Effectiveness of Physiologic Testing in PPI Non-Responders

项目摘要 在美国，胃食管反流病的患病率估计高达20%， 这些患者中高达50%在质子泵抑制剂（PPI）治疗时仍有症状。可惜 了解无应答机制的临床方法并不标准化，患者通常 接受各种食管功能测试：1）pH阻抗，2）96小时以上的无线pH监测，3） 高分辨率阻抗测压法（HRIM），和4）粘膜阻抗。目前争议较大 关于PPI无应答者的最佳技术、最佳研究方案和治疗方法， （PPINR）组，导致不适当的资源利用和未能提供有效的个性化 在乎因此，PPINR在美国造成了巨大的医疗负担。 我们研究的第一个目的是确定上述诊断的相关生理参数。 预测PPI需求的能力。随后，在目标二中，这些结果将被应用于指导 正式开发用于管理PPINR的临床算法， 基于治疗失败机制的途径。 我们将首先在两个中心进行为期4年的240例PPINR受试者的前瞻性比较试验。 受试者将完成症状问卷并接受诊断测试（PPI的pH阻抗 治疗，HRIM，PPI治疗和粘膜阻抗的96小时无线pH监测）。 那些谁有一个 pH值检查阳性和/或恢复PPI治疗将接受酸抑制治疗， 右兰索拉唑。实验1a和1b将比较96小时无线pH监测与pH监测的能力。 分别预测PPI需求和对右兰索拉唑的反应。 实验1C将 探索粘膜阻抗在预测PPI方面是否等同于96小时无线pH监测 要求。最后，实验1d将确定HRIM指标是否可用于确定返流 负担、机制和对治疗的反应。接下来，我们将制定反流测试的质量措施， 为PPINR集团制定简化的管理战略。兰德/加州大学洛杉矶分校拨款 将与一个专家工作组一起使用方法，以制定正式的经验证的质量措施， 回流测试基于目标1的结果以及现有的文献和证据。 这将是 为期12个月（4至5年）。

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).