Development and Validation of a Novel and HIV-Relevant Prediction Model for Fracture

新型 HIV 相关骨折预测模型的开发和验证

基本信息

批准号：
10684448
负责人：
Evelyn Hsieh
金额：
$ 35.98万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684448
关键词：
Admission activity Adoption Age Aging Alcohol abuse Algorithms Assessment tool Benzodiazepines Body mass index Bone Density Boston Calibration Caring Cessation of life Clinical Cohort Studies Data Data Set Development Discrimination Dual-Energy X-Ray Absorptiometry Economics Electronic Health Record Europe Exhibits Foundations Fracture Future General Population Glucocorticoids Goals HIV Health Healthcare Systems Hepatitis B Virus Hepatitis C Individual Intervention Intervention Trial Life Measures Medical center Methodology Methods Modeling National Institute of Arthritis and Musculoskeletal and Skin Diseases North America Nursing Homes Online Systems Opioid Osteoporosis Outcome Persons Pharmaceutical Preparations Physiological Polypharmacy Prevention Probability Proton Pump Inhibitors Provider Qualitative Methods Race Research Rheumatoid Arthritis Risk Risk Assessment Risk Factors Role Scanning Screening procedure Smoking Social isolation Subgroup Substance Use Disorder Time Treatment Side Effects United States Validation Veterans Work aged antiretroviral therapy base care providers clinical care clinical decision-making clinical practice clinical risk cohort comorbidity cost demographics electronic data electronic structure experience falls fracture risk fragility fracture frailty high risk hospitalization rates improved informatics tool insight low and middle-income countries middle age modifiable risk multiple chronic conditions novel physically handicapped predictive modeling prevent risk prediction risk prediction model risk stratification sex social tool user-friendly

项目摘要

ABSTRACT Fragility fractures (fractures) among persons with HIV (PWH) account for $99 million in excess costs each year in the United States. Our prior research has shown a significantly higher annual rate of fractures among PWH – most of whom are middle-aged – compared with uninfected individuals (2.0% vs 1.4%). Such fractures are associated with increased rates of hospitalization and nursing home admissions, long-term physical disability, social isolation, and death. Because middle-age is a time when people are most economically and socially productive, fractures at this time of life set the stage for economic hardship and poorer health outcomes as these individuals grow older. Highly effective methods exist for preventing fragility fractures, reducing rates by 25%-50%. However, there are no risk prediction models that reliably identify PWH at greatest risk. The Fracture Risk Assessment Tool (FRAX) is the most widely used model for predicting fractures in the general population. It incorporates demographics (age, sex, race) and key risk factors (body mass index, previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, and hazardous alcohol use). For settings where dual-energy x-ray absorptiometry is available, sensitivity of FRAX can be improved by adding bone mineral density (BMD) to the algorithm. However, our prior studies suggest that FRAX underperforms among PWH, exhibiting poor discrimination (C statistic 0.59) and sensitivity (0.06). We believe this is because FRAX does not account for risk factors that are important to PWH. For example, FRAX does not account for falls, hepatitis C and B viruses, substance use disorder, multimorbidity, polypharmacy, use of other medications associated with fractures, or physiologic frailty – all of which have been associated with fractures among PWH. Finally, FRAX does not account for antiretroviral therapy (ART) use. Individual ART as well as ART classes have been independently associated with fracture. Leveraging an outstanding team of collaborators and research platforms, we will develop, validate and disseminate a Fracture Risk Assessment Calculator based on FRAX but that incorporates HIV-relevant risk factors (FRAC-HIV) to calculate the probability of a fracture among PWH in the next year. We have extensive experience working with the Veterans Aging Cohort Study (VACS), the largest cohort of PWH in North America, which will serve as our development cohort. To assess generalizability, we will externally validate the model using electronic health record data from Yale New Haven Healthcare System and Boston Medical Center. Our final aim sets the stage for the implementation of this predictive model via the development of a web-based fracture risk prediction calculator, which will be directly informed by insights from providers who care for PWH. FRAC-HIV will reconceptualize and facilitate clinical decision-making for fracture prevention in PWH by emphasizing the role of clinically modifiable risk factors. Our findings will lay the foundation for future intervention trials that will incorporate FRAC-HIV into clinical care algorithms to prevent fractures among PWH.

抽象的艾滋病毒（PWH）患者中的脆弱性骨折（骨折）每年占9900万美元的超额费用在美国。我们先前的研究表明，PWH中的年度骨折率明显更高 - 与未感染的个体相比，大多数是中年人（2.0％比1.4％）。这样的断裂是与住院率提高和护理家庭入院率有关，长期身体残疾，社会隔离和死亡。因为中年是人们在经济和社会上最受欢迎的时期生产力，生命时期的骨折为经济困难奠定了阶段，健康结果较差这些人长大了。存在预防脆弱性裂缝的高效方法，从而降低了率 25％-50％。但是，没有风险预测模型可靠地识别出最大风险的PWH。断裂风险评估工具（FRAX）是预测骨折中裂缝的最广泛使用的模型一般人口。它结合了人口统计学（年龄，性别，种族）和关键危险因素（体重指数，先前的骨折，父母骨折，当前吸烟，糖皮质激素使用，类风湿关节炎，继发性骨质疏松症和危险饮酒）。对于可用双能X射线绝对模拟的设置，通过将骨矿物质密度（BMD）添加到算法中，可以提高FRAX的敏感性。但是，我们的先前的研究表明，PWH之间的FRAX表现不佳，表现出较差的歧视（C统计0.59）和灵敏度（0.06）。我们认为这是因为Frax并不考虑对风险因素 PWH。例如，Frax不考虑跌倒，丙型肝炎和B病毒，药物使用障碍，多种疾病，多功能，使用与骨折相关的其他药物或生理脆弱的药物 - 所有与PWH之间的裂缝有关。最后，FRAX不考虑抗逆转录病毒治疗（艺术）使用。个人艺术和艺术阶级与骨折独立相关。利用杰出的合作者和研究平台团队，我们将开发，验证和基于FRAX传播裂缝风险评估计算器，但融合了与HIV相关的风险因素（FRAC-HIV）计算明年PWH中骨折的可能性。我们有广泛的与退伍军人老化队列研究（VACS）一起工作的经验，该研究是北部最大的PWH队列美国将作为我们的发展队列。为了评估可推广性，我们将在外部验证使用耶鲁纽黑文医疗系统和波士顿医疗的电子健康记录数据的模型中心。我们的最终目标为实施该预测模型的实施奠定了基础基于Web的断裂风险预测计算器，这将由提供者的见解直接告知关心PWH。 FRAC-HIV将重新概念化并促进预防断裂的临床决策 PWH通过强调临床可修改的危险因素的作用。我们的发现将为未来奠定基础干预试验将将FRAC-HIV纳入临床护理算法中，以防止PWH之间的断裂。