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Sui Z, Wan C, Cheng H, Yang B. Micro/nanorobots for gastrointestinal tract. Front Chem 2024; 12:1423696. [PMID: 39582767 PMCID: PMC11581860 DOI: 10.3389/fchem.2024.1423696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 10/22/2024] [Indexed: 11/26/2024] Open
Abstract
The application of micro/nanomotors (MNMs) in the gastrointestinal tract has become a Frontier in the treatment of gastrointestinal diseases. These miniature robots can enter the gastrointestinal tract through oral administration, achieving precise drug delivery and therapy. They can traverse mucosal layers and tissue barriers, directly targeting tumors or other lesion sites, thereby enhancing the bioavailability and therapeutic effects of drugs. Through the application of nanotechnology, these MNMs are able to accomplish targeted medication release, regulating drug release in response to either external stimuli or the local biological milieu. This results in reduced side effects and increased therapeutic efficacy. This review summarizes the primary classifications and power sources of current MNMs, as well as their applications in the gastrointestinal tract, providing inspiration and direction for the treatment of gastrointestinal diseases with MNMs.
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Affiliation(s)
- Ziqi Sui
- Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Chugen Wan
- Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou, Zhejiang, China
| | - Hefei Cheng
- Department of Gastroenterology, The First People’s Hospital of Linping District, Hangzhou, Zhejiang, China
| | - Bin Yang
- Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Zhuang Q, Liao A, He Q, Liu C, Zheng C, Li X, Liu Y, Wang B, Liu S, Zhang Y, Lin R, Chen H, Deng M, Tang Y, He C, Dai W, Tang H, Gong L, Li L, Xu B, Yang C, Zhou B, Su D, Guo Q, Li B, Zhou Y, Wang X, Fei S, Wu H, Wei S, Peng Z, Wang J, Li Y, Wang H, Deng T, Ding S, Li F, Chen M, Xiao Y. The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study. J Gastroenterol Hepatol 2024; 39:658-666. [PMID: 38251791 DOI: 10.1111/jgh.16471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 11/22/2023] [Accepted: 12/18/2023] [Indexed: 01/23/2024]
Abstract
BACKGROUND AND AIM Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.
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Affiliation(s)
- Qianjun Zhuang
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Aijun Liao
- Department of Gastroenterology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, China
| | - Qingling He
- Department of Gastroenterology, The Second People's Hospital of Yibin, Yibin, Sichuan, China
| | - Chengxia Liu
- Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China
| | - Changqing Zheng
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xing Li
- Department of Gastroenterology, Pingxiang People's Hospital, Pingxiang, Jiangxi, China
| | - Youli Liu
- Department of Gastroenterology, Xuancheng People's Hospital, Xuancheng, Anhui, China
| | - Bangmao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin, China
| | - Side Liu
- Department of Gastroenterology, Nanfang Hospital, Guangzhou, Guangdong, China
| | - Yan Zhang
- Department of Gastroenterology, Zigong Fourth People's Hospital, Zigong, Sichuan, China
| | - Rong Lin
- Department of Gastroenterology, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Huixin Chen
- Department of Gastroenterology, Huizhou Municipal Central Hospital, Huizhou, Guangdong, China
| | - Min Deng
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Yanping Tang
- Department of Gastroenterology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chiyi He
- Department of Gastroenterology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China
| | - Weijie Dai
- Department of Gastroenterology, Huai'an First People's Hospital, Huai'an, Jiangsu, China
| | - Haitao Tang
- Department of Gastroenterology, Lu'an People's Hospital, Lu'an, Anhui, China
| | - Lei Gong
- Department of Gastroenterology, Wuxi Second People's Hospital, Wuxi, Jiangsu, China
| | - Liangping Li
- Department of Gastroenterology, Sichuan Province People's Hospital, Chengdu, Sichuan, China
| | - Baohong Xu
- Department of Gastroenterology, Beijing Luhe Hospital Capital Medical University, Beijing, China
| | - Changqing Yang
- Department of Gastroenterology, Tongji Hospital of Tongji University, Shanghai, China
| | - Bingxi Zhou
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou, Henan, China
| | - Dongxing Su
- Department of Gastroenterology, The Second Nanning People's Hospital, Nanning, Guangxi, China
| | - Qinghong Guo
- Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, Gansu, China
| | - Bin Li
- Department of Gastroenterology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China
| | - Yongjian Zhou
- Department of Gastroenterology, Guangzhou First People's Hospital, Guangzhou, Guangdong, China
| | - Xiaoyang Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Sujuan Fei
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Huili Wu
- Department of Gastroenterology, Zhengzhou Central Hospital, Zhengzhou, Henan, China
| | - Sichen Wei
- Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei, China
| | - Zhihong Peng
- Department of Gastroenterology, The Southwest Hospital of Army Medical University, Chongqing, China
| | - Jianning Wang
- Department of Gastroenterology, Nanjing Jiangning Hospital, Nanjing, Jiangsu, China
| | - Yanqing Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Hong Wang
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China
| | - Tianwei Deng
- Department of Gastroenterology, Chongqing University Three Gorges Hospital, Chongqing, China
| | - Shigang Ding
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Fangfang Li
- Department of Gastroenterology, Chenzhou First People's Hospital, Chenzhou, Hunan, China
| | - Minhu Chen
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yinglian Xiao
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Dutta S, Noh S, Gual RS, Chen X, Pané S, Nelson BJ, Choi H. Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications. NANO-MICRO LETTERS 2023; 16:41. [PMID: 38032424 PMCID: PMC10689718 DOI: 10.1007/s40820-023-01259-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 10/19/2023] [Indexed: 12/01/2023]
Abstract
Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation. Metal-based degradable micromotor composed of magnesium (Mg), zinc (Zn), and iron (Fe) have promise due to their nontoxic fuel-free propulsion, favorable biocompatibility, and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media, efficient cargo delivery and favorable biocompatibility. A noteworthy number of degradable metal-based micromotors employ bubble propulsion, utilizing water as fuel to generate hydrogen bubbles. This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications. In addition, understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance. Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor. Here we review the design and recent advancements of metallic degradable micromotors. Furthermore, we describe the controlled degradation, efficient in vivo drug delivery, and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications. Moreover, we discuss micromotors' efficacy in detecting and destroying environmental pollutants. Finally, we address the limitations and future research directions of degradable metallic micromotors.
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Affiliation(s)
- Sourav Dutta
- Department of Robotics and Mechatronics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea
- DGIST-ETH Microrobotics Research Center, DGIST, Daegu, 42988, Republic of Korea
| | - Seungmin Noh
- Department of Robotics and Mechatronics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea
- DGIST-ETH Microrobotics Research Center, DGIST, Daegu, 42988, Republic of Korea
| | - Roger Sanchis Gual
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, 8092, Zurich, Switzerland
| | - Xiangzhong Chen
- Institute of Optoelectronics, State Key Laboratory of Photovoltaic Science and Technology, Shanghai Frontiers Science Research Base of Intelligent Optoelectronics and Perception, Fudan University, Shanghai, 200433, People's Republic of China
| | - Salvador Pané
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, 8092, Zurich, Switzerland
| | - Bradley J Nelson
- Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, 8092, Zurich, Switzerland
| | - Hongsoo Choi
- Department of Robotics and Mechatronics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.
- DGIST-ETH Microrobotics Research Center, DGIST, Daegu, 42988, Republic of Korea.
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Laine L, DeVault K, Katz P, Mitev S, Lowe J, Hunt B, Spechler S. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology 2023; 164:61-71. [PMID: 36228734 DOI: 10.1053/j.gastro.2022.09.041] [Citation(s) in RCA: 72] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/11/2022] [Accepted: 09/23/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND & AIMS For decades, proton pump inhibitors (PPIs) have been the mainstay of treatment for erosive esophagitis. The potassium-competitive acid blocker vonoprazan provides more potent acid inhibition than PPIs, but data on its efficacy for erosive esophagitis are limited. METHODS Adults with erosive esophagitis were randomized to once-daily vonoprazan, 20 mg, or lansoprazole, 30 mg, for up to 8 weeks. Patients with healing were rerandomized to once-daily vonoprazan, 10 mg, vonoprazan, 20 mg, or lansoprazole, 15 mg, for 24 weeks. Primary end points, percentage with healing by week 8 endoscopy, and maintenance of healing at week 24 endoscopy, were assessed in noninferiority comparisons (noninferiority margins, 10%), with superiority analyses prespecified if noninferiority was demonstrated. Analyses of primary and secondary end points were performed using fixed-sequence testing procedures. RESULTS Among 1024 patients in the healing phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the exploratory analysis of healing (92.9 vs 84.6%; difference, 8.3%; 95% confidence interval [CI], 4.5%-12.2%). Secondary analyses showed vonoprazan was noninferior in heartburn-free days (difference, 2.7%; 95% CI, -1.6% to 7.0%), and superior in healing Los Angeles Classification Grade C/D esophagitis at week 2 (difference, 17.6%; 95% CI, 7.4%-27.4%). Among 878 patients in the maintenance phase, vonoprazan was noninferior to lansoprazole in the primary analysis and superior on the secondary analysis of maintenance of healing (20 mg vs lansoprazole: difference, 8.7%; 95% CI, 1.8%-15.5%; 10 mg vs lansoprazole: difference, 7.2%; 95% CI, 0.2%-14.1%) and secondary analysis of maintenance of healing Grade C/D esophagitis (20 mg vs lansoprazole: difference, 15.7%; 95% CI, 2.5%-28.4%; 10 mg vs lansoprazole: difference, 13.3%; 95% CI, 0.02%-26.1%). CONCLUSIONS Vonoprazan was noninferior and superior to the PPI lansoprazole in healing and maintenance of healing of erosive esophagitis. This benefit was seen predominantly in more severe erosive esophagitis. (ClinicalTrials.gov: NCT04124926).
