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Ribolsi M, Cicala M, Zentilin P, Neri M, Mauro A, Efthymakis K, Petitti T, Savarino V, Penagini R. Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease. Aliment Pharmacol Ther 2018; 48:1074-1081. [PMID: 30294924 DOI: 10.1111/apt.14986] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 06/18/2018] [Accepted: 08/22/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing. AIMS To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated. METHODS Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency ≥3 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms ≥3 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring. RESULTS Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group. CONCLUSIONS True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group.
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Affiliation(s)
- Mentore Ribolsi
- Digestive Disease Unit, Campus Bio Medico University, Rome, Italy
| | - Michele Cicala
- Digestive Disease Unit, Campus Bio Medico University, Rome, Italy
| | | | - Matteo Neri
- Section of Internal Medicine, Department of Medicine and Aging Sciences and Center for Excellence on Ageing (Ce.S.I.Met), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Milan, Italy
| | - Konstantinos Efthymakis
- Section of Internal Medicine, Department of Medicine and Aging Sciences and Center for Excellence on Ageing (Ce.S.I.Met), "G. D'Annunzio" University and Foundation, Chieti, Italy
| | | | | | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - University of Milan, Milan, Italy
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Stanghellini V, Tosetti C, Benedetto E, Condoluci M, De Bastiani R, Cogliandro R, Mastronuzzi T, De Polo M, Di Mita F, Napoli L, Ubaldi E, Nebiacolombo C, Cottone C, Grattagliano I, Zamparella M, Baldi E, Sanna G. Nickel sensitization in patients with gastro-esophageal reflux disease. United European Gastroenterol J 2016; 4:184-190. [PMID: 27087945 PMCID: PMC4804365 DOI: 10.1177/2050640615595917] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Accepted: 06/21/2015] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Gastro-esophageal reflux disease (GERD) leads to frequent medical visits, and available therapies fail in up to 40% of patients. Food allergies may be involved in GERD pathogenesis; however, allergens other than food have received little attention. Nickel allergy is common in the general population and some high-nickel foods are associated with GERD. However, the potential relationship between nickel allergy and GERD remains unaddressed. AIM This study aimed to evaluate the prevalence of nickel sensitization in patients with and without GERD and to compare clinical and demographic features. METHODS This prospective, multicenter study included 210 adult GERD patients and 140 patients without GERD who presented at the general practitioner. All GERD patients had undergone treatment with proton pump inhibitors and upper digestive endoscopy within the previous five years. Demographic and clinical data were collected by questionnaire and patients underwent a nickel patch allergy test. RESULTS Patients with and without GERD presented similar characteristics, with the exception of nickel sensitization, which was significantly more prevalent among GERD patients than controls (39.5% vs. 16.4%; p = 0.001). Nickel-positive GERD patients were more frequently female (90.4% vs. 65.4%, p = 0.003) and asthmatic (18.1% vs. 4.7%; p = 0.038), compared to nickel-negative GERD patients. At six-month follow-up, most of the patients, with or without nickel sensitization, reported improved symptoms without differences in drug prescription. CONCLUSION Nickel sensitization is particularly prevalent in GERD patients seen in general practice. Whether allergies other than food allergy play a role in GERD remains to be elucidated.
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Affiliation(s)
- Vincenzo Stanghellini
- Department of Digestive Diseases and Internal Medicine, University of Bologna, Italy
| | - Cesare Tosetti
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Edoardo Benedetto
- Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Rende, Italy
| | | | - Rudi De Bastiani
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Rosanna Cogliandro
- Department of Digestive Diseases and Internal Medicine, University of Bologna, Italy
| | - Tecla Mastronuzzi
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Manuela De Polo
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Francesco Di Mita
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Luigi Napoli
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Enzo Ubaldi
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Cristina Nebiacolombo
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Carmelo Cottone
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Ignazio Grattagliano
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Maria Zamparella
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Elisabetta Baldi
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
| | - Guido Sanna
- General Practitioner and Gastroenterologist, Italian Group for Primary Care Gastroenterology (GIGA-CP), Italy
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Penagini R, Sweis R, Mauro A, Domingues G, Vales A, Sifrim D. Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2015; 21:265-72. [PMID: 25843078 PMCID: PMC4398246 DOI: 10.5056/jnm14075] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 12/01/2014] [Accepted: 12/07/2014] [Indexed: 12/13/2022] Open
Abstract
Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management.
