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acidic reflux (1 patient was negative for acid refluxes and weakly acidic refluxes separately,but was positive considering both refluxes as a whole). Twenty-eight (41%) patients hadno association between reflux and symptoms. Identifying patients with symptomatic weaklyacidic reflux reduces the number of patients with unexplained chest pain from 91 (46%)to 64 (32%) and from 51 (75%) to 28 (41%) among patients off-PPI and on-PPI, respectively(p<0.01). Conclusion: Monitoring for weakly acidic reflux in NCCP patients increases ourability to identify patients in whom symptoms are associated with reflux, mainly in patientson-PPI therapy. Our data support the use of ambulatory impedance-pH monitoring in adiagnostic algorithm for patients with unexplained chest pain. The impact of this improveddiagnostic value on NCCP management remains to be investigated by outcome studies.
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Defining PPI Non-Responders Into Reflux PhenotypesJoan Chen, Yinglian Xiao, Chang Lu, Lubomyr Boris, Mary Kwasny, Andy Jain, Peter J.Kahrilas, John E. Pandolfino
Background: Up to 30% of patients remain symptomatic on proton pump inhibitor (PPI)therapy and PPI non-responders (PPINR) represent a challenging population to manage.We hypothesize that management of PPINR could be improved by developing a well-definedcategorization based on physiologic parameters from pH-impedance monitoring (pH-Imp).Our goal was to assess the reproducibility and construct validity of a conceptual model forPPINR phenotypes and to investigate differences among the phenotypes in a patient cohort.Methods: A conceptual model of PPINR phenotypes was developed using pH-Imp parameters- % time pH<4.0, number of reflux events, symptom index (SI), and symptom associationprobability (SAP) - while on PPI. Four distinct phenotypes were developed: P1) Persistentacid reflux, P2) Hypersensitive, P3) GERD with functional overlap, and P4) Functionalheartburn (Table 1). 25 cases were created from patients with symptoms while on PPI.Demographic data, symptoms, PPI dose, response to PPI, EGD results and pH-Imp datawere included in each case. 7 international experts in GERD and 7 trainees were asked toclassify each patient into one of 4 PPINR phenotypes. They were then asked about continua-tion of PPI therapy, and to select from 4 treatment options [a: Increase acid suppression,b: Baclofen, c: Antidepressant, d: Surgery]. The results were compared amongst experts andtrainees. Additionally, charts of 192 consecutive patients with reflux symptoms on PPI, whohad undergone pH-Imp studies from 1/1/2008 to 8/8/2011were retrospectively reviewed toassess the prevalence of the phenotypes. Differences among phenotypes were assessed usingKruskal-Wallis analysis. Results: There was a high level of agreement in phenotype assignment(88% amongst experts and 80% in trainees). Agreement in treatment choice within eachphenotype was best observed in P1 and P4, where nearly all raters targeted reducing refluxburden in P1 (98%) and antidepressants in P4 (95%). Additionally, 100% of the raterswould continue PPI in P1 while 63% would discontinue PPI in P4. Among the 192 patientcohort, 22.4%, 19.3%, 7.8%, and 50.5% were categorized into the respective phenotypes.There was no significant difference in demographics (age, sex, BMI), use of antidepressantsbetween the phenotypes. However, there was a significant difference in presence of hiatalhernia (P1-72%, P2-51%, P3-43%, P4-47%; p = 0.039). Conclusion: A categorization modelto classify PPINR phenotypes using reflux parameters showed high reproducibility andconstruct validity. However, PPINR phenotypes defined solely on reflux parameters did notdistinguish significant demographic or physiologic differences. These findings suggest thatmeasures beyond reflux parameters, such as markers of hypersensitivity and hypervigilance,may be required in defining clinically relevant PPINR phenotypes.Table 1 - PPINR Phenotype Criteria
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Increased Anxiety Levels Do Not Affect Symptoms Severity or EnhancePerception of Reflux EpisodesBoudewijn F. Kessing, Albert J. Bredenoord, Caroline M. Saleh, Andreas J. Smout
Background: In a laboratory setting, increased anxiety levels are associated with more severesymptoms of gastroesophageal reflux disease (GERD) and can enhance the perception ofreflux events. The role of baseline anxiety levels on acid perception and symptom reportingin patients with symptoms of gastroesophageal reflux disease is not known. We aimed todetermine whether increased anxiety levels affect symptom severity in gastroesophagealreflux disease or enhance perception of reflux episodes Methods: We prospectively included122 patients (mean±SEM age: 49±1, 91 female) who were referred to our center for anambulatory 24-h pH-impedance measurement as part of the work-up for reflux symptoms.Severity of typical GERD symptoms (regurgitation, acid taste in the mouth, retrosternalburning and retrosternal pain) was assessed using the Reflux Disease Questionnaire (RDQ).Anxiety levels were assessed using the Hospital Anxiety and Depression Scale (HADS-A),whereas a HADS-A score ≥11 was considered as cut-off value for a high probability for ananxiety disorder. Results: Median (IQR) HADS-A score was 5 (4-9). In 21 patients (17%)the HADS-A score was suggestive of an anxiety disorder (HADS-A ≥11). Median acidexposure time (% time pH<4) was 6.6 (2.6-12.7) and 53 patients exhibited a positivesymptom association probability (SAP ≥95%). HADS-A scores did not correlate withincreased severity of complaints of regurgitation, acid taste in the mouth, retrosternal pain,
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retrosternal burning or total RDQ score. Moreover, patients with HADS-A scores ≥11 didnot exhibit more severe symptoms than patients with HADS-A scores <11. HADS-A scoresdid not correlate with the total number of reported GERD symptoms during the measurementor with the number of reported symptoms during the measurement that were associatedwith an objectively measured reflux episode. However, a weak correlation was found betweenthe HADS-A score and the number of reported symptoms during the measurement thatwere not associated with a reflux episode (r=0.2, p<0.05). Moreover, patients with HADS-A scores ≥11 did not exhibit a different symptom index (number of symptoms associatedwith a reflux event/total number of symptoms) than patients with HADS-A scores <11 (19(0-50) vs 33 (0-67) %, NS). Anxiety levels were not different between patients with a positiveSAP and patients with a negative SAP. Furthermore, patients with a physiological acidexposure time (<6%) did not exhibit different HADS-A scores than patients with a pathologicalacid exposure time (≥6%) and no correlation between the total acid exposure time and theHADS-A score was found. Conclusion: Increased anxiety levels are not associated withincreased symptom severity in gastroesophageal reflux disease or enhance perception ofreflux episodes.