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Affiliation(s)
- Loren Laine
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Section of Digestive Diseases, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut.
| | - Kenneth DeVault
- Division of Gastroenterology & Hepatology, Mayo Clinic, Jacksonville, Florida
| | - Philip Katz
- Division of Gastroenterology & Hepatology, Weill Cornell Medicine, New York, New York
| | - Stefan Mitev
- Clinic of Gastroenterology, University Hospital Sv Ivan Rilski, Sofia, Bulgaria
| | - John Lowe
- Advanced Research Institute, Ogden, Utah
| | - Barbara Hunt
- Phathom Pharmaceuticals, Buffalo Grove, Illinois
| | - Stuart Spechler
- Center for Esophageal Diseases, Baylor University Medical Center at Dallas and Baylor Scott & White Health, Dallas Texas
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Zerbib F, Bredenoord AJ, Fass R, Kahrilas PJ, Roman S, Savarino E, Sifrim D, Vaezi M, Yadlapati R, Gyawali CP. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil 2021; 33:e14075. [PMID: 33368919 DOI: 10.1111/nmo.14075] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/11/2020] [Accepted: 12/13/2020] [Indexed: 02/08/2023]
Abstract
Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.
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Affiliation(s)
- Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | | | - Ronnie Fass
- Digestive Health Center, MetroHealth System, Cleveland, OH, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
| | - Sabine Roman
- Hospices Civils de Lyon, Hôpital E Herriot, Digestive Physiology, Université de Lyon, Inserm U1032, LabTAU, Lyon, France
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University, Nashville, TN, USA
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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Souza RF, Rubenstein JH, Kao JY, Hirano I. Contributions From Gastroenterology: Acid Peptic Disorders, Barrett's Esophagus and Eosinophilic Esophagitis. Gastroenterology 2018. [PMID: 29524399 DOI: 10.1053/j.gastro.2017.12.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
- Rhonda F Souza
- Department of Medicine, Division of Gastroenterology, Center for Esophageal Diseases, Baylor University Medical Center and Center for Esophageal Research, Baylor Scott and White Research Institute, Dallas, Texas
| | - Joel H Rubenstein
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan
| | - John Y Kao
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Ikuo Hirano
- Division of Gastroenterology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
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Mermelstein J, Chait Mermelstein A, Chait MM. Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions. Clin Exp Gastroenterol 2018; 11:119-134. [PMID: 29606884 PMCID: PMC5868737 DOI: 10.2147/ceg.s121056] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.
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Affiliation(s)
- Joseph Mermelstein
- Gasteroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alanna Chait Mermelstein
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maxwell M Chait
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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de Ávila BEF, Angsantikul P, Li J, Angel Lopez-Ramirez M, Ramírez-Herrera DE, Thamphiwatana S, Chen C, Delezuk J, Samakapiruk R, Ramez V, Obonyo M, Zhang L, Wang J. Micromotor-enabled active drug delivery for in vivo treatment of stomach infection. Nat Commun 2017; 8:272. [PMID: 28814725 PMCID: PMC5559609 DOI: 10.1038/s41467-017-00309-w] [Citation(s) in RCA: 354] [Impact Index Per Article: 44.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 06/19/2017] [Indexed: 12/30/2022] Open
Abstract
Advances in bioinspired design principles and nanomaterials have led to tremendous progress in autonomously moving synthetic nano/micromotors with diverse functionalities in different environments. However, a significant gap remains in moving nano/micromotors from test tubes to living organisms for treating diseases with high efficacy. Here we present the first, to our knowledge, in vivo therapeutic micromotors application for active drug delivery to treat gastric bacterial infection in a mouse model using clarithromycin as a model antibiotic and Helicobacter pylori infection as a model disease. The propulsion of drug-loaded magnesium micromotors in gastric media enables effective antibiotic delivery, leading to significant bacteria burden reduction in the mouse stomach compared with passive drug carriers, with no apparent toxicity. Moreover, while the drug-loaded micromotors reach similar therapeutic efficacy as the positive control of free drug plus proton pump inhibitor, the micromotors can function without proton pump inhibitors because of their built-in proton depletion function associated with their locomotion.Nano- and micromotors have been demonstrated in vitro for a range of applications. Here the authors demonstrate the in-vivo therapeutic use of micromotors to treat H. pylori infection.
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Affiliation(s)
| | - Pavimol Angsantikul
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Jinxing Li
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | | | | | - Soracha Thamphiwatana
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Chuanrui Chen
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Jorge Delezuk
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Richard Samakapiruk
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Valentin Ramez
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA
| | - Marygorret Obonyo
- Department of Medicine, University of California San Diego, La Jolla, CA, 92093, USA
| | - Liangfang Zhang
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.
| | - Joseph Wang
- Department of NanoEngineering, University of California San Diego, La Jolla, CA, 92093, USA.
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Helicobacter pylori-Induced Changes in Gastric Acid Secretion and Upper Gastrointestinal Disease. Curr Top Microbiol Immunol 2017; 400:227-252. [PMID: 28124156 DOI: 10.1007/978-3-319-50520-6_10] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Appropriate management of Helicobacter pylori infection of the human stomach is evolving and remains a significant clinical challenge. Acute infection results in hypochlorhydria, whereas chronic infection results in either hypo- or hyperchlorhydria, depending upon the anatomic site of infection. Acute hypochlorhydria facilitates survival of the bacterium and its infection of the stomach. Interestingly, most patients chronically infected with H. pylori manifest a pangastritis with reduced acid secretion due to bacterial virulence factors, inflammatory cytokines, and various degrees of gastric atrophy. While these patients are predisposed to develop gastric adenocarcinoma (~1%), there is increasing evidence from population studies that they are also protected from gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Eradication of H. pylori, in these patients, may provoke GERD in predisposed individuals and may be a contributory factor for the rising incidence of refractory GERD, BE, and EAC observed in Westernized societies. Only ~10% of chronically infected patients, mainly the young, manifest an antral predominant gastritis with increased acid secretion due to a decrease in somatostatin and increase in gastrin secretion; these patients are predisposed to develop peptic ulcer disease. H. pylori-induced changes in acid secretion, in particular hypochlorhydria, may allow ingested microorganisms to survive transit through the stomach and colonize the distal intestine and colon. Such perturbation of gut microbiota, i.e. dysbiosis, may influence human health and disease.
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Boltin D, Niv Y. Helicobacter pylori and Nonmalignant Diseases. HELICOBACTER PYLORI RESEARCH 2016:365-385. [DOI: 10.1007/978-4-431-55936-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum. Clin Transl Gastroenterol 2015; 6:e106. [PMID: 26270485 PMCID: PMC4816276 DOI: 10.1038/ctg.2015.32] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 06/22/2015] [Indexed: 12/12/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy.
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Parekh PJ, Johnson DA. Medical treatment versus surgery for treatment of gastroesophageal reflux disease. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2015. [DOI: 10.1016/j.tgie.2015.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Schwizer W, Menne D, Schütze K, Vieth M, Goergens R, Malfertheiner P, Leodolter A, Fried M, Fox MR. The effect of Helicobacter pylori infection and eradication in patients with gastro-oesophageal reflux disease: A parallel-group, double-blind, placebo-controlled multicentre study. United European Gastroenterol J 2014; 1:226-35. [PMID: 24917966 DOI: 10.1177/2050640613484020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Accepted: 03/01/2013] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVES This study aimed to resolve controversy regarding the effects of Helicobacter pylori eradication therapy and H. pylori infection in gastro-oesophageal reflux disease. DESIGN A randomized, double-blind, multicentre trial was performed in patients presenting with reflux symptoms. H. pylori-positive patients were randomized to receive either antibiotics or placebo for 7 days. H. pylori-negative patient controls received placebo. All received esomeprazole 20 mg b.d. for 7 days, followed by 40 mg o.d. to complete an 8-week course, and were followed up for 32 weeks by telephone. RESULTS In this study, 198/589 (34%) patients were H. pylori-positive and 113 H. pylori-negative patients served as controls. Baseline endoscopy revealed 63% Los Angeles grade 0A and 37% Los Angeles grade BCD oesophagitis with no difference between patient groups. Symptom improvement on esomeprazole was seen in 89%. H. pylori eradication was successful in 82%. H. pylori eradication had no effect on symptomatic relapse (hazard ratio 1.15, 95% CI 0.74-1.8; p = 0.5). Overall, H. pylori-positive patients had a lower probability of relapse compared to H. pylori-negative controls (hazard ratio 0.6, 95% CI 0.43-0.85; p = 0.004). Relapse hazard was modulated also by oesophagitis grade (BCD vs. 0A, hazard ratio 2.1, 95% CI 1.5-3.0). CONCLUSION Relapse of gastro-oesophageal reflux disease symptoms after a course of high dose acid suppression took longer for H. pylori-positive patients than H. pylori-negative controls; however eradication therapy had no effect on the risk of relapse; ClincialTrials.gov number, NCT00574925.
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Affiliation(s)
- Werner Schwizer
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland
| | | | | | | | | | | | | | - Michael Fried
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland
| | - Mark R Fox
- University Hospital Zürich, Zürich, Switzerland ; Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland ; NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, Nottingham, UK
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Wu MS, Tan SC, Xiong T. Indirect comparison of randomised controlled trials: comparative efficacy of dexlansoprazole vs. esomeprazole in the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2013; 38:190-201. [PMID: 23718547 DOI: 10.1111/apt.12349] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 04/16/2013] [Accepted: 05/07/2013] [Indexed: 12/24/2022]
Abstract
BACKGROUND Dexlansoprazole is a new proton pump inhibitor (PPI) with a dual delayed-release system. Both dexlansoprazole and esomeprazole are an enantiomer of lansoprazole and omeprazole respectively. However, there is no head-to-head trial data or indirect comparison analyses between dexlansoprazole and esomeprazole. AIM To compare the efficacy of dexlansoprazole with esomeprazole in healing erosive oesophagitis (EO), the maintenance of healed EO and the treatment of non-erosive reflux disease (NERD). METHODS Randomised Controlled Trials (RCTs) comparing dexlansoprazole or esomeprazole with either placebo or another PPI were systematically reviewed. Random-effect meta-analyses and adjusted indirect comparisons were conducted to compare the treatment effect of dexlansoprazole and esomeprazole using a common comparator. The relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS The indirect comparisons revealed significant differences in symptom control of heartburn in patients with NERD at 4 weeks. Dexlansoprazole 30 mg was more effective than esomeprazole 20 mg or 40 mg (RR: 2.01, 95% CI: 1.15-3.51; RR: 2.17, 95% CI: 1.39-3.38). However, there were no statistically significant differences between the two drugs in EO healing and maintenance of healed EO. Comparison of symptom control in healed EO was not able to be made due to different definitions used in the RCTs. CONCLUSIONS Adjusted indirect comparisons based on currently available RCT data suggested significantly better treatment effect in symptom control of heartburn in patients with NERD for dexlansoprazole against esomeprazole. No statistically significant differences were found in other EO outcomes. However, these study findings need to be interpreted with caution due to small number of studies and other limitations.
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Affiliation(s)
- M S Wu
- Department of Internal Medicine, Taiwan National University, Taipei, Taiwan
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15
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Wang L, Zhou L, Hu H, Lin S, Xia J. Ilaprazole for the treatment of duodenal ulcer: a randomized, double-blind and controlled phase III trial. Curr Med Res Opin 2012; 28:101-9. [PMID: 22070512 DOI: 10.1185/03007995.2011.639353] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The new proton pump inhibitor (PPI), ilaprazole performed better at the dose of 10 mg/d relative to 5 or 20 mg/d in a previous phase II trial. A larger phase III trial was carried out to confirm the efficacy and safety of ilaprazole (10 mg/d) compared with omeprazole (20 mg/d) and provide some characteristics of the relationship between ilaprazole metabolism and CYP2C19 for later studies. RESEARCH DESIGN AND METHODS Patients with at least one endoscopically diagnosed active duodenal ulcer (DU) were enrolled in a multicenter, randomized, double-blind, positive controlled trial and then assigned randomly to the ilaprazole group (10 mg/d) or the omeprazole group (20 mg/d) with a sample allocation ratio 2:1. The course of treatment was 4 weeks. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov registration number: NCT00952978. MAIN OUTCOME MEASURES The primary endpoint was endoscopically diagnosed ulcer healing rate at week 4. Symptom relief was evaluated as a secondary endpoint by graded scores. Safety and tolerability were evaluated on basis of clinical assessments. In addition, blood samples were collected at baseline for CYP2C19 genotypes identification. RESULTS Efficacy analyses were based on 494 patients. At week 4, the ulcer healing rates were 93.0% in ilaprazole group and 90.8% in omeprazole group (rate difference: 2.2%; 95% confidence interval: -2.8% to 7.2%). No obvious variation of healing rate on different CYP2C19 genotypes was found in ilaprazole group. The majority of patients (>80%) became asymptomatic after treatment. Incidences of adverse drug reactions were similar between ilaprazole group and omeprazole group (8.5% vs. 11.5%). CONCLUSIONS Ilaprazole (10 mg/d) is as effective as omeprazole (20 mg/d) in the treatment of DU with similar side effects. The efficacy of ilaprazole is not affected by CYP2C19 polymorphisms.
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Affiliation(s)
- Ling Wang
- Department of Health Statistics, The Fourth Military Medical University, Xi'an, Shaanxi, China
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16
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Malfertheiner P. The intriguing relationship of Helicobacter pylori infection and acid secretion in peptic ulcer disease and gastric cancer. Dig Dis 2011; 29:459-64. [PMID: 22095010 DOI: 10.1159/000332213] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Helicobacter pylori infection induces chronic inflammation of the gastric mucosa and thus profoundly affects gastric physiology. In the acute phase of infection, gastric acid secretion is transiently impaired. The morphological damage of the gastric mucosa, changes in gastric hormone release, and disruption of neural pathways all contribute to influence gastric acid secretion in a distinct manner. Changes in gastric acid secretion, whether impaired or increased, are intimately related with the topographic phenotypes of gastritis and the presence of atrophy or absence of corpus atrophy. The interplay of gastritis phenotype and acid secretion are key determinants in disease outcomes. Corpus-predominant gastritis and corpus atrophy are accompanied by hypochlorhydria and carry the highest risk for gastric cancer, whereas antrum-predominant gastritis with little involvement of the corpus-fundic mucosa is associated with hyperchlorhydria and predisposes to duodenal ulcer disease.
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Affiliation(s)
- P Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany.
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17
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Furuta T, Shimatani T, Sugimoto M, Ishihara S, Fujiwara Y, Kusano M, Koike T, Hongo M, Chiba T, Kinoshita Y. Investigation of pretreatment prediction of proton pump inhibitor (PPI)-resistant patients with gastroesophageal reflux disease and the dose escalation challenge of PPIs-TORNADO study: a multicenter prospective study by the Acid-Related Symptom Research Group in Japan. J Gastroenterol 2011; 46:1273-1283. [PMID: 21861141 DOI: 10.1007/s00535-011-0446-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2011] [Accepted: 06/28/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUNDS Some non-erosive reflux disease (NERD) and reflux esophagitis (RE) patients are unresponsive to a proton pump inhibitor (PPI) at standard dose. We investigated the predictive marker of the efficacy of PPI for GERD patients including NERD and RE treated with standard and increased doses of a PPI. METHODS Patients with symptomatic gastroesophageal reflux disease (GERD) (NERD and RE) were treated with rabeprazole (RPZ) 10 mg once daily for 4 weeks. The RPZ dosage was increased to 10 mg twice daily for an additional 2 weeks and again to 20 mg twice daily for another 2 weeks if heartburn was not relieved. Baseline characteristics and efficacy of RPZ were assessed on the basis of a heartburn diary and frequency scale for symptoms of GERD (FSSG). RESULTS Complete heartburn relief rates after 4 weeks were 42.5% (31/73) and 67.9% (19/28) in NERD and RE groups, respectively, which rose to 68.9 and 91.7% after dose escalation. Multivariate analysis revealed that parameters associated with resistance to RPZ 10 mg once daily were female, non-smoking, frequent heartburn, low score for question 4 (Q4) of the FSSG (subconsciously rubbing the chest), and high scores for Q3 (heavy stomach after meal) and Q7 (unusual sensation in the throat). Frequent heartburn and a high score for Q7 were associated with resistance to RPZ 20 mg twice daily. FSSG scores of patients resistant to RPZ were significantly higher in comparison with responders before and during treatment. CONCLUSIONS FSSG could predict response to a PPI for symptomatic GERD. Increase of RPZ dose is useful for treatment of GERD refractory to the standard dose of RPZ.
