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Wang Q, Ma S, Liu M, Tao Y, Sun Z. Gut microbiota, inflammatory cytokines and gastro-esophageal reflux disease: A Mendelian randomization analysis. Medicine (Baltimore) 2025; 104:e41386. [PMID: 39889191 PMCID: PMC11789916 DOI: 10.1097/md.0000000000041386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 01/08/2025] [Accepted: 01/10/2025] [Indexed: 02/02/2025] Open
Abstract
Gut microbiota has been recognized as an extrahepatic manifestation of gastro-esophageal reflux disease (GERD) in observational studies. However, the directionality and causality of the association and whether cytokines act as a mediator remain unclear. We aim to estimate the casual relationship between gut microbiota, inflammatory cytokines and GERD using a 2-sample Mendelian randomization method. Gut microbiota, cytokines, and GERD were identified using summary data from the genome-wide association studies and the FinnGen consortium. The primary method for causal estimation was the inverse-variance weighted approach, complemented by a range of sensitivity analyses aimed at assessing heterogeneity, horizontal pleiotropy, and the robustness of the findings. Furthermore, mediation analysis was conducted to evaluate the association between gut microbiota and GERD, with 5 cytokines, and to calculate the mediated proportions. We found 3 positive and 3 negative causal associations observed between genetic predisposition in gut microbiota and GERD. Additionally, 2 positive and 3 negative causal associations were identified between cytokines and GERD. Our analysis unveiled that TNF-related apoptosis-inducing ligand levels (TRAIL) mediated the causal relationships between the genera Family XIII UCG001 and Senegalimassilia, and GERD. We identified causal effects between 6 bacterial traits, 5 inflammatory cytokines, and GERD. Notably, we furnished causal evidence linking TRAIL levels to a substantial proportion of the risk attributed to genus Family XIII UCG001 and genus Senegalimassilia, thereby mediating the risk of GERD. These findings offer novel avenues for therapeutic interventions targeting individuals with GERD.
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Affiliation(s)
- Qilin Wang
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Shenghui Ma
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Mengjie Liu
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Yu Tao
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
| | - Zhiguang Sun
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
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Fox M. Update Motility Disorders: Gastro-Oesophageal Reflux Disease - Diagnostic and Conservative Approach. Visc Med 2024; 40:299-309. [PMID: 39664098 PMCID: PMC11631173 DOI: 10.1159/000541358] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 09/06/2024] [Indexed: 12/13/2024] Open
Abstract
Background Gastro-oesophageal reflux disease (GORD) is extremely common, with at least 1 in 10 people in the general population reporting heartburn and acid regurgitation on a weekly basis. GORD can also be associated with a variety of atypical symptoms, including chest pain, chronic cough, and laryngopharyngeal symptoms. The causes of GORD are multifactorial, and the severity of symptoms is influenced by peripheral and central factors, including psychosocial stress and anxiety. Therefore, for a variety of reasons, no single investigation provides a definitive diagnosis, and standard treatment with acid suppressants is not always effective. Summary This review introduces the Lyon Consensus, now in its second iteration, a classification system that provides a "conclusive" positive or negative diagnosis of GORD by integrating the results of endoscopy, ambulatory reflux monitoring, and high-resolution manometry. Different algorithms are applied to patients with high and low pre-test probability of a causal relationship between reflux episodes and patient symptoms. The results of these studies identify patients with "actionable" results that require escalation, revision, or discontinuation of GORD treatment. Guidance is provided on the range of conservative treatments available for GORD, including dietary and lifestyle advice, antacids and alginates, and drugs that suppress acid secretion. Key Messages GORD is a common disorder; however, the causes of reflux and symptoms can be complex. As a result, the diagnosis can be missed, and management is sometimes challenging, especially for patients with atypical symptoms. The Lyon classification establishes a conclusive diagnosis of GORD, based on results of endoscopic and physiological investigation. Typical symptoms usually respond to empiric use of alginate-antacid preparations and acid suppression; however, the management of treatment refractory symptoms is tailored to the individual.
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Affiliation(s)
- Mark Fox
- Digestive Function: Basel, Laboratory and Clinic for Motility Disorders and Functional Digestive Diseases, Centre for Integrative Gastroenterology, Klinik Arlesheim, Arlesheim, Switzerland
- Department of Gastroenterology and Hepatology, University Zürich, Zurich, Switzerland
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Kim YS, Park Y, Kim Y, Son HE, Rhee J, Pyun CW, Park C, Kim H. Ameliorative Effects of HT074-Inula and Paeonia Extract Mixture on Acute Reflux Esophagitis in Rats via Antioxidative Activity. Antioxidants (Basel) 2024; 13:891. [PMID: 39199137 PMCID: PMC11352064 DOI: 10.3390/antiox13080891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/16/2024] [Accepted: 07/18/2024] [Indexed: 09/01/2024] Open
Abstract
HT074, a multiherbal mixture containing extracts from Inula britannica flowers and Paeonia lactiflora roots, is used in Korean medicine for gastric disorders. This study investigated the protective mechanisms of HT074 against acute reflux esophagitis (RE) in rats. Nitric oxide (NO) production and mRNA expression of antioxidant-related genes (Nrf2, HO-1, SOD, CAT, and GPx2) were evaluated in LPS-induced RAW 264.7 cells. Gastroesophageal reflux (GER) was induced in rats, followed by HT074 (100, 300 mg/kg) or ranitidine (50 mg/kg) administration. Esophageal damage and histological changes were assessed. Gastric pH and protein expression levels of Nrf2, HO-1, SOD, CAT, and GPx-1/2 were measured. HT074 pretreatment reduced NO production and increased the expression of HO-1, CAT, and GPx2 in LPS-induced RAW 264.7 cells. In GER-induced rats, HT074 significantly decreased esophageal lesions and increased the expression of HO-1, SOD, GPx-1/2, and Nrf2. HT074 did not affect gastric pH. These findings suggest that HT074 protects against GER-induced esophagitis by inhibiting NO production and enhancing antioxidant activity. Therefore, HT074 could be a promising therapeutic agent for GER disease.
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Affiliation(s)
- Young-Sik Kim
- Department of Herbology, College of Korean Medicine, Woosuk University, Jeonju 54986, Republic of Korea; (Y.-S.K.); (Y.K.); (H.-E.S.); (J.R.)
| | - Yeonjin Park
- Department of Herbal Pharmacology, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (Y.P.); (C.P.)
| | - Yongbin Kim
- Department of Herbology, College of Korean Medicine, Woosuk University, Jeonju 54986, Republic of Korea; (Y.-S.K.); (Y.K.); (H.-E.S.); (J.R.)
| | - Hyo-Eun Son
- Department of Herbology, College of Korean Medicine, Woosuk University, Jeonju 54986, Republic of Korea; (Y.-S.K.); (Y.K.); (H.-E.S.); (J.R.)
| | - Jinhui Rhee
- Department of Herbology, College of Korean Medicine, Woosuk University, Jeonju 54986, Republic of Korea; (Y.-S.K.); (Y.K.); (H.-E.S.); (J.R.)
| | - Chang-Won Pyun
- NEUMED R&BD Institute, NeuMed Inc., 88 Imun-ro, Dongdaemun-gu, Seoul 02440, Republic of Korea;
| | - Chanoh Park
- Department of Herbal Pharmacology, College of Korean Medicine, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea; (Y.P.); (C.P.)
| | - Hocheol Kim
- Department of Herbal Pharmacology, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea
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Nehra D, Clements CDM, Bezzaa SL, Tabbakh Y, Walsh CM. Patient-reported outcomes of laparoscopic magnetic sphincter augmentation for gastro-oesophageal reflux disease. Ann R Coll Surg Engl 2024; 106:344-352. [PMID: 37609688 PMCID: PMC10981991 DOI: 10.1308/rcsann.2023.0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2023] [Indexed: 08/24/2023] Open
Abstract
INTRODUCTION Gastro-oesophageal reflux disease (GORD) is a chronic progressive disease, associated with substantial clinical and economic burden. Proton pump inhibitors (PPIs) are considered first-line treatment; however, there are concerns around the long-term impact of their usage. Surgical treatment with Nissen fundoplication can be considered but, because of the potential side effects, few patients undergo surgery and there remains a substantial therapeutic gap within the current treatment pathway. Laparoscopic magnetic sphincter augmentation (MSA) using the LINX® device is an alternative surgical approach. METHODS The objective of this study was to investigate patient-reported outcomes following laparoscopic MSA surgery using the LINX® device in a UK setting. A retrospective questionnaire obtained data regarding postoperative symptoms, medication use and patient satisfaction. RESULTS Out of 131 patients surveyed, 97 responses were received, with a minimum follow-up time of 1 year. In those who reported heartburn and regurgitation preoperatively, improvement was reported in 93% (84/90) and 90% (86/96) of patients, respectively. Eighty-eight per cent (73/83) of patients were able to completely stop or reduce their medication by at least 75%. Seventy-seven per cent (73/95) of patients were "very satisfied" or "satisfied". CONCLUSIONS This study is the first to present patient-reported outcomes of MSA using the LINX® device for patients with GORD in the UK. It demonstrates that the device has favourable outcomes and could effectively bridge the current therapeutic gap that exists between PPI medication and Nissen fundoplication.
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Affiliation(s)
- D Nehra
- Epsom and St Helier University Hospitals NHS Trust, UK
| | - CDM Clements
- Epsom and St Helier University Hospitals NHS Trust, UK
| | - SL Bezzaa
- Epsom and St Helier University Hospitals NHS Trust, UK
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Shacker M, Latorre-Rodríguez AR, Mittal SK. Prevalence and severity of abdominal bloating in patients with gastroesophageal reflux disease. Dis Esophagus 2024; 37:doad058. [PMID: 37738150 DOI: 10.1093/dote/doad058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 08/23/2023] [Accepted: 08/24/2023] [Indexed: 09/24/2023]
Abstract
Abdominal bloating (AB) is a common symptom among patients with gastroesophageal reflux disease (GERD); however, in clinical practice, its prevalence is likely underestimated due to the lack of objective tools to measure its frequency and severity. It is associated with dissatisfaction and worse quality of life, but data on its prevalence before and after mechanical control of GERD (i.e. fundoplication, magnetic sphincter augmentation, and antireflux mucosectomy) are lacking. To assess and determine the pre- and postoperative prevalence and severity of AB among patients with GERD, we conducted a structured literature search using MeSH and free-text terms in MEDLINE (via Pubmed), EMBASE, and Taylor & Francis Online between January 1977 and October 2022. Fifteen articles reporting the prevalence or severity of AB using quality-of-life questionnaires before or after antireflux surgery (ARS) were included. Overall, a high prevalence of AB before ARS was found. A decline in the prevalence and severity of AB was documented postoperatively in most cases independent of the surgical approach. Among surgical approaches, a complete fundoplication had the highest reported postoperative AB. Overall, patients reported less severe and less frequent AB after ARS than before. The traditional belief that postoperative bloating is a sequela of ARS should be reevaluated.
