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Abstract
Objective Number of reflux episodes, an adjunctive metric on pH-impedance monitoring, is incompletely studied. We aimed to determine if number of reflux episodes associates with therapeutic outcome in regurgitation predominant gastro-oesophageal reflux disease (GERD).
Design We performed post hoc analysis of postintervention pH-impedance data from adult patients with moderate/severe regurgitation despite QD proton pump inhibitor (PPI), randomised to either two times a day PPI or magnetic sphincter augmentation (MSA) in 2:1 allocation. After 6 and 12 months, symptom response was defined by improvement in Foregut Symptom Questionnaire (FSQ) regurgitation score to none or minimal, ≥50% reduction in GERD health-related quality of life (HRQL) score and satisfaction with therapy. Univariate and multivariate analyses were performed to determine predictors of symptom improvement.
Results Of 152 randomised patients, 123 (age 46.9±1.2 year, 43% female) had complete data. Symptom and satisfaction scores significantly improved after MSA compared with two times a day PPI. Both acid exposure time (13.4%±0.7% to 1.3±0.2%, p<0.001) and reflux episodes (86±4 to 48±4, p<0.001) declined with therapy. Reduction to <40 reflux episodes was significantly more frequent in those with symptom response by FSQ regurgitation score, GERD HRQL score and satisfaction with therapy (p≤0.03 for each); <35 episodes performed better on receiver operating characteristic analysis. On multivariate analysis, improvement in regurgitation score remained independently predictive of satisfaction with therapy (p<0.001 for each). In patients crossing over to MSA, >80 episodes pretreatment predicted improvement.
Conclusions Reduction of reflux episodes on pH-impedance to physiological levels associates with improved outcomes, while pathological levels predict improvement with MSA in regurgitation predominant GERD.
Trail registration number ClinicalTrials.gov: NCT02505945.
- ambulatory pH monitoring
- gastroesophageal reflux disease
- anti-reflux therapy
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Significance of this study
What is already known on this subject?
Numbers of reflux episodes can be accurately extracted from pH-impedance monitoring.
The Lyon Consensus suggests <40 reflux episodes as physiological, and >80 as pathological adjunctive criteria for gastro-oesophageal reflux disease (GERD).
The value of number of reflux episodes as a predictor of GERD treatment outcome has not been established.
What are the new findings?
Magnetic sphincter augmentation (MSA) improves regurgitation in proven GERD better than maximal medical management.
Reduction of reflux episodes to physiological levels, particularly to <35 is associated with improved treatment outcome in regurgitation predominant GERD.
Reflux episodes >80 despite medical therapy predicts satisfaction with GERD management after MSA.
How might it impact on clinical practice in the foreseeable future?
Number of reflux episodes on pH-impedance monitoring has clinical value in the evaluation of GERD, and in assessment of GERD treatment outcome.
Introduction
Gastro-oesophageal reflux disease (GERD) is defined as troublesome symptoms or complications resulting from the reflux of gastric contents into the oesophagus.1 Presentations can include both typical (heartburn and regurgitation) and/or atypical (chest pain, cough and ear–nose–throat complaints) symptoms. Despite the fact that dysfunction of the lower oesophageal sphincter is the predominant pathophysiological pathway, this is not the usual management target, and acid suppression is effective in the majority of typical presentations. However, as many as 40% are dissatisfied with medical management.2 This proportion increases in the subpopulation presenting primarily with regurgitation wherein proton pump inhibitor (PPI) therapy only provides 17% therapeutic gain over placebo.3 Where acid suppression is insufficient to control regurgitation in proven GERD, symptoms can be prevented by augmenting the esophagogastric junction (EGJ) barrier mechanically in order to reduce aggregate refluxate burden in the distal oesophagus.4–6
When symptoms persist on therapy, ambulatory reflux monitoring is performed to identify pathological reflux and quantify refluxate burden in unproven GERD, and to assess the mechanism of persistent symptoms in proven GERD.7 8 Association of symptoms with reflux episodes is often used as an adjunctive measure, but definitive evidence is only provided by abnormal acid exposure time (AET).8 The number of reflux episodes is readily quantified through pH-impedance monitoring; while this metric has been extensively studied, correlation with outcomes has not been shown to date.9 When the EGJ barrier is mechanically augmented, the number of reflux episodes decreases.10 Consequently, frequency of refluxate presence on ambulatory reflux monitoring, independent of pH, could potentially serve as a measure predicting symptom response following mechanical EGJ augmentation in regurgitation-predominant GERD.