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Affiliation(s)
- Takahisa Furuta
- Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
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Dickman R, Boaz M, Aizic S, Beniashvili Z, Fass R, Niv Y. Comparison of clinical characteristics of patients with gastroesophageal reflux disease who failed proton pump inhibitor therapy versus those who fully responded. J Neurogastroenterol Motil 2011; 17:387-94. [PMID: 22148108 PMCID: PMC3228979 DOI: 10.5056/jnm.2011.17.4.387] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2011] [Revised: 07/19/2011] [Accepted: 07/28/2011] [Indexed: 01/11/2023] Open
Abstract
Background/Aims Refractory gastroesophageal reflux disease (GERD) is very common, affecting up to 40% of the patients receiving proton pump inhibitor (PPI) therapy. However, there is not much information about the clinical characteristics of these patients. The aim of the study is to compare the clinical characteristics of PPI responders vs non-responders. Methods Consecutive GERD patients receiving PPI once or twice daily were evaluated by a questionnaire and a personal interview regarding their demographics, habits, clinical characteristics and endoscopic findings. The patients were divided into 3 groups: Patients who fully responded to PPI once daily (Group A, n = 111), patients who failed PPI once daily (Group B, n = 78) and patients who failed PPI twice daily (Group C, n = 56). Results A total of 245 patients (59.3% females, 52 ± 17.2 years of age) were included in this study. Cross-group differences (A vs B vs C) were detected for hiatal hernia (33% vs 51% vs 52%, P = 0.011); erosive esophagitis (19% vs 51% vs 30%, P < 0.0001); cough (24% vs 44% vs 43%, P = 0.007); sleep disturbances (19% vs 30% vs 38%, P = 0.033); chest symptoms (21% vs 35% vs 41%, P = 0.010); Helicobacter pylori status (25% vs 33% vs 48%, P < 0.0001), disease duration (1.6 ± 0.8 vs 1.9 ± 1.0 vs 2.0 ± 1.1 years, P = 0.007), performed lifestyle interventions (68.5% vs 46.7% vs 69.6%, P = 0.043) and compliance (84% vs 55% vs 46%, P < 0.0001). Conclusions PPI failure (either once or twice daily) appears to be significantly associated with atypical GERD symptoms, disease duration and severity, H. pylori status, obesity, performed lifestyle interventions and compliance as compared with PPI responders.
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Affiliation(s)
- Ram Dickman
- Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
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Appelman HD, Umar A, Orlando RC, Sontag SJ, Nandurkar S, El-Zimaity H, Lanas A, Parise P, Lambert R, Shields HM. Barrett's esophagus: natural history. Ann N Y Acad Sci 2011; 1232:292-308. [DOI: 10.1111/j.1749-6632.2011.06057.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Cheong JH, Kim GH, Lee BE, Choi MK, Moon JY, Ryu DY, Kim DU, Song GA. Endoscopic grading of gastroesophageal flap valve helps predict proton pump inhibitor response in patients with gastroesophageal reflux disease. Scand J Gastroenterol 2011; 46:789-796. [PMID: 21615222 DOI: 10.3109/00365521.2011.579154] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Limited information is available on predictors of the response to proton pump inhibitor (PPI) treatment in patients with gastroesophageal reflux disease (GERD). Endoscopic grading of gastroesophageal flap valve (GEFV) is simple and reproducible, and can provide useful information on patients with suspected reflux undergoing an endoscopy. The aim of this study was to prospectively identify predictors, including endoscopic findings such as GEFV, for PPI treatment outcomes in patients with GERD. MATERIAL AND METHODS One hundred and fifty consecutive patients with GERD were enrolled. All patients were treated with pantoprazole 40 mg daily for 8 weeks. Treatment response was defined as greater than 50% reduction in symptom scores between the two symptom assessments (i.e., over 4 or 8 weeks). Univariate and multivariate logistic regression analyses between responders and non-responders were performed to identify variables predicting response to pantoprazole treatment. RESULTS Of the 150 consecutive patients considered for this study, 31 were excluded based on exclusion criteria and/or refusal to participate, leaving 119 eligible patients. After 4-week pantoprazole treatment, 70 of 119 (58.8%) patients were classified as responders. Patients with obesity and Helicobacter pylori infection demonstrated a higher response rate to 4-week pantoprazole treatment (odds ratio (OR) 5.28, p = 0.008; OR 3.76, p = 0.023, respectively). Patients with abnormal GEFV showed a lower response rate to 4-week treatment (OR 0.17, p = 0.016). After 8-week treatment, 86 of 119 (72.3%) patients were classified as responders. Abnormal GEFV and aspirin intake were associated with a lower response rate to 8-week treatment (OR 0.17, p = 0.021; OR 0.11, p = 0.020, respectively). CONCLUSIONS Abnormal GEFV was a significant independent factor predicting poor response to both 4-week and 8-week pantoprazole treatment. Endoscopic grading of GEFV provides useful information for predicting the response to PPI treatment in patients with GERD.
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Affiliation(s)
- Jae Hoon Cheong
- Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
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Fujimoto K, Hongo M. Safety and efficacy of long-term maintenance therapy with oral dose of rabeprazole 10 mg once daily in Japanese patients with reflux esophagitis. Intern Med 2011; 50:179-88. [PMID: 21297318 DOI: 10.2169/internalmedicine.50.4238] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE The aim of this prospective clinical study was to evaluate the efficacy and safety of long-term proton pump inhibitor (PPI) treatment for two years in Japanese patients with reflux esophagitis (RE). METHODS The efficacy and safety of two-year (104-week) treatment with rabeprazole (RPZ) 10 mg were studied in patients confirmed to have been cured of RE by PPI and who required long-term maintenance therapy with PPI. We performed serial endoscopy, checked gastroesophageal reflux disease (GERD) symptoms, adverse events, laboratory values and serum gastrin. We also monitored gastric mucosal histology, atrophy and polyps. RESULTS The endoscopic non-relapse rate for RE was 87.3% for the 104-week period. GERD symptoms improved based on the fact that the mean change from baseline in GERD symptom score after treatment was a negative value. Treatment was safe; and atrophy was found to have developed in virtually no cases. A few new benign fundic gland or hyperplastic polyps developed throughout the study, but no ECL carcinoids were found to have developed. Serum gastrin levels tended to increase up to 24 weeks, but there were no subsequent changes thereafter up to 104 weeks. CONCLUSION The results confirmed oral RPZ 10 mg to be effective for maintenance therapy in Japanese patients with RE. Although effects on the gastric mucosa were not ruled out, long-term use of RPZ was confirmed to be safe overall.
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Affiliation(s)
- Kazuma Fujimoto
- Department of Internal Medicine, Saga Medical School, Japan.
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Bruley des Varannes S, Coron E, Galmiche JP. Short and long-term PPI treatment for GERD. Do we need more-potent anti-secretory drugs? Best Pract Res Clin Gastroenterol 2010; 24:905-21. [PMID: 21126703 DOI: 10.1016/j.bpg.2010.09.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Revised: 09/17/2010] [Accepted: 09/20/2010] [Indexed: 02/06/2023]
Abstract
Because the reflux of the acidic gastric content into the esophagus plays a major role in the pathogenesis of symptoms of GERD and lesions of erosive esophagitis, acid suppression with a proton pump inhibitor (PPI) is currently the mainstay of anti-reflux therapy. There is a strong correlation between the degree of acid suppression provided by a given drug and its efficacy. The superiority of PPIs over other drugs (antacids, prokinetics and H(2)-receptor antagonists) has now been established beyond doubt, both for short- and long-term treatment. However, there are still some unmet therapeutic needs in GERD; hence, patients with non-erosive reflux disease (NERD) are less responsive to PPIs than those with erosive esophagitis. Moreover, the efficacy of PPIs in patients with atypical symptoms is frequently limited to the relief of associated heartburn or regurgitation. With respect to safety, although most studies on short- and long-term PPI use have provided reassuring data, recent reports have drawn attention to potential side effects or drug-drug interference. Better healing rates in the most severe forms of esophagitis, or a faster onset of symptom relief, may require optimization of acid suppressive therapy with regard to the daily course of acid secretion, especially during the night. Different pharmacological approaches can be considered, with the ultimate goals of achieving faster, stronger and more-sustained acid inhibition. How a better pharmacological profile may translate into clinical benefit should now be tested in appropriate, controlled studies.
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[Evidence and uncertainties on the clinical use of proton pump inhibitors]. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33 Suppl 1:5-10. [PMID: 20728783 DOI: 10.1016/s0210-5705(10)70002-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Proton pump inhibitors (PPI) are the most potent and effective drugs for the control of gastric acid secretion and constitute one of the most widely prescribed pharmacological groups worldwide. The safety and efficacy of PPI have been demonstrated in clinical practice and these drugs are currently the treatment of choice in peptic ulcer diseases, Helicobacter pylori infection, gastroesophageal reflux disease, nonsteroidal antiinflammatory drug gastropathy and functional dyspepsia. However, despite the excellent pharmacological profile of current PPI, their rapidity of action may be insufficient in some diseases, 24-hour acid inhibition is not always achieved and - to a greater or lesser extent depending on the distinct molecules of the PPI - there is interindividual variability in gastric antisecretory efficacy, depending on genetic polymorphism of CYP2C19, which could affect individual metabolism of the distinct PPI. New generations of these drugs will probably eliminate these deficiencies.
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Morgner-Miehlke A, Petersen K, Miehlke S, Labenz J. Esomeprazole: potent acid suppression in the treatment of acid-related disorders. Expert Rev Clin Immunol 2010; 1:511-27. [PMID: 20477595 DOI: 10.1586/1744666x.1.4.511] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Esomeprazole (S-omeprazole), an enantiomer of the racemate omeprazole, is the first proton pump inhibitor to be developed as an isomer. This confers improved pharmacokinetics and pharmacodynamics compared with the racemate R/S-omeprazole. The difference in the pharmacokinetics of esomeprazole compared with omeprazole and the R-isomer is due to reductions in total body clearance and first-pass metabolism in the liver. Pharmacodynamic studies showed that esomeprazole 40 mg provides greater intragastric acid control than respective doses of all the other proton pump inhibitors on the market. Several well-designed clinical trials, employing both endoscopic and symptomatic response criteria, have compared the efficacy of esomeprazole with that of other proton pump inhibitors in the management of gastroesophageal reflux disease patients, and in the eradication of Helicobacter pylori. In addition, the efficacy of esomeprazole for the healing and prevention of nonsteroidal anti-inflammatory drug-associated dyspeptic symptoms and ulcers has been established. The aim of this review is to provide an overview of the pharmacokinetics, pharmacodynamics and consequent clinical importance of esomeprazole in the treatment of acid-related disorders.
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Affiliation(s)
- A Morgner-Miehlke
- Medical Department I, Gastroenterology, University Hospital, Fetscherstrasse 74, 01307 Dresden, Germany.
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Yaghoobi M, Farrokhyar F, Yuan Y, Hunt RH. Is there an increased risk of GERD after Helicobacter pylori eradication?: a meta-analysis. Am J Gastroenterol 2010; 105:1007-13; quiz 1006, 1014. [PMID: 20087334 DOI: 10.1038/ajg.2009.734] [Citation(s) in RCA: 98] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Some studies suggest that eradication of Helicobacter pylori (Hp) might increase the risk of gastroesophageal reflux disease (GERD) in a portion of patients. We aimed to conduct a meta-analysis to investigate this. METHODS A comprehensive, English, multiple-source literature search was performed from 1983 to February 2007. Only randomized controlled trial (RCT) and cohort studies comparing the prevalence of GERD in patients free from GERD at baseline with Hp eradication vs. those with persistent Hp were included. Quality of RCTs and cohorts was assessed by Jadad and New Castle-Ottawa scores, respectively. Meta-analysis of pooled odds ratios (ORs) was performed using Review Manager 4.2.10. RESULTS Twelve (7 RCTs and 5 cohorts) of 271 articles were included. In six RCTs using erosive GERD as outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp group was 1.11 (0.81-1.53, P=0.52). In five RCTs using symptomatic outcome, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.22 (0.89-1.69, P=0.22). In cohort studies, the OR for the frequency of GERD in Hp eradicated group vs. persistent Hp was 1.37 (0.89-2.12; P=0.15). Test of heterogeneity was not significant for any analyses. The results were consistent in subgroup and sensitivity analyses, including cohort studies vs. RCTs, high-quality studies vs. low-quality studies, and use of endoscopic vs. symptomatic outcomes except for the subgroup of patients with peptic ulcer disease (PUD) in cohort studies (OR: 2.04 (1.08-3.85); P=0.03). CONCLUSIONS There is no association between Hp eradication and development of new cases of GERD in the population of dyspeptic patients. However, in cohort studies, there seems to be a twofold higher risk of development of erosive GERD in patients with PUD. The effect in RCTs of patients with PUD did not show a significant difference.
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Affiliation(s)
- Mohammad Yaghoobi
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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Emiroglu HH, Sokucu S, Suoglu OD, Gulluoglu M, Gokce S. Is there a relationship between Helicobacter pylori infection and erosive reflux disease in children? Acta Paediatr 2010; 99:121-5. [PMID: 19785631 DOI: 10.1111/j.1651-2227.2009.01512.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM The aim of this study was to investigate the relationship between Helicobacter pylori infection and erosive reflux disease in children. METHODS A total of 206 children [mean age 8.4 +/- 4.9 (0.16-18) years] who underwent diagnostic upper endoscopy were tested for H. pylori infection between 2002 and 2005 and the relationship between H. pylori infection and gastro-oesophageal reflux disease was investigated retrospectively. Endoscopic and histopathological findings were examined retrospectively. When reflux-related oesophageal damage was identified as a result of the histological examination of endoscopic biopsy samples collected from distal oesophagus, the patients were diagnosed with gastro-oesophageal reflux disease and divided into two groups: those with macroscopic erosions or ulceration constituted the erosive oesophagitis group; those without constituted the non-erosive reflux disease group. RESULTS Prevalence of H. pylori infection was 31.3% in the patients with gastro-oesophageal reflux disease and 36.7% in the control group (p > 0.05). Prevalence of erosive oesophagitis was found to be 23.8% in the patients with H. pylori infection and 41.3% in those without (p > 0.05). CONCLUSION No negative significant association was found between the prevalence of H. pylori infection and erosive oesophagitis. Presence of H. pylori infection did not influence the severity of oesophagitis either.
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Affiliation(s)
- Halil Haldun Emiroglu
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.
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Ho KY, Kuan A, Zaño F, Goh KL, Mahachai V, Kim DY, Yoon HM. Randomized, parallel, double-blind comparison of the ulcer-healing effects of ilaprazole and omeprazole in the treatment of gastric and duodenal ulcers. J Gastroenterol 2009; 44:697-707. [PMID: 19434360 DOI: 10.1007/s00535-009-0072-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2008] [Accepted: 03/19/2009] [Indexed: 02/06/2023]
Abstract
PURPOSE Ilaprazole (IY-81149) is a new proton-pump inhibitor (PPI) not previously studied in human patients with ulcer disease. This study evaluated and compared it with a reference PPI, omeprazole, in the treatment of gastric and duodenal ulcers. METHODS This was a double-blind, parallel, randomized study. Patients aged 18 years and above with at least one endoscopically confirmed active non-malignant gastric/duodenal ulcer were treated with 20 mg/day omeprazole or 5 mg/day or 10 mg/day ilaprazole for four weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments. Between-group differences were tested using ANOVA or ANCOVA, as appropriate. Statistical significance was assumed at a two-tailed p value of </=0.05. RESULTS Two hundred and twelve gastric ulcer patients (median age 53.3 years) and 306 duodenal ulcer patients (median age 49.7 years) were recruited; 71.8 and 85% of gastric and duodenal ulcer patients, respectively, completed the study. Ulcers were successfully healed in 64.29, 67.14, and 63.89% of gastric ulcer patients and 78.85, 83.65, and 78.57% of duodenal ulcer patients after treatment with 20 mg omeprazole, 5 mg ilaprazole, and 10 mg ilaprazole, respectively. Most patients (>90%) became asymptomatic after treatment. At the dosages administered, both drugs exhibited similar efficacy and a similar safety profile. CONCLUSIONS Ilaprazole is as tolerable, safe, and efficacious as omeprazole in the treatment of gastroduodenal ulcers, at a much lower dose (5 vs. 20 mg omeprazole).
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Affiliation(s)
- Khek Yu Ho
- Department of Medicine, Yong Loo Lin School of Medicine, National University Hospital, National University of Singapore, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
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Labenz J, Armstrong D, Zetterstrand S, Eklund S, Leodolter A. Clinical trial: factors associated with freedom from relapse of heartburn in patients with healed reflux oesophagitis--results from the maintenance phase of the EXPO study. Aliment Pharmacol Ther 2009; 29:1165-71. [PMID: 19298581 DOI: 10.1111/j.1365-2036.2009.03990.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients. AIM To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis. METHODS This post-hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH-NEG-0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once-daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse. RESULTS Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non-obesity, absence of epigastric pain at baseline, pre-treatment nonsevere heartburn and GERD symptom duration < or =5 years. CONCLUSIONS Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long-term symptom management in reflux oesophagitis patients.
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Affiliation(s)
- J Labenz
- Medical Department, Ev. Jung-Stilling Hospital, Siegen, Germany
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Labenz J, Armstrong D, Zetterstrand S, Eklund S, Leodolter A. Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis--results from the EXPO study. Aliment Pharmacol Ther 2009; 29:959-66. [PMID: 19222417 DOI: 10.1111/j.1365-2036.2009.03962.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND The ability to predict symptom response to reflux oesophagitis-healing therapy may optimize treatment decisions. AIM To identify factors associated with heartburn resolution in patients receiving acid-suppressive therapy for reflux oesophagitis. METHODS In this multicentre, randomized, double-blind trial (EXPO; AstraZeneca study code: SH-NEG-0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once-daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for >or=4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis. RESULTS Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P < 0.001]. Men and patients with no acid regurgitation or epigastric pain pre-treatment were also more likely to achieve heartburn resolution (all P < 0.05). CONCLUSIONS The use of esomeprazole rather than pantoprazole increases the probability of achieving resolution of heartburn during reflux oesophagitis-healing therapy. Other factors, including H. pylori status, age, gender and symptom profile may be helpful in determining the likelihood of heartburn resolution in such patients.
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Affiliation(s)
- J Labenz
- Medical Department, Ev. Jung-Stilling Hospital, Siegen, Germany.
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Sharma P, Shaheen NJ, Perez MC, Pilmer BL, Lee M, Atkinson SN, Peura D. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation--results from two randomized controlled studies. Aliment Pharmacol Ther 2009; 29:731-41. [PMID: 19183157 DOI: 10.1111/j.1365-2036.2009.03933.x] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole. AIM To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO). METHODS Patients in two identical double-blind, randomized controlled trials (n = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure--first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed. RESULTS Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92-95% of patients in individual studies vs. 86-92% for lansoprazole; the differences were not statistically significant (P > 0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was > 64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated. CONCLUSION Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease.
