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Linked Content This article is linked to Holmberg et al paper. To view this article, visit https://doi.org/10.1111/apt.15274. [ABSTRACT FROM AUTHOR]

Summary: Background: Potassium‐competitive acid blockers (P‐CABs) are emerging as novel treatments for acid‐related disorders including gastroesophageal reflux disease. Tegoprazan and revaprazan are approved P‐CABs in South Korea, but the pharmacodynamics and safety/tolerability of the two drugs have never been compared. Aims: To evaluate the pharmacodynamics and safety/tolerability of tegoprazan and revaprazan after single and multiple oral doses Methods: A randomised, open‐label, active‐controlled study was conducted in Helicobacter pylori‐negative healthy Korean male subjects. Tegoprazan 50 mg or revaprazan 200 mg was administered orally, once daily for 7 days; 24‐h intragastric pH monitoring and serum gastrin were measured for pharmacodynamic evaluation. Safety parameters including serum microRNA‐122 (miR‐122) level were also collected. Results: After a single dose, the %Time pH ≥4 for tegoprazan was greater than that for revaprazan (54.5% vs 25.1%). After multiple doses, the %Time pH ≥4 for tegoprazan was also greater than that for revaprazan (68.2% vs 25.3%). %Time pH ≥4 during 12 hours at nighttime for tegoprazan was greater than that for revaprazan (71.8% vs 31.9%). The changes in the serum gastrin were not clinically significant for either drug. Despite the slight increases of serum miR‐122 for each drug, tegoprazan and revaprazan were well tolerated considering other safety parameters including AST and ALT levels. Conclusion: Tegoprazan 50 mg showed stronger gastric acid suppression than revaorazan 200 mg. Both drugs were well tolerated. [ABSTRACT FROM AUTHOR]

Summary: Background: Neuromodulators are considered potential therapeutic options for refractory gastro‐oesophageal reflux‐induced chronic cough. Aim: To compare the efficacy of gabapentin and baclofen in patients with suspected refractory gastro‐oesophageal reflux‐induced chronic cough. Methods: Two hundred and thirty‐four patients with suspected refractory gastro‐oesophageal reflux‐induced chronic cough, who failed an 8‐week course of omeprazole and domperidone, were recruited into the open‐labelled study and randomly assigned to receive either gabapentin (maximum daily dose of 900 mg) or baclofen (maximum daily dose of 60 mg) for 8 weeks as add‐on therapy to the previous treatment. The primary end point was the successful rate of cough resolution; and the secondary end‐points included cough sensitivity to capsaicin and gastro‐oesophageal reflux disease questionnaire score and reported side effects. Results: One hundred and eleven patients in the gabapentin group and 106 in the baclofen group completed the study. The overall success rate for cough resolution was comparable (57.3% vs 53.0%, χ2 = 0.357, P = 0.550) between the two groups. In parallel, cough sensitivity to capsaicin and gastro‐oesophageal reflux disease questionnaire score decreased after treatment with either gabapentin or baclofen. However, gabapentin was associated with less frequent somnolence (20.5% vs 35.0%, χ2 = 6.156, P = 0.013) and dizziness (11.1% vs 23.9%, χ2 = 6.654, P = 0.010) than baclofen. Conclusions: Gabapentin and baclofen have similar therapeutic efficacy for suspected refractory gastro‐oesophageal reflux‐induced chronic cough. However, gabapentin may be preferable because of fewer side effects. Trial Register: http://www.chictr.org/; No.: ChiCTR‐ONC‐13003066. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors and laparoscopic anti-reflux surgery ( LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease ( GERD). Aim To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. Methods In the LOTUS trial , 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. Results A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups ( P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed ( P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. Conclusions Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology. [ABSTRACT FROM AUTHOR]