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Wireless Oesophageal pH Monitoring: Feasibility, Safety and EstablishingNormal Values in a Multiracial Cohort of Asymptomatic Asian SubjectsDaphne Ang, Eng Kiong Teo, Tiing Leong Ang, Andrew Kwek, Kwong Ming Fock
Background: The wireless oesophageal pH capsule (Bravo®) has been used in the evaluationof patients with gastroesophageal reflux disease (GERD). Normal values have not been wellstudied in Asians. It was assumed that values used for the conventional nasopharyngeal pHcatheter system could be extrapolated to the wireless system. However, studies have shownthat the conventional and wireless systems do not record identical values. Limited data fromwireless capsule recordings in healthy European and American subjects have shown variedresults. Aims: (1) obtain normal values for the wireless capsule recording in healthy Asians,and (2) determine the safety and tolerability of wireless capsule monitoring. Methods:50 healthy volunteers (age range 21-65 years) without symptoms of GERD and othergastroenterological or systemic diseases and with no previous thoracic, oesophageal or gastricsurgery and who were not on any long term medications were recruited for the study.Subjects underwent gastroscopy and transoral insertion of thewireless capsule that was placed6cm above the squamocolumnar junction. This was followed by endoscopic confirmation ofcapsule placement. Acid exposure was monitored via a portable receiver during the 48 hourrecording period. Subjects completed a questionnaire evaluating any interference with eating,working, exercise and sleep during the study using a Likert scoring system (no effect=1,mild effect=2, moderate effect=3, severe effect=4). Results: Forty-seven volunteers completedthe study. Two subjects were excluded due to technical failure to capture data. Five andthree subjects had their capsules dislodged on days 1 and 2 respectively. Results wereanalysed in 40 (85.1%) subjects [29M, 11F (30Chinese, 7Malays, 3Indians)] with a median(SD) age 32.0(7.6) years at 24 hours and 37(78.7%) subjects [27M, 10F (29Chinese, 5Malays,3Indians) subjects with a median(SD)age 32.0(7.4) at 48 hours. The median percentagetime with oesophageal pH<4 was 1.70% (95th percentile 7.5%) for 40 subjects at day 1and 1.50% (95th percentile 6.3%) for 37 subjects at day 2. The 95th percentile for overallacid exposure time (AET) for 48 hour recordings in 37 subjects was 5.78% (Table 1). Nosignificant differences in pH parameters were observed during days 1 and 2 of studyrecordings in 37 subjects. Symptom scores (mean, SD) for effects on eating, work, exerciseand sleep were 2.0 ± 0.7, 1.0 ± 0.5, 1.3 ± 0.6 and 1.0 ± 0.4 respectively. Conclusion: Capsuledislodgement and failure of data capture were the predominant problems encountered. Thewireless capsule was otherwise well tolerated. This is the first study to establish normalvalues for the wireless capsule in a multiracial Asian cohort of healthy volunteers andprovides a basis for its use in clinical practice in Asian patients who are referred forGERD evaluation.Characteristics of oesophageal acid exposure during 48 hour recording in 37 asymptom-atic subjects.
Results expressed as median(5th-95th centile)
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Measurement of Esophago-Gastric Junction Cross-Sectional Area andDistensibility by Endoflip® (Endolumenal Functional Lumen Imaging Probe)for the Diagnosis of Patients With Gastro-Esophageal Reflux Disease (GERD)Emily Tucker, Rami Sweis, Angela Anggiansah, Emmanouil Telakis, Jeff Wright, Kevin R.Knowles, Terry Wong, Mark R. Fox
Introduction: EndoFLIP® (Crospon, Ireland) is an innovative device designed to assess thecross sectional area (CSA) and distensiblilty of the esophagogastric junction (EGJ) by com-bined impedance planimetry and pressure measurement. Initial studies have suggested thatthis probe may distinguish between gastro-esophageal reflux disease (GERD) patients andhealthy volunteers (HV). (Kwiatek et al. Gastrointest Endosc 2011) Aim: To assess thediagnostic agreement of EndoFLIP® measurements with clinical and physiologic GERDdiagnosis. Methods: 22 healthy volunteers, (HV; female=16, age 21-46, mean body massindex (BMI) 24 kg/m2) and 20 patients with GERD symptoms (female=14, age 19-78, meanBMI 33 kg/m2) were studied. Patients were older (p<0.0001) and had larger greater BMI
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