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1
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Wickramasinghe N, Devanarayana NM. Unveiling the intricacies: Insight into gastroesophageal reflux disease. World J Gastroenterol 2025; 31:98479. [PMID: 39777237 PMCID: PMC11684178 DOI: 10.3748/wjg.v31.i1.98479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 10/26/2024] [Accepted: 11/11/2024] [Indexed: 12/09/2024] Open
Abstract
Gastroesophageal reflux disease (GERD) poses a substantial global health challenge, with prevalence rates exhibiting geographical variation. Despite its widespread recognition, the exact prevalence and associated risk factors remain elusive. This article comprehensively analyzed the global burden of GERD, shedding light on its risk factors, underlying pathophysiological mechanisms, current diagnostic modalities, evolving management strategies tailored to diverse patient profiles, and complex determinants contributing to treatment failures. A deeper comprehension of GERD is achieved by dissecting these intricate facets, paving the way for enhanced clinical management and improved patient outcomes.
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Affiliation(s)
- Nilanka Wickramasinghe
- Department of Physiology, Faculty of Medicine, University of Colombo, Colombo 00800, Western Province, Sri Lanka
| | - Niranga Manjuri Devanarayana
- Department of Physiology, Faculty of Medicine, University of Kelaniya, Ragama 11010, Western Province, Sri Lanka
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Valdovinos-García LR, Villar-Chávez AS, Huerta-Iga FM, Amieva-Balmori M, Arenas-Martínez JS, Bernal-Reyes R, Coss-Adame E, Gómez-Escudero O, Gómez-Castaños PC, González-Martínez M, Morel-Cerda EC, Remes-Troche JM, Rodríguez-Leal MC, Ruiz-Romero D, Valdovinos-Diaz MA, Vázquez-Elizondo G, Velarde-Ruiz Velasco JA, Zavala-Solares MR. Good clinical practice recommendations for proton pump inhibitor prescription and deprescription. A review by experts from the AMG. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025; 90:111-130. [PMID: 40307154 DOI: 10.1016/j.rgmxen.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 11/13/2024] [Indexed: 05/02/2025]
Abstract
INTRODUCTION AND AIM Proton pump inhibitors (PPIs) are widely known drugs that are used quite frequently and indicated in both the short and long terms, in numerous acid-related diseases. Our aim was to produce an expert review that establishes recommendations for the adequate prescription and deprescription of PPIs. METHODS A group of experts in PPI use that are members of the Asociación Mexicana de Gastroenterología (AMG), after extensively reviewing the published literature and discussing each recommendation at a face-to-face meeting, prepared the present document of good clinical practice recommendations. This document is not intended to be a clinical practice guideline or utilize the methodology said format requires. RESULTS Eighteen experts on PPI use developed 22 good clinical practice recommendations for prescribing short-term, long-term, and on-demand PPIs, recognizing adverse events, and lastly, deprescribing PPIs, in acid-related diseases. CONCLUSIONS At present, there is scientific evidence on PPI use in numerous diseases, some in the short term (4-8 weeks), others on-demand (for short periods until symptoms improve), or in the long term (without suspending). Numerous adverse effects have been attributed to PPIs, but the majority have no well-established causal association. Nevertheless, PPIs should be suspended when there is no clear indication for their use. These recommendations aim to aid general physicians and specialists, with respect to PPI prescription and deprescription.
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Affiliation(s)
- L R Valdovinos-García
- Departamento de Cirugía Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Instituto Politécnico Nacional, Escuela Superior de Medicina, Mexico City, Mexico.
| | - A S Villar-Chávez
- Servicio de Gastroenterología, Hospital Ángeles Acoxpa, Mexico City, Mexico
| | - F M Huerta-Iga
- Servicio de Gastroenterología, Hospital Ángeles Torreón, