{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:43:41Z","timestamp":1790649821421,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2018,10,7]],"date-time":"2018-10-07T00:00:00Z","timestamp":1538870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The real size of the gastro\u2010oesophageal reflux disease (<jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>) population not responding to proton pump inhibitor (<jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content>) therapy has still not been fully elucidated. Causes of <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To evaluate the prevalence of refractoriness to optimal <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> therapy and the contribution of non\u2010erosive reflux disease (<jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content>), reflux hypersensitivity, and functional heartburn, to <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> refractoriness. The association of functional <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> symptoms in non\u2010responders was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Frequency and severity of <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>), globus, and ear nose and throat (<jats:styled-content style=\"fixed-case\">ENT<\/jats:styled-content>) symptoms were evaluated in patients previously classified as non\u2010responders. Patients with at least one of the oesophageal symptoms with a frequency \u22653 \/week were treated with esomeprazole 40\u00a0mg once daily for 8\u00a0weeks and then re\u2010evaluated. Non\u2010responders (patients with oesophageal symptoms \u22653 times per week) underwent 24\u00a0hour multichannel intraluminal impedance\u2010<jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content> monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI\u2010refractory underwent the esomeprazole trial; 60 did not respond. <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>, epigastric pain, and post\u2010prandial distress episodes were associated with a poor response on multivariate analysis. <jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content>, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI\u2010refractory group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>True refractoriness in patients with <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal <jats:styled-content style=\"fixed-case\">PPI<\/jats:styled-content> dosing, the rate of refractoriness was 20%. True <jats:styled-content style=\"fixed-case\">NERD<\/jats:styled-content> constitutes only a third of the PPI\u2010refractory group.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.14986","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T06:34:33Z","timestamp":1538980473000},"page":"1074-1081","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non\u2010erosive reflux disease"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-1758","authenticated-orcid":false,"given":"Mentore","family":"Ribolsi","sequence":"first","affiliation":[{"name":"Digestive Disease Unit Campus Bio Medico University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cicala","sequence":"additional","affiliation":[{"name":"Digestive 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