We hypothesised that numbers of reflux episodes on pH impedance monitoring would predict response to mechanical EGJ augmentation in patients with regurgitation predominance poorly responsive to acid suppression. We used an existing cohort of patients randomised to magnetic sphincter augmentation (MSA) compared with escalation of PPI therapy in regurgitation predominant GERD with posttherapy pH-impedance monitoring to test this hypothesis.11
Methods
We performed a post hoc analysis of a previously reported dataset collected as part of a study evaluating MSA in treatment of persisting reflux symptoms despite once daily PPI.6 11 In the original study, patients were studied prospectively and were randomised to receive either two times a day omeprazole 20 mg or laparoscopic MSA in 2:1 allocation (ClinicalTrials.gov: NCT02505945) in a study sponsored by Torax Medical. The sponsoring company provided deidentified demographic, clinical and oesophageal testing data to the study investigators involved in blinded analysis of pH-impedance testing (MFV and CPG). The company was not at all involved in the analysis, data interpretation, manuscript preparation or review of this manuscript. All authors had full access to study data, and participated in analysis, interpretation and preparation of the manuscript. Only patients with all symptom questionnaire and post-therapy pH-impedance data points at 6 months were included for this report. Patients were evaluated at 6 and 12 months, and eligible patients on two times a day PPI could crossover to the MSA arm at 6 months. Informed consent was obtained from each patient.
Study design
Patients ≥21 years of age actively seeking alternative treatment for regurgitation symptoms occurring despite once daily PPI were recruited into the study, as previously reported.11 Patients were screened using medical history, questionnaires, physical exam, endoscopy, ambulatory pH monitoring off PPI for at least 7 days (catheter-based pH monitoring: 1.6%, catheter-based pH impedance monitoring: 27.0% and wireless pH monitoring: 71.3%) and manometry or barium oesophagram. Inclusion criteria consisted of moderate to severe regurgitation on Foregut Symptom Questionnaire (FSQ) while on once daily PPI for at least 8 weeks, body mass index <35, abnormal pH monitoring off PPI (using worst day data when 48 hours wireless pH monitoring was used) and normal oesophageal motility. Exclusion criteria included major motility disorders, prior foregut surgery, hiatus hernia >3 cm, Barrett’s oesophagus or Los Angeles grade C or D oesophagitis. This report focused primarily on post hoc analysis of results of post-therapy pH-impedance monitoring performed at 6 months, and pretherapy and post-therapy questionnaires as described below. For this reason, it was not possible to involve patients or public in the design, conduct, interpretation or dissemination of this research.
Questionnaires
GERD Health-Related Quality of Life (HRQL) questionnaire (including satisfaction with therapy) and FSQ were administered twice at baseline (off and on PPI therapy) and again at 6 and 12 months after intervention. FSQ was used to identify patients with moderate to severe regurgitation while taking once daily PPI for at least 8 weeks (required for study inclusion).12 FSQ characterises regurgitation to none, mild (after straining or large meals), moderate (predictable with position change, lying down, straining) or severe (constant). Baseline quality of life was assessed using the GERD HRQL questionnaire, obtained from patients on as well as off PPI therapy (after a 7-day wash-out period). The 10 question GERD-HRQL evaluates heartburn (six questions), dysphagia (two questions), bloating (one question) and impact of medications on daily life (one question). Scores range from 0 to 5 based on frequency and impact on quality of life.13
Study procedures
The medical management arm consisted of two times a day omeprazole (20 mg, 30 min before breakfast and dinner). The MSA arm consisted of laparoscopic placement of the MSA device by a trained investigator. In addition to questionnaires, patients underwent 24-hour pH impedance testing at 6 months. This was performed on PPI in the medical management arm and off PPI in the MSA arm. All pH impedance studies were interpreted manually in blinded fashion with diagnostic agreement by two investigators (MFV and CPG), neither of whom were involved in managing study patients or performing study procedures. Metrics extracted from pH impedance studies included AET, Symptom Index (SI), symptom association probability (SAP) and numbers of reflux episodes (including both acidic and weakly acidic reflux episodes). Eligible patients without improvement despite two times a day PPI could crossover to MSA after 6 months. Individuals from both treatment groups underwent additional questionnaire evaluation at 12 months.