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Affiliation(s)
- Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy
| | - Rami Sweis
- University College London Hospital, London, United Kingdom
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Universita degli Studi di Milano, Milan, Italy
| | | | - Andres Vales
- Esophageal Lab, Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Daniel Sifrim
- Bart's and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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Falk GL, Beattie J, Ing A, Falk SE, Magee M, Burton L, Wall HVD. Scintigraphy in laryngopharyngeal and gastroesophageal reflux disease: A definitive diagnostic test? World J Gastroenterol 2015; 21:3619-3627. [PMID: 25834329 PMCID: PMC4375586 DOI: 10.3748/wjg.v21.i12.3619] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2014] [Revised: 07/28/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the utility of scintigraphic studies in predicting response to laparoscopic fundoplication (LF) for chronic laryngopharyngeal reflux symptoms.
METHODS: Patients with upper aero-digestive symptoms that remained undiagnosed after a period of 2 mo were studied with conventional pH and manometric studies. Patients mainly complained of cough, sore throat, dysphonia and globus. These patients were imaged after ingestion of 99m-technetium diethylene triamine pentaacetic acid. Studies were quantified with time activity curves over the pharynx, upper and lower oesophagus and background. Late studies of the lungs were obtained for aspiration. Patients underwent LF with post-operative review at 3 mo after surgery.
RESULTS: Thirty four patients (20 F, 14 M) with an average age of 57 years and average duration of symptoms of 4.8 years were studied. Twenty four hour pH and manometry studies were abnormal in all patients. On scintigraphy, 27/34 patients demonstrated pharyngeal contamination and a rising or flat pharyngeal curve. Lung aspiration was evident in 50% of patients. There was evidence of pulmonary aspiration in 17 of 34 patients in the delayed study (50%). Pharyngeal contamination was found in 27 patients. All patients with aspiration showed pharyngeal contamination. In the 17 patients with aspiration, graphical time activity curve showed rising activity in the pharynx in 9 patients and a flat curve in 8 patients. In those 17 patients without pulmonary aspiration, 29% (5 patients) had either a rising or flat pharyngeal graph. A rising or flat curve predicted aspiration with a positive predictive value of 77% and a negative predictive value of 100%. Over 90% of patients reported a satisfactory symptomatic response to LF with an acceptable side-effect profile.
CONCLUSION: Scintigraphic reflux studies offer a good screening tool for pharyngeal contamination and aspiration in patients with gastroesophageal reflux disease.
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Rezailashkajani M, Roshandel D, Shafaee S, Zali MR. A cost analysis of gastro-oesophageal reflux disease and dyspepsia in Iran. Dig Liver Dis 2008; 40:412-7. [PMID: 18342588 DOI: 10.1016/j.dld.2008.01.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2007] [Revised: 01/19/2008] [Accepted: 01/30/2008] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM To provide a first-time report on the health care utilization and costs of gastro-oesophageal reflux disease and dyspepsia in Iran. METHODS A consecutive sample of 501 patients referred for upper endoscopy to an outpatient gastroenterology clinic in central Tehran (May 2005 to January 2006) was investigated using two interview-assisted questionnaires for gastro-oesophageal reflux disease (i.e. heartburn or regurgitation on a weekly basis for at least the past 3 months, and symptom onset at least 12 months prior to the study) or dyspepsia symptom (based on Rome II criteria). The frequency of health resource utilization (i.e. physician visit, hospitalization, laboratory tests, instrumental studies, and medications) and productivity loss (days off work) due to gastro-oesophageal reflux disease/dyspepsia-related symptoms in the past 12 months were recorded. Societal perspective was used, and cost of illness per person per year was estimated in purchasing power parity dollars (PPP$). RESULTS The cost of illness per person per year for patients with gastro-oesophageal reflux disease, and dyspepsia alone were around PPP$195 and PPP$215, respectively. There was no statistically significant difference in the cost of illness between the two patient groups. The direct costs of disease comprised 88%, and 82% of the total costs in gastro-oesophageal reflux disease and dyspepsia patients, respectively with the costs of medications being the dominant component. There was also no statistically significant difference in the cost of disease between the gastro-oesophageal reflux disease patients with and without oesophagitis (based on Los Angeles criteria). CONCLUSION As drugs cost was found to be a dominant cost component, cost-minimization studies to find the best medication therapy strategies considering the regional factors is suggested.