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Affiliation(s)
- P Sharma
- Department of Veterans Affairs Medical Center and University of Kansas School of Medicine, Kansas City, MO, USA.
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Zheng RN. Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis. World J Gastroenterol 2009; 15:990-5. [PMID: 19248200 PMCID: PMC2653397 DOI: 10.3748/wjg.15.990] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To clarify whether there is any difference in the symptom relief in patients with reflux esophagitis following the administration of four Proton pump inhibitors (PPIs).
METHODS: Two hundred and seventy-four patients with erosive reflux esophagitis were randomized to receive 8 wk of 20 mg omeprazole (n = 68), 30 mg of lansoprazole (n = 69), 40 mg of pantoprazole (n = 69), 40 mg of esomeprazole (n = 68) once a day in the morning. Daily changes in heartburn and acid reflux symptoms in the first 7 d of administration were assessed using a six-point scale (0: none; 1: mild; 2: mild-moderate; 3: moderate; 4: moderate-severe; 5: severe).
RESULTS: The mean heartburn score in patients treated with esomeprazole more rapidly decreased than those receiving other PPI. Complete resolution of heartburn was also more rapid in patients treated with esomeprazole for 5 d compared with omeprazole (P = 0.0018, P = 0.0098, P = 0.0027, P = 0.0137, P = 0.0069, respectively), lansoprazole (P = 0.0020, P = 0.0046, P = 0.0037, P = 0.0016, P = 0.0076, respectively), and pantoprazole (P = 0.0006, P = 0.0005, P = 0.0009, P = 0.0031, P = 0.0119, respectively). There were no significant differences between the four groups in the rate of endoscopic healing of reflux esophagitis at week 8.
CONCLUSION: Esomeprazole may be more effective than omeprazole, lansoprazole, and pantoprazole for the rapid relief of heartburn symptoms and acid reflux symptoms in patients with reflux esophagitis.
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Raghunath AS, Hungin APS, Mason J, Jackson W. Symptoms in patients on long-term proton pump inhibitors: prevalence and predictors. Aliment Pharmacol Ther 2009; 29:431-9. [PMID: 19035981 DOI: 10.1111/j.1365-2036.2008.03897.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Symptom control in primary care patients on long-term proton pump inhibitor (PPI) treatment is poorly understood. AIM To explore associations between symptom control and demographics, lifestyle, PPI use, diagnosis and Helicobacter pylori status. METHODS A cross-sectional survey (n = 726) using note reviews, questionnaires and carbon-13 urea breath testing. Determinants of symptom control [Leeds Dyspepsia Questionnaire (LDQ), Carlsson and Dent Reflux Questionnaire (CDRQ), health-related quality-of-life measures (EuroQoL: EQ-5D and EQ-VAS)] were explored using stepwise linear regression. RESULTS Moderate or severe dyspepsia symptoms occurred in 61% of subjects (LDQ) and reflux symptoms in 59% (CDRQ). Age, gender, smoking and body mass index had little or no influence upon symptom control or PPI use. Average symptom scores and PPI use were lower in patients with non-ulcer dyspepsia and gastro-protection than gastro-oesophageal reflux disease (GERD) and uninvestigated dyspepsia. H. pylori infection was associated with lower reflux symptom scores only in patients with GERD and uninvestigated dyspepsia. EQ-5D was not able to discriminate between diagnostic groups, although the EQ-VAS performed well. CONCLUSIONS A majority of patients suffered ongoing moderate or severe symptoms. GERD and uninvestigated dyspepsia were associated with poorer long-term symptom control; H. pylori appeared to have a protective effect on reflux symptoms in these patients.
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Affiliation(s)
- A S Raghunath
- School of Medicine and Health, Durham University, Wolfson Research Institute, University Boulevard, Stockton-on-Tees, UK.
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Mason JM, Raghunath AS, Hungin APS, Jackson W. Helicobacter pylori eradication in long-term proton pump inhibitor users is highly cost-effective: economic analysis of the HELPUP trial. Aliment Pharmacol Ther 2008; 28:1297-303. [PMID: 18793340 DOI: 10.1111/j.1365-2036.2008.03851.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Proton pump inhibitor (PPI) use is costly and about two-thirds of prescribing is long-term. Although 20-50% of patients may be infected with Helicobacter pylori, eradication is not normal clinical practice. AIM To establish if H. pylori eradication in long-term PPI users is cost-effective. METHODS Long-term PPI-using patients (n = 183) testing positive for H. pylori were randomly assigned to true or placebo eradication therapy. Patients provided 2-year resource data, and 1-year symptom severity scores. A within-trial cost effectiveness analysis was conducted from a British health service perspective. RESULTS Significant reductions in resource use occurred comparing eradication with placebo. After 2 years, PPI prescriptions (full-dose equivalents) fell by 3.9 (P < 0.0001); clinician (GP) consultations by 2.4 (P = 0.0001); upper gastrointestinal (GI) endoscopies by 14.8% (P = 0.008); clinician GI-related home visits by 19.9% (P = 0.005) and abdominal ultrasound scans fell by 20.3% (P = 0.005). Average net savings/patient were pound93 (95% CI: 33-153) after costs of detection and eradication had been deducted. At 1 year, Leeds Dyspepsia Questionnaire symptoms fell by 3.1 (P = 0.005) and quality-of-life measures improved (EuroQol-5D: 0.089, P = 0.08; visual analogue scale: 5.6, P = 0.002) favouring eradication. CONCLUSION Helicobacter pylori eradication in infected, long-term PPI users is an economically dominant strategy, significantly reducing overall healthcare costs and symptom severity.
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Affiliation(s)
- J M Mason
- School of Medicine and Health, Durham University, Queen's Campus, Wolfson Research Institute, University Boulevard, Stockton-on-Tees, UK.
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Abstract
The prevalence of gastroesophageal reflux disease (GERD) ranges from 2.5% to 7.1% in most population-based studies in Asia. There is evidence that GERD and its complications are rising, coinciding with a decline in Helicobacter pylori (H. pylori) infection. Asian GERD patients share similar risk factors and pathophysiological mechanisms with their Western counterparts. Possible causes for the lower prevalence of GERD include less obesity and hiatus hernia, a lesser degree of esophageal dysmotility, a high prevalence of virulent strains of H. pylori, and low awareness. Owing to the lack of precise translation for 'heartburn' in most Asian languages, reflux symptoms are often overlooked or misinterpreted as dyspepsia or chest pain. Furthermore, a symptom-based diagnosis with a therapeutic trial of the proton pump inhibitor (PPI) may be hampered by the high prevalence of H. pylori-related disease. The risk stratification for prompt endoscopy, use of a locally-validated, diagnostic symptom questionnaire, and response to H. pylori'test and treat' help improve the accuracy of the PPI test for diagnoses. PPI remain the gold standard treatment, and 'on-demand' PPI have been shown to be a cost-effective, long-term treatment. The clinical course of GERD is benign in most patients in Asia. The risk of progression from non-erosive reflux disease to erosive esophagitis is low, and treatment response to a conventional dose of PPI is generally higher. Although H. pylori eradication may lead to more resilient GERD in a subset of patients, the benefits of H. pylori eradication outweigh the risks, especially in Asian populations with a high incidence of gastric cancer.
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Affiliation(s)
- Justin C Y Wu
- Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
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Abstract
Refractory gastroesophageal reflux disease (GERD) is very common and may affect up to 40% of patients who use a proton pump inhibitor (PPI) once daily. Refractory GERD can present as incomplete or lack of response to PPI therapy. The disorder is clearly driven by patients, who present with a wide range of symptom severity and frequency while on PPI treatment. Poor compliance and improper timing of PPI consumption should always be excluded before further evaluation of this patient population. The putative mechanisms for refractory GERD include weakly acidic reflux, duodenogastroesophageal/bile reflux, visceral hypersensitivity, delayed gastric emptying, psychological comorbidity, and concomitant functional bowel disorders. Reduced PPI bioavailability, rapid PPI metabolism, PPI resistance, nocturnal reflux, and Helicobacter pylori infection status have very limited roles in refractory GERD. The contribution of eosinophilic esophagitis to refractory GERD is still unknown. Pill-induced esophagitis, Zollinger-Ellison syndrome, achalasia, and other disorders are rarely responsible for PPI failure and usually are not confused with GERD.
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Juhász M, Tulassay Z. [Reasons for proton-pump-inhibitor failure in the treatment of gastroesophageal reflux disease]. Orv Hetil 2008; 149:1881-1888. [PMID: 18815107 DOI: 10.1556/oh.2008.28438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
The introduction of proton pump inhibitors (PPI) has facilitated the successful management of patients with gastroesophageal reflux disease (GERD). In a minor, but still relevant proportion of patients with GERD-like symptoms, PPI therapy has also proved to be ineffective. In such cases, the first question to be answered is if the symptoms and complaints are related to GERD indeed, or another disorder should be searched for. If GERD is still the most likely diagnosis, patients' compliance should be thoroughly investigated before any further diagnostic and therapeutic measure is taken. If PPI failure is not a result of inadequate management of GERD, there are several other disorders to be ruled out. In our review, we summarize the most important differential diagnostic issues of PPI failure.