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Affiliation(s)
- Mark Shacker
- School of Medicine, Creighton University, Phoenix, AZ, USA
| | | | - Sumeet K Mittal
- School of Medicine, Creighton University, Phoenix, AZ, USA
- Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
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Dong R, Zhang Q, Peng H. Gastroesophageal reflux disease and the risk of respiratory diseases: a Mendelian randomization study. J Transl Med 2024; 22:60. [PMID: 38229096 PMCID: PMC10790464 DOI: 10.1186/s12967-023-04786-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 12/05/2023] [Indexed: 01/18/2024] Open
Abstract
BACKGROUND Observational studies have suggested a suspected association between gastroesophageal reflux disease (GERD) and respiratory diseases, but the causality remains equivocal. The goal of this study was to evaluate the causal role of GERD in respiratory diseases by employing Mendelian randomization (MR) studies. METHODS We conducted Mendelian randomization analysis based on summary data of genome-wide association studies (GWASs) and three MR statistical techniques (inverse variance weighted, weighted median and MR-Egger) were employed to assess the probable causal relationship between GERD and the risk of respiratory diseases. Sensitivity analysis was also carried out to ensure more trustworthy results, which involves examining the heterogeneity, pleiotropy and leave-one-SNP-out method. We also identified 33 relevant genes and explored their distribution in 26 normal tissues. RESULTS In the analysis, for every unit increase in developing GERD, the odds ratio for developing COPD, bronchitis, pneumonia, lung cancer and pulmonary embolism rose by 72% (ORIVW = 1.72, 95% CI 1.50; 1.99), 19% (ORIVW = 1.19, 95% CI 1.11; 1.28), 16% (ORIVW = 1.16, 95% CI 1.07; 1.26), 0. 3% (ORIVW = 1.003, 95% CI 1.0012; 1.0043) and 33% (ORIVW = 1.33, 95% CI 1.12; 1.58), respectively, in comparison with non-GERD cases. In addition, neither heterogeneity nor pleiotropy was found in the study. This study also found that gene expression was higher in the central nervous system and brain tissue than in other normal tissues. CONCLUSIONS This study provided evidence that people who developed GERD had a higher risk of developing COPD, bronchitis, pneumonia, lung cancer and pulmonary embolism. Our research suggests physicians to give effective treatments for GERD on respiratory diseases. By exploring the gene expression, our study may also help to reveal the role played by the central nervous system and brain tissue in developing respiratory diseases caused by GERD.
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Affiliation(s)
- Rui Dong
- Department of Respiratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Qianqian Zhang
- Department of Respiratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hongxing Peng
- Department of Respiratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Fox M, Gyawali CP. Dietary factors involved in GERD management. Best Pract Res Clin Gastroenterol 2023; 62-63:101826. [PMID: 37094911 DOI: 10.1016/j.bpg.2023.101826] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/10/2023] [Accepted: 02/15/2023] [Indexed: 04/26/2023]
Abstract
Gastroesophageal reflux disease (GERD) is extremely common, and even modest weight gain has been associated with higher symptom burden as well as objective evidence of reflux on endoscopy and physiological measurement. Certain trigger foods, especially citrus, coffee, chocolate, fried food, spicy food and red sauces are frequently reported to worsen reflux symptoms, although hard evidence linking these items to objective GERD is lacking. There is better evidence that large meal volume and high calorie content can increase esophageal reflux burden. Conversely, sleeping with the head end of the bed raised, avoiding lying down close to meals, sleeping on the left side and weight loss can improve reflux symptoms and objective reflux evidence, especially when the esophagogastric junction 'reflux barrier' is compromised (e.g., in the presence of a hiatus hernia). Consequently, attention to diet and weight loss are both important elements of management of GERD, and need to be incorporated into management plans.
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Affiliation(s)
- Mark Fox
- Digestive Function: Basel, Laboratory and Clinic for Motility Disorders and Functional Digestive Diseases, Centre for Integrative Gastroenterology, Klinik Arlesheim, Arlesheim, Switzerland; Department of Gastroenterology and Hepatology, University Hospital, Zürich, Switzerland
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, USA.
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8
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The impact of low-fat and full-fat dairy foods on symptoms of gastroesophageal reflux disease: an exploratory analysis based on a randomized controlled trial. Eur J Nutr 2022; 61:2815-2823. [PMID: 35294608 DOI: 10.1007/s00394-022-02855-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 02/22/2022] [Indexed: 11/04/2022]
Abstract
PURPOSE Gastroesophageal reflux disease (GERD) is a widely prevalent condition. High consumption of dairy foods and dietary fat are associated with worse GERD symptoms. However, existing data are inconsistent and mostly based on observational studies. The purpose of this exploratory analysis of a randomized controlled trial was to investigate the impact of low-fat and full-fat dairy food consumption on GERD symptoms. METHODS Seventy-two participants with metabolic syndrome completed a 4-week wash-in diet during which dairy intake was limited to three servings of nonfat milk per week. Participants were then randomized to either continue the limited dairy diet or switch to a diet containing 3.3 servings per day of either low-fat or full-fat milk, yogurt and cheese for 12 weeks. Here, we report intervention effects on the frequency of acid reflux, and the frequency and severity of heartburn, exploratory endpoints assessed by a questionnaire administered before and after the 12-week intervention. RESULTS In the per-protocol analysis (n = 63), there was no differential intervention effect on a cumulative heartburn score (p = 0.443 for the time by diet interaction in the overall repeated measures analysis of variance). Similarly, the intervention groups did not differentially affect the odds of experiencing acid regurgitation (p = 0.651). The intent-to-treat analyses (n = 72) yielded similar results. CONCLUSION Our exploratory analyses suggest that, in men and women with the metabolic syndrome, increasing the consumption of either low-fat or full-fat dairy foods to at least three servings per day does not affect common symptoms of GERD, heartburn and acid regurgitation compared to a diet limited in dairy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02663544, registered on January 26, 2016.
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The Causes of Gastroesophageal Reflux after Laparoscopic Sleeve Gastrectomy: Quantitative Assessment of the Structure and Function of the Esophagogastric Junction by Magnetic Resonance Imaging and High-Resolution Manometry. Obes Surg 2021; 30:2108-2117. [PMID: 32207049 DOI: 10.1007/s11695-020-04438-y] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The incidence of de novo gastroesophageal reflux disease (GERD) after LSG is substantial. However, an objective correlation with the structural gastric and EGJ changes has not been demonstrated yet. We aimed to prospectively evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on the structure and function of the esophagogastric junction (EGJ) and stomach. METHODS Investigations were performed before and after > 50% reduction in excess body weight (6-12 months after LSG). Subjects with GERD at baseline were excluded. Magnetic Resonance Imaging (MRI), high-resolution manometry (HRM), and ambulatory pH-impedance measurements were used to assess the structure and function of the EGJ and stomach before and after LSG. RESULTS From 35 patients screened, 23 (66%) completed the study (age 36 ± 10 years, BMI 42 ± 5 kg/m2). Mean excess weight loss was 59 ± 18% after 7.1 ± 1.7-month follow-up. Esophageal acid exposure (2.4 (1.5-3.2) to 5.1 (2.8-7.3); p = 0.040 (normal < 4.0%)) and reflux events increased after surgery (57 ± 24 to 84 ± 38; p = 0.006 (normal < 80/day)). Esophageal motility was not altered by surgery; however, intrabdominal EGJ length and pressure were reduced (both p < 0.001); whereas the esophagogastric insertion angle (35° ± 11° to 51° ± 16°; p = 0.0004 (normal < 60°)) and esophageal opening diameter (16.9 ± 2.8 mm to 18.0 ± 3.7 mm; p = 0.029) were increased. The increase in reflux events correlated with changes in EGJ insertion angle (p = 0.010). Patients with > 80% reduction in gastric capacity (TGV) had the highest prevalence of symptomatic GERD. CONCLUSION LSG has multiple effects on the EGJ and stomach that facilitate reflux. In particular, EGJ disruption as indicated by increased (more obtuse) esophagogastric insertion angle and small gastric capacity were associated with the risk of GERD after LSG. clinicaltrials.gov: NCT01980420.
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Nestegard O, Johnsen KM, Sørbye SW, Halvorsen FA, Tønnessen T, Paulssen EJ, Melby KK, Goll R, Florholmen J. Clinical characterization of Helicobacter pylori infected patients 15 years after unsuccessful eradication. PLoS One 2020; 15:e0238944. [PMID: 32966303 PMCID: PMC7510978 DOI: 10.1371/journal.pone.0238944] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 08/26/2020] [Indexed: 01/03/2023] Open
Abstract
Background and aims Patients that have failed therapy for Helicobacter pylori (H. pylori) infection are incompletely characterized. The aim of this study was to characterize a H. pylori treatment resistant cohort compared to the cohorts of newly diagnosed, earlier eradicated and non-infected. Material and methods Patients were selected from routine referrals to the Endoscopy units at three different Norwegian hospitals. In all four cohorts, gastric biopsies were scored according to the Sydney classification, and symptoms according to the Gastrointestinal Symptom Rating Scale score, including sub-scores for upper gastrointestinal symptoms and functional bowel symptoms. Patients in the H. pylori resistant group were treated with a triple therapy regimen that consisted of levofloxacin, amoxicillin and a proton pump inhibitor. Results We included 185 patients, 42 H. pylori treatment resistant, 50 newly diagnosed, 61 previously H. pylori eradicated and 32 never infected. The treatment-resistant cohort had higher scores for upper gastrointestinal symptoms and functional bowel symptoms compared to the other groups except for the group being never H. pylori infected. The H. pylori resistant patients had lower Sydney scores than patients with newly diagnosed H. pylori infection. The triple combination showed a high efficacy of 91% to eradicate H. pylori. Conclusions Patients with treatment-resistant H. pylori infection had more gastrointestinal symptoms, but a lower Sydney score than patients with newly diagnosed infection. A treatment regimen including levofloxacin showed a high efficacy in eradicating H. pylori in patients that previously had failed eradication treatment.
