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Du Y, Spencer A, Roy P, Abdulhamid A, Dalessio S, Levenick J, Maranki J, Razjouyan H, Coates MD. Asymptomatic Erosive Esophagitis. Dig Dis Sci 2025; 70:462-468. [PMID: 39694991 PMCID: PMC12145923 DOI: 10.1007/s10620-024-08793-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/06/2024] [Indexed: 12/20/2024]
Abstract
Gastroesophageal reflux disease (GERD) is a very common condition characterized by chronic symptoms, such as heartburn or epigastric and/or substernal pain, that are frequently associated with mucosal damage resulting from abnormal reflux of gastric contents into the esophagus (Fass et al. in Nat Rev Dis Primers 7:55, 2021; Richter and Rubenstein in Gastroenterology 154:267-276, 2018). However, this damage can manifest in patients who do not exhibit typical GERD symptoms. Asymptomatic erosive esophagitis (AEE) is a condition in which there is esophageal mucosal injury typical for GERD, such as erosions, ulcerations, and/or Barrett's esophagus, visible in upper endoscopy, without concurrent symptoms attributable to GERD. AEE has been challenging to study, and it is not yet clear what causes this condition. As a result, there are no definitive guidelines on how to manage it. AEE also has the potential to be very impactful on public health, as those who are affected may go years without a diagnosis, putting them at risk for a variety of complications, including strictures and even cancer. Further careful study is necessary in order to more effectively address this condition. Here, we provide a comprehensive review of the scientific literature regarding AEE, examining its prevalence, clinical characteristics, potential causes and contributing factors, as well as identifying avenues for better characterization and management of this patient population.
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Affiliation(s)
- Yixuan Du
- Penn State College of Medicine, Hershey, PA, USA
| | | | - Pabitra Roy
- Penn State College of Medicine, Hershey, PA, USA
| | - Ahmed Abdulhamid
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA
| | - Shannon Dalessio
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA
| | - John Levenick
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA
| | - Jennifer Maranki
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA
| | - Hadie Razjouyan
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA
| | - Matthew D Coates
- Division of Gastroenterology & Hepatology, Penn State College of Medicine, Hershey, PA, 17033, USA.
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Xie M, You JHS. Deprescribing of proton pump inhibitors in older patients: A cost-effectiveness analysis. PLoS One 2024; 19:e0311658. [PMID: 39374218 PMCID: PMC11458043 DOI: 10.1371/journal.pone.0311658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 09/23/2024] [Indexed: 10/09/2024] Open
Abstract
Over-prescribing of proton-pump inhibitors (PPIs) is widely observed in older patients. Clinical findings have showed that deprescribing service significantly decreased inappropriate PPIs utilization. We aimed to examine the cost-effectiveness of PPI deprescribing service from the perspective of Hong Kong public healthcare provider. A decision-analytic model was constructed to examine the clinical and economic outcomes of PPI deprescribing service (deprescribing group) and usual care (UC group) in a hypothetical cohort of older PPI-users aged ≥65 years in the ambulatory care setting. The model inputs were retrieved from literature and public data. The model time-frame was one-year. Base-case analysis and sensitivity analysis were performed. Primary model outcomes were direct medical cost and quality-adjusted life-years (QALYs) loss. In base-case analysis, the deprescribing service (versus UC) reduced total direct medical cost by USD235 and saved 0.0249 QALY per PPI user evaluated. The base-case results were robust to variation of all model inputs in one-way sensitivity analysis. In probabilistic sensitivity analysis, the deprescribing group was accepted as cost-effective (versus the UC group) in 100% of the 10,000 Monte Carlo simulations. In conclusion, the PPI deprescribing service saved QALYs and reduced total direct medical cost in older PPIs users, and showed a high probability to be accepted as the cost-effective option from the perspective of public healthcare provider in Hong Kong.
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Affiliation(s)
- Mingxi Xie
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Joyce H. S. You
- School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
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Savarino V, Marabotto E, Zentilin P, De Bortoli N, Visaggi P, Furnari M, Bodini G, Giannini E, Savarino E. How safe are heartburn medications and who should use them? Expert Opin Drug Saf 2023; 22:643-652. [PMID: 37477199 DOI: 10.1080/14740338.2023.2238592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
INTRODUCTION Heartburn is a frequent symptom occurring in daily clinical practice and is mainly associated with gastroesophageal reflux disease (GERD). However, it can be stimulated by various factors and diseases other than GERD can present with heartburn. Therefore, physicians must be very careful in distinguishing GERD from non-GERD conditions in their patients, particularly when heartburn is refractory to anti-reflux medications. AREAS COVERED The aim of this narrative review was to analyze the medical literature regarding the prevalence of heartburn and the various clinical disorders which can be present with this symptom. The type of medications usually adopted for treating heartburn and their grade of safety have been reviewed using an extensive computerized (Medline/PubMed) search with particular focus on the last 20 years. EXPERT OPINION Many drugs can be used for relieving heartburn in patients with GERD, although PPIs are the pharmacological agents with the greatest efficacy. However, it must be highlighted that many non-GERD conditions may present clinically with this symptom whose intensity does not differ between GERD and functional esophageal disorders, which represent about 50% of all patients with suspected GERD. It is very important to identify these functional conditions because their treatment differs completely from that of GERD.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Manuele Furnari
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Giannini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Pennington E, Bell S, Hill JE. Should video laryngoscopy or direct laryngoscopy be used for adults undergoing endotracheal intubation in the pre-hospital setting? A critical appraisal of a systematic review. JOURNAL OF PARAMEDIC PRACTICE : THE CLINICAL MONTHLY FOR EMERGENCY CARE PROFESSIONALS 2023; 15:255-259. [PMID: 38812899 PMCID: PMC7616025 DOI: 10.1002/14651858] [Citation(s) in RCA: 2724] [Impact Index Per Article: 1362.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The safety and utility of endotracheal intubation by paramedics in the United Kingdom is a matter of debate. Considering the controversy surrounding the safety of paramedic-performed endotracheal intubation, any interventions that enhance patient safety should be evaluated for implementation based on solid evidence of their effectiveness. A systematic review performed by Hansel and colleagues (2022) sought to assess compare video laryngoscopes against direct laryngoscopes in clinical practice. This commentary aims to critically appraise the methods used within the review by Hansel et al (2022) and expand upon the findings in the context of clinical practice.
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Affiliation(s)
| | - Steve Bell
- Consultant Paramedic, North West Ambulance Service NHS Trust
| | - James E Hill
- University of Central Lancashire, Colne, Lancashire
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Barberio B, Visaggi P, Savarino E, de Bortoli N, Black CJ, Ford AC. Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis. Neurogastroenterol Motil 2023; 35:e14469. [PMID: 36153790 PMCID: PMC10078414 DOI: 10.1111/nmo.14469] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/29/2022] [Accepted: 09/12/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. METHODS We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. KEY RESULTS We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. CONCLUSIONS & INFERENCES Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.
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Affiliation(s)
- Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Affiliation(s)
- Ronnie Fass
- From the Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, and Case Western Reserve University - both in Cleveland
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7
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Vandenplas Y, Kindt S. Gastroesophageal Reflux. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:125-155. [DOI: 10.1007/978-3-030-80068-0_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Tack M. Problems with the MetaBLIND study: An examination of data on blinding patients in trials with patient-reported outcomes. J Health Psychol 2021:13591053211059391. [PMID: 34875934 DOI: 10.1177/13591053211059391] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
MetaBLIND is the largest meta-epidemiological study on the impact of blinding in randomized trials to date. We examined MetaBLIND data on the impact of blinding patients on patient-reported outcomes. 68 out of 132 included trials tested knowledge recall and had questionable relevance to clinical trials. In 17 out of 18 comparisons, the number of trials in the blinded or nonblinded group was 2 or lower. In several key trials, the blinding status was uncertain. Effect sizes compared in MetaBLIND appear to reflect random differences in study design and setting rather than the impact of blinding trial participants.
