Effectiveness of Physiologic Testing in PPI Non-Responders

项目摘要 据估计，美国胃食道反流病的患病率高达20%， 在接受质子泵抑制剂(PPI)治疗的患者中，高达50%的患者仍有症状。不幸的是， 临床上对无反应机制的认识还不规范，患者往往会 接受各种食道功能测试：1)pH阻抗，2)超过96小时的无线pH监测，3) 高分辨率阻抗测压(HRIM)和4)粘膜阻抗。目前有很大争议 存在关于PPI无反应者的最佳技术、最佳研究方案和治疗方法 (PPINR)群，导致资源利用不当，无法提供有效的个性化服务 关心。因此，PPINR在美国造成了很大的医疗负担。 本研究的第一个目的是确定上述诊断的相关生理参数。 工具预测PPI需求的能力。随后，在目标二中，这些结果将用于指导 具有个性化临床的PPINRs临床管理算法的正式开发 基于治疗失败机制的途径。 我们将首先对两个中心的240名PPINR受试者进行为期4年的前瞻性对照试验。 受试者将完成症状问卷并接受诊断性测试(PPI上的pH阻抗 治疗，HRIM，96小时无线pH监测，关闭PPI治疗和粘膜阻抗)。 那些拥有 PH阳性研究和/或恢复PPI治疗将获得酸抑制治疗的升级 右旋索拉唑。实验1a和1b将比较96小时无线酸碱度监测的能力与酸碱度 阻抗分别用于预测PPI需求和对右兰索拉唑的反应。 实验1c将 探讨粘膜阻抗是否等同于96小时无线pH监测预测PPI 要求。最后，实验1D将确定是否可以利用HRIM指标来确定回流 负担、机制和治疗反应。接下来，我们将制定回流测试的质量措施 以便为PPINR集团制定简化的管理战略。兰德/加州大学洛杉矶分校的适宜性 将与一个专家工作组一起利用方法论来制定正式的有效质量衡量标准 根据目标1的结果以及现有的文献和证据进行回流测试。 这将是 为期12个月(4至5岁)。

Project Summary The prevalence of gastroesophageal reflux disease is estimated to be as high as 20% in the United States, and up to 50% of these patients remain symptomatic on proton pump inhibitor (PPI) therapy. Unfortunately, the clinical approach to understand the mechanism of nonresponse is not standardized, and patients will often undergo various esophageal function tests: 1) pH-impedance, 2) wireless pH monitoring over 96 hours, 3) high-resolution impedance manometry (HRIM), and 4) mucosal impedance. Currently significant controversy exists regarding the best technique, optimal study protocol and treatment approach for the PPI non-responder (PPINR) group, resulting in inappropriate resource utilization and a failure to provide effective personalized care. As such, PPINRs contribute to a large healthcare burden in the United States. The first aim of our study is to identify the relevant physiologic parameters of the aforementioned diagnostic tools in their ability to predict PPI requirement. Subsequently, in aim two these results will be applied to guide the formal development of a clinical algorithm for the management of PPINRs with personalized clinical pathways based on mechanism of treatment failure. We will first perform a prospective comparison trial of 240 PPINR subjects at two centers over a 4 year period. Subjects will complete symptom questionnaires and undergo diagnostic testing (pH-impedance on PPI therapy, HRIM, 96-hour wireless pH monitoring off of PPI therapy and mucosal impedance). Those who have a positive pH study and/or resume PPI therapy will receive escalation of acid suppression therapy with dexlansoprazole. Experiments 1a & 1b will compare the ability of 96-hour wireless pH monitoring vs pH impedance to predict PPI requirement and response to dexlansoprazole, respectively. Experiment 1c will explore whether mucosal impedance is equivalent to 96-hour wireless pH monitoring in predicting PPI requirement. Lastly, Experiment 1d will determine whether HRIM metrics can be utilized to determine reflux burden, mechanism and response to treatment. Next, we will develop quality measures for reflux testing in order to develop a simplified management strategy for the PPINR group. The RAND/UCLA Appropriateness Methodology will be utilized with an expert working group to develop formal validated quality measures for reflux testing based on results from aim 1 in addition to the available literature & evidence. This will be conducted over twelve-months (years 4 to 5).