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Affiliation(s)
- Oddmund Nestegard
- Department Gastroenterology, Vestre Viken Hospital, Hønefoss, Norway
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
- * E-mail:
| | - Kay-Martin Johnsen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Sveinung W. Sørbye
- Department of Pathology, University Hospital of North Norway, Tromsø, Norway
| | | | - Tor Tønnessen
- Department Gastroenterology, Vestre Viken Hospital, Drammen, Norway
| | - Eyvind J. Paulssen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Kjetil K. Melby
- Department of Microbiology, University Hospital Oslo and University of Oslo, Oslo, Norway
| | - Rasmus Goll
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
| | - Jon Florholmen
- Department of Clinical Medicine, Research Group of Gastroenterology and Nutrition, UiT The Arctic University of Norway, Tromsø, Norway
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Sweis R, Fox M. The global burden of gastro-oesophageal reflux disease: more than just heartburn and regurgitation. Lancet Gastroenterol Hepatol 2020; 5:519-521. [PMID: 32178771 DOI: 10.1016/s2468-1253(20)30002-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 01/06/2020] [Accepted: 01/06/2020] [Indexed: 06/10/2023]
Affiliation(s)
- Rami Sweis
- Gastrointestinal Services, University College London Hospital, London, UK
| | - Mark Fox
- Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland; Digestive Function: Basel, Laboratory and Clinic for Motility Disorders and Functional Gastrointestinal Diseases, Centre for Integrative Gastroenterology, Klinik Arlesheim, CH-4144 Arlesheim, Switzerland.
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12
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History of gastroesophageal reflux disease in patients with suspected coronary artery disease. Heart Vessels 2019; 34:1631-1638. [PMID: 30993440 DOI: 10.1007/s00380-019-01413-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 04/12/2019] [Indexed: 12/15/2022]
Abstract
It is well known that patients with gastroesophageal reflux disease (GERD) experience GERD-related chest pain, but little is known about the relationship between GERD and coronary artery disease (CAD). We evaluated medical history of GERD in patients with suspected CAD and its association with types of CAD. We enrolled 236 patients who underwent coronary angiography (CAG). We assessed past medical history of each patient, making note of esophageal or stomach diseases such as GERD including reflux esophagitis and non-erosive reflux disease. The patients were divided into the following three subgroups based on the CAG results. Group I, patients with o-CAD (> 50% stenosis with ischemic findings, n = 141); Group II, patients with vasospastic angina (VSA, with positive spasm provocation test without organic coronary stenosis, n = 52); and Group III, patients without organic coronary stenosis or VSA (n = 43). Group I included more men than women (p < 0.001) and the frequencies of smoking, lipid disorders, and diabetes mellitus in this group were higher than those in the other groups (p < 0.01). The frequency of medical history of GERD was significantly higher in Group II (21%) than in Group I (3%) or Group III (7%, p < 0.0001). Logistic regression analysis showed that a medical history of GERD (OR 7.8; p < 0.01) was one of the factors associated with the presence of VSA. Our findings showed that a medical history of GERD was frequently observed in approximately one-fifth of patients with VSA, indicating that VSA may be present in patients with chest pain and a medical history of GERD.
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13
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Clinical measurement of gastrointestinal motility and function: who, when and which test? Nat Rev Gastroenterol Hepatol 2018; 15:568-579. [PMID: 29872118 DOI: 10.1038/s41575-018-0030-9] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Symptoms related to abnormal gastrointestinal motility and function are common. Oropharyngeal and oesophageal dysphagia, heartburn, bloating, abdominal pain and alterations in bowel habits are among the most frequent reasons for seeking medical attention from internists or general practitioners and are also common reasons for referral to gastroenterologists and colorectal surgeons. However, the nonspecific nature of gastrointestinal symptoms, the absence of a definitive diagnosis on routine investigations (such as endoscopy, radiology or blood tests) and the lack of specific treatments make disease management challenging. Advances in technology have driven progress in the understanding of many of these conditions. This Review serves as an introduction to a series of Consensus Statements on the clinical measurements of gastrointestinal motility, function and sensitivity. A structured, evidence-based approach to the initial assessment and empirical treatment of patients presenting with gastrointestinal symptoms is discussed, followed by an outline of the contribution of modern physiological measurement on the management of patients in whom the cause of symptoms has not been identified with other tests. Discussions include the indications for and utility of high-resolution manometry, ambulatory pH-impedance monitoring, gastric emptying studies, breath tests and investigations of anorectal structure and function in day-to-day practice and clinical management.
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Zhao J, McMahon B, Fox M, Gregersen H. The esophagiome: integrated anatomical, mechanical, and physiological analysis of the esophago-gastric segment. Ann N Y Acad Sci 2018; 1434:5-20. [DOI: 10.1111/nyas.13869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 04/27/2018] [Accepted: 05/04/2018] [Indexed: 12/24/2022]
Affiliation(s)
- Jingbo Zhao
- GIOME Academy, Department of Clinical Medicine; Aarhus University; Aarhus Denmark
| | - Barry McMahon
- Trinity Academic Gastroenterology Group; Tallaght Hospital and Trinity College; Dublin Ireland
| | - Mark Fox
- Abdominal Center: Gastroenterology; St. Claraspital Basel Switzerland
- Neurogastroenterology and Motility Research Group; University Hospital Zürich; Zürich Switzerland
| | - Hans Gregersen
- GIOME, Department of Surgery; Prince of Wales Hospital and Chinese University of Hong Kong; Shatin Hong Kong SAR
- California Medical Innovations Institute; San Diego California
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Ebrahimi-Mameghani M, Sabour S, Khoshbaten M, Arefhosseini SR, Saghafi-Asl M. Total diet, individual meals, and their association with gastroesophageal reflux disease. Health Promot Perspect 2017; 7:155-162. [PMID: 28695104 PMCID: PMC5497367 DOI: 10.15171/hpp.2017.28] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 02/26/2017] [Indexed: 01/03/2023] Open
Abstract
Background: To identify the association of total diet and individual meals with gastroesophageal reflux disease (GERD). Methods: This age- and sex-matched case-control study was carried out among 217 subjects (106 cases and 111 controls). Data were collected using a demographic questionnaire and a GERD checklist and a 3-day food record. Results: Cases consumed more fat (median: 26.3 [3.2-71.5] g vs. 21.8 [4.3-58.1] g; P=0.04)and more energy percent form carbohydrates (median: 72.5 [0-100] vs. 69.0 [0-100]; P=0.02)at lunch, and less energy (median: 129.5 kcal [0-617.6] vs. 170.5 kcal [0-615.7]; P=0.01) and protein (2.4 [0-19.4] g vs. 3.1 [0-21.8] g; P=0.01) at evening snack, compared to controls.The volume of food was significantly different between the two group only at lunch (median:516 [161-1292] g vs. 468 [198-1060] g; P=0.02). The percentage of energy from total dietary protein showed a significant association with GERD after adjusting for confounders (odds ratio[OR]=0.89; 95% CI: 0.81-0.98). Regarding the individual meals, amount of fat consumed at lunch (OR=1.02; 95% CI: 1.00-1.05), and amount of protein intake at evening snack (OR=0.92;95% CI: 0.85-1.00) were significantly associated with GERD. Meanwhile, caloric density and meal frequency did not differ significantly between the two groups. Conclusion: Amount of fat consumed at lunch is positively associated with GERD, whereas the percentage of energy from total protein and amount of protein intake at evening snack are more likely to be inversely associated with GERD.
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Affiliation(s)
- Mehranghiz Ebrahimi-Mameghani
- Nutrition Research Center, Department of Nutrition in Community, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Siamak Sabour
- Safety Promotion and Injury Prevention Research Center, Department of Clinical Epidemiology, School of Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Manouchehr Khoshbaten
- Professor in Gastroenterology and Hepatology, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Rafi Arefhosseini
- Nutrition Research Center, Department of Biochemistry & Diet Therapy, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Saghafi-Asl
- Nutrition Research Center, Department of Biochemistry & Diet Therapy, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Fox M, Omari T, Rommel N. Supraesophageal reflux disease: solving a riddle wrapped in a mystery inside an enigma. Gastroenterology 2015; 149:1318-20. [PMID: 26416325 DOI: 10.1053/j.gastro.2015.09.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Mark Fox
- Department of Gastroenterology, Abdominal Center, St. Claraspital, Basel and Zürich Neurogastroenterology and Motility Research Group, Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.
| | - Taher Omari
- Human Physiology, Medical Science and Technology, School of Medicine, Flinders University, Adelaide, South Australia
| | - Nathalie Rommel
- KU Leuven, Neurosciences, ExpORL, and KU Leuven, Translational Research Center for Gastrointestinal Diseases (TARGID), University Hospital Leuven, Leuven; Department of Gastroenterology (Neurogastroenterology and Motility), University Hospital Leuven, Leuven, Belgium
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Robinson K. Helicobacter pylori-Mediated Protection against Extra-Gastric Immune and Inflammatory Disorders: The Evidence and Controversies. Diseases 2015; 3:34-55. [PMID: 28943607 PMCID: PMC5548235 DOI: 10.3390/diseases3020034] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 03/03/2015] [Accepted: 03/05/2015] [Indexed: 12/11/2022] Open
Abstract
A large number of studies link H. pylori infection with a reduced risk of developing extra-gastric conditions such as allergy, asthma, inflammatory bowel disease, coeliac disease and multiple sclerosis. The strength of the evidence for these protective associations is quite variable, and published studies often do not agree. This review article discusses some of the reasons for these discrepancies, and the difficulties faced when designing studies. Examples of some protective disease associations are described in detail, where the evidence is most abundant and thought to be more reliable. The most convincing of these are supported by published mechanistic data, for example with animal models, or incidence of disease exacerbation in humans following H. pylori eradication. Although controversial, this field is very important as the prevalence of H. pylori is decreasing throughout the world whilst many chronic diseases are becoming more common. These trends are likely to continue in the future, therefore it is important that we fully understand if and how H. pylori confers protection.
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Affiliation(s)
- Karen Robinson
- Nottingham Digestive Diseases Biomedical Research Unit, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK.