Background The diagnosis of gastro-oesophageal reflux disease ( GERD) in clinical practice is limited by the sensitivity and specificity of symptoms and diagnostic testing. Aim To determine if adding histology as a criterion and excluding patients with epigastric pain enhances the diagnosis for GERD. Methods Patients with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months and who had evaluable distal oesophageal biopsies were included (Diamond study: NCT00291746). Epithelial hyperplasia was identified when total epithelial thickness was at least 430 μm. Investigation-based GERD criteria were: presence of erosive oesophagitis, pathological oesophageal acid exposure and/or positive symptom-acid association probability. Symptoms were assessed using the Reflux Disease Questionnaire and a pre-specified checklist. Results Overall, 127 (55%) of the 231 included patients met investigation-based GERD criteria and 195 (84%) met symptom-based criteria. Epithelial hyperplasia was present in 89 individuals, of whom 61 (69%) met investigation-based criteria and 83 (93%) met symptom-based criteria. Adding epithelial hyperplasia as a criterion increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose ( NND): 8], to 155 (67%). The proportion of patients with a symptom-based GERD diagnosis who met investigation-based criteria including epithelial hyperplasia was significantly greater when concomitant epigastric pain was absent than when it was present ( P < 0.05; NND: 8). Conclusions Histology increases diagnosis of GERD and should be performed when clinical suspicion is high and endoscopy is negative. Excluding patients with epigastric pain enhances sensitivity for the diagnosis of GERD. [ABSTRACT FROM AUTHOR]

SUMMARY Background Mean nocturnal baseline impedance ( MNBI), a novel pH-impedance metric, may be a surrogate marker of reflux burden. Aim To assess the predictive value of MNBI on symptomatic outcomes after anti-reflux therapy. Methods In this prospective observational cohort study, pH-impedance studies performed over a 5-year period were reviewed. Baseline impedance was extracted from six channels at three stable nocturnal 10-min time periods, and averaged to yield MNBI. Distal and proximal oesophageal MNBI values were calculated by averaging MNBI values at 3, 5, 7 and 9 cm, and 15 and 17 cm respectively. Symptomatic outcomes were measured as changes in global symptom severity ( GSS, rated on 100-mm visual analogue scales) on prospective follow-up after medical or surgical anti-reflux therapy. Univariate and multivariate analyses assessed the predictive value of MNBI on symptomatic outcomes. Results Of 266 patients, 135 (50.8%) were tested off proton pump inhibitor ( PPI) therapy and formed the study cohort (52.1 ± 1.1 years, 63.7% F). The 59 with elevated acid exposure time ( AET) had lower composite and distal MNBI values than those with physiological AET ( P < 0.0001), but similar proximal MNBI ( P = 0.62). Linear AET negatively correlated with distal MNBI, both individually and collectively (Pearson's r = −0.5, P < 0.001), but not proximal MNBI (Pearson's r = 0, P = 0.72). After prospective follow-up (94 patients were followed up for 3.1 ± 0.2 years), univariate and multivariate regression models showed that distal MNBI, but not proximal MNBI, was independently predictive of linear GSS improvement. Conclusions Distal oesophageal MNBI negatively correlates with AET and, when assessed off PPI therapy, is independently predictive of symptomatic improvement following anti-reflux therapy. [ABSTRACT FROM AUTHOR]

Background Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor ( PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. Aim To assess the efficacy of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. Methods This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using the Heartburn Reflux Dyspepsia Questionnaire (HRDQ). Based on symptom score during run-in, eligible patients were randomised to Gaviscon Advance 10 mL four times a day or placebo in addition to a once daily PPI. The primary endpoint was change in HRDQ score post-treatment compared to baseline. Results One hundred and thirty-six patients were randomised. Change in HRDQ reflux score was significantly greater for Gaviscon Advance (mean: −5.0, s.d.: 4.7) than for placebo (mean: −3.5, s.d.: 5.5) with an LS mean difference of 1.6 [95% CI −3.1 to −0.1], P = 0.03. A decrease in the mean (s.d.) number of nights with symptoms was observed from 3.6 (2.8) to 3.0 (3.0) in the placebo group and from 3.9 (2.8) to 2.2 (2.7) for the Gaviscon Advance group. This reduction was significantly greater in the Gaviscon Advance group than in the placebo group [ LS mean difference = −0.9, 95% CI (−1.6 to −0.2), P < 0.01]. Conclusion In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (Eudra CT/ IND Number: 2011-005486-21). [ABSTRACT FROM AUTHOR]