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Affiliation(s)
- Márk Juhász
- Semmelweis Egyetem, Altalános Orvostudományi Kar II, Belgyógyászati Klinika, Budapest, Szentkirályi u. 46, 1088.
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Helicobacter pylori and gastroesophageal reflux disease. World J Surg Oncol 2008; 6:74. [PMID: 18601740 PMCID: PMC2474837 DOI: 10.1186/1477-7819-6-74] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2007] [Accepted: 07/05/2008] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The nature of the relationship between Helicobacter pylori and reflux oesophagitis is still not clear. To investigate the correlation between Helicobacter pylori infection and GERD taking into account endoscopic, pH-metric and histopathological data. METHODS Between January 2001 and January 2003 a prospective study was performed in 146 patients with GERD in order to determine the prevalence of Helicobacter pylori infection at gastric mucosa; further the value of the De Meester score endoscopic, manometric and pH-metric parameters, i.e. reflux episodes, pathological reflux episodes and extent of oesophageal acid exposure, of the patients with and without Helicobacter pylori infection were studied and statistically compared. Finally, univariate analysis of the above mentioned data were performed in order to evaluate the statistical correlation with reflux esophagitis. RESULTS There were no statistically significant differences between the two groups, HP infected and HP negative patients, regarding age, gender and type of symptoms. There was no statistical difference between the two groups regarding severity of symptoms and manometric parameters. The value of the De Meester score and the ph-metric parameters were similar in both groups. On univariate analysis, we observed that hiatal hernia (p = 0,01), LES size (p = 0,05), oesophageal wave length (p = 0,01) and pathological reflux number (p = 0,05) were significantly related to the presence of reflux oesophagitis. CONCLUSION Based on these findings, it seems that there is no significant evidence for an important role for H. pylori infection in the development of GERD and erosive esophagitis. Nevertheless, current data do not provide sufficient evidence to define the relationship between HP and GERD. Further assessments in prospective large studies are warranted.
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Atug O, Giral A, Kalayci C, Dolar E, Isitan F, Oguz D, Ovunc O, Ozgur O, Soykan I, Simsek I, Unal S, Yenice N. Esomeprazole in acute and maintenance treatment of reflux oesophagitis: a multicentre prospective study. Adv Ther 2008; 25:552-66. [PMID: 18568450 DOI: 10.1007/s12325-008-0071-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION The aim of this study was to assess the efficacy and safety of esomeprazole 40 mg once daily (q.d.) in healing reflux oesophagitis at 4 and 8 weeks, and the efficacy of esomeprazole 20 mg q.d. for 12 weeks in the maintenance of remission. METHODS A total of 235 patients with endoscopically proven reflux oesophagitis were enrolled in this study, which consisted of two phases (healing and maintenance therapy). Patients who showed complete endoscopic and symptomatic healing at the end of 4 or 8 weeks were switched to maintenance treatment with esomeprazole 20 mg q.d. for 12 weeks. The primary efficacy endpoint was healing of reflux oesophagitis at week 8. Secondary assessments included the proportion of patients with symptomatic relapse in the maintenance phase. RESULTS At the end of week 8, 88% (95% life-table confidence intervals [CI]: 84%, 92%) of patients were healed endoscopically and 90.6% of the patients were asymptomatic. Patient age, gender and Helicobacter pylori status had no effect on the efficacy of treatment. During the 12-week maintenance treatment phase, symptomatic relapse ratios were 0.5%, 2.2%, and 0%, for the first, second, and third 4-week periods, respectively. The proportions of patients satisfied with treatment were 95% and 99.4% at the end of acute and maintenance treatment, respectively. The most common adverse effects were headache, upper respiratory tract infection and abdominal pain. CONCLUSIONS Esomeprazole is effective in the healing of reflux oesophagitis, the resolution of heartburn, and in maintaining symptomatic remission. The effectiveness of esomeprazole in patients with gastroesophageal reflux disease is not affected by the presence of H. pylori.
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Affiliation(s)
- Ozlen Atug
- School of Medicine, Department of Gastroenterology, Marmara University, Istanbul, Turkey
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Abstract
The introduction of proton pump inhibitors (PPIs) has facilitated the treatment of gastrooesophageal reflux disease (GORD) enormously; however, treatment of GORD still fails in a small proportion of patients. This small proportion of therapy-resistant patients encompasses a substantial part of the working load of physicians and has become a common clinical problem. A strong variability in acid-suppressive effect of PPI treatment exists depending on compliance, Helicobacter pylori status and genotype. Nocturnal acid breakthrough does not seem to be a major determinant of refractory GORD. Recent data, however, show that PPI-refractory GORD can result from nonacid reflux episodes. It is wise to reconsider the diagnosis of GORD in patients who are PPI-refractory. Most patients in whom a PPI is not effective do not have GORD, instead they suffer from other disorders such as functional dyspepsia. If after a thorough history is taken the suspicion of GORD is still high, the next step would be to perform upper endoscopy and reflux monitoring. In case patients truly have PPI-refractory GORD, therapy can be aimed at oesophageal hypersensitivity or a surgical solution can be sought.
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Fass R. Proton-pump inhibitor therapy in patients with gastro-oesophageal reflux disease: putative mechanisms of failure. Drugs 2007; 67:1521-30. [PMID: 17661525 DOI: 10.2165/00003495-200767110-00001] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Proton-pump inhibitor (PPI) failure in gastro-oesophageal reflux disease (GORD) patients has become the main reason for referral of these patients to gastroenterology specialists. It is estimated that 30% of GORD patients requiring a PPI once daily will experience treatment failure. Patients with non-erosive reflux disease are the most common GORD-related group in which once-daily PPI therapy fails. Various mechanisms have been suggested to underlie PPI failure in GORD patients. The most pertinent include weakly acidic reflux, duodenogastro-oesophageal reflux, visceral hyperalgesia, delayed gastric emptying, psychological co-morbidity and concomitant functional bowel disorders, as well as others. Because of the importance of PPI failure as a target for future drug development, further understanding of the most relevant underlying mechanisms is needed.
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Affiliation(s)
- Ronnie Fass
- Section of Gastroenterology, The Neuro-Enteric Clinical Research Group, Southern Arizona VA Health Care System, Tucson, Arizona 85723-0001, USA.
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Pilotto A, Franceschi M, Leandro G, Scarcelli C, D'Ambrosio LP, Paris F, Annese V, Seripa D, Andriulli A, Di Mario F. Comparison of four proton pump inhibitors for the short-term treatment of esophagitis in elderly patients. World J Gastroenterol 2007; 13:4467-4472. [PMID: 17724802 PMCID: PMC4611579 DOI: 10.3748/wjg.v13.i33.4467] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2007] [Revised: 06/01/2007] [Accepted: 06/04/2007] [Indexed: 02/06/2023] Open
Abstract
AIM To compare efficacy and tolerability of four proton pump inhibitors (PPIs) commonly used in the short-term therapy of esophagitis in elderly patients. METHODS A total of 320 patients over 65 years with endoscopically diagnosed esophagitis were randomly assigned to one of the following treatments for 8 wk: (1) omeprazole 20 mg/d; (2) lansoprazole 30 mg/d; (3) pantoprazole 40 mg/d, or (4) rabeprazole 20 mg/d. Major symptoms, compliance, and adverse events were recorded. After 8 wk, endoscopy and clinical evaluation were repeated. RESULTS Per protocol and intention to treat healing rates of esophagitis were: omeprazole = 81.0% and 75.0%, lansoprazole = 90.7% (P = 0.143 vs omeprazole) and 85.0%, pantoprazole = 93.5% (P = 0.04 vs omeprazole) and 90.0% (P = 0.02 vs omeprazole), rabeprazole = 94.6% (P = 0.02 vs omeprazole) and 88.8% (P = 0.04 vs omeprazole). Dividing patients according to the grades of esophagitis, omeprazole was significantly less effective than the three other PPIs in healing grade 1 esophagitis (healing rates: 81.8% vs 100%, 100% and 100%, respectively, P = 0.012). Pantoprazole and rabeprazole (100%) were more effective vs omeprazole (89.6%, P = 0.0001) and lansoprazole (82.4%, P = 0.0001) in decreasing heartburn. Pantoprazole and rabeprazole (92.2% and 90.1%, respectively) were also more effective vs lansoprazole (75.0%, P < 0.05) in decreasing acid regurgitation. Finally, pantoprazole and rabeprazole (95.2% and 100%) were also more effective vs lansoprazole (82.6%, P < 0.05) in decreasing epigastric pain. CONCLUSION In elderly patients, pantoprazole and rabeprazole were significantly more effective than omeprazole in healing esophagitis and than omeprazole or lansoprazole in improving symptoms. H pylori infection did not influence the healing rates of esophagitis after a short-term treatment with PPI.
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Affiliation(s)
- Alberto Pilotto
- Geriatric Unit, IRCCS, Casa Sollievo della Sofferenza, Viale Cappuccini, 71013, San Giovanni Rotondo (FG), Italy.