Statistical analysis
For the purpose of this study, objective treatment success was defined as a reduction in number of reflux episodes to <40 on pH-impedance monitoring (physiological levels per Lyon consensus).8 Symptom responders were defined as follows: (1) improvement in FSQ regurgitation score to none or minimal, (2) ≥50% reduction in GERD HRQL score and (3) satisfaction with therapy extracted from GERD HRQL, which is a three response question where neutral and dissatisfied were combined and compared against satisfied with therapy.
Data are reported as the mean±SE of the mean, unless otherwise stated. Categorical data were compared using the χ2 test with Fisher’s exact test; continuous data were compared using analysis of variance or the two-tailed Student’s t-test, as appropriate. Univariate and multivariate analysis was used to correlate objective pH-impedance metrics with symptom response. Receiver operating characteristic (ROC) analysis was performed to determine the optimal threshold of number of reflux episodes in predicting improvement in GERD HRQL, and satisfaction with therapy. The cohort crossing over from two times a day PPI to MSA at 6 months was separately analysed to determine predictors for improvement in GERD HQRL and satisfaction with therapy. In all cases, p<0.05 was required for statistical significance. Statistical analyses were performed using IBM SPSS Statistics V.26.
Results
Of 152 randomised patients, 123 (age 46.9±1.2 year, range 21–76 year, 43% female) had all data points available for analysis and were part of this report. Among dominant symptoms, heartburn was reported by 84 patients (68.3%), regurgitation by 88 (71.5%) and reflux-related pain by 31 (25.2%). Additionally, all patients were required to have regurgitation as a symptom for enrolment and randomisation. Demographics, symptom scores and reflux metrics were similar at baseline between treatment groups (table 1). In both the two times a day PPI and MSA arms, there were no patients satisfied with PPI therapy prior to randomisation, as required by study inclusion criteria. Preintervention and off PPI, 95.5% in the MSA arm and 97.5% in the two times a day PPI arm had severe regurgitation (≥2 on FSQ). Preintervention while on once daily PPI, 100% in both arms had severe regurgitation (≥2 on FSQ) (figure 1).
Proportions of patients demonstrating at least moderate regurgitation symptoms on the Foregut Symptom Questionnaire regurgitation score before and after intervention. *p<0.001 compared to MSA arm. MSA, magnetic sphincter augmentation; PPI, proton pump inhibitor.
Baseline demographics and clinical presentation
Symptom outcomes
There was a significant reduction in FSQ score in the MSA arm at 6 months (2.32±0.1 to 0.32±0.11, p<0.001). While there was a statistically significant reduction in FSQ on two times a day PPI, the relative reduction in regurgitation burden was less robust (2.13±0.04 to 1.99±0.6, p=0.03) (table 1). The proportion of patients with severe regurgitation at 6 months was significantly lower in the MSA arm compared with two times a day PPI arm (9.1% vs 89.9%, p<0.001, figure 1). Similarly, 50% reduction in GERD HRQL was reported by 88.6% (39 of 44) of patients in the MSA arm compared with 15.2% (12 of 79) in the two times a day PPI arm. Further, 36 (81.8%) of those in undergoing MSA were satisfied at 6 months compared with 2 (2.5%) of those who received two times a day PPI (table 2). At the 12-month time point, the response to MSA was sustained (table 2) and those who crossed over from two times a day PPI to MSA had similar improvement compared with those remaining on two times a day PPI (figure 2).
GERD health-related quality of life (HRQL) scores before and after intervention in the study groups. *p<0.001 compared to MSA arm. GERD, gastro-oesophageal reflux disease; MSA, magnetic sphincter augmentation; PPI, proton pump inhibitor.
Questionnaire and PH-impedance metrics
pH-impedance monitoring postintervention
There was a significant decline in AET (13.4%±0.7% to 1.3±0.2%, p<0.001) with therapy. The decline was similar in MSA arm (14.1±1.0 to 0.9%±0.2%, p<0.001) compared with two times a day PPI arm (13.0±0.9 to 1.6%±0.2%, p<0.001, table 1) and therefore was not discriminative between groups. Reflux symptom association was available in 48 patients at the 6-month time point. In keeping with reduced symptoms following MSA, SI for heartburn and regurgitation were positive less often following MSA compared with two times a day PPI (heartburn: 22.2% vs 59.0%, respectively, p=0.07; regurgitation: 28.6% vs 81.1%, respectively, p=0.01). While SAP positivity was also lower following MSA compared with two times a day PPI (heartburn: 25.0% vs 43.2%, respectively; regurgitation: 50.0% vs 70.3%, respectively) differences were not statistically significant (p≥0.37).