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9
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Kim SH, Cho KB, Chun HJ, Lee SW, Kwon JG, Lee DH, Kim SG, Jung H, Kim JW, Lee JS, Park H, Choi SC, Jee SR, Kim H, Ko KH, Park SJ, Lee YC, Park SH, Kim AR, Kim EJ, Park HW, Kim BT, Song GS. Randomised clinical trial: comparison of tegoprazan and placebo in non-erosive reflux disease. Aliment Pharmacol Ther 2021; 54:402-411. [PMID: 34227708 PMCID: PMC8361733 DOI: 10.1111/apt.16477] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 02/23/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease. AIM To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD. METHODS In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated. RESULTS Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted. CONCLUSIONS Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD. Registration number: ClinicalTrials.gov identifier NCT02556021.
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Fass R, Boeckxstaens GE, El-Serag H, Rosen R, Sifrim D, Vaezi MF. Gastro-oesophageal reflux disease. Nat Rev Dis Primers 2021; 7:55. [PMID: 34326345 DOI: 10.1038/s41572-021-00287-w] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2021] [Indexed: 02/07/2023]
Abstract
Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.
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Affiliation(s)
- Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH, USA.
| | - Guy E Boeckxstaens
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Hashem El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Rachel Rosen
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
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Zhang M, Pandolfino JE, Zhou X, Tan N, Li Y, Chen M, Xiao Y. Assessing different diagnostic tests for gastroesophageal reflux disease: a systematic review and network meta-analysis. Therap Adv Gastroenterol 2019; 12:1756284819890537. [PMID: 31803253 PMCID: PMC6876191 DOI: 10.1177/1756284819890537] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 10/15/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The aim of the current systematic review and network meta-analysis (NMA) was to assess the diagnostic characteristics of the gastroesophageal reflux disease questionnaire (GERDQ), proton-pump inhibitor (PPI) test, baseline impedance, mucosal impedance, dilated intercellular spaces (DIS), salivary pepsin, esophageal pH/pH impedance monitoring and endoscopy for gastroesophageal reflux disease (GERD). METHODS We searched PubMed and the Cochrane Controlled Trial Register database (from inception to 10 April 2018) for studies assessing the diagnostic characteristics of the GERDQ, PPI test, baseline impedance, mucosal impedance, DIS, or salivary pepsin and esophageal pH/pH impedance monitoring/endoscopy in patients with GERD. Direct pairwise comparison and a NMA using Bayesian methods under random effects were performed. We also assessed the ranking probability. RESULTS A total of 40 studies were identified. The NMA found no significant difference among the baseline impedance, mucosal impedance, and esophageal pH/pH impedance monitoring and endoscopy in terms of both sensitivity and specificity. It was also demonstrated that the salivary pepsin detected by the Peptest device had comparable specificity to esophageal pH/pH impedance monitoring and endoscopy. Results of ranking probability indicated that esophageal pH/pH impedance monitoring and endoscopy had highest sensitivity and specificity, followed by mucosal impedance and baseline impedance, whereas GERDQ had the lowest sensitivity and PPI test had the lowest specificity. CONCLUSIONS In a systematic review and NMA of studies of patients with GERD, we found that baseline impedance and mucosal impedance have relatively high diagnostic performance, similar to esophageal pH/pH impedance monitoring and endoscopy.
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Affiliation(s)
- Mengyu Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Xuyu Zhou
- Medical Information Research Institute, Sun Yat-sen University, Guangzhou, China
| | - Niandi Tan
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuwen Li
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Minhu Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yinglian Xiao
- Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
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Mastracci L, Fiocca R, Engström C, Attwood S, Ell C, Galmiche JP, Hatlebakk JG, Långström G, Eklund S, Lind T, Lundell L. The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery. Aliment Pharmacol Ther 2017; 45:1339-1349. [PMID: 28326569 DOI: 10.1111/apt.14038] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Revised: 10/20/2016] [Accepted: 02/20/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.
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Affiliation(s)
- L Mastracci
- Department of Anatomic Pathology, University of Genova and IRCCS S.Martino/IST University Hospital, Genoa, Italy
| | - R Fiocca
- Department of Anatomic Pathology, University of Genova and IRCCS S.Martino/IST University Hospital, Genoa, Italy
| | - C Engström
- Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - S Attwood
- Department of Surgery, North Tyneside General Hospital, North Shields, UK
| | - C Ell
- Department of Gastroenterology, Dr Horst Schmidt-Hospital, Wiesbaden, Germany
| | - J P Galmiche
- Department of Gastroenterology and Hepatology, Nantes University and INSERM, Nantes, France
| | - J G Hatlebakk
- Department of Medicine, Haukeland University Hospital, Bergen, Norway
| | | | - S Eklund
- AstraZeneca Gothenburg, Mölndal, Sweden
| | - T Lind
- Formerly of AstraZeneca Gothenburg, Mölndal, Sweden
| | - L Lundell
- Department of Surgery, Centre for Digestive Diseases, Karolinska University Hospital and CLINTEC, Karolinska Institutet, Stockholm, Sweden
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13
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Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas‐Fernandez C, Pottie K, Farrell B, Cochrane Upper GI and Pancreatic Diseases Group. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev 2017; 3:CD011969. [PMID: 28301676 PMCID: PMC6464703 DOI: 10.1002/14651858.cd011969.pub2] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.
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Affiliation(s)
- Taline A Boghossian
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Farah Joy Rashid
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Wade Thompson
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Vivian Welch
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Paul Moayyedi
- McMaster UniversityDepartment of Medicine, Division of Gastroenterology1200 Main Street WestRoom 4W8EHamiltonONCanadaL8N 3Z5
| | - Carlos Rojas‐Fernandez
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
| | - Kevin Pottie
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | - Barbara Farrell
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
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Sun S, Cui Z, Zhou M, Li R, Li H, Zhang S, Ba Y, Cheng G. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil 2017; 29. [PMID: 27577963 DOI: 10.1111/nmo.12926] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 07/21/2016] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND PURPOSE Proton pump inhibitors (PPIs) are commonly used as potent gastric acid secretion antagonists for gastro-esophageal disorders and their overall safety in patients with gastro-esophageal reflux disease (GERD) is considered to be good and they are well-tolerated. However, recent studies have suggested that PPIs may be a potential independent risk factor for cardiovascular adverse events. The aim of our meta-analysis was to examine the association between PPI monotherapy and cardiovascular events in patients with GERD. METHODS A literature search involved examination of relevant databases up to July 2015 including PubMed, Cochrane Library, EMBASE, and ClinicalTrial.gov, as well as selected randomized controlled trials (RCTs) reporting cardiovascular events with PPI exposure in GERD patients. In addition, the pooled risk ratio (RR) and heterogeneity were assessed based on a fixed effects model of the meta-analysis and the I2 statistic, respectively. KEY RESULTS Seventeen RCTs covering 7540 patients were selected. The pooled data suggested that the use of PPIs was associated with a 70% increased cardiovascular risk (RR=1.70, 95% CI: [1.13-2.56], P=.01, I2 =0%). Furthermore, higher risks of adverse cardiovascular events in the omeprazole subgroup (RR=3.17, 95% CI: [1.43-7.03], P=.004, I2 =25%) and long-term treatment subgroup (RR=2.33, 95% CI: [1.33-4.08], P=.003, I2 =0%) were found. CONCLUSION & INFERENCES PPI monotherapy can be a risk factor for cardiovascular adverse events. Omeprazole could significantly increase the risk of cardiovascular events and, so, should be used carefully.
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Affiliation(s)
- S Sun
- Shenyang Pharmaceutical University, Shenyang, China
| | - Z Cui
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - M Zhou
- Shenyang Pharmaceutical University, Shenyang, China
| | - R Li
- Shenyang Pharmaceutical University, Shenyang, China
| | - H Li
- Shenyang Pharmaceutical University, Shenyang, China
| | - S Zhang
- Shenyang Pharmaceutical University, Shenyang, China
| | - Y Ba
- Shenyang Pharmaceutical University, Shenyang, China
| | - G Cheng
- Shenyang Pharmaceutical University, Shenyang, China
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15
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Ang D, How CH, Ang TL. Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy. Singapore Med J 2016; 57:546-551. [PMID: 27779277 PMCID: PMC5075954 DOI: 10.11622/smedj.2016167] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.
