Glucocorticoid use and osteonecrosis in chronic pediatric inflammatory diseases

糖皮质激素在儿科慢性炎症性疾病中的使用和骨坏死

• 批准号: 8784410
• 负责人: Daniel Benjamin Horton
• 金额: $ 7.41万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-21 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784410
• 关键词: Accounting; Adolescent; Adult; Adverse effects; Affect; Age; Anti-Inflammatory Agents; Arthritis; Asthma; Award; Bone Diseases; Bone necrosis; British; Cessation of life; Child; Childhood; Childhood Leukemia; Chronic; Chronic Childhood Arthritis; Chronic Disease; Clinic; Clinical Investigator; Clinical Research; Cohort Studies; Complication; Data; Databases; Development; Diagnosis; Disease; Dose; Foundations; Fracture; Future; Glucocorticoids; Grant; Immunosuppressive Agents; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Joints; Knowledge; Lead; Learning; Legg-Perthes Disease; Literature; Lupus; Medical; Medical Records; Mentors; Methods; Modeling; Modification; Monitor; National Research Service Awards; Necrosis; Newly Diagnosed; Oncology; Operative Surgical Procedures; Oral; Osteoporosis; Outcome; Pain; Patients; Pattern; Pediatrics; Pharmaceutical Preparations; Pharmacoepidemiology; Population; Postdoctoral Individual National Research Service Award; Process; Psoriasis; Publishing; Regimen; Regression Analysis; Replacement Arthroplasty; Reporting; Research; Research Design; Research Personnel; Research Training; Rheumatology; Risk; Role; Safety; Series; Steroids; Subgroup; Systemic Lupus Erythematosus; Techniques; Testing; Therapeutic; Tissues; Toxic effect; Training; Training Programs; Transplantation; United Kingdom; Ursidae Family; Validation; Weight-Bearing state; bone; career; clinical practice; cohort; comparative effectiveness; disability; disabling disease; disease diagnosis; dosage; hazard; high risk; insight; leukemia; medical specialties; population based; prevent; public health relevance; skeletal; skills; treatment duration; treatment strategy

DESCRIPTION (provided by applicant): Glucocorticoids (GCs) are widely used medications for many chronic pediatric inflammatory diseases. Among the many toxicities attributed to GCs, osteonecrosis (ON, also called avascular necrosis) is one of the more serious, leading in some individuals to severe pain, disability, and the need for surgical joint replacement. Despite a long described association with high-dose GC exposure for diseases such as pediatric leukemia, the risk for ON in association with these commonly used medications in the broader pediatric population is still not well understood. Additional questions remain about whether certain inflammatory diseases affect the risk of ON independent of GC dosage, and whether this association changes with age. The proposed project aims to expand understanding of the relationship between GC use and ON through the following broad objectives: 1) examine how different patterns of GC exposure affect the development of ON in children and adolescents; 2) determine whether age and underlying inflammatory disease modify the association between GCs and ON; 3) train the applicant in methods of pharmacoepidemiology as they apply to treatments of disorders of chronic inflammation; and 4) support the applicant's development as an independent clinical investigator. The applicant will leverage a large medical records database from the United Kingdom to achieve the stated objectives. This database contains extensive demographic, medical, and therapeutic information and has been used successfully for prior pharmacoepidemiologic research. Cohorts with and without GC exposure will be assembled from a population of children and adolescents with diverse inflammatory diseases. Through a series of different models to represent GC use, the association between GCs and newly diagnosed, clinically apparent ON will be evaluated through Cox proportional hazards regression. These models will then be used as a foundation to test for effect modification by age and disease diagnosis. If appropriate, subgroup analysis will be performed. The applicant will complete these objectives with the help of directed one-on-one mentoring from a senior investigator and a team of participating co-mentors and collaborators, as part of ongoing participation in a rigorous clinical research training program. As a result of the support from the NRSA, the applicant will develop and refine the skills necessary to conduct further research in the pharmacoepidemiology of antiinflammatory and immunosuppressant medications as part of a K23/K08 award. Moreover, the results of the project supported by this F32 award will contribute valuably to multiple fields of pediatrics, by quantifying the risk of serious bone diseae from a widely prescribed medication, and by evaluating some of the key factors that might modify this risk. Insights from this study may eventually lead to better strategies for treating, monitoring for, and preventing ON in the future.

描述（由申请人提供）：糖皮质激素（GC）是许多慢性儿科炎性疾病的广泛使用的药物。在归因于GC的众多毒性中，骨坏死（也称为血管坏死）是最严重的一种，导致某些人遭受严重的疼痛，残疾和手术关节置换的需求。尽管很长 描述的与小儿白血病等疾病的高剂量GC暴露相关，与这些常用的儿科种群中这些常用药物相关的风险仍然不太了解。关于某些炎症性疾病是否影响GC剂量独立的风险以及该关联是否随着年龄的变化而存在的其他问题。拟议的项目旨在扩大对GC使用之间的关系以及通过以下广泛目标之间的关系：1）检查GC暴露模式如何影响儿童和青少年的ON发展； 2）确定年龄和潜在的炎症性疾病是否改变了GC之间的关联； 3）培训申请人的药物ePIDEMIology方法，因为它们适用于慢性炎症疾病的治疗方法； 4）支持申请人作为独立临床研究者的发展。申请人将利用英国的大型医疗记录数据库来实现既定目标。该数据库包含广泛的人口，医学和治疗信息，并已成功地用于先前的药物ePidemiologic研究。有和没有GC暴露的队列将由多种炎症性疾病的儿童和青少年组装。通过代表GC使用的一系列不同模型，GC和新诊断的关联将通过COX比例危害回归评估。然后，这些模型将作为基础，以测试按年龄和疾病诊断进行效果修饰的基础。如果适当，将执行子组分析。申请人将借助高级调查员和参与的合作者和合作者团队的指导一对一指导来完成这些目标，这是持续参加严格的临床研究培训计划的一部分。由于 NRSA，申请人将开发并完善对抗炎和免疫抑制剂药物药物学的进一步研究所需的技能，这是K23/K08奖的一部分。此外，通过该F32奖励支持的项目结果将通过量化与普通处方药的严重骨骼疾病的风险，并评估一些可能修改这种风险的关键因素，从而为多个儿科的多个领域做出了重要贡献。这项研究的见解最终可能会带来更好的治疗，监视和预防的策略。