Background A previous single-centre study showed that lower oesophageal sphincter electrical stimulation therapy (LES-EST) in gastro-oesophageal reflux disease (GERD) patients improves reflux symptoms and decreases oesophageal acid exposure. Aim To evaluate safety and efficacy of LES-EST in GERD patients with incomplete response to proton pump inhibitors (PPIs) in a prospective, international, multicentre, open-label study. Methods GERD patients, partially responsive to PPIs, received LES-EST. GERD health-related quality of life (GERD-HRQL), daily symptom diaries, quality of life scores, oesophageal acid exposure, and LES resting and residual pressure were measured before and after initiation of LES-EST. Stimulation sessions were optimised based on residual symptoms and oesophageal acid exposure. Results Forty-four patients were enrolled and 6-month data from 41 patients are available. Hiatal repair was performed in 16 patients. One device-related, one procedure-related and one unrelated severe adverse event were reported. GERD-HRQL improved from 31.0 (IQR 26.2-36.8) off-PPI and 16.5 (IQR 9.0-22.8) on-PPI to 4 (IQR 1-8) at 3-month and 5 (IQR 3-9) at 6-month follow-up ( P < 0.0001 vs. on- and off-PPI). Oesophageal acid exposure (pH < 4.0) improved from 10.0% (IQR 7.5-12.9) to 3.8% (IQR 1.9-12.3) at 3 months ( P = 0.0027) and 4.4% (IQR 2.2-7.2) at 6 months ( P < 0.0001). Conclusions These interim results show an acceptable safety record of LES-EST to date, combined with good short-term efficacy in GERD patients who are partially responsive to PPI therapy. A remarkable reduction in regurgitation symptoms, without the risk of intervention-requiring dysphagia may prove to be an advantage compared with other anti-reflux procedures. ClinicalTrials.gov Identifier: NCT01574339. [ABSTRACT FROM AUTHOR]

Background No validated patient-reported outcome ( PRO) measure exists for functional dyspepsia ( FD) assessment. Verbal descriptions of different upper abdominal symptoms may be poorly distinguishable to patients. Aim To investigate whether understanding of FD symptoms is enhanced by pictograms symbolising the nature of the symptoms, besides verbal descriptors. Methods Consecutive FD patients were randomised to fill out a questionnaire assessing nineupper gastrointestinal symptoms (post-prandial fullness, early satiation, epigastric pain, epigastric burning, bloating centred in the upper abdomen, nausea, vomiting, heartburn, regurgitation) with or without accompanying pictograms. Symptoms were rated for frequency and severity (0-5), and patients also identified the most bothersome symptom. Subsequently, in-depth history was taken by an expert clinician, who filled out the same symptom ratings. Concordance between patient and clinician ratings was quantified using chi-square and kappa statistics. Results Content validity of pictograms was first confirmed by 15 FD patients. Next, 76 patients (52 women, age 42.2 ± 1.9) were randomised to questionnaires with or without pictograms. The concordance with clinician's assessment as gold standard rose from 36 without to 48% for questions with pictograms ( P < 0.0001). Considering the Rome III subdivision, benefit in concordance with pictograms was present for post-prandial distress, epigastric pain syndrome and reflux symptoms. Kappa statistics confirmed these gains (weighted kappa values for concordance of symptom frequency ratings rose from 0.214 to 0.446 with pictograms), and also showed better concordance of the most bothersome symptom with pictograms. Conclusion Pictograms accompanying verbal descriptors significantly improve concordance of functional dyspepsia symptom ratings by patients with evaluation by their physicians. [ABSTRACT FROM AUTHOR]