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Curcic J, Schwizer A, Kaufman E, Forras-Kaufman Z, Banerjee S, Roy S, Pal A, Hebbard GS, Boesiger P, Fried M, Steingoetter A, Schwizer W, Fox M. Effects of baclofen on the functional anatomy of the oesophago-gastric junction and proximal stomach in healthy volunteers and patients with GERD assessed by magnetic resonance imaging and high-resolution manometry: a randomised controlled double-blind study. Aliment Pharmacol Ther 2014; 40:1230-40. [PMID: 25230154 DOI: 10.1111/apt.12956] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 05/23/2014] [Accepted: 08/25/2014] [Indexed: 12/14/2022]
Abstract
BACKGROUND The mechanism of reflux protection may involve a 'flap valve' at the oesophago-gastric junction (OGJ). AIM To assess the effects of baclofen, a gamma-aminobutyric acid receptor type-B (GABA-B) agonist known to suppress reflux events, on the 'functional anatomy' of the OGJ and proximal stomach after a large test meal. METHODS Twelve healthy volunteers (HVs) and 12 patients with gastro-oesophageal reflux disease (GERD); with erosive oesophagitis or pathological oesophageal acid exposure completed a randomised, double-blind, cross-over study. On 2 test days participants received 40-mg baclofen or placebo before ingestion of a large test meal. OGJ structure and function were assessed by high-resolution manometry (HRM) and magnetic resonance imaging (MRI) using validated methods. Measurements of the oesophago-gastric angle were derived from three-dimensional models reconstructed from anatomic MRI images. Cine-MRI and HRM identified postprandial reflux events. Mixed model analysis and Wilcoxon rank signed tests assessed differences between participant groups and treatment conditions. RESULTS In both HVs and GERD patients, baclofen reduced the frequency of postprandial reflux events. The oesophago-gastric insertion angle in GERD patients was reduced (-4.1 ± 1.8, P = 0.025), but was unchanged in healthy controls. In both study groups, baclofen augmented lower oesophageal sphincter (LES) pressure (HVs: +7.3 ± 1.8 mmHg, P < 0.0001, GERD: +4.50 ± 1.49 mmHg, P < 0.003) and increased LES length (HVs: +0.48 ± 0.11 cm, P < 0.0003, GERD: +0.35 ± 0.06 cm, P < 0.0001). CONCLUSIONS Baclofen inhibits transient LES relaxations and augments LES pressure and length. Additionally, baclofen has effects on the 'functional anatomy' of the OGJ and proximal stomach in GERD patients, which may suppress reflux by means of a 'flap valve' mechanism.
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Affiliation(s)
- J Curcic
- Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland; Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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Schwizer W, Menne D, Schütze K, Vieth M, Goergens R, Malfertheiner P, Leodolter A, Fried M, Fox MR. The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study. United European Gastroenterol J 2014; 1:226-35. [PMID: 24917966 DOI: 10.1177/2050640613484020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 03/01/2013] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. DESIGN A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. RESULTS In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). CONCLUSION Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.
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Affiliation(s)
- Werner Schwizer
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland
| | | | | | | | | | | | | | - Michael Fried
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland
| | - Mark R Fox
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland ; NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, Nottingham, UK
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Mouly S, Charlemagne A, Lejeunne P, Fagnani F. Therapeutic management of uncomplicated gastroesophageal reflux disease in france in 2005: Potential cost savings of omeprazole substitution. Curr Ther Res Clin Exp 2014; 70:282-98. [PMID: 24683238 DOI: 10.1016/j.curtheres.2009.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2009] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) cost the French health care system >€1 billion in 2005, and ~50% of PPI prescriptions were for the treatment of gastroesophageal reflux disease (GERD). OBJECTIVES This study aimed to describe the current use of PPIs for GERD, to estimate the total annual costs of treatment, and to evaluate the economic impact of the various possible substitutions among PPIs available for this indication in France. METHODS Data from a sample of patients aged ≥20 years who visited their general practitioner (GP) at least once in 2005 for uncomplicated, symptomatic GERD were retrieved from the Thales database (a group of 1200 representative GPs connected to a computerized network). Costs of the prescriptions presented for reimbursement and costs of those reimbursed by the French health care insurance system were analyzed. We then evaluated the economic consequences of replacing full-dose generic omeprazole (after substitution from brand-name omeprazole by the pharmacists) with other compounds that are indicated for mild symptoms at half dose (ie, lansoprazole 15 mg, pantoprazole 20 mg, rabeprazole 10 mg, and esomeprazole 20 mg). The results were adjusted to account for the proportions of patients who had full health care coverage and the treatment duration as reported in the database. RESULTS are presented from the perspective of the French health care insurance system. RESULTS In 2005, a total of 122,571 patients (mean age, 55.7 years; 45.5% men; 13.8% with a history of at least 1 gastrointestinal disorder) met the inclusion criteria. Extrapolated to the French population, this sample corresponded to ≈5.7 million people (ie, 13% of the adult population who visited a GP during the year). PPIs were prescribed as first-line treatment for GERD in 84.1% of the consultations (14.3% in association with other antiulcer drugs). Omeprazole, as a proprietary or generic drug, was prescribed most often (78.9%) and at full dose (20 mg), while other compounds (lansoprazole, pantoprazole, rabeprazole, and esomeprazole) were prescribed at half dose in 64.3% of cases. The extrapolated annual cost of PPIs reimbursed for this indication was €465.02 million at a mean reimbursement level of 72.7%. Brand-name omeprazole still accounted for ≈11% of the total cost reimbursed. Complete replacement of brand-name omeprazole with its generic counterpart would have reduced costs by €18.35 million (a decrease of 4.3% in the total reimbursed expenditure). The switch from generic full-dose omeprazole to a half dose of other PPIs would have allowed further savings ranging from €2.59 million (with lansoprazole) to €13.19 million (with pantoprazole). CONCLUSION In accordance with recent recommendations for the treatment of uncomplicated GERD and based on the 2006 PPI pricing, switching from branded full-dose omeprazole to generic omeprazole or to the use of half doses of other PPIs may allow cost savings in France.
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Affiliation(s)
- Stéphane Mouly
- Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot - Paris VII, Unit of Therapeutic Research, Internal Medicine Department, Lariboisière Hospital, Paris, France
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Zamora Z, Molina V, Mas R, Ravelo Y, Perez Y, Oyarzabal A. Protective effects of D-002 on experimentally induced gastroesophageal reflux in rats. World J Gastroenterol 2014; 20:2085-2090. [PMID: 24587681 PMCID: PMC3934479 DOI: 10.3748/wjg.v20.i8.2085] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 12/13/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of beeswax alcohols (D-002) on the esophageal damage induced by gastroesophageal reflux (GER) in rats.
METHODS: Sixty male rats were randomized into six groups (10 rats/group): a negative control and five groups with experimentally induced GER: a positive vehicle control, three treated with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10 mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER was produced by simultaneous ligation of the pyloric end and the forestomach. Esophageal lesions index (ELI), gastric secretion volume and acidity, and esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were measured. Statistical significance was considered at P < 0.05.
RESULTS: As compared to the negative control, the positive control group exhibited increased ELI (5.2 ± 0.33 vs 0 ± 0, P = 0.0003), gastric secretion volume (2.69 ± 0.09 vs 0.1 ± 0.0, P = 0.0003) and acidity (238 ± 19.37 vs 120.0 ± 5.77, P = 0.001), and esophageal concentrations of MDA (2.56 ± 0.1 vs 1.76 ± 0.28, P = 0.001) and SH groups (1.02 ± 0.05 vs 0.56 ± 0.08, P = 0.0003). D-002 (25, 100 and 200 mg/kg) reduced ELI (3.36 ± 0.31, 2.90 ± 0.46 and 2.8 ± 0.23, respectively) vs the positive control (5.2 ± 0.33) (P = 0.004; P = 0.002; P = 0.001, respectively). There were no significant changes in acidity with D-002 treatment, and only the highest dose reduced the volume of the gastric secretion (1.92 ± 0.25) vs the positive control (2.69 ± 0.09, P = 0.013). D-002 (25, 100 and 200 mg/kg) lowered the esophageal MDA (2.05 ± 0.16, 1.98 ± 0.22 and 1.93 ± 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH group concentration (0.87 ± 0.06, 0.79 ± 0.08 and 0.77 ± 0.06, respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 ± 0.10 and 1.02 ± 0.05, respectively). Omeprazole decreased ELI (2.54 ± 0.47), gastric secretion volume (1.97 ± 0.14) and acidity (158.5 ± 22.79), esophageal MDA (1.87 ± 0.13) and SH group (0.72 ± 0.05) concentrations vs the positive control (P = 0.002; P = 0.001; P = 0.02; P = 0.003; P = 0.002, respectively).
CONCLUSION: Acute oral administration of D-002 decreased macroscopic esophageal lesions and oxidative stress in rats with experimentally induced GER, without modifying gastric secretion acidity.
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Sweis R, Anggiansah A, Wong T, Brady G, Fox M. Assessment of esophageal dysfunction and symptoms during and after a standardized test meal: development and clinical validation of a new methodology utilizing high-resolution manometry. Neurogastroenterol Motil 2014; 26:215-28. [PMID: 24238326 DOI: 10.1111/nmo.12252] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2013] [Accepted: 09/25/2013] [Indexed: 12/21/2022]
Abstract
BACKGROUND In the absence of major dysmotility, esophageal manometry with water swallows rarely explains the causes of esophageal symptoms and disease. This methodology development study assessed esophageal function and symptoms during a test meal in patients with reflux symptoms and asymptomatic controls. The impact of this approach on manometric diagnosis and clinical outcome was reviewed. METHODS 18 patients with reflux symptoms and 10 healthy volunteers underwent high resolution manometry (HRM) with 5 mL water swallows, 200 mL water drink, and standardized solid test meal followed by 10 min postprandial observation. The number of symptoms associated with esophageal dysfunction (SAD) divided by total symptoms (dysfunction symptom index [D-SI]) was calculated. Ambulatory reflux pH-monitoring was performed. Final diagnosis and clinical outcome were documented at 2 years. KEY RESULTS Meal intake took longer in patients than controls (552 vs 339 s) and this was associated with a higher number of ineffective swallows in this group (51% vs 28%; p < 0.001). No swallowing problems occurred with water swallows but 12/18 (66%) patients had SAD during either the meal or postprandial observations with D-SI >50% in 9/12 (75%). Compared with water swallows, manometric classification was altered in 12/18 (67%) and clinical diagnosis was altered in 7/18 (39%) patients due to test meal observations. CONCLUSIONS & INFERENCES A novel methodology for the detection of symptomatic dysmotility during a test meal and postprandial observation is presented. This technique increased the diagnostic yield of esophageal dysfunction in patients presenting with reflux symptoms. Long-term follow-up indicated that these observations can guide effective clinical management.
