A new paradigm of short stature: Incorporating parent and youth characteristics into understanding GH-related decision making and trajectories of quality of life and self-esteem

项目总结/摘要 生长激素（GH）治疗是"扩展生物技术"的范例，其中生物医学技术 最初设计用于治疗疾病（生长激素缺乏症; GHD）扩大，与良好的鼓励- 预期的医生和行业的支持，到治疗的条件，模糊之间的界限， 疾病和变异（特发性身材矮小; ISS），估计潜在的国家成本为400亿美元。在 我们之前的研究，家长们表示，关注身材矮小对心理社会功能的影响， 无论是在童年时期还是在成年时期，都对他们寻求医疗护理的决定产生重大影响。 因为孩子身材矮小然而，到目前为止，身高一直是GH治疗的主要结局指标， 尽管身高是心理社会适应和健康相关生活质量（QoL）的不良预测因子。很长的- 这项研究的长期目标是确定是什么促使青少年更好的生活质量和心理社会调整， 身材矮小。虽然普遍的假设认为，身高的增加直接提供了 的好处，我们假设身高对生活质量和自尊的影响是由特征的修改， 父母和青年的影响超过身高增加本身的程度，有或没有GH治疗。 因此，拟议的纵向混合方法研究将对8 - 14岁的青少年进行为期两年的跟踪研究， 在我们的生长中心和父母参与者进行挑衅性GH测试。使用半结构化 访谈和新的定量措施，具体目标1将探讨青年和家长的看法短 身高及其对QoL的影响、对GH治疗的感知和期望以及决策 关于身材矮小和生长激素治疗的评估，重点是青年在决策中的作用， 尚未进行研究，但在慢性（年）选择性治疗（ISS）的背景下至关重要， 侵入性（每日注射），并具有潜在的副作用。使用定量测量QoL和 自尊的积极方面，具体目标2将描述青年生活质量和自尊的轨迹2 挑衅性GH检测后几年，包括患有GHD的青少年、接受GH治疗的ISS和未接受GH治疗的ISS GH。具体目标3将定义特定的父母和青年特征，这些特征改变了身高与 这两年的生活质量和自尊。本申请中提出的研究将解决一个关键的差距 在我们理解患者和父母的特征如何改变矮个子的潜在影响方面， 将目前持有的传统矮小症疾病模型转变为更丰富的框架，包括 父母特征、教养方式和青年特征以及身高。拟议的工作将 从而为将来确定性、长期、随机对照试验检测GH的疗效奠定基础 或其他针对身材矮小的干预措施，包括QoL和心理社会调整作为主要结局， 并使该领域和临床护理能够以循证、价值驱动的方式向前发展。

PROJECT SUMMARY/ABSTRACT Growth hormone (GH) treatment is a paradigm of “expansive biotechnology,” wherein a biomedical technology originally designed for treatment of disease (GH deficiency; GHD) expanded, with the encouragement of well- intended physicians and support of industry, into treatment of conditions that blur the boundary between disease and variation (idiopathic short stature; ISS), with an estimated potential national cost of $40 billion. In our prior research, parents indicated that concerns about the impact of short stature on psychosocial function, both in childhood and projected into adulthood, have a major influence on their decision to seek medical care for a child's short stature. Yet thus far height has been the primary outcome measure of GH treatment, even though height is a poor predictor of psychosocial adjustment and health-related quality of life (QoL). The long- term goal of this research is to determine what drives better QoL and psychosocial adjustment in youth with short stature. While the prevailing assumption holds that the attainment of increased height directly provides benefit, we hypothesize that the impact of height on QoL and self-esteem is modified by characteristics of the parent and youth to a degree that exceeds the impact from height gain itself, with or without GH treatment. Thus, the proposed longitudinal mixed-methods study will follow for two years youth aged 8-14 years who undergo provocative GH testing in our Growth Center and a parent participant. Using semi-structured interviews and novel quantitative measures, Specific Aim 1 will explore youth and parent perceptions of short stature and its impact on QoL, perceptions and expectations vis-a-vis GH treatment, and decision-making regarding evaluation of short stature and GH treatment, with a focus on the youth's role in decision-making, which has not been studied but is critical in the context of an elective treatment (ISS) that is chronic (years), invasive (daily injections), and carries potential side effects. Using quantitative measures of both QoL and the positive aspects of self-esteem, Specific Aim 2 will describe trajectories of youth QoL and self-esteem for 2 years after provocative GH testing, including youth with GHD, ISS treated with GH, and ISS not treated with GH. Specific Aim 3 will define specific parent and youth characteristics that modify the relationship of height to QoL and self-esteem for those two years. The research proposed in this application will address a critical gap in our understanding of how patient and parent characteristics alter the potential impact of being short, and transform the currently held, traditional disease model of short stature into a richer framework that includes parent characteristics, parenting styles and youth characteristics as well as height. The proposed work will thereby lay the foundation for future definitive, long-term, randomized controlled trials testing the efficacy of GH or other interventions for short stature that include QoL and psychosocial adjustment as primary outcomes, and enable the field and clinical care to move forward in an evidence-based, value-driven way.