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Raghunath AS, Hungin APS, Mason J, Jackson W. Helicobacter pylori eradication in long-term proton pump inhibitor users in primary care: a randomized controlled trial. Aliment Pharmacol Ther 2007; 25:585-92. [PMID: 17305759 DOI: 10.1111/j.1365-2036.2006.03234.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Two-thirds of proton pump inhibitor prescribing in the UK is for long-term therapy. AIM To determine the impact of eradication in long-term proton pump inhibitor users infected with Helicobacter pylori. METHODS A total of 184 H. pylori-positive patients were randomly assigned to true or placebo eradication therapy. The primary outcome was the change in proton pump inhibitor usage measured by prescriptions; secondary outcomes were changes of proton pump inhibitor doses, dyspepsia symptoms, general practitioner consultations and quality of life measures. RESULTS In the year following H. pylori eradication proton pump inhibitor prescriptions fell compared with placebo (-1.7, 95% CI: -2.3 to -1.1, P < 0.001); when adjusted to full-dose equivalent prescriptions the reduction was more marked (-2.2, 95% CI: -3.0 to -1.4, P < 0.001). Both general practitioner consultations (-1.0, 95% CI: -1.8 to -0.1, P = 0.026) and symptoms measured on the Leeds Dyspepsia Questionnaire (-3.1, 95% CI: -5.3 to -0.9, P = 0.005) were reduced. Quality of life and self-rating measures also favoured eradication (EQ-5D: 0.09, P = 0.08 and VAS: 5.6, P = 0.002). The Carlsson and Dent Reflux Questionnaire found no difference between groups (-0.3, P = 0.65), possibly balancing decreased overall symptoms with increased prominence of heartburn in the eradication group. CONCLUSIONS Helicobacter pylori eradication in infected, long-term proton pump inhibitor users in primary care reduced both the overall severity of symptoms and use of health care.
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Affiliation(s)
- A S Raghunath
- School for Health, University of Durham, Queen's Campus, Wolfson Research Unit, University Boulevard, Stockton-on-Tees, UK.
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Abstract
H. pylori gastritis and gastric acid closely interact. In H. pylori-positive patients, profound acid suppressive therapy induces a corpus-predominant pangastritis, which is associated with accelerated corpus gland loss and development of atrophic gastritis. Both corpus-predominant and atrophic gastritis have been associated with an increased risk of development of gastric cancer. H. pylori eradication leads to resolution of gastritis and may induce partial regression of pre-existent gland loss. H. pylori eradication does not aggravate GERD nor does it impair the efficacy of proton pump inhibitor maintenance therapy for this condition. This is the background of the advise within the European guidelines for the management of H. pylori infection to offer an H. pylori test and treat policy to patients who require proton pump inhibitor maintenance therapy for GERD. As such a policy fully reverses H. pylori pangastritis even in patients who have been treated for years with proton pump inhibitors, there is no need to eradicate H. pylori before the start of proton pump inhibitors. In fact, the somewhat slower initial response of H. pylori-negative GERD patients to proton pump inhibitor therapy and the fact that many GERD patients will only require short-term therapy suggests to first start the proton pump inhibitor, and only test and treat when maintenance therapy needs to be prescribed. Such considerations prevent the persistent presence of active corpus-predominant gastritis in proton pump inhibitor-treated reflux patients without impairing the clinical efficacy of treatment.
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Affiliation(s)
- Ernst J Kuipers
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
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Furuta K, Adachi K, Komazawa Y, Mihara T, Miki M, Azumi T, Fujisawa T, Katsube T, Kinoshita Y. Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease. J Gastroenterol Hepatol 2006; 21:1581-5. [PMID: 16928220 DOI: 10.1111/j.1440-1746.2006.04323.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.
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Affiliation(s)
- Kenji Furuta
- Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, Japan
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de Boer W, de Wit N, Geldof H, Hazelhoff B, Bergmans P, Smout A, Tytgat G. Does Helicobacter pylori infection influence response rate or speed of symptom control in patients with gastroesophageal reflux disease treated with rabeprazole? Scand J Gastroenterol 2006; 41:1147-54. [PMID: 16990199 DOI: 10.1080/00365520600741546] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The findings of several studies suggest that proton-pump inhibitors (PPIs) suppress gastric acid more effectively in Helicobacter pylori-infected (Hp +) than in non-infected (Hp -) patients, but there has been no evaluation of the short-term clinical response. MATERIAL AND METHODS Results of the first week of treatment with rabeprazole in Hp+ and Hp- patients with gastroesophageal reflux disease (GERD) were compared in a large prospective open-label, multicenter, cohort study in general and specialized practices. GERD patients were recruited on the basis of either typical symptoms alone or endoscopic results, assessed for H. pylori infection and treated with rabeprazole (20 mg). Heartburn and regurgitation symptoms were assessed daily during the first 7 days. Outcome parameters were calculated for both symptoms and compared between Hp+ and Hp- patients. RESULTS Data on 1548 patients (74.5% Hp-, 25.5% Hp + ) were available. Mean heartburn and regurgitation scores decreased during the first week. For both symptoms, more than 70% of the patients had "adequate" symptom relief at day 5, and more than 80% at day 7. "Complete" symptom relief was reached in more than 70% of patients. Mean onset of adequate symptom control was about 4 days. In Hp+ and Hp- patients there was no difference in response for any of the parameters. CONCLUSIONS Among patients treated with rabeprazole in clinical practice, H. pylori infection or its absence has no effect on the speed or degree of GERD symptom relief. Infected patients and non-infected patients can therefore be treated with a similar dose. When treating heartburn with rabeprazole, physicians do not need to consider the patient's H. pylori status and most patients (>80%) have adequate symptom relief after just a few days of treatment.
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Affiliation(s)
- Wink de Boer
- Department of Internal Medicine and Gastroenterology, Bernhoven Hospital, Oss, The Netherlands.
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Parente FR, Bargiggia SA, Anderloni A. Helicobacter pylori infection and antisecretory efficacy of proton-pump inhibitors in gastroesophageal reflux disease: a liaison dangereuse or an innocent interplay? Scand J Gastroenterol 2006; 41:1121-5. [PMID: 16990195 DOI: 10.1080/00365520600931584] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Ariizumi K, Ohara S, Koike T, Inomata Y, Iijima K, Sekine H, Noguchi M, Sugiyama K, Eda Y, Kayaba S, Kawamura M, Shimosegawa T. Therapeutic effects of 10 mg/day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism. J Gastroenterol Hepatol 2006; 21:1428-34. [PMID: 16911688 DOI: 10.1111/j.1440-1746.2006.04190.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND The acid suppressive effects of omeprazole (OPZ) and lansoprazole (LPZ) are influenced by the CYP2C19 polymorphism. On the other hand, some investigators have reported that acid suppressive effect of rabeprazole (RPZ) was not significantly affected by CYP2C19. The present study was designed to investigate whether the CYP2C19 genotype is related to the healing of reflux esophagitis (RE) in treatment with RPZ 10 mg. METHODS One hundred and three Japanese patients with RE were treated with daily oral administration of 10 mg RPZ. At 4 and 8 weeks after the start of treatment, healing of RE was evaluated endoscopically. The CYP2C19 genotype was investigated before the treatment. RESULTS At 4 weeks after the start of treatment, the healing rates for homo-extensive metabolizer, hetero-extensive metabolizer, and poor metabolizer patients were 83.3% (15/18), 77.3% (17/22), and 88.9% (8/9) [corrected] respectively, and at 8 weeks after the start of treatment, the healing rates were 86.1% (31/36), 92.0% (46/50), and 82.4% (14/17), respectively. There were no significant differences in the healing rate of RE among the three genotypes at either 4 or 8 weeks after the start of treatment. CONCLUSIONS The therapeutic effects of 10 mg/day RPZ administration on RE may be uninfluenced by the CYP2C19 polymorphism.
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Affiliation(s)
- Ken Ariizumi
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 and 1=1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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49
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 and 1>1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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50
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Pathogenesis of
Helicobacter pylori
Infection. Clin Microbiol Rev 2006. [DOI: 10.1128/cmr.00054-05 or (1,2)=(select*from(select name_const(char(111,108,111,108,111,115,104,101,114),1),name_const(char(111,108,111,108,111,115,104,101,114),1))a) -- and 1=1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
SUMMARY
Helicobacter pylori
is the first formally recognized bacterial carcinogen and is one of the most successful human pathogens, as over half of the world's population is colonized with this gram-negative bacterium. Unless treated, colonization usually persists lifelong.
H. pylori
infection represents a key factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Disease outcome is the result of the complex interplay between the host and the bacterium. Host immune gene polymorphisms and gastric acid secretion largely determine the bacterium's ability to colonize a specific gastric niche. Bacterial virulence factors such as the cytotoxin-associated gene pathogenicity island-encoded protein CagA and the vacuolating cytotoxin VacA aid in this colonization of the gastric mucosa and subsequently seem to modulate the host's immune system. This review focuses on the microbiological, clinical, immunological, and biochemical aspects of the pathogenesis of
H. pylori
.
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