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Affiliation(s)
- R Sweis
- Esophageal Laboratory, Guys and St Thomas' NHS Foundation Trust, London, UK; Department of Gastroenterology, Guys and St Thomas' NHS Foundation Trust, London, UK
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Tucker E, Sweis R, Anggiansah A, Wong T, Telakis E, Knowles K, Wright J, Fox M. Measurement of esophago-gastric junction cross-sectional area and distensibility by an endolumenal functional lumen imaging probe for the diagnosis of gastro-esophageal reflux disease. Neurogastroenterol Motil 2013; 25:904-10. [PMID: 23981175 DOI: 10.1111/nmo.12218] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 07/29/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Measurement of esophago-gastric junction (EGJ) cross-sectional area (CSA) and distensibility by an Endolumenal Functional Lumen Imaging Probe (EndoFLIP®) may distinguish between gastro-esophageal reflux disease (GERD) patients and healthy volunteers (HV). We aimed to assess the agreement of EndoFLIP® measurements with clinical and physiologic diagnosis of GERD. METHODS Twenty-one HV and 18 patients with typical GERD symptoms were studied. After gastroscopy, EGJ CSA, and distensibility were measured by EndoFLIP®. Forty-eight hour esophageal pH monitoring was then performed by a wireless system. The ability of EndoFLIP® to discriminate GERD patient and HVs was assessed. Planned secondary analysis then assessed whether EGJ CSA and distensibility were increased in individuals with pathologic acid exposure. KEY RESULTS Healthy volunteers were younger and had lower body mass index (BMI; both p < 0.001). Pathologic acid exposure was present in 3/21 (14%) HVs and 9/18 (50%) patients (p = 0.126). At 30 mL EndoFLIP® bag volume, EGJ CSA was higher (p = 0.058) and EGJ distensibility was lower (p = 0.020) in HVs than patients. Secondary analysis showed that EGJ measurements were similar in participants with and without pathologic acid exposure (CSA 98 mm² vs 107 mm²; p = 0.789, distensibility; p = 0.704). An inverse association between BMI and CSA (R² = 0.2758, p = 0.001) and distensibility (R² = 0.2005, p = 0.005) was present. CONCLUSIONS & INFERENCES Endolumenal Functional Lumen Imaging Probe is not useful for GERD diagnosis because EGJ CSA and distensibility do not distinguish between HVs and GERD patients defined by clinical presentation or pH measurement. This unexpected result may be due to an important, confounding interaction of obesity.
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Affiliation(s)
- E Tucker
- NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases at Nottingham University Hospital NHS Trust, University of Nottingham, Nottingham, UK
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Evaluation of short-term and long-term results after laparoscopic antireflux surgery: esophageal manometry and 24-h pH monitoring versus quality of life index. Langenbecks Arch Surg 2013; 398:1107-14. [DOI: 10.1007/s00423-013-1118-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2013] [Accepted: 09/06/2013] [Indexed: 12/15/2022]
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Tielemans MM, Jaspers Focks J, van Rossum LGM, Eikendal T, Jansen JBMJ, Laheij RJF, van Oijen MGH. Gastrointestinal symptoms are still prevalent and negatively impact health-related quality of life: a large cross-sectional population based study in The Netherlands. PLoS One 2013; 8:e69876. [PMID: 23922836 PMCID: PMC3726702 DOI: 10.1371/journal.pone.0069876] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Accepted: 06/14/2013] [Indexed: 12/15/2022] Open
Abstract
Background Over the last decades important risk factors for gastrointestinal symptoms have shifted, which may have changed its population prevalence. The aim of this study was to assess the current prevalence of gastrointestinal symptoms, appraise associated factors and assess health-related quality of life in the general population. Methods A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Demographic characteristics, gastrointestinal symptoms, health-related quality of life, medication use and co-morbidity were reported. We used multivariable logistic regression analysis to determine factors associated with gastrointestinal symptoms. Results A total of 18,317 questionnaires were returned, and 16,758 were eligible for analysis. Prevalence of gastrointestinal symptoms was 26%. Most frequent symptoms were bloating (63%), borborygmi (60%) and flatulence (71%). Female gender (adjusted OR (aOR) 1.59, 95% CI 1.43–1.77), asthma/COPD (aOR 1.47, 95% CI 1.21–1.79), use of paracetamol (aOR 1.33, 95% CI 1.20–1.47), antidepressants (aOR 1.56, 95% CI 1.22–2.00) and acid-suppressive medication were independently associated with presence of gastrointestinal symptoms. Age over 65 years (aOR 0.75, 95% CI 0.65–0.87), and use of statins (aOR 0.75, 95% CI 0.61–0.93) were associated with a lower prevalence of gastrointestinal symptoms. Respondents with gastrointestinal symptoms had a lower mean health-related quality of life of 0.81 (SD = 0.21) compared to 0.92 (SD = 0.14) for persons without gastrointestinal symptoms (P<0.01). Conclusions Prevalence of gastrointestinal symptoms in the Dutch community is high and associated with decreased health-related quality of life.
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Affiliation(s)
- Merel M Tielemans
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
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Fox M. Commentary: revisiting the past--does it hold the key to the future treatment of refractory GERD? Author's reply. Aliment Pharmacol Ther 2013; 38:203-4. [PMID: 23772901 DOI: 10.1111/apt.12359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Accepted: 05/10/2013] [Indexed: 12/08/2022]
Affiliation(s)
- M Fox
- Division of Gastroenterology & Hepatology, University Hospital Zurich, Zurich, Switzerland.
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Vardar R, Sweis R, Anggiansah A, Wong T, Fox MR. Upper esophageal sphincter and esophageal motility in patients with chronic cough and reflux: assessment by high-resolution manometry. Dis Esophagus 2013; 26:219-25. [PMID: 22591118 DOI: 10.1111/j.1442-2050.2012.01354.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The pathophysiology of chronic cough and its association with dsymotility and laryngopharyngeal reflux remains unclear. This study applied high-resolution manometry (HRM) to obtain a detailed evaluation of pharyngeal and esophageal motility in chronic cough patients with and without a positive reflux-cough symptom association probability (SAP). Retrospective analysis of 66 consecutive patients referred for investigation of chronic cough was performed. Thirty-four (52%) were eligible for inclusion (age 55 [19-77], 62% female). HRM (ManoScan 360, Given/Sierra Scientific Instruments, Mountain View, CA) with 10 water swallows was performed followed by a 24-hour ambulatory pH monitoring. Of this group, 21 (62%) patients had negative reflux-cough SAP (group A) and 13 (38%) had positive SAP (group B). Results from 23 healthy controls were available for comparison (group C). Detailed analysis revealed considerable heterogeneity. A small number of patients had pathological upper esophageal sphincter (UES) function (n=9) or esophageal dysmotility (n=1). The overall baseline UES pressure was similar, but average UES residual pressure was higher in groups A and B than in control group C (-0.2 and -0.8mmHg vs. -5.4mmHg; P<0.018 and P<0.005). The percentage of primary peristaltic contractions was lower in group B than in groups A and C (56% vs. 79% and 87%; P=0.03 and P<0.002). Additionally, intrabolus pressure at the lower esophageal sphincter was higher in group B than in group C (15.5 vs. 8.9; P=0.024). HRM revealed changes to UES and esophageal motility in patients with chronic cough that are associated with impaired bolus clearance. These changes were most marked in group B patients with a positive reflux-cough symptom association.
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Affiliation(s)
- R Vardar
- Ege University School of Medicine, Division of Gastroenterology, Izmir, Turkey
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Anggiansah R, Sweis R, Anggiansah A, Wong T, Cooper D, Fox M. The effects of obesity on oesophageal function, acid exposure and the symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2013; 37:555-63. [PMID: 23305085 DOI: 10.1111/apt.12208] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Revised: 12/06/2012] [Accepted: 12/21/2012] [Indexed: 01/09/2023]
Abstract
BACKGROUND Obese patients have an increased risk of gastro-oesophageal reflux disease; however, the mechanism underlying this association is uncertain. AIM To test the hypothesis that mechanical effects of obesity on oesophageal function increase acid exposure and symptoms. METHODS Height, weight and waist circumference (WC) were measured in patients with typical reflux symptoms referred for manometry and 24 h ambulatory pH studies. Symptom severity was assessed by questionnaire. The association between obesity [WC, body mass index (BMI)], oesophageal function, acid exposure and reflux symptoms was assessed. RESULTS Physiological measurements were obtained from 582 patients (median age 48, 56% female) of whom 406 (70%) completed symptom questionnaires. The prevalence of general obesity was greater in women (BMI ≥ 30 kg/m(2) ; F 23%:M 16%; P = 0.056), however more men had abdominal obesity (WC ≥ 99 cm (M 41%:F 28%; P = 0.001)). Oesophageal acid exposure increased with obesity (WC: R = 0.284, P < 0.001) and was associated also with lower oesophageal sphincter (LOS) pressure, reduced abdominal LOS length and peristaltic dysfunction (all P < 0.001). Univariable regression showed a negative association of WC with both LOS pressure and abdominal LOS length (R = -0.221 and -0.209 respectively; both P < 0.001). However, multivariable analysis demonstrated that the effects of increasing WC on oesophageal function do not explain increased acid reflux in obese patients. Instead, independent effects of obesity and oesophageal dysfunction on acid exposure were present. Reflux symptoms increased with acid exposure (R = 0.300; P < 0.001) and this association explained increased symptom severity in obese patients. CONCLUSIONS Abdominal obesity (waist circumference) is associated with oesophageal dysfunction, increased acid exposure and reflux symptoms; however, this analysis does not support the mechanical hypothesis that the effects of obesity on oesophageal function are the cause of increased acid exposure in obese patients.
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Affiliation(s)
- R Anggiansah
- Oesophageal Laboratory, Guys and St Thomas' NHS Foundation Trust, London, UK
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Tai CM, Huang CK, Lee YC, Chang CY, Lee CT, Lin JT. Increase in gastroesophageal reflux disease symptoms and erosive esophagitis 1 year after laparoscopic sleeve gastrectomy among obese adults. Surg Endosc 2012; 27:1260-6. [PMID: 23232995 DOI: 10.1007/s00464-012-2593-9] [Citation(s) in RCA: 130] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2012] [Accepted: 09/17/2012] [Indexed: 12/21/2022]
Abstract
BACKGROUND Although laparoscopic sleeve gastrectomy (LSG) is an effective treatment for morbid obesity, the effects of LSG on gastroesophageal reflux disease (GERD) are controversial. This study evaluated the changes of GERD symptoms and erosive esophagitis (EE) in severely obese patients who underwent LSG. METHODS Forty-seven severely obese women and 19 severely obese men (mean age of 37.2 ± 12.7 years) who underwent LSG between August 2007 and November 2009 were enrolled. All patients completed the Reflux Disease Questionnaire and underwent esophagogastroduodenoscopy preoperatively and at least 1 year after LSG. RESULTS The median follow-up period was 12 months (range, 12-21). After surgery, significant decreases were reported in mean body mass index (36.3 ± 4.1 vs. 25.8 ± 2.9 kg/m(2)), mean waist circumference (109.5 ± 12.8 vs. 85.7 ± 9.5 cm), and prevalence of metabolic syndrome (54.5 vs. 7.6 %; P < 0.001 for both). Conversely, a significant increase was observed in the prevalence of GERD symptoms (12.1 vs. 47 %) and EE (16.7 vs. 66.7 %) after LSG (P < 0.001 for both). The prevalence of hiatal hernias also increased significantly (6.1 vs. 27.3 %; P < 0.001) after LSG, and it was significantly higher in patients with than those without EE after LSG (9.1 vs. 36.4 %, respectively; P = 0.02). CONCLUSIONS Although LSG can achieve significant weight loss and improvement of comorbidities in severely obese patients, the prevalence and severity of GERD symptoms and EE increase after the operation. The occurrence of EE after LSG is related to the presence of a hiatal hernia after the operation.