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Affiliation(s)
- M Rezailashkajani
- Research Centre for Gastroenterology and Liver Diseases, Shaheed Beheshti Medical University, Iran.
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Giannini EG, Zentilin P, Dulbecco P, Vigneri S, Scarlata P, Savarino V. Management strategy for patients with gastroesophageal reflux disease: a comparison between empirical treatment with esomeprazole and endoscopy-oriented treatment. Am J Gastroenterol 2008; 103:267-75. [PMID: 18289194 DOI: 10.1111/j.1572-0241.2007.01659.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Whether patients with typical gastroesophageal reflux disease (GERD) symptoms and without alarm features should be treated empirically or undergo endoscopy first is a debated issue. In this study, our aim was to assess the efficacy, and to compare the direct costs and impact on health-related quality of life (HRQL), of two treatment strategies (empirical vs endoscopy-oriented treatment) in a large population of patients with GERD. METHODS In total, 612 patients were randomized to either empirical treatment with esomeprazole 40 mg once daily (od) (group 1, N = 309) or endoscopy and treatment according to endoscopic findings (group 2, N = 303, esomeprazole 40 mg od in patients with reflux esophagitis and esomeprazole 20 mg od in patients without esophagitis) for 4 wk, followed by esomeprazole 20 mg od maintenance treatment in both groups. Direct costs and HRQL were analyzed in both treatment arms. RESULTS At the end of the acute treatment phase (week 4), 267 patients in group 1 (86.4%) and 265 patients in group 2 (87.5%) were considered responders to treatment (intention-to-treat analysis, P= 0.878). Empirical treatment proved to be cost-effective by saving 38.72 euros per treated patient. At the end of the maintenance phase (week 24), a similar proportion of patients responded to treatment in the two groups (71.8%vs 68.3%, P= 0.389). HRQL improved from baseline to week 24 in both groups (difference between study groups not significant). CONCLUSIONS In patients with GERD, empirical treatment with esomeprazole proved to be cost-effective compared with endoscopy-oriented treatment, and did not negatively affect patient HRQL. These results should be taken into account in the management of GERD patients in clinical practice.
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Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
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Pace F, Pallotta S, Vakil N. Gastroesophageal reflux disease is a progressive disease. Dig Liver Dis 2007; 39:409-14. [PMID: 17379585 DOI: 10.1016/j.dld.2006.11.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2006] [Revised: 11/13/2006] [Accepted: 11/23/2006] [Indexed: 12/11/2022]
Abstract
It is controversial whether gastrooesophageal reflux disease represents a spectrum disease from a nonerosive to a complicated one, or whether it is a categorial disease, i.e. it can be divided into three categories, such as nonerosive gastrooesophageal reflux disease, erosive gastrooesophageal reflux disease and Barrett's esophagus (BE) with little or no transition from one category to the other. This controversy might be of general interest, because it has some implications in the management of the patient. However, literature data concerning the natural history of gastrooesophageal reflux disease are very limited, and in particular very few papers have dealt with the issue of describing the natural history of patients with nonerosive gastrooesophageal reflux disease. Aim of the present review is to reassess these scanty data, and to try to demonstrate that progression from milder to more severe forms of gastrooesophageal reflux disease is possible and documented.
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Affiliation(s)
- F Pace
- Department of Gastroenterology, L. Sacco University Hospital, Milan, Italy.
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