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Affiliation(s)
- Daphne Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Choon How How
- Care and Health Integration, Changi General Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
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16
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Hall MGG, Wenner J, Öberg S. The combination of pH monitoring in the most distal esophagus and symptom association analysis markedly improves the clinical value of esophageal pH tests. Scand J Gastroenterol 2016; 51:129-36. [PMID: 26329672 DOI: 10.3109/00365521.2015.1076889] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The poor sensitivity of esophageal pH monitoring substantially limits the clinical value of the test. The aim of this study was to compare the diagnostic accuracy of esophageal pH monitoring and symptom association analysis performed at the conventional level with that obtained in the most distal esophagus. MATERIAL AND METHODS Eighty-two patients with typical reflux symptoms and 49 asymptomatic subjects underwent dual 48-h pH monitoring with the electrodes positioned immediately above, and 6 cm above the squamo-columnar junction (SCJ). The degree of esophageal acid exposure and the temporal relationship between reflux events and symptoms were evaluated. RESULTS The sensitivity of pH recording and the diagnostic yield of Symptom Association Probability (SAP) were significantly higher for pH monitoring performed at the distal compared with the conventional level (82% versus 65%, p<0.001 and 74% versus 62%, p<0.001, respectively). The greatest improvement was observed in patients with non-erosive disease. In this group, the sensitivity increased from 46% at the standard level to 66% immediately above the SCJ, and with the combination of a positive SAP as a marker for a positive pH test, the diagnostic yield further increased to 94%. CONCLUSION The diagnostic accuracy of esophageal pH monitoring in the most distal esophagus is superior to that performed at the conventional level and it is further improved with the combination of symptom association analysis. PH monitoring with the pH electrode positioned immediately above the SCJ should be introduced in clinical practice and always combined with symptom association analysis.
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Affiliation(s)
| | - Jörgen Wenner
- a Department of Gastroenterology , Skåne University Hospital , Lund , Sweden and
| | - Stefan Öberg
- b Department of Surgery , Helsingborg Hospital, Clinical Sciences, Lund University , Lund , Sweden
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Djilani M. Traitement à court terme des symptômes de reflux : rôle du pharmacien. ACTUALITES PHARMACEUTIQUES 2016. [DOI: 10.1016/j.actpha.2016.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Muthusamy VR, Lightdale JR, Acosta RD, Chandrasekhara V, Chathadi KV, Eloubeidi MA, Fanelli RD, Fonkalsrud L, Faulx AL, Khashab MA, Saltzman JR, Shaukat A, Wang A, Cash B, DeWitt JM. The role of endoscopy in the management of GERD. Gastrointest Endosc 2016; 81:1305-10. [PMID: 25863867 DOI: 10.1016/j.gie.2015.02.021] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 02/11/2015] [Indexed: 02/08/2023]
Abstract
We recommend that uncomplicated GERD be diagnosed on the basis of typical symptoms without the use of diagnostic testing, including EGD. We recommend EGD for patients who have symptoms suggesting complicated GERD or alarm symptoms. We recommend that EGD not be routinely performed solely for the assessment of extraesophageal GERD symptoms. We recommend that endoscopic findings of reflux esophagitis be classified according to an accepted grading scale or described in detail. We suggest that repeat EGD be performed in patients with severe erosive esophagitis after at least an 8-week course of PPI therapy to exclude underlying BE or dysplasia. 44BB We recommend against obtaining tissue samples from endoscopically normal tissue to diagnose GERD or exclude BE in adults. We suggest that endoscopy be considered in patients with multiple risk factors for Barrett’s esophagus. We recommend that tissue samples be obtained to confirm endoscopically suspected Barrett’s esophagus. We suggest that endoscopic antireflux therapy be considered for selected patients with uncomplicated GERD after careful discussion with the patient regarding potential adverse effects, benefits, and other available therapeutic options.
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Maradey-Romero C, Fass R. Novel Upcoming Therapies. DIAGNOSIS AND TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE 2016:93-115. [DOI: 10.1007/978-3-319-19524-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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20
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Abstract
Gastroesophageal reflux disease has a variable presentation on upper endoscopy. Gastroesophageal reflux disease can be divided into 3 endoscopic categories: Barrett's esophagus, erosive esophagitis, and normal mucosa/nonerosive reflux disease (NERD). Each of these phenotypes behave in a distinct manner, in regards to symptom response to treatment, and risk of development of complications such as esophageal adenocarcinoma. Recently, it has been proposed to further differentiate NERD into 2 categories: those with and those without "minimal changes." These minimal changes include endoscopic abnormalities, such as villous mucosal surface, mucosal islands, microerosions, and increased vascularity at the squamocolumnar junction. Although some studies have shown that patients with minimal changes may have higher rates of esophageal acid exposure compared with those without minimal changes, it is currently unclear if these patients behave differently than those currently categorized as having NERD. The clinical utility of identifying these lesions should be weighed against the cost of the requisite equipment and the additional time required for diagnosis, compared with conventional white light endoscopy.
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Katz P, Kahrilas PJ, Johnson DA, Lind T, Röhss K, Traxler B, Hugo V, Dent J. Daytime intragastric acid control: post hoc analyses of esomeprazole 20 mg and over-the-counter proton-pump inhibitors. Therap Adv Gastroenterol 2015; 8:322-30. [PMID: 26557888 PMCID: PMC4622284 DOI: 10.1177/1756283x15592583] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES In mild gastroesophageal reflux disease, which accounts for the great majority of cases, the major burden of reflux occurs during daytime hours, after food intake. The aim of these analyses was to evaluate intragastric pH control during the typical 14-hour daytime awake period by proton-pump inhibitors (PPIs) given at over-the-counter (OTC) dosages. METHODS In one double-blind and three open-label, randomized, crossover studies, intragastric pH was monitored for 24 hours on day 5 of treatment. The 24-hour data have been reported previously. Post hoc analyses reassessed these studies for the 14-hour daytime period, comparing esomeprazole 20 mg with currently available OTC PPIs omeprazole, pantoprazole (not available in the US) and lansoprazole. RESULTS Subjects maintained intragastric pH >4 for a significantly greater mean percentage of the 14-hour daytime period with esomeprazole 20 mg compared with any of the PPI comparators at OTC dosages. Geometric mean ratios (95% confidence intervals) for esomeprazole 20 mg versus the comparators were: 1.45 (1.14-1.85; p = 0.003) versus omeprazole 20 mg; 2.50 (2.01-3.11; p < 0.0001) versus pantoprazole 20 mg; and 1.69 (1.46-1.97; p < 0.0001) and 1.89 (1.05-3.37; p = 0.03) versus lansoprazole 15 mg. A greater proportion of subjects had better pH control with esomeprazole than with the other PPIs (range: 69-97%). CONCLUSIONS Across the 14-hour daytime period, esomeprazole 20 mg once daily given 30 minutes before breakfast for 5 days provided acid control for a significantly greater average proportion of time versus the PPI comparators omeprazole, pantoprazole and lansoprazole at currently available OTC dosages.
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Affiliation(s)
| | | | | | | | | | | | | | - John Dent
- Royal Adelaide Hospital and University of Adelaide, Australia
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22
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Sano H, Iwakiri K, Kawami N, Tanaka Y, Sakamoto C. Mechanisms of acid reflux and how refluxed Acid extends proximally in patients with non-erosive reflux disease. Digestion 2015; 90:108-15. [PMID: 25196607 DOI: 10.1159/000365588] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2014] [Accepted: 06/27/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. METHODS Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). RESULTS Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). CONCLUSIONS TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.