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Affiliation(s)
- Chi-Ming Tai
- Bariatric and Metabolic International Surgery Center, E-Da Hospital, Kaohsiung, Taiwan, ROC.
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Abstract
BACKGROUND Weak and absent esophageal peristalsis are frequently encountered esophageal motility disorders, which may be associated with dysphagia and which may contribute to gastroesophageal reflux disease. Recently, rapid developments in the diagnostic armamentarium have taken place, in particular, in high-resolution manometry with or without concurrent intraluminal impedance monitoring. PURPOSE This article aims to review the current insights in the terminology, pathology, pathophysiology, clinical manifestations, diagnostic work-up,and management of weak and absent peristalsis.
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Affiliation(s)
- André Smout
- Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, The Netherlands.
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Overland S, Knapstad M, Wilhelmsen I, Mykletun A, Glozier N. Do gastrointestinal complaints increase the risk for subsequent medically certified long-term sickness absence? The HUSK study. BMC Gastroenterol 2011; 11:88. [PMID: 21801382 PMCID: PMC3166917 DOI: 10.1186/1471-230x-11-88] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2010] [Accepted: 07/29/2011] [Indexed: 01/13/2023] Open
Abstract
Background Gastrointestinal complaints are very common in the general population and very often co-occur with common mental disorders. We aimed to study the prospective impact of gastrointestinal complaints on long term sickness absence, and address the contribution from co-occurring common mental disorders and other somatic symptoms. Method Health data on 13 880 40-45 year olds from the Hordaland Health Study (1997-99) were linked to national registries on sickness absence. As part of a wider health screening, gastrointestinal complaints were ascertained. Participant's anxiety and depression, and the presence of other somatic symptoms were evaluated. In Cox regression models, we predicted sickness absences over an average 5.4 years follow-up, with adjustment for confounders, anxiety and depression and other somatic symptoms. Results After adjusting for gender, level of education and smoking, those reporting GI complaints had higher risk for later sickness absence (HR = 1.42, 95% CI 1.34-1.51). GI complaints were associated with both anxiety (OR = 3.66, 95% CI 3.31-4.04) and depression (OR = 3.28, 95% CI 2.89-3.72), and a high level of other somatic symptoms (OR = 8.50, 95% CI 7.69-9.40). The association of GI complaints was still independently associated with future sickness absence (HR = 1.17, 95% CI 1.10-1.16) adjusting for mental illness and other somatic symptoms. Discussion Sickness absence is a complex behavioural outcome, but our results suggest GI complaints contribute by increasing the risk of long term sickness absence independently of comorbid mental illness and presence of other somatic symptoms. Occupational consequences of illness are important, and should also be addressed clinically with patients presenting with GI complaints.
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Affiliation(s)
- Simon Overland
- Faculty of Psychology, University of Bergen, Bergen, Norway.
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Curcic J, Fox M, Kaufman E, Forras-Kaufman Z, Hebbard GS, Roy S, Pal A, Schwizer W, Fried M, Treier R, Boesiger P. Gastroesophageal Junction: Structure and Function as Assessed by Using MR Imaging. Radiology 2010; 257:115-24. [DOI: 10.1148/radiol.10092340] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Breckan RK, Paulssen EJ, Asfeldt AM, Mortensen L, Straume B, Florholmen J. The impact of body mass index and Helicobacter pylori infection on gastro-oesophageal reflux symptoms: a population-based study in Northern Norway. Scand J Gastroenterol 2010; 44:1060-6. [PMID: 19593688 DOI: 10.1080/00365520903093728] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Increased body mass index (BMI) has been proposed as a risk factor for gastro-oesophageal reflux symptoms. The aim of this study was to evaluate the effect of BMI and Helicobacter pylori on reflux symptoms in an adult population. MATERIAL AND METHODS For this cross-sectional, population-based study from Bodø and Sørreisa communities in Northern Norway, a total of 3927 adults were invited to complete a questionnaire on gastrointestinal symptoms and to provide stool samples for the assessment of H. pylori. Reflux symptoms were considered present when a reflux syndrome score was > or =2 according to the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS The response rate was 44.2%, and 44.7% of the respondents were male. Age-adjusted prevalences were: for overweight, 35.6% (95% CI (32.4%; 38.8%)); for obesity, 10.0% (8.4%; 11.6%); for H. pylori: 21.2% (19.1%; 23.9%) and for reflux symptoms: 21.7% (19.5%; 23.9%). In the logistic regression analyses, H. pylori and smoking were not risk factors for reflux symptoms, whereas male gender (OR 4.78 (95%CI (1.88; 12.1)), age (1.01 (1.00; 1.03)) and overweight (1.51 (1.14; 2.00)) were. When stratified by gender, overweight and age were independent risk factors for reflux symptoms in females only, whereas H. pylori infection was protective against such symptoms in men. Models including these parameters could only explain 3% of the variations in reflux symptoms. CONCLUSIONS BMI is an independent risk factor for gastro-oesophageal reflux symptoms among healthy female adults, but contributes only to a minor part of the variation in these symptoms. H. pylori is protective against reflux symptoms in men.
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Affiliation(s)
- Ragnar K Breckan
- Department of Internal Medicine, Nordland Hospital, Bodø, Norway.
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Ponce J, Mearin F, Ponce M, Balboa A, Zapardiel J. [Symptom profile in gastroesophageal reflux disease in untreated patients and those with persistent symptoms despite treatment]. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33:271-9. [PMID: 20133018 DOI: 10.1016/j.gastrohep.2009.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2009] [Revised: 11/04/2009] [Accepted: 11/10/2009] [Indexed: 01/10/2023]
Abstract
AIM 1. To analyze the symptom profile of gastroesophageal reflux disease (GERD) with typical clinical manifestations (heartburn and/or regurgitation); 2. to compare untreated patients with those with persistent symptoms despite treatment; 3. to evaluate severity according to physicians' and patients' opinions; and 4. to determine the diagnostic and therapeutic approaches used. METHODS We performed a prospective, observational, cross-sectional study under conditions of standard clinical practice. RESULTS A total of 2356 patients were included. Dyspeptic symptoms were highly frequent (close to 90% in both groups) and supraesophageal symptoms were also common (50-60%). Patients with persistent symptoms despite treatment were older, and had more supraesophageal symptoms; in addition, the typical supraesophageal and dyspeptic symptoms of GERD were more severe in these patients. Severity evaluations by patients and doctors were concordant but patients considered severity to be greater. Older age was a risk factor for supraesophageal symptoms, female gender for dyspeptic symptoms and body mass index for greater severity of GERD symptoms. Endoscopy was requested in about 60% of the patients. Diet counseling was advised in most patients and postural recommendations were made in more than half. Proton pump inhibitors were prescribed in almost all patients, and were associated with prokinetics and/or antacids in many patients. CONCLUSIONS Dyspeptic symptoms should not be considered as independent of GERD, and typical and atypical symptoms are associated in 50% of patients. Gastroenterologists follow clinical practice guidelines fairly closely but diagnostic procedures seem to be overindicated.
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Affiliation(s)
- Julio Ponce
- Servicio de Medicina Digestiva, Hospital Universitario La Fe, Valencia, España.
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Gastroesophageal reflux disease: medical or surgical treatment? Gastroenterol Res Pract 2009; 2009:371580. [PMID: 20069112 PMCID: PMC2804043 DOI: 10.1155/2009/371580] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2009] [Revised: 10/14/2009] [Accepted: 10/26/2009] [Indexed: 12/14/2022] Open
Abstract
Background. Gastroesophageal reflux disease is a common condition with increasing prevalence worldwide. The disease encompasses a broad spectrum of clinical symptoms and disorders from simple heartburn without esophagitis to erosive esophagitis with severe complications, such as esophageal strictures and intestinal metaplasia. Diagnosis is based mainly on ambulatory esophageal pH testing and endoscopy. There has been a long-standing debate about the best treatment approach for this troublesome disease. Methods and Results. Medical treatment with PPIs has an excellent efficacy in reversing the symptoms of GERD, but they should be taken for life, and long-term side effects do exist. However, patients who desire a permanent cure and have severe complications or cannot tolerate long-term treatment with PPIs are candidates for surgical treatment. Laparoscopic antireflux surgery achieves a significant symptom control, increased patient satisfaction, and complete withdrawal of antireflux medications, in the majority of patients. Conclusion. Surgical treatment should be reserved mainly for young patients seeking permanent results. However, the choice of the treatment schedule should be individualized for every patient. It is up to the patient, the physician and the surgeon to decide the best treatment option for individual cases.
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Abstract
AIM : The aim of this study was to correlate the data obtained with multiple intraluminal esophageal impedance and pH (MII-pH) recordings in infants and children referred for suspected gastroesophageal reflux disease with esophageal histology. MATERIALS AND METHODS : In a prospective study, results of esophageal biopsies and MII-pH recording obtained in 45 children (mean age +/- SD: 69 +/- 55 months) were analyzed. Regarding the MII-pH data, an automatic (Autoscan Bioview Analysis Software, version 5.3.4, Sandhill Scientific Inc, Highlands Ranch, CO) and a manual reading were performed; an automatic pH analysis (meal included) was also performed. RESULTS : Acidic, weakly acidic, and alkaline reflux episodes accounted, respectively, for 48.7%, 49.5%, and 1.8% of the total number of reflux episodes detected by MII-pH. Esophagitis was present in 25 (56%) children. Concordance between classic pH-study analysis (alone) and esophageal histology was found in 19 of 45 (42%) children. According to the MII-pH analysis, the mean and median value of the pH were significantly higher in the group with esophagitis than in the group with normal esophageal histology. A longer clearance time was found in the group with esophagitis than in subjects with normal histology. Gas reflux episodes represented 21% of the total reflux episodes and were comparable in both groups. CONCLUSIONS : Multiple intraluminal esophageal impedance and pH analysis does not provide a distinct parameter to predict esophageal mucosal injury in children. In our population, MII-pH shows comparable acidic, weakly acidic, alkaline, and gas reflux in children with and without esophagitis. Further research is needed to analyze clearance parameters.
