。该项目的具体目的是：(1)在Thal中提供综合护理，筛查潜在并发症，并实施预防并发症的策略；（II）以血友病中心和美国疾病控制与预防中心采用的“做五”战略为模板，启动一项患者/家庭教育计划，以促进全面护理、血源性病毒疫苗、充分螯合和血液安全监测。（III）与美国国立卫生研究院发起的地中海贫血临床研究网络（CHB和CHOA属于该网络，首席研究员Neufeld博士是TCRN指导委员会主席）建立研究合作。每个目标都包含一个评估临床结果的研究组成部分，旨在为进一步的研究产生假设，并提供改善护理和减少并发症的机会。叙述:

DESCRIPTION (provided by applicant): This is a new application for a comprehensive Thalassemia care center, at Children's Hospital Boston (CHB), with off-site collaboration with the Thalassemia program of Children's Hospital of Atlanta. Both organizations have been participants as subcontractors in the first five year period of the CDC-led Thalassemia project. The objectives of this proposal are to provide assessment for, and prevention and management of complications of Thalassemia. The target populations include individuals in New England and in the Atlanta region, with transfusion-dependent beta Thalassemia (Thal), alpha Thal (homozygous and hemoglobin H disease), Thal intermedia, and related disorders. The burden of disease in Thal is high. No other single group of humans receives as many fresh red cell transfusions in a lifetime as patients with transfusion-dependent Thal (essentially monthly transfusion for life). Therefore, screening for blood borne diseases is a crucial part of management. In addition, with transfusions comes obligatory iron overload, and iron-related heart disease, liver disease, and endocrinopathies are major causes of morbidity and mortality in this patient group. Good compliance with oral iron chelators is highly correlated with improved survival, but even apparently well-chelated patients, plus non-transfused Thal intermedia patients, can develop over decades, life-threatening iron-related complications including heart failure, arrhythmia, cirrhosis, diabetes, as well as infertility and other reproductive endocrine disorders. Faced with these challenges, the keys to management, surveillance and prevention of complications include regular comprehensive visits at expert centers with specialists and tests skilled in Thal care, ongoing blood safety surveillance and tests for iron and its sequelae, as well as community outreach, collaboration with patient support groups, family and patient education, and continuing psychosocial assessment and support. The Thalassemia program at CHB has been active for more than 40 years, and has led many of the developments in the field, particularly in chelation therapy. The specific aims of this project are: (I) to provide comprehensive care in Thal, screen for potential complications, and implement strategies to prevent complications; (II) to initiate a patient/family education program modeled on the Do the Five strategy used by hemophilia centers and CDC to promote comprehensive care, vaccines for blood-borne viruses, adequate chelation, and blood safety monitoring. (III) To establish research collaboration with the NIH-sponsored Thalassemia Clinical Research Network (to which CHB and CHOA belong; and principal investigator Dr. Neufeld is chair of the TCRN steering committee.) Each aim contains a research component for assessment of clinical outcomes, aimed at generating hypothesis for further research, and providing opportunities to improve care and reduce complications.Narrative: The purpose of this project is to improve care and long-term health outcomes in patients with Thalassemia (Cooley's Anemia). This is a new application to join an ongoing cooperative endeavor of several large US Thalassemia programs, with Children's Hospital, Boston as the primary site, and Emory/Children's Healthcare of Atlanta as a collaborating site. The goals will be achieved by providing comprehensive medical services to patients with transfusion-dependent Thalassemia, and screening patients for blood-borne infections and for complications of the disorder, which are related to transfusional iron overload and to treatment of iron problems. We propose a nationwide educational strategy analogous to the efforts launched in the hemophilia community, with CDC support, for comprehensive care. We propose to pilot a new database under development at Children's Memorial Hospital in Chicago, to improve data abstraction from the electronic medical records. Finally, we propose formal collaboration with the Thalassemia clinical research network of the National Heart, Blood, and Lung Institute, to leverage the ongoing longitudinal screening in both networks.