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Affiliation(s)
- Hirohito Sano
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
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23
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Boardman HF, Heeley G. The role of the pharmacist in the selection and use of over-the-counter proton-pump inhibitors. Int J Clin Pharm 2015; 37:709-16. [PMID: 26100836 PMCID: PMC4594082 DOI: 10.1007/s11096-015-0150-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 06/09/2015] [Indexed: 12/13/2022]
Abstract
Background Heartburn and other symptoms of gastro-oesophageal reflux occur in ~30 % of survey respondents in multiple countries worldwide. Heartburn and acid regurgitation are common complaints in the pharmacy, where patients frequently seek relief through medication and advice. The growing number of proton-pump inhibitors available in the over-the-counter setting provides an efficacious choice to patients experiencing frequent heartburn. Pharmacists can assist patients in their treatment decisions whilst inquiring about alarm symptoms that should prompt a physician referral. Aim of the review Provide pharmacists with a review of current clinical research and expert guidelines on use of over-the-counter proton-pump inhibitors. Methods This narrative review was conducted to identify publications relevant to the following themes: overview of available treatments for frequent episodes of heartburn/acid regurgitation; treatment algorithms providing guidance on when to use over-the-counter proton-pump inhibitors; and the role of the pharmacist in the use of over-the-counter proton-pump inhibitors. Results Frequent symptoms of acid reflux, such as heartburn and acid regurgitation, can interfere substantially with daily life activities. Proton-pump inhibitors are the most efficacious treatment for frequent reflux symptoms and are recommended as an appropriate initial treatment in uncomplicated cases. Proton-pump inhibitors have varying pharmacokinetics and pharmacodynamics across the class; 20 mg esomeprazole has higher bioavailability and exposure than over-the-counter omeprazole, for example. However, differences in clinical efficacy for symptom relief have not been demonstrated. The safety and tolerability of proton-pump inhibitors have been well established in clinical trial and post-marketing settings, and use of a short regimen is associated with a very low likelihood of missing a more serious condition. Pharmacists can assist patients with accurate self-diagnosis by asking short, simple questions to characterize the nature, severity, and frequency of symptoms. Additionally, pharmacists can inquire about alarm symptoms that should prompt referral to a physician. Pharmacists should inform those patients for whom over-the-counter proton-pump inhibitors are appropriate on their proper use. Conclusion Over-the-counter proton-pump inhibitors have a valuable role in the treatment of frequent heartburn. Pharmacists have the opportunity to guide patients through selection of the best treatment option for their symptoms.
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Affiliation(s)
- Helen F Boardman
- School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
| | - Gordon Heeley
- Lloydspharmacy, 113 Sneinton Road, Nottingham, NG2 4QL, UK
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Sun J, Yuan YZ, Hou XH, Zou DW, Lu B, Chen MH, Liu F, Wu KC, Zou XP, Li YQ, Zhou LY. Esomeprazole regimens for reflux symptoms in Chinese patients with chronic gastritis. World J Gastroenterol 2015; 21:6965-6973. [PMID: 26078574 PMCID: PMC4462738 DOI: 10.3748/wjg.v21.i22.6965] [Citation(s) in RCA: 3] [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] [Received: 10/28/2014] [Revised: 01/19/2015] [Accepted: 02/11/2015] [Indexed: 02/07/2023] Open
Abstract
AIM To compare symptom control with esomeprazole regimens for non-erosive reflux disease and chronic gastritis in patients with a negative endoscopy. METHODS This randomized, open-label study was designed in line with clinical practice in China. Patients with typical reflux symptoms for ≥ 3 mo and a negative endoscopy who had a Gastroesophageal Reflux Disease Questionnaire score ≥ 8 were randomized to initial treatment with esomeprazole 20 mg once daily either for 8 wk or for 2 wk. Patients with symptom relief could enter another 24 wk of maintenance/on-demand treatment, where further courses of esomeprazole 20 mg once daily were given if symptoms recurred. The primary endpoint was the symptom control rate at week 24 of the maintenance/on-demand treatment period. Secondary endpoints were symptom relief rate, success rate (defined as patients who had symptom relief after initial treatment and after 24 wk of maintenance treatment), time-to-first-relapse and satisfaction rate. RESULTS Based on the data collected in the modified intention-to-treat population (MITT; patients in the ITT population with symptom relief after initial esomeprazole treatment, n = 262), the symptom control rate showed a small but statistically significant difference in favor of the 8-wk regimen (94.9% vs 87.3%, P = 0.0473). Among the secondary endpoints, based on the data collected in the ITT population (n = 305), the 8-wk group presented marginally better results in symptom relief after initial esomeprazole treatment (88.3% vs 83.4%, P = 0.2513) and success rate over the whole study (83.8% vs 72.8%, P = 0.0258). The 8-wk regimen was found to provide a 46% reduction in risk of relapse vs the 2-wk regimen (HR = 0.543; 95%CI: 0.388-0.761). In addition, fewer unscheduled visits and higher patient satisfaction supported the therapeutic benefits of the 8-wk regimen over the 2-wk regimen. Safety was comparable between the two groups, with both regimens being well tolerated. CONCLUSION Chinese patients diagnosed with chronic gastritis achieved marginally better control of reflux symptoms with an 8-wk vs a 2-wk esomeprazole regimen, with a similar safety profile.
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25
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More art than science: impedance analysis prone to interpretation error. J Gastrointest Surg 2015; 19:987-92. [PMID: 25876531 DOI: 10.1007/s11605-015-2809-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 03/19/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Impedance monitoring for reflux evaluation does not have standardized scoring, which can confound interpretation between observers. We investigated the variability of impedance testing interpretation between physicians and computer software. METHODS Raw impedance data from 38 patients that underwent impedance monitoring at a tertiary referral center between 2008 and 2013 were collected. Two physicians and computer software each analyzed the same impedance dataset for reflux activity and symptom-reflux correlation. RESULTS Normalized reflux activity interpretations did not differ between physicians and the computer for acid or non-acid reflux. However, for weakly acidic reflux, there was significant difference between physicians (p < 0.01) and between physician and computer (p < 0.01). In analyzing all reflux, significant variability existed between physicians (p < 0.01) but not between physician and computer. Variability in interpretation altered diagnosis in 24 % of patients when comparing between physicians, 18 % of patients when comparing both physicians to the computer, and an additional 24 % of cases when comparing a single physician to the computer. Symptom-reflux correlation differed in 7 % of physician-physician comparisons versus 8 % of computer-physician comparisons. CONCLUSION Impedance testing analysis is subject to marked variability between physicians and computer software, making impedance prone to interpretation error that can lead to differences in diagnosis and management.
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Mwandri MB, Mwita JC, Magafu MGMD, Mgwaya M, Kilonzo KG, Urasa SJ, Urasa S. Risks, precipitants and clinical presentation of gastro-oesophageal reflux disease at the Kilimanjaro Christian medical centre in Tanzania [corrected]. Pan Afr Med J 2014; 19:119. [PMID: 25745527 PMCID: PMC4341257 DOI: 10.11604/pamj.2014.19.119.3575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2013] [Accepted: 09/06/2014] [Indexed: 12/14/2022] Open
Abstract
Introduction Risk factors and precipitants of gastro-oesophageal disease (GERD) differ widely in communities. We conducted an observational study to describe these risks, precipitants and clinical presentation of GERD patients at Kilimanjaro Christian Medical Centre (KCMC) in Tanzania. Methods We consecutively recruited 92 GERD patients who were referred for endoscopy at KCMC from March to November 2008. By using structured questionnaire we enquired: risk factors, precipitants and symptoms of GERD and upper gastrointestinal endoscopic findings. Their upper gastrointestinal endoscopic findings were as well documented. Results The mean (± SD) age of the study population was 47.32 (±17) years. Reported symptoms included water brash (37%), dyspepsia (6%), chronic cough (11%) and hemoptysis (5%). More than half (56%) of the patients surveyed identified food precipitants for their GERD symptoms. Triggers of GERD symptoms were boiled beans 19%, spicy food 11%, sour/fermented meals 10%, roasted tomato 9%, silver cyprinid fish (dagaa) 5%, beans with cooked green banana (matoke) 2% and fermented milk 1%. Most of the studied patients had normal body mass index (52%), and 25% admitted to be consuming alcohol though they didn't associate it with their GERD symptoms. The most common endoscopy finding was “loose lower oesophageal sphincter” (85%). Conclusion Most GERD patients referred for endoscopy at KCMC were found to have water brash and “loose lower oesophageal sphincters” as described by endoscopists to denote mechanical abnormality of the lower oesophageal sphincter. GERD symptoms were precipitated by common locally available food and spices.