Reflux episodes also decreased (86±4 to 48±4, p<0.001) with therapy. Additionally, the decline in reflux episodes was higher in the MSA arm compared with the two times a day PPI arm (62.2±9.7 vs 23.7±6.4, p=0.001). Reflux episodes decreased to physiological levels (<40 episodes) more often with MSA than with PPI therapy (70.5% vs 44.3%, p=0.008). Reflux episodes decreased by 69.3% in those with improved regurgitation scores, compared with 16.7% in those that did not improve (p=0.029), with weak correlation between numbers of reflux episodes and GERD HRQL (Spearman’s r=0.277, p=0.002) as well as FSQ regurgitation scores (Spearman’s r=0.312, p<0.001).
Univariate and multivariate analyses
Reduction to <40 reflux episodes was achieved significantly more often in those with symptom response by FSQ regurgitation score, GERD HRQL score and satisfaction with therapy (p≤0.03 for each, figure 3). Symptom reflux association did not predict outcomes measures (GERD HRQL, FSQ regurgitation score or satisfaction with therapy) except SI for regurgitation, which was positive rather than negative more often in patients dissatisfied with therapy (93.8% vs 66.7%, respectively, p=0.039). On multivariate analysis, improvement in regurgitation score and GERD HRQL remained independent predictors of satisfaction with therapy (p≤0.001 for each).
Comparison of proportions achieving physiological reflux episodes following GERD therapy in responders and non-responders to three symptom metrics. Responders demonstrated improvement in Foregut Symptom Questionnaire regurgitation score to none or minimal, ≥50% reduction in GERD health-related quality of life (GERD HRQL) score and satisfaction with therapy extracted from GERD HRQL questionnaire. GERD, gastro-oesophageal reflux disease.
ROC analysis
Using numbers of reflux episodes as a test variable, optimal sensitivity and specificity in predicting 50% improvement in GERD HRQL was 63% and 63%, respectively, and was achieved at a threshold of 36 reflux episodes; at 35 reflux episodes the sensitivity was 64% with a specificity of 59% (area under the curve (AUC): 0.71, p<0.001) (figure 4). In predicting dissatisfaction with therapy, a threshold of 35 reflux episodes was found to be optimal with a sensitivity and specificity of 64% and 67%, respectively; at 36 reflux episodes, sensitivity was 63% and specificity was 70% (AUC: 0.76, p<0.001) (figure 4). On repeat multivariate analysis using 35 as a threshold, improvement in regurgitation score and GERD HRQL remained independent predictors of satisfaction with therapy (p≤0.001), while numbers of reflux episodes trended strongly (p=0.1).
Receiver operating characteristic curves evaluating performance characteristics of numbers of reflux episodes in predicting satisfaction with therapy and GERD health-related quality of life (HRQL). The optimal performance characteristics were achieved at a threshold of 35 reflux episodes on pH impedance monitoring while on two times a day proton pump inhibitor or following magnetic sphincter augmentation. AUC, area under the curve; GERD, gastro-oesophageal reflux disease.
Cross-over cohort
At the 6-month time point, 31 of 79 patients in the two times a day PPI arm (39.2%) crossed over to the MSA arm. Of the 79 patients, 74 had questionnaire data available at the 12-month time point; 29 (26.7%) reported ≥50% reduction in GERD HRQL, 36 (45.6%) reported improvement in FSQ regurgitation scores and 24 (30.4%) were satisfied with therapy. On multivariate analysis, number of reflux episodes on the 6-month pH-impedance study (p<0.001) and FSQ regurgitation score (p=0.045) were independent predictors of satisfaction with therapy.
Cross-over MSA patients were further analysed, in whom mean numbers of reflux episodes at the 6-month pH-impedance study was 95.1±8, which trended towards weak correlation with FSQ regurgitation scores (Spearman’s r=0.353, p=0.052) but not GERD HRQL (Spearman’s r=0.102, p=0.584). Acid reflux episodes accounted for only 39.2% of the total reflux episodes (acid: mean 42.8±9 episodes; weakly acid or non-acid: 52.4±4 episodes). Neither type of reflux episode correlated individually with FSQ regurgitation scores (Spearman’s r=0.132 and 0.147, respectively, p≥0.4) or GERD HRQL (Spearman’s r=0.271 and −0.305, respectively, p≥0.1).