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Yamamura H, Ugawa S, Ueda T, Nagao M, Joh T, Shimada S. Epithelial Na+ channel delta subunit is an acid sensor in the human oesophagus. Eur J Pharmacol 2008; 600:32-6. [PMID: 18951889 DOI: 10.1016/j.ejphar.2008.10.022] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2008] [Accepted: 10/09/2008] [Indexed: 01/11/2023]
Abstract
Gastro-oesophageal reflux disease is caused by the reflux of gastric contents into the oesophagus, and thus the oesophageal lumen is damaged by gastric acid. The acid sensor involved in oesophageal epithelial defense is still unclear. Recently, we described that the epithelial Na(+) channel delta subunit (ENaCdelta) is a candidate molecule for a pH sensor in the human brain. Here, using reverse transcription-polymerase chain reaction and in situ hybridization methods, we showed that the proton-sensitive ENaCdelta was strongly expressed in the epithelial layer of the human oesophagus, representative peripheral tissue that can be exposed to an acidic environment. Other ENaC subunits (alpha, beta, and gamma) were also localized there. Based on the expression pattern, human oesophageal ENaC complex was mimicked in the Xenopus oocyte expression system and the response to acidic pH was recorded using a two-electrode voltage-clamp technique. The human oesophageal-mimicking ENaCdeltabetagammaalpha complex generated an amiloride-sensitive inward current at the holding potential of -60 mV. The ENaCdeltabetagammaalpha current was significantly activated by acidic pH (pH 4.0), approximately equal to the luminal value when gastric acid refluxes into the oesophagus. In conclusion, ENaCdelta is a candidate molecule for pH sensing in the gastrointestinal system in humans, providing a novel therapeutic target for gastro-oesophageal reflux disease.
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Affiliation(s)
- Hisao Yamamura
- Department of Molecular Morphology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
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Watson NF, Mystkowski SK. Aerophagia and gastroesophageal reflux disease in patients using continuous positive airway pressure: a preliminary observation. J Clin Sleep Med 2008; 4:434-8. [PMID: 18853700 PMCID: PMC2576329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
STUDY OBJECTIVES Aerophagia is a complication of continuous positive airway pressure (CPAP) therapy for sleep disordered breathing (SDB), whereupon air is forced into the stomach and bowel. Associated discomfort can result in CPAP discontinuation. We hypothesize that aerophagia is associated with gastroesophageal reflux disease (GERD) via mechanisms involving GERD related lower esophageal sphincter (LES) compromise. METHODS Twenty-two subjects with aerophagia and 22 controls, matched for age, gender, and body mass index, who were being treated with CPAP for SDB were compared in regard to clinical aspects of GERD, GERD associated habits, SDB severity as measured by polysomnography, and mean CPAP pressure. RESULTS More subjects with aerophagia had symptoms of GERD (77.3% vs. 36.4%; p < 0.01) and were on GERD related medications (45.5% vs. 18.2%, p < 0.05) than controls. Regarding polysomnography, mean oxygen saturation percentages were lower in the aerophagia group than controls (95.0% vs. 96.5%, p < 0.05). No other differences were observed, including mean CPAP pressures. No one in the aerophagia group (vs. 27.3% of the control group) was a current tobacco user (p < 0.01). There was no difference in caffeine or alcohol use between the 2 groups. CONCLUSIONS These results imply aerophagia is associated with GERD symptoms and GERD related medication use. This finding suggests a relationship between GERD related LES pathophysiology and the development of aerophagia in patients with SDB treated with CPAP.
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Mouly S, Charlemagne A, Le jeunne P, Fagnani F. Étude pharmaco-économique sur la prise en charge du reflux gastro-œsophagien en France en 2005 en médecine générale. Presse Med 2008; 37:1397-406. [DOI: 10.1016/j.lpm.2007.11.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2007] [Revised: 11/28/2007] [Accepted: 11/30/2007] [Indexed: 01/06/2023] Open
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Abstract
PURPOSE To emphasize the relationship between gastroesophageal reflux disease (GERD) and asthma symptoms or exacerbations. DATA SOURCES Selective review of the scientific literature. CONCLUSIONS Although studies in recent years have offered insight into the relationship between GERD and asthma symptoms, many nurse practitioners (NPs) fail to recognize atypical GERD symptoms, which may explain difficult-to-treat asthma and exacerbation. It has become evident that patients suffering from persistent asthma display an increased prevalence of GERD. IMPLICATIONS FOR PRACTICE While there are increasing constraints that limit the provider-patient interaction time, it is imperative that NPs develop keen assessment skills to effectively diagnose and treat asthma symptoms that are a product of GERD. Awareness of the asthma-GERD relationship allows NPs to quickly obtain pertinent information and successfully determine how to efficiently treat symptomatic asthmatic patients.
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Affiliation(s)
- Sandra Huggins
- Southern Adventist University School of Nursing, Ooltewah, Tennessee 37363, USA.
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Cui YY, Zhu L, Wang H, Advenier C, Chen HZ, Devillier P. Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux. Life Sci 2008; 82:949-55. [DOI: 10.1016/j.lfs.2008.02.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2007] [Revised: 01/30/2008] [Accepted: 02/20/2008] [Indexed: 11/25/2022]
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Talley NJ, Locke GR, McNally M, Schleck CD, Zinsmeister AR, Melton LJ. Impact of gastroesophageal reflux on survival in the community. Am J Gastroenterol 2008; 103:12-9. [PMID: 17900322 DOI: 10.1111/j.1572-0241.2007.01546.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Concerns have been raised regarding the risks associated with gastroesophageal reflux (GER). We examined the association of gastroesophageal reflux with survival. METHODS Between 1988 and 1993, valid symptom surveys were mailed to population-based cohorts. Respondents were classified into 4 GER symptom categories: daily, at least weekly (not daily), infrequent (less than weekly), and none. Administrative records were used to identify deaths during the follow-up (through June 2006). Association between survival and GER subgroups was assessed using proportional hazards regression to compute hazard ratios (HRs, 95% confidence intervals), adjusting for age, gender, education level, Charlson Comorbidity Index, alcohol, and tobacco. RESULTS At baseline, 5,288 eligible subjects (mean age 53 yr, 51% female) responded (response rates over 70%); 2% reported daily heartburn, 13% weekly (not daily) heartburn, 40% infrequent heartburn, and 35% no heartburn. At 10 yr, 83% (95% CI 81-84%) of the no heartburn group was alive. An overall association between heartburn category and survival was detected (P < 0.001). Compared to no heartburn, daily heartburn was not associated with an increased risk of death (HR 1.16, 95% CI 0.82-1.65), but better survival was observed for weekly (HR 0.67, 95% CI 0.55-0.83) and infrequent (HR 0.80, 95% CI 0.70-0.92) heartburn. Increasing age, male gender, greater Charlson index, and tobacco use all predicted worse survival. CONCLUSIONS In this population-based study with over 50,000 person-years of follow-up, reflux symptoms were not associated with worse survival. The vast majority of heartburn sufferers can be reassured of the benign nature of their condition.
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Affiliation(s)
- Nicholas J Talley
- Dyspepsia Center, Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
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Lee J, Anggiansah A, Anggiansah R, Young A, Wong T, Fox M. Effects of age on the gastroesophageal junction, esophageal motility, and reflux disease. Clin Gastroenterol Hepatol 2007; 5:1392-8. [PMID: 17936081 DOI: 10.1016/j.cgh.2007.08.011] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The prevalence of complicated gastroesophageal reflux disease (GERD) increases with age; however, the mechanism by which this occurs is uncertain. This study assessed (1) whether physiologic degradation of the gastroesophageal junction and esophageal motility occurs with aging, and (2) whether these effects are associated with increased esophageal acid exposure and reflux symptoms in the elderly. METHODS Retrospective study of 1307 patients referred for investigations of reflux symptoms (median age, 49 years; range, 15-92 years) was conducted. Manometry assessed LES pressure, LES length, and esophageal peristalsis. Ambulatory pH studies assessed esophageal acid exposure (% time pH <4) during a period of 24 hours; reflux symptoms were assessed by validated questionnaire. RESULTS On multivariate regression, esophageal acid exposure was associated independently with decreasing LES pressure (P < .0001) and abdominal LES length (P < .0004). Dysmotility exacerbated reflux in the recumbent position (P < .004). Acid exposure increased with age (P < .0001), a 1.1%/24 hours (95% confidence interval, 0.4%-1.4%) increase in acid exposure every decade (more pronounced in the recumbent position). The age-related increase in acid exposure was associated independently with decreasing abdominal LES length (P < .001) and increasing dysmotility (P < 0.01). Reflux symptoms increased with acid exposure (P < .001); however, at any given level of exposure, symptom severity was less in the elderly (P < .006). CONCLUSIONS Age was associated with an increase in esophageal acid exposure; however, the severity of reflux symptoms reduced with age. These changes were associated with progressive decrease in abdominal LES length and esophageal motility. Increasing GERD severity in the elderly is related to degradation of the gastroesophageal junction and impaired esophageal clearance.
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Affiliation(s)
- Jacqueline Lee
- Department of Gastroenterology, Guy's and St. Thomas' Hospital, London, United Kingdom
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Kacar S, Uysal S, Kuran S, Dagli U, Ozin Y, Karabulut E, Sasmaz N. Transcutaneous cervical esophagus ultrasound in adults: Relation with ambulatory 24-h pH-monitoring and esophageal manometry. World J Gastroenterol 2007; 13:5245-52. [PMID: 17876896 PMCID: PMC4171307 DOI: 10.3748/wjg.v13.i39.5245] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the gastroesophageal refluxate in the cervical esophagus (CE) and measure transcutaneous cervical esophageal ultrasound (TCEUS) findings [anterior wall thickness (WT) of CE, esophageal luminal diameter (ELD), esophageal diameter (ED)]; to compare TCEUS findings in the patient subgroups divided according to 24-h esophageal pH monitoring and manometry; and to investigate possible cut-off values according to the TCEUS findings as a predictor of gastroesophageal reflux (GER).
METHODS: In 45/500 patients, refluxate was visualized in TCEUS. 38/45 patients underwent esophagogastroduodenoscopy (EGD), 24-h pH monitoring and manometry.
RESULTS: The 38 patients were grouped according to 24-h pH monitoring as follows: Group A: GER-positive (n = 20) [Includes Group B: isolated proximal reflux (PR) (n = 6), Group C: isolated distal reflux (DR) (n = 6), and Group D: both PR/DR (n = 8)]; Group E: no reflux (n = 13); and Group F: hypersensitive esophagus (HSE) (n = 5). Groups B + D indicated total PR patients (n = 14), Groups E + F reflux-negatives with HSE (n = 18), and Groups A + F reflux-positives with HSE (n = 25). When the 38 patients were grouped according to manometry findings, 24 had normal esophageal manometry; 7 had hypotensive and 2 had hypertensive lower esophageal sphincter (LES); and 5 had ineffective esophageal motility disorder (IEM). The ELD measurement was greater in group A + F than group E (P = 0.023, 5.0 ± 1.3 vs 3.9 ± 1.4 mm). In 27/38 patients, there was at least one pathologic acid reflux and/or pathologic manometry finding. The cut-off value for ELD of 4.83 mm had 79% sensitivity and 61% specificity in predicting the PR between Groups B + D and E (AUC = 0.775, P = 0.015).