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Affiliation(s)
| | | | | | | | - Kajiru Gad Kilonzo
- Kilimanjaro Christian Medical Centre, Tanzania P.O.Box 3010, Moshi, Tanzania
| | - Sarah Japhet Urasa
- Kilimanjaro Christian Medical Centre, Tanzania P.O.Box 3010, Moshi, Tanzania
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McRorie JW, Gibb RD, Miner PB. Evidence-based treatment of frequent heartburn: the benefits and limitations of over-the-counter medications. J Am Assoc Nurse Pract 2014; 26:330-9. [PMID: 24825071 DOI: 10.1002/2327-6924.12133] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE This review summarizes the pharmacological effects of over-the-counter (OTC) heartburn drugs, and the implications for treating frequent heartburn. DATA SOURCES PubMed and SCOPUS were searched across all years to identify well-controlled, randomized clinical studies that assessed mechanism of action and efficacy. CONCLUSIONS Antacids can transiently neutralize acid in the esophagus, but do not significantly affect gastric pH or prevent subsequent heartburn episodes. Histamine-2 receptor antagonists (H2 RAs) rapidly develop tolerance with repeat dosing, and exhibit an analgesic effect that may provide heartburn relief while leaving the esophagus exposed to acid. Proton pump inhibitors (PPIs) provide a sustained inhibition of gastric acid production, and are superior to antacids and H2 RAs for control of gastric acid and treatment of frequent heartburn. IMPLICATIONS FOR PRACTICE When recommending therapies for frequent heartburn, it is of particular importance to understand the strengths and weaknesses of available OTC medications. Antacids and H2 RAs are not recommended for treatment of frequent heartburn, while OTC PPIs are both indicated for, and effective for, treatment of frequent heartburn. A PPI dose of 20 mg is optimal for empiric treatment of frequent heartburn, and consistent with the 2013 treatment guidelines established by the American College of Gastroenterology (ACG) for treatment with a minimum effective dose.
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Mejia A, Kraft WK. Acid peptic diseases: pharmacological approach to treatment. Expert Rev Clin Pharmacol 2014; 2:295-314. [PMID: 21822447 DOI: 10.1586/ecp.09.8] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Acid peptic disorders are the result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defense. They are common entities present in daily clinical practice that, owing to their chronicity, represent a significant cost to healthcare. Key elements in the success of controlling these entities have been the development of potent and safe drugs based on physiological targets. The histamine-2 receptor antagonists revolutionized the treatment of acid peptic disorders owing to their safety and efficacy profile. The proton-pump inhibitors (PPIs) represent a further therapeutic advance due to more potent inhibition of acid secretion. Ample data from clinical trials and observational experience have confirmed the utility of these agents in the treatment of acid peptic diseases, with differential efficacy and safety characteristics between and within drug classes. Paradigms in their speed and duration of action have underscored the need for new chemical entities that, from a single dose, would provide reliable duration of acid control, particularly at night. Moreover, PPIs reduce, but do not eliminate, the risk of ulcers in patients taking NSAIDs, reflecting untargeted physiopathologic pathways and a breach in the ability to sustain an intragastric pH of more than 4. This review provides an assessment of the current understanding of the physiology of acid production, a discussion of medications targeting gastric acid production and a review of efficacy in specific acid peptic diseases, as well as current challenges and future directions in the treatment of acid-mediated diseases.
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Affiliation(s)
- Alex Mejia
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 1170 Main Building, 132 South 10th Street, Philadelphia, PA 19107-5244, USA, Tel.: +1 203 243 7501
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Maradey-Romero C, Fass R. New and future drug development for gastroesophageal reflux disease. J Neurogastroenterol Motil 2013; 20:6-16. [PMID: 24466441 PMCID: PMC3895610 DOI: 10.5056/jnm.2014.20.1.6] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2013] [Revised: 10/25/2013] [Accepted: 11/09/2013] [Indexed: 12/14/2022] Open
Abstract
Medical therapy remains the most popular treatment for gastroesophageal reflux disease (GERD). Whilst interest in drug development for GERD has declined over the last few years primarily due to the conversion of most proton pump inhibitor (PPI)'s to generic and over the counter compounds, there are still numerous areas of unmet needs in GERD. Drug development has been focused on potent histamine type 2 receptor antagonist's, extended release PPI's, PPI combination, potassium-competitive acid blockers, transient lower esophageal sphincter relaxation reducers, prokinetics, mucosal protectants and esophageal pain modulators. It is likely that the aforementioned compounds will be niched for specific areas of unmet need in GERD, rather than compete with the presently available anti-reflux therapies.
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Affiliation(s)
- Carla Maradey-Romero
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
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Cicala M, Emerenziani S, Guarino MPL, Ribolsi M. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease. World J Gastroenterol 2013; 19:6529-6535. [PMID: 24151377 PMCID: PMC3801364 DOI: 10.3748/wjg.v19.i39.6529] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 07/31/2013] [Accepted: 08/16/2013] [Indexed: 02/06/2023] Open
Abstract
Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.
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Chen CL, Hsu PI. Current advances in the diagnosis and treatment of nonerosive reflux disease. Gastroenterol Res Pract 2013; 2013:653989. [PMID: 23935610 PMCID: PMC3725792 DOI: 10.1155/2013/653989] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2013] [Accepted: 06/13/2013] [Indexed: 02/06/2023] Open
Abstract
Nonerosive reflux disease (NERD) is a distinct pattern of gastroesophageal reflux disease (GERD). It is defined as a subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions/breaks at conventional endoscopy. In clinical practice, patients with reflux symptoms and negative endoscopic findings are markedly heterogeneous. The potential explanations for the symptom generation in NERD include microscopic inflammation, visceral hypersensitivity (stress and sleep), and sustained esophageal contractions. The use of 24-hour esophageal impedance and pH monitoring gives further insight into reflux characteristics and symptom association relevant to NERD. The treatment choice of NERD still relies on acid-suppression therapy. Initially, patients can be treated by a proton pump inhibitor (PPI; standard dose, once daily) for 2-4 weeks. If initial treatment fails to elicit adequate symptom control, increasing the PPI dose (standard dose PPI twice daily) is recommended. In patients with poor response to appropriate PPI treatment, 24-hour esophageal impedance and pH monitoring is indicated to differentiate acid-reflux-related NERD, weakly acid-reflux-related NERD (hypersensitive esophagus), nonacid-reflux-related NERD, and functional heartburn. The response is less effective in NERD as compared with erosive esophagitis.
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Affiliation(s)
- Chien-Lin Chen
- Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien 970, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung 813, Taiwan
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Determinants of symptoms in gastroesophageal reflux disease: nonerosive reflux disease, symptomatic, and silent erosive reflux disease. Eur J Gastroenterol Hepatol 2013; 25:764-71. [PMID: 23459104 DOI: 10.1097/meg.0b013e32835f594c] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Nonerosive reflux disease (NERD) is detected frequently. Furthermore, as general checkups including endoscopy have become popular, silent erosive esophagitis (EE), which is defined as EE without the typical symptoms of gastroesophageal reflux disease (GERD), is also frequently encountered. We investigated the determinants of symptom presentation in symptomatic EE, NERD, and silent EE, which are representative GERD groups. MATERIALS AND METHODS Participants in a prospective health-screening cohort underwent upper endoscopy from June 2009 to September 2010. GERD was defined as heartburn and/or acid regurgitation at least weekly or EE by endoscopy. All participants were asked to complete a validated questionnaire, which included questions about gastrointestinal symptoms and the somatization symptom checklist (SSC). RESULTS Among 4565 participants (men, 51.9%; mean age, 46.0±10.2 years), GERD was found in 678 participants (14.9%) and EE in 335 participants (7.3%). Each group of participants was classified into the following three categories: (i) symptomatic EE (n=38, 5.6%); (ii) NERD (n=343, 50.6%); and (iii) silent EE (n=297, 43.8%). Male sex and obesity were common predictors in both the symptomatic and the silent EE groups compared with the control group. Higher scores on the SSC [odds ratio (OR), 3.7; 95% confidence interval (CI), 1.8-7.8] and overlap of functional dyspepsia (OR, 35.4; 95% CI, 14.9-84.3) were predictors of symptomatic EE compared with asymptomatic EE. Symptomatic EE was more strongly associated with male sex (OR, 7.8; 95% CI, 2.9-20.9) than was NERD. CONCLUSION Somatization was the most important determinant of GERD symptoms. Silent EE was prevalent among participants with GERD, even though its natural history and clinical significance are unknown.