Following crossover to MSA, at the 12-month time point, 77.4% reported at least 50% GERD HRQL improvement, 93.5% reported improvement in FSQ regurgitation scores and 77.4% reported satisfaction with therapy compared with the 6 month pre-MSA evaluation. On ROC analysis of the cross-over MSA patients, optimal prediction of ≥50% improvement in GERD HRQL was achieved with ≥80 reflux episodes (sensitivity 62%, specificity 67%, AUC 0.69); since the FSQ regurgitation score was a 3-point Likert score and most patients improved their score, there was not enough spread for meaningful ROC analysis. On multivariate analysis within the cross-over cohort, while no variables independently predicted satisfaction with therapy, only reflux episodes at the 80 threshold trended strongly (p=0.1).
Discussion
We performed a post hoc analysis of a prospectively collected database from proven GERD patients randomised to receive either MSA or two times a day PPI, for the purpose of identifying pH impedance metrics predictive of treatment success. The patient population was enriched with regurgitation predominant GERD and at least moderate regurgitation on validated questionnaires while on once daily PPI. Treatment success was defined a priori and included resolution of regurgitation, at least 50% reduction in GERD HRQL score, and satisfaction with therapy. As previously reported, these endpoints were reached significantly more often after MSA compared with two times a day PPI.6 11 We report that reduction of number of reflux episodes to physiological levels (<40) measured by pH-impedance is associated with improved GERD symptoms and satisfaction with therapy, and >80 reflux episodes suggests a need for invasive management, since this threshold predicted good outcome from MSA in the cross-over cohort where pH-impedance monitoring was performed prior to intervention. While the Lyon consensus established a threshold of <40 reflux episodes for physiologic reflux,8 our ROC analysis data suggest that 35 reflux episodes correlate better with symptom improvement; the threshold of 80 reflux episodes for pathological reflux is upheld by our analysis. We therefore demonstrate the utility of assessing numbers of reflux episodes on pH-impedance monitoring in regurgitation predominant GERD, as one of several determinants of symptom severity, evidence of GERD and prediction of response to therapy in regurgitation predominant GERD.
Regurgitation is a unique mechanical symptom that does not adequately improve with antisecretory therapy in contrast to heartburn.3 Mechanical augmentation of the antireflux barrier has a higher success rate than medical management as demonstrated in studies using traditional antireflux surgery10 and transoral incisionless fundoplication.5 Therefore, it is no surprise that there is a significantly higher therapeutic benefit from MSA compared with escalation of PPI as has already been reported.6 11 We used this therapeutic response to determine which factors on pH impedance monitoring correlated with outcome.
Acid-based metrics on pH impedance monitoring have been established as primary predictors of outcome from antireflux therapy.9 14 15 In fact, only AET and impedance-based SAP were predictive of treatment outcome in unselected GERD patients.9 Despite enthusiasm for pH impedance monitoring as the preferred evaluation technique in GERD in the early 2000s,16 no study to date has established clinical utility of calculating numbers of reflux episodes. One of the reasons for this is the significant inter-reviewer variability in identification of reflux episodes on pH-impedance monitoring, the lack of uniformity of automated analysis between pH-impedance thresholds.17 18 The Lyon consensus used expert opinion and normative thresholds rather than hard evidence in suggesting physiological (<40), indeterminate (40–80) and pathological (>80) thresholds.8 We demonstrate for the first time in a regurgitation predominant population that total reflux episode numbers can be used to predict outcome, although breaking reflux episodes into acidic vs weakly acidic or non-acidic did not provide additional discriminant value. Additionally, though the Lyon consensus threshold demonstrated value in predicting outcomes, ROC analysis indicated that a cut-off of <35 reflux episodes may be more clinically meaningful threshold for a management goal, while >80 reflux episodes may indicate need for invasive management. Performance characteristics of numbers of reflux episodes were modest, with sensitivity and specificity in the 60% range for both the <35 episode threshold in predicting response, and the >80 episode threshold in predicting need for therapy. These performance characteristics are not different from that of AET (sensitivity 69%, specificity 70%),19 and SAP in predicting GERD symptom response (sensitivity 65%, specificity 73%),20 although one would expect these values to be lower for regurgitation-predominant GERD. Therefore, the positioning of numbers of reflux episodes as an adjunctive or supportive metric in the Lyon consensus appears appropriate, and our data support utilisation particularly in regurgitation-predominant GERD.