CONCLUSION: Visualizing refluxate in TCEUS was useful as a pre-diagnostic tool for estimating GER or manometric pathology in 71.1% of adults in our study, but it was not diagnostic for CE WT.
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Affiliation(s)
- Sabite Kacar
- Gastroenterology Department, Turkiye Yuksek Ihtisas Hospital, Dikmen Cad 220/A, No 17 Dikmen, Ankara, Turkey
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Daugule I, Rumba I, Alksnis J, Ejderhamn J. Helicobacter pylori infection among children with gastrointestinal symptoms: a high prevalence of infection among patients with reflux oesophagitis. Acta Paediatr 2007; 96:1047-9. [PMID: 17524023 DOI: 10.1111/j.1651-2227.2007.00329.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
AIM To investigate the link between H.pylori infection and dyspepsia in children, and association with reflux oesophagitis. PATIENTS AND METHODS H.pylori status was detected by rapid urease test and/or culture in 130 consecutive symptomatic children coming for upper gastrointestinal endoscopy: 40 - aged 8-12 years (55% boys); 90 - aged 13-18 years (21% boys). Endoscopic findings were analyzed. H.pylori prevalence in the age group 8-12 years was compared to the prevalence among 55 asymptomatic children, aged 7-12 years (13C-urea breath test). STATISTICAL ANALYSIS chi(2) test, Fisher's test, and logistic regression analysis. RESULTS The prevalence of H.pylori infection among patients with gastrointestinal symptoms was 54%. It was significantly higher among patients with reflux oesophagitis compared to patients with hyperaemic gastropathy: OR = 5.5; p = 0.03, 95% CI: 1.15-26.3. In logistic regression analysis, no significant difference between the prevalence of H.pylori infection between asymptomatic and symptomatic children could be demonstrated (OR = 1.8; 95% CI: 0.62-5.14). CONCLUSIONS The prevalence of H.pylori was significantly higher among patients with reflux oesophagitis compared to patients with hyperaemic gastropathy alone. Adjusting for age the prevalence of H.pylori infection was not higher among symptomatic children compared to asymptomatic children of the same age.
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Affiliation(s)
- Ilva Daugule
- Faculty of Medicine, University of Latvia, Riga, Latvia.
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AlHabib KF, Vedal S, Champion P, FitzGerald JM. The utility of ambulatory pH monitoring in patients presenting with chronic cough and asthma. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2007; 21:159-63. [PMID: 17377644 PMCID: PMC2657683 DOI: 10.1155/2007/985491] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To evaluate the prevalence of gastroesophageal reflux disease (GERD) in patients presenting with asthma and chronic cough. PATIENTS AND METHODS The charts of 358 consecutive patients who were referred for ambulatory gastroesophageal pH monitoring to the Lung Centre in Vancouver, British Columbia, were reviewed, and the data of 108 (30%) patients with asthma and 134 (37%) patients with chronic cough were analyzed. The maintenance treatment for GERD was discontinued before patients underwent the pH monitoring study. One hundred eighteen (33%) patients were excluded. RESULTS Reflux episodes identified reflux events as the percentage of time where the pH was less than four. For asthma patients, 70 (64.8%) had distal total reflux, 50 (46.3%) had distal upright reflux, 41 (38.3%) had distal supine reflux and 73 (67.6%) had other distal refluxes. Proximal total reflux in asthmatic patients was present in 56 (52%), proximal upright reflux in 55 (51%) and proximal supine reflux in 56 (52%) patients. For chronic cough patients, 70 (52.6%) had distal total reflux, 59 (44.4%) had distal upright reflux, 45 (34.4%) had distal supine reflux and 75 (56%) patients had other distal refluxes. In chronic cough patients, proximal total reflux was present in 70 (52%), proximal upright reflux in 80 (60%) and proximal supine reflux in 59 (44%). Presenting respiratory and/or reflux symptoms were absent in approximately 25% of patients with asthma and reflux, and in approximately 50% of patients with chronic cough and reflux. During pH monitoring, symptoms did not differ significantly between those with and without distal reflux in both study groups, except for more significant heartburn in patients with chronic cough and reflux (RR 2.0). CONCLUSIONS The data of the present study support the observation that there is a high prevalence of GERD in patients with asthma or chronic cough. The use of different pH parameters for detecting acid reflux during 24 h ambulatory pH monitoring, such as proximal esophageal acid measurement, should be considered as part of the routine interpretation of such testing. A low threshold for diagnosing GERD in patients with asthma or chronic cough is essential, because respiratory and/or reflux symptoms can be absent or atypical in some of these patients.
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Affiliation(s)
| | | | | | - JM FitzGerald
- Correspondence: Dr J Mark FitzGerald, Centre for Clinical Epidemiology and Evaluation, Research Pavilion, Vancouver General Hospital, 828 – West 12th Avenue, Vancouver, British Columbia V5Z 1M9. Telephone 604-875-4565, fax 604-875-4695, e-mail
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Fox M, Barr C, Nolan S, Lomer M, Anggiansah A, Wong T. The effects of dietary fat and calorie density on esophageal acid exposure and reflux symptoms. Clin Gastroenterol Hepatol 2007; 5:439-44. [PMID: 17363334 DOI: 10.1016/j.cgh.2006.12.013] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The effects of diet on gastroesophageal reflux disease are not well understood. This study assessed the effects of dietary fat and calorie density on esophageal acid exposure and reflux symptoms in patients with reflux symptoms. METHODS Patients referred for the investigation of reflux symptoms were recruited (most with nonerosive disease). A catheter-free system provided esophageal pH monitoring over 4 days in 4 dietary conditions. A high-fat (50%) vs low-fat (25%) diet (calorie-controlled), and a high-calorie (1000 kcal) vs low-calorie (500 kcal) diet (fat-controlled) were provided in randomized order, and meal volume was controlled. The effects of meal consistency also were studied. RESULTS Complete data were available for 15 patients (6 men, 9 women; age, 48 y; range, 26-70 y; body mass index, 26 kg/m2; body mass index range, 21-35 kg/m2). Demographic variables and meal sequence had no effect on reflux parameters. Dietary composition had effects on esophageal acid exposure (F statistic [analysis of variance] = 7.4, P < .005) and symptoms (Friedman test = 24.2, P < .001). No effect of meal consistency was present. Esophageal acid exposure was greater during the high-calorie than the low-calorie diet (mean, 8.6% +/- 2.0% vs 5.2% +/- 1.4% time pH < 4/24 h; P < .01). No difference was observed between the high-fat and low-fat diets (mean, 8.6% +/- 2.0% vs 8.2% +/- 1.6% time pH < 4/24 h; P = NS). In contrast, the frequency of reflux symptoms was not affected by calorie density (median, 6; range, 2-12 vs median, 8; range, 2-13; P = NS) but was increased by the high-fat compared with the low-fat diet (median, 11; range, 5-18 vs median, 6; range, 2-12; P < .05). CONCLUSIONS Calorie density determines the severity of esophageal acid exposure in gastroesophageal reflux disease after a meal; however, the percentage fat content of the diet has important effects on the frequency of reflux symptoms.
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Affiliation(s)
- Mark Fox
- Department of Gastroenterology, St Thomas' Hospital, London, United Kingdom.
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Abstract
Disorders of the foregut are an increasingly common cause of symptoms in Western populations. This review summarizes recent advances in the understanding and treatment of gastroesophageal reflux disease, dyspepsia and celiac disease.
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Affiliation(s)
- Alan C Moss
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA
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50
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Halkin H, Dushenat M, Silverman B, Shalev V, Loebstein R, Lomnicky Y, Friedman N. Brand versus generic alendronate: gastrointestinal effects measured by resource utilization. Ann Pharmacother 2006; 41:29-34. [PMID: 17190847 DOI: 10.1345/aph.1h218] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Adverse reactions related to the upper gastrointestinal tract (UGIT) that are associated with generic alendronate formulations may differ from those associated with the brand drug. OBJECTIVE To test the hypothesis that adverse UGIT effects of alendronate formulations may differ between generic and brand products. METHODS We conducted a database health resource utilization analysis of UGIT outcomes in patients who started treatment with generic or brand alendronate formulations during 2001-2005. We included 6962 patients who were treated continuously for 3 months with 1 of 4 alendronate formulations: brand 10 mg/day (Merck, Sharpe & Dohme, n = 1418), generic A 10 mg/day (Teva, Israel, n = 650), generic B 10 mg/day (Unipharm, Israel, n = 628), and brand 70 mg/wk (n = 4266). In these patients, who had neither filled a prescription for alendronate nor had any gastrointestinal problems in the year preceding the study, we compared incidence rates of new use of gastric medications (H2-blockers, proton-pump inhibitors, or antacids), gastroenterology visits, endoscopies, and hospital admissions. RESULTS Incident rate ratios (IRR) for treatment discontinuation were higher with both daily generic products (IRR 1.3; 95% CI 1.04 to 1.63). Adherence (medication possession ratio [MPR] >80%) was better with brand 10 mg/day (IRR 1.19; 95% CI 1.11 to 1.27). All comparisons were adjusted for use of concurrent corticosteroids, nonsteroidal antiinflammatory drugs, and potassium supplements. Hospitalization rates (2.7-3.2%) were similar in all groups. New use of gastric medications (3.4-4.9%) was lower with brand 10 mg/day (IRR 0.71; 95% CI 0.53 to 0.95). Rates of UGIT endoscopy (n = 49) in patients receiving 10 mg were 0.6% (brand), 1.1% (generic A), and 1.6% (generic B), with generic B higher (IRR 2.88; 95% CI 1.14 to 7.29) in the entire cohort, but not among new users (n = 273) of gastric drugs (IRR 2.46; 95% CI 0.55 to 11.05). Endoscopic findings were normal in 22 patients, hiatal hernia with no mucosal lesion was present in 10 patients, and there was mild-to-moderate esophagitis or gastritis in 17 patients; there were no significant differences among the formulations. CONCLUSIONS We found insufficient evidence to indicate major differences in UGIT adverse effects related to use of daily generic, as compared with brand, alendronates.
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Affiliation(s)
- Hillel Halkin
- Chairman, Formulary Committee, Maccabi Healthcare Services, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University
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