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Savarino E, Zentilin P, Savarino V. NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol 2013; 10:371-80. [PMID: 23528345 DOI: 10.1038/nrgastro.2013.50] [Citation(s) in RCA: 171] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonerosive reflux disease (NERD) represents the more common phenotypic presentation of GERD and comprises patients who have typical symptoms without any mucosal breaks at endoscopy. However, these patients are markedly heterogeneous from a pathophysiological point of view and should be correctly classified by means of 24 h impedance-pH testing, which enables detection of both acidic and weakly acidic reflux and correlation with symptoms. This technique is able to identify two subsets of NERD (that is, patients with an excess of acid or with a hypersensitive oesophagus to both acid and weakly acidic reflux) and patients with functional heartburn (who do not have any kind of reflux underlying their symptoms and must be excluded from the realm of GERD). The mechanisms of symptom generation are not clear in patients with NERD, but the presence of microscopic oesophagitis, including the dilation of intercellular spaces, seems to have a relevant role. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to PPI therapy, while those with hypersensitive oesophagus to weakly acidic reflux need to be treated with reflux inhibitors or surgery, although the experience in this field is very scant. Patients with functional heartburn should undergo therapy with pain modulators, but large placebo-controlled trials are necessary.
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Affiliation(s)
- Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Via Giustiniani 2, 35128 Padua, Italy
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Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME, Cochrane Upper GI and Pancreatic Diseases Group. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2013; 2013:CD002095. [PMID: 23728637 PMCID: PMC7066537 DOI: 10.1002/14651858.cd002095.pub5] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis. OBJECTIVES Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD). SEARCH METHODS We searched MEDLINE (January 1966 to November 2011), EMBASE (January 1988 to November 2011), and EBMR in November 2011. SELECTION CRITERIA Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis). DATA COLLECTION AND ANALYSIS Two authors independently assessed trial quality and extracted data. MAIN RESULTS Thirty-four trials (1314 participants) were included: fifteen in the empirical treatment group, fifteen in the ENRD group and four in both. In empirical treatment of GORD the risk ratio (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87).In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.71 (ten trials, 95% CI 0.65 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). AUTHORS' CONCLUSIONS PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.
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Affiliation(s)
- Kirsten E Sigterman
- Technische Universität München Klinikum rechts der IsarInstitut für Allgemeinmedizin / Institute of General PracticeOrleansstrasse 47MunichGermany81667
| | | | - Peter A Bonis
- Tufts Medical Centre/Division of GastroenterologyTufts Medical Centre800 Washington StreetBox 63BostonMAUSA02111
| | - Joseph Lau
- Brown University Public Health ProgramCenter for Evidence‐based Medicine121 S. Main StreetProvidenceRIUSA02912
| | - Mattijs E Numans
- VU University Medical CenterDepartment of General Practice and Elderly Care Medicine, EMGO Institute for Health and Care Research, and Alzheimer CenterVan der Boechorststraat 712AmsterdamNetherlands
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Talalwah NA, Woodward S. Gastro-oesophageal reflux. Part 2: medical treatment. ACTA ACUST UNITED AC 2013; 22:277-84. [DOI: 10.12968/bjon.2013.22.5.277] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
| | - Sue Woodward
- Florence Nightingale School of Nursing and Midwifery, King’s College London
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Bytzer P, Jones R, Vakil N, Junghard O, Lind T, Wernersson B, Dent J. Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2012; 10:1360-6. [PMID: 22813439 DOI: 10.1016/j.cgh.2012.06.030] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2012] [Revised: 06/26/2012] [Accepted: 06/28/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The efficacy of proton-pump inhibitor (PPI) therapy often is assessed to determine whether patients' symptoms are acid-related and if patients have gastroesophageal reflux disease (GERD), although the accuracy of this approach is questionable. We evaluated the diagnostic performance of the PPI test, in conjunction with other tests, for the diagnosis of GERD. METHODS We analyzed data from the DIAMOND study, a multinational trial that compared the ability of the reflux disease questionnaire with that of symptom-based clinical diagnosis to identify GERD in primary care patients with frequent upper-gastrointestinal symptoms. Patients (n = 308) were given placebo and further evaluated by endoscopy, wireless esophageal pH-metry, and symptom association monitoring. Those with GERD (n = 197) were identified based on the presence of reflux esophagitis, esophageal pH level less than 4 for more than 5.5% of 24 hours, or positive results from symptom association monitoring (or a positive result from the PPI test in patients with borderline levels of esophageal acidity). All patients then were given single-blind therapy with esomeprazole (40 mg once daily) for 2 weeks and symptoms were recorded daily. RESULTS A positive response to the PPI test was observed in 69% of patients with GERD and in 51% of those without GERD. Response to placebo did not influence the diagnostic ability of the subsequent PPI test. More patients with reflux esophagitis had a positive result from the PPI test than patients without GERD (57% vs 35%; P = .002) or patients with GERD but no esophagitis. A clinical diagnosis by the primary care physician of an acid-related disease was not associated with response to PPIs. CONCLUSIONS In a well-characterized population of primary care patients with frequent upper-gastrointestinal symptoms of any type, the PPI test has limited ability to identify patients with GERD, diagnosed by current standard tests. (ClinicalTrials.gov Number, NCT00291746.).
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Affiliation(s)
- Peter Bytzer
- Department of Medicine, Køge University Hospital, Køge, Denmark.
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Lucioni C, Mazzi S, Rossi C. Proton pump inhibitors in acute treatment of reflux oesophagitis : a cost-effectiveness analysis. Clin Drug Investig 2012; 25:325-36. [PMID: 17532670 DOI: 10.2165/00044011-200525050-00005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Gastro-oesophageal reflux disease is a common medical problem that places a significant financial burden on outpatient pharmaceutical expenditure. A substantial proportion of this expenditure can be attributed to the use of proton pump inhibitors (PPIs). The aim of this analysis was to evaluate the cost-effectiveness of PPIs currently licensed in Italy in the acute treatment of reflux oesophagitis. METHODS A decision analysis model that simulated the sequential management of reflux oesophagitis over the course of 8 weeks was constructed. Healing rates were derived from a published meta-analysis of PPIs for reflux oesophagitis. Costs of PPIs were based on retail prices in Italy, endoscopies and specialist (outpatient) visits were costed on the basis of public tariffs, and opportunity costs were calculated for general practitioner visits. The clinical effectiveness of a PPI was measured in terms of the proportion of patients healed at 8 weeks. An incremental cost-effectiveness analysis was performed, using omeprazole, the recognised 'gold standard' PPI in Italy, as the common comparator. The perspective of the analysis was the Italian National Health System (NHS). A sensitivity analysis was conducted in which the key parameters in the model were varied according to a Monte Carlo simulation of 1000 patients. RESULTS Esomeprazole 40 mg/day was a dominant treatment option compared with omeprazole 20 mg/day (88.8% patients healed vs 82.2%, respectively; total treatment cost euro164.85 vs euro169.56, respectively (year of costing, 2002). Furthermore, on the basis of the 95% CIs generated by the Monte Carlo simulation, esomeprazole 40 mg/day appears to be more cost-effective than both lansoprazole 30 mg/day and pantoprazole 40 mg/day. CONCLUSIONS Esomeprazole 40 mg/day can be considered a cost-effective treatment option for the acute treatment of reflux oesophagitis in Italy.
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Affiliation(s)
- C Lucioni
- Wolters Kluwer Health/ADIS International, Milan, Italy
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Weijenborg PW, Cremonini F, Smout AJPM, Bredenoord AJ. PPI therapy is equally effective in well-defined non-erosive reflux disease and in reflux esophagitis: a meta-analysis. Neurogastroenterol Motil 2012; 24:747-57, e350. [PMID: 22309489 DOI: 10.1111/j.1365-2982.2012.01888.x] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate the rate of symptom relief in response to PPI in NERD patients. METHODS MEDLINE (1966-2010), Cochrane Comprehensive Trial Register (1997-2010) and EMBASE (1985-2010) databases were searched and manual searches from studies' references were performed. Randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term PPI treatment. The primary outcome of selected studies was defined as complete or partial heartburn relief. Two reviewers independently extracted data and assessed study quality of selected articles. Random effects models and meta-regression were used to combine and analyze results. KEY RESULTS The pooled estimate of complete relief of heartburn after 4 weeks of PPI therapy in patients with ERD was 0.72 (95% CI 0.69-0.74) (32 studies), vs 0.50 (0.43-0.57) (eight studies) in empirically treated patients, 0.49 (0.44-0.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.69-0.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive pH-test. CONCLUSIONS & INFERENCES In well-defined NERD patients, the estimated complete symptom response rate after PPI therapy is comparable to the response rate in patients with ERD. The previously reported low response rate in studies with patients classified as NERD is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease.
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Affiliation(s)
- P W Weijenborg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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Nwokediuko SC. Current trends in the management of gastroesophageal reflux disease: a review. ISRN GASTROENTEROLOGY 2012; 2012:391631. [PMID: 22844607 PMCID: PMC3401535 DOI: 10.5402/2012/391631] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Accepted: 05/28/2012] [Indexed: 12/11/2022]
Abstract
Gastroesophageal reflux disease (GERD) is a chronic disorder of the upper gastrointestinal tract with global distribution. The incidence is on the increase in different parts of the world. In the last 30 to 40 years, research findings have given rise to a more robust understanding of its pathophysiology, clinical presentation, and management. The current definition of GERD (The Montreal definition, 2006) is not only symptom-based and patient-driven, but also encompasses esophageal and extraesophageal manifestations of the disease. The implication is that the disease can be confidently diagnosed based on symptoms alone. Nonerosive reflux disease (NERD) remains the predominant form of GERD. Current thinking is that NERD and erosive reflux disease (ERD) are distinct phenotypes of GERD rather than the old concept which regarded them as components of a disease spectrum. Non erosive reflux disease is a very heterogeneous group with significant overlap with other functional gastrointestinal disorders. There is no gold standard for the diagnosis of GERD. Esophageal pH monitoring and intraluminal impedance monitoring have thrown some light on the heterogeneity of NERD. A substantial proportion of GERD patients continue to have symptoms despite optimal PPI therapy, and this has necessitated research into the development of new drugs. Several safety concerns have been raised about chronic use of proton pump inhibitors but these are yet to be substantiated in controlled studies. The debate about efficacy of long-term medical treatment compared to surgery continues, however, recent data indicate that modern surgical techniques and long-term PPI therapy have comparable efficacy. These and other issues are subjects of further research.
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Affiliation(s)
- Sylvester Chuks Nwokediuko
- Gastroenterology Unit, Department of Medicine, University of Nigeria Teaching Hospital Ituku/Ozalla, PMB, Enugu 01129, Nigeria
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Fass R. Alternative therapeutic approaches to chronic proton pump inhibitor treatment. Clin Gastroenterol Hepatol 2012; 10:338-45; quiz e39-40. [PMID: 22178462 DOI: 10.1016/j.cgh.2011.12.020] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2011] [Revised: 12/05/2011] [Accepted: 12/06/2011] [Indexed: 02/07/2023]
Abstract
Chronic consumption of proton pump inhibitors (PPIs) by patients with gastroesophageal reflux disease is very common, primarily because of their potent and profound effect on acid secretion that results in an unsurpassed rate of symptom resolution and esophageal healing. However, there have been a growing number of reports over the past few years about various side effects caused by chronic PPI treatment. Concerns have been raised by patients and physicians alike about the common practice of prescribing PPIs, often more than once daily, on a long-term basis. As a result, there has been a resurgence of interest in alternative therapeutic modalities for chronic PPI treatment. These include novel endoscopic and surgical techniques, as well as other available therapeutic strategies that are likely to be revisited, such as histamine-2-receptor antagonists, intermittent and on-demand PPI treatment, and antireflux surgery, among others.
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Affiliation(s)
- Ronnie Fass
- The Neuroenteric Clinical Research Group, Southern Arizona VA Health Care System and University of Arizona Health Sciences Center, Tucson, Arizona 85723-0001, USA.
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41
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Simmonds WM. Nonerosive reflux disease as a presentation of gastro-oesophageal reflux disease. S Afr Fam Pract (2004) 2011. [DOI: 10.1080/20786204.2011.10874108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Affiliation(s)
- WM Simmonds
- Department of Internal Medicine, Free State University and Universitas Hospital, Bloemfontein
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van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics 2011; 127:925-35. [PMID: 21464183 DOI: 10.1542/peds.2010-2719] [Citation(s) in RCA: 142] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
INTRODUCTION Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate. OBJECTIVES We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD. METHODS We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events. RESULTS Twelve studies were included with data from children aged 0-17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage). CONCLUSIONS PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.
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Affiliation(s)
- Rachel J van der Pol
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, C2-312, 1105 AZ Amsterdam, Netherlands.
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Korrapati V, Babich JP, Balani A, Grendell JH, Kongara KR. Does deep sedation impact the results of 48 hours catheterless pH testing? World J Gastroenterol 2011; 17:1304-7. [PMID: 21455329 PMCID: PMC3068265 DOI: 10.3748/wjg.v17.i10.1304] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2010] [Revised: 09/27/2010] [Accepted: 10/04/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To study a cohort of patients undergoing 48 h Bravo pH testing receiving deep sedation with propofol.
METHODS: We retrospectively reviewed the charts of 197 patients (81 male, 116 female) who underwent Bravo esophageal pH monitoring from July 2003 to January 2008. All patients underwent Bravo pH probe placement via esophagogastroduodenoscopy (EGD) and received propofol for sedation. Patients on a proton pump inhibitor (89 patients) were excluded. Acid reflux variables measured included the total, upright, and supine fractions of time at pH < 4 and DeMeester score, and were compared between day 1 and day 2.
RESULTS: Of the 108 patients that were included in the study, the most common indication for Bravo pH monitoring was heartburn, with chest pain being the second most common. A signed rank test revealed no statistically significant difference between day 1 and day 2 reflux episodes.
CONCLUSION: Patients who received propofol for sedation for EGD with Bravo pH capsule placement did not experience any significant difference in reflux episodes from day 1 to day 2.
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Moayyedi P, Santana J, Khan M, Preston C, Donnellan C. WITHDRAWN: Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev 2011:CD003244. [PMID: 21328259 DOI: 10.1002/14651858.cd003244.pub3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful. OBJECTIVES To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments. SEARCH STRATEGY We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks. DATA COLLECTION AND ANALYSIS Two reviews independently assessed trial quality and extracted data. MAIN RESULTS We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59). AUTHORS' CONCLUSIONS PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.
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Affiliation(s)
- Paul Moayyedi
- Department of Medicine, Division of Gastroenterology, McMaster University, 1200 Main Street West, Room 4W8E, Hamilton, Ontario, Canada, L8N 3Z5
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Non-erosive reflux disease (NERD), symptomatic and asymptomatic erosive reflux disease (ERD): from hypersensitive to hyposensitive esophagus. Dig Dis Sci 2011; 56:90-6. [PMID: 20467897 DOI: 10.1007/s10620-010-1275-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Accepted: 04/27/2010] [Indexed: 02/06/2023]
Abstract
AIMS To compare the esophageal sensitivity to acid and saline in patients with symptomatic and asymptomatic erosive reflux disease (ERD), non-erosive reflux disease (NERD) and controls, and to assess the response to proton-pump inhibitors in patients with symptomatic ERD and NERD. METHODOLOGY Patients with GERD and a control group of healthy asymptomatic volunteers were recruited. All subjects underwent esophagogastroduodenoscopy and the acid-saline perfusion test. Symptomatic ERD and NERD patients were given rabeprazole 20 mg twice daily for 2 weeks and their response to treatment assessed. RESULTS A total of 105 subjects were recruited: ERD=37 (symptomatic=24, asymptomatic=13), NERD=34 and controls=34. During saline perfusion, only the NERD group recorded a significantly higher sensitivity score compared to controls (2.74±7.28 vs. 0) (p=0.035). During acid perfusion, symptomatic ERD (15.42±13.42) and NERD (16.71±15.04) had significantly higher scores versus controls and asymptomatic ERD patients (both p<0.001). The mean %∆ reflux symptom score following treatment was significantly higher in symptomatic ERD patients compared to NERD patients (89.08±21.67 vs. 58.53±32.54; p<0.001). CONCLUSIONS Patients with NERD were a generally hypersensitive group while asymptomatic ERD patients represent a hyposensitive group of patients which merits further study.
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van Pinxteren B, Sigterman KE, Bonis P, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2010:CD002095. [PMID: 21069670 DOI: 10.1002/14651858.cd002095.pub4] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Approximately 25% of adults regularly experience heartburn, a symptom of gastro-oesophageal reflux disease (GORD). Most patients are treated empirically (without specific diagnostic evaluation e.g. endoscopy. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Patients without visible damage to the oesophagus have endoscopy negative reflux disease (ENRD). The pathogenesis of ENRD, and its response to treatment may differ from GORD with oesophagitis. OBJECTIVES Summarise, quantify and compare the efficacy of short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in adults with GORD, treated empirically and in those with endoscopy negative reflux disease (ENRD). SEARCH STRATEGY We searched MEDLINE (January 1966 to November 2008), EMBASE (January 1988 to November 2008), and EBMR in November 2008. SELECTION CRITERIA Randomised controlled trials reporting symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be either from an empirical treatment group (no endoscopy used in treatment allocation) or from an endoscopy negative reflux disease group (no signs of erosive oesophagitis). DATA COLLECTION AND ANALYSIS Two authors independently assessed trial quality and extracted data. MAIN RESULTS Thirty-two trials (9738 participants) were included: fifteen in the empirical treatment group, thirteen in the ENRD group and four in both. In empirical treatment of GORD the relative risk (RR) for heartburn remission (the primary efficacy variable) in placebo-controlled trials for PPI was 0.37 (two trials, 95% confidence interval (CI) 0.32 to 0.44), for H2RAs 0.77 (two trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (one trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were more effective than H2RAs (seven trials, RR 0.66, 95% CI 0.60 to 0.73) and prokinetics (two trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, the RR for heartburn remission for PPI versus placebo was 0.73 (eight trials, 95% CI 0.67 to 0.78) and for H2RA versus placebo was 0.84 (two trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.78 (three trials, 95% CI 0.62 to 0.97) and for PPI versus prokinetic 0.72 (one trial, 95% CI 0.56 to 0.92). AUTHORS' CONCLUSIONS PPIs are more effective than H2RAs in relieving heartburn in patients with GORD who are treated empirically and in those with ENRD, although the magnitude of benefit is greater for those treated empirically.
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Affiliation(s)
- Bart van Pinxteren
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, Utrecht, Netherlands, 3508 GA
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de Leone A, Tonini M, Dominici P, Grossi E, Pace F. The proton pump inhibitor test for gastroesophageal reflux disease: optimal cut-off value and duration. Dig Liver Dis 2010; 42:785-790. [PMID: 20452300 DOI: 10.1016/j.dld.2010.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2009] [Revised: 03/23/2010] [Accepted: 04/06/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND There is no accepted gold standard for the diagnosis of gastroesophageal reflux disease (GERD). AIM To assess the optimal cut-off value and duration of the proton pump inhibitor (PPI) test in GERD patients with and without oesophagitis. METHODS Prospective study of 544 patients undergoing upper GI endoscopy and treated for 2 weeks with PPIs at double dose, and for 3 additional months at standard dose. The status of the patient at end of treatment was used as an independent diagnostic standard, i.e. patients completely asymptomatic were considered as "true" GERD patients. RESULTS PPI test was positive in 89.7-97.8% of the patients according to the cut-off or duration of test used. Test sensitivity ranged from 95.5% to 98.8%, whereas specificity did not exceed 36.3%. Positive predictive values ranged from 87% to 80%, negative predictive values ranged from 58% to 70%, respectively. CONCLUSIONS The PPI test is a sensitive but poorly specific test in GERD patients. Its optimal duration is 1 week, and the optimal cut-off value is a decrease of heartburn score ≥75%. The diagnostic yield is higher in erosive oesophagitis compared with non-erosive reflux disease patients, similarly to the symptomatic response to 3-month PPI therapy.
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Affiliation(s)
- Annalisa de Leone
- Division of Gastroenterology, Department of Clinical Sciences, L. Sacco University Hospital, Via G.B. Grassi, Milano, Italy.
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Chiba N, Fennerty MB. Gastroesophageal Reflux Disease. EVIDENCE‐BASED GASTROENTEROLOGY AND HEPATOLOGY 2010:17-61. [DOI: 10.1002/9781444314403.ch2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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El-Serag H, Becher A, Jones R. Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies. Aliment Pharmacol Ther 2010; 32:720-37. [PMID: 20662774 DOI: 10.1111/j.1365-2036.2010.04406.x] [Citation(s) in RCA: 208] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Persistent gastro-oesophageal reflux disease (GERD) symptoms can occur despite proton pump inhibitor (PPI) therapy. AIM To assess the prevalence and potential determinants of persistent GERD symptoms in primary care and community-based studies. METHODS Studies were identified by systematic PubMed and Embase searches; pooled prevalence data are shown as sample-size weighted means and 95% confidence intervals. RESULTS Nineteen studies in individuals with GERD taking a PPI were included. In interventional, nonrandomized primary care trials, the prevalence of persistent troublesome heartburn and regurgitation was 17% (6-28%) and 28% (26-30%) respectively; in randomized trials, it was 32% (25-39%) and 28% (26-30%), respectively. In observational primary care and community-based studies, 45% (30-60%) of participants reported persistent GERD symptoms. Overall, persistent GERD symptoms despite PPI treatment were more likely in studies with a higher proportion of female participants [>60% vs. <50%, risk ratio (RR): 3.66; P < 0.001], but less likely in studies from Europe than in those from the USA (RR: 0.71; P < 0.001), and were associated with decreased psychological and physical well-being. CONCLUSIONS Persistent GERD symptoms despite PPI treatment are common in the primary care and community setting. Alternative approaches to management are required.
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Affiliation(s)
- H El-Serag
- Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, USA.
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Pace F, Pace M. The proton pump inhibitor test and the diagnosis of gastroesophageal reflux disease. Expert Rev Gastroenterol Hepatol 2010; 4:423-7. [PMID: 20678016 DOI: 10.1586/egh.10.38] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring or pH-impedance monitoring, and a significant percentage of patients with abnormal esophageal acid (or weak acid) exposure have no or minimal clinical symptoms of reflux. On the other hand, endoscopic lesions are only present in a minority of GERD patients. In clinical practice, presumptive diagnosis of GERD is reasonably assumed by the substantial reduction or elimination of suspected reflux symptoms during the therapeutic trial of acid reduction therapy, the so-called proton pump inhibitor (PPI) test. We aimed to assess the optimal cutoff value and duration of this test in GERD patients with and without esophagitis. We conducted a prospective study of 544 patients, endoscopically investigated and treated for 2 weeks with PPIs at double dose, and for an additional 3 months at standard dose. The status of the patient at the end of the study was used as an independent diagnostic standard. We found esophagitis present in 55.8% and absent in 44.2% of patients (corresponding to a diagnosis of nonerosive reflux disease [NERD]). The test was positive in 89.7-97.8% of the patients according to the cutoff or duration of the test used. The sensitivity of the PPI test was excellent, ranging from 95.5 to 98.8%, whereas the specificity was poor, not exceeding 36.3%. Erosive esophagitis patients responded more favorably to the PPI test and subsequent PPI therapy compared with NERD patients. In conclusion, the PPI test is a sensitive but less specific test. Its optimal duration is 1 week, and the optimal cutoff value is a decrease of heartburn score of more than 75%. NERD patients respond less satisfactorily to PPIs, even when functional heartburn patients are excluded and only 'true' NERD patients are considered.
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Affiliation(s)
- Fabio Pace
- Department of Clinical Sciences, 'L. Sacco', University of Milan, Milan, Italy.
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