Predicting Short- and Long-term Risk of Serious Infections in Older Patients with Inflammatory Bowel Diseases

预测老年炎症性肠病患者严重感染的短期和长期风险

• 批准号: 10288725
• 负责人: Siddharth Singh
• 金额: $ 10.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10288725
• 关键词: Accounting; Adrenal Cortex Hormones; Aftercare; Antibiotics; Area Under Curve; Biological Products; Cessation of life; Characteristics; Chronic; Clinical; Clinical Treatment; Clinical Trials; Combined Modality Therapy; Data; Denmark; Disease; Elderly; Equilibrium; Evidence based treatment; Evolution; Goals; Health Care Costs; Hospitalization; Immune; Immunomodulators; Incidence; Infection; Inflammatory Bowel Diseases; Intravenous; Knowledge; Mission; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Opioid; Outcome; Participant; Patient risk; Patients; Population; Prediction of Response to Therapy; Predisposition; Prevalence; Principal Investigator; Provider; Public Health; Relative Risks; Research; Risk; Risk Estimate; Safety; Steroids; Testing; Therapeutic immunosuppression; Time; Treatment Effectiveness; Treatment Efficacy; United States National Institutes of Health; Weighing patient; aging population; base; clinical decision support; cohort; comparative effectiveness; comparative safety; disability; disorder control; disorder risk; evidence base; frailty; high risk; human old age (65+); individualized medicine; ineffective therapies; innovation; mortality; multiple chronic conditions; older patient; optimal treatments; patient population; personalized predictions; personalized risk prediction; point of care; resilience; risk prediction model; risk selection; risk stratification; support tools; treatment effect; treatment risk; treatment strategy

PROJECT SUMMARY/ABSTRACT Despite rising incidence, prevalence and healthcare costs of inflammatory bowel diseases (IBD) in older adults, there continues to be paucity of evidence-based treatment guidance for management of these understudied and susceptible patients. The long-term goal is to inform evidence-based, risk-congruent treatment approach for older patients with IBD, balancing patients’ dynamic risk of disease- vs. treatment- related complications with specific treatment’s efficacy vs. safety. The overall objectives in this application are to accurately predict the short- and long-term risk of serious infections with immunosuppressive therapy in older patients with IBD, based on pre-treatment baseline clinical characteristics and time-varying treatment effect. The central hypothesis is that pre-treatment clinical characteristics can accurately predict short-term risk of serious infections in older patients with starting immunosuppressive therapy; this risk evolves over time, on therapy, and can be accurately predicted by accounting for time-varying impact of treatment effectiveness. By controlling disease effectively and decreasing the need for corticosteroids and/or opiates, an effective, yet potent immunosuppressive therapy will be associated with lower risk of serious infections over time. The rationale for this project is that accurate individualized risk prediction for treatment-related complications in older adults with IBD on immunosuppressive therapy will provide patients and providers knowledge to tailor therapy based on patients’ predicted risk of disease- and treatment complications. The central hypothesis will be tested by pursuing two specific aims: 1) develop and validate a model that accurately predicts the short- term risk of serious infections in older patients with IBD starting immunosuppressive therapy; and 2) develop and validate a model that accurately predicts the long-term risk of serious infections in older patients with IBD while on immunosuppressive therapy. Under the first aim, the applicant will develop and validate a risk prediction model to accurately identify patients at high- vs. low-risk of serious infections in the short-term (within 6 months of treatment initiation) based on pre-treatment baseline patient-, disease- and treatment characteristics. For the second aim, a separate risk prediction model will be developed and validated to accurately predict long-term (6 to 24 months after treatment initiation) risk of serious infections, accounting for time-varying treatment effect, in older patients from the same cohort who have been on immunosuppressive therapy for 6 months. The context for this proposal will be the comprehensive, longitudinal Danish nationwide register of all older patients with IBD in Denmark. The research proposed in this application is innovative, in the applicant’s opinion, because it incorporates time-varying treatment effect, in addition to patients’ intrinsic susceptibility to infections, in predicting the dynamic risk of serious infections with immunosuppressive therapy in older patients with IBD. The proposed research is significant because it is expected to fill a key evidence gap in individualized prediction of treatment-related complications in a susceptible patient population.

项目摘要/摘要 尽管事件增加，炎症性肠病的患病率和医疗保健成本（IBD）年龄较大 成年人，仍然缺乏基于证据的治疗指南 研究和易感患者。长期目标是为基于证据的风险一致性提供信息 IBD老年患者的治疗方法，平衡患者的疾病动态风险与治疗 - 与特定治疗的效率与安全性相关并发症。此应用程序中的总体目标是 准确预测通过免疫抑制治疗的严重感染的短期和长期风险 基于治疗前基线临床特征和时变治疗的老年IBD患者 影响。中心假设是预处理临床特征可以准确预测短期风险 开始免疫抑制治疗的老年患者的严重感染；随着时间的流逝，这种风险的发展 治疗，可以通过考虑治疗有效性的时变影响来准确预测。经过 有效控制疾病并减少对皮质类固醇和/或鸦片的需求，这是一种有效的 随着时间的流逝，有效的免疫抑制疗法将与严重感染的风险降低有关。 该项目的基本原理是准确的个性化风险预测与治疗相关并发症 IBD接受免疫抑制治疗的老年人将为患者和提供者知识量身定制 基于患者预测疾病和治疗并发症的风险的治疗。中心假设将 通过追求两个具体目标来测试：1）开发和验证一个准确预测短期的模型 IBD老年患者的严重感染风险开始免疫抑制治疗； 2）发展 并验证一个模型，该模型可以准确预测IBD患者老年患者严重感染的长期风险 在接受免疫抑制治疗时。在第一个目标下，申请人将发展并验证风险 预测模型可以准确鉴定高VS的患者。在短期内低风险的严重感染 （在治疗计划的6个月内）基于治疗前的基线患者，疾病和治疗 特征。对于第二个目标，将开发并确认单独的风险预测模型 准确预测严重感染的长期（治疗计划后6至24个月） 时间变化的治疗效果，来自接受免疫抑制的同一队列的老年患者 治疗6个月。该提案的背景将是全国综合的丹麦纵向 在丹麦的所有老年患者的注册。本应用程序中提出的研究是创新的， 申请人的意见，因为它纳入了随时间变化的治疗效果，除了患者的内在效果 在预测免疫抑制治疗严重感染的动态风险方面，感染的敏感性 在年龄较大的IBD患者中。拟议的研究很重要，因为预计它将填补关键证据差距 在易感患者人群中与治疗相关并发症的个性化预测中。