Oesophageal acid exposure burden is expected to improve with acid suppression and with mechanical GERD therapies. Accordingly, as AET improved in both arms to a significant degree on the postintervention pH-impedance study, this was not discriminative of outcome. Reflux symptom association was identified more often in the two times a day PPI arm since reflux episodes are known to persist despite acid control.21 However, very limited numbers of patients in the MSA arm reported reflux symptom association, an indicator that reflux episodes were significantly reduced with mechanical therapy. This is further indication that numbers of reflux episodes can serve as a surrogate for symptom severity in regurgitation predominant GERD. We acknowledge that our findings will apply most directly to regurgitation predominant GERD, especially when regurgitation symptoms persist despite appropriate trials of acid suppressive therapy. However, regurgitation-predominant GERD forms an important subset of patients with persistent or refractory GERD symptoms, and existing literature supports invasive management, including fundoplication and MSA in this setting.5 6 10 22 We demonstrate that evaluating numbers of reflux episodes could direct management towards invasive therapies when high, or potentially direct attention away from invasive therapies when in the low or physiological range in symptomatic patients.
The strengths of this study consisted of the prospective randomised design and use of validated questionnaires at multiple time points during the original trial, which enabled designation of symptom based outcome metrics. Our analysis was limited by data collection from multiple sites using various forms of reflux monitoring prior to study inclusion. Therefore, pH-impedance metrics analysed at the 6-month time point could not be objectively compared with preinclusion data, and only AET could be reliably compared; hence the MSA crossover group was additionally analysed since pH impedance monitoring was performed prior to intervention in this cohort. Both acidic and weakly acidic reflux episodes were combined into a single metric, and were not analysed separately; daytime and nighttime periods were not analysed separately on pH-impedance monitoring. Acidic reflux episodes could have contributed to persisting symptoms in patients managed with MSA, since pH-impedance studies were performed off therapy in this cohort. Rumination and supragastric belching could have participated in symptomatology in some of the patients with regurgitation. However, all had abnormal AET, suggesting that GERD was part of the pathophysiology. Symptom improvement overwhelmingly favoured MSA, and the small proportion of MSA-treated patients symptomatic from acidic reflux or with potential rumination/supragastric belching would not have changed the final conclusions, although placebo response could have contributed. Additionally, late follow-up data from 12 months did not include pH impedance testing. Nevertheless, pH-impedance data were available following 6 months of therapy in both arms and this proved useful in predicting outcome. Novel impedance metrics including mean nocturnal baseline impedance and postreflux swallow induced peristaltic wave could have enhanced the analysis but were not collected as part of this trial.
In conclusion, in addition to demonstrating the value of MSA in regurgitation predominant GERD, we show that achieving physiological levels of reflux episodes as measured by pH-impedance monitoring associates with patient-reported satisfaction and symptom improvement, and pathological reflux episode numbers indicate value in invasive GERD management.
References
Footnotes
Contributors Guarantor of the article: CPG. Author roles: BDR: study concept and design, data collection, analysis, manuscript preparation and review; LRV: data analysis, critical review of the manuscript; MDC: data analysis, critical manuscript review; RB: critical review of manuscript; MFV: study concept and design, data collection and critical review of manuscript; CPG: study concept and design, data collection and analysis, manuscript preparation and critical review.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests RB: Consultant for Ethicon EndoSurgery, Intuitive Surgical, Becton Dickinson and Co; MFV: consultant for Medtronic, research support from Diversatek; CPG: consultant for Medtronic, Diversatek, Ironwood, Isothrive and Quintiles.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval At each of the 21 participating sites, the protocol was approved by the Institutional Review Board (or equivalent body). Since the present study consists of post hoc analysis of previously collected deidentified pH-impedance data with no links to the original study patients, additional institutional review board approval was not deemed necessary.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement No data are available. This is a post hoc analysis of pH-impedance study data from a published clinical study comparing magnetic sphincter augmentation to a two times per day PPI regimen. The original study sponsors (Torax) provided deidentified pH-impedance study data and related clinical data to two study investigators (MFV and CPG) who performed blinded interpretation of the pH-impedance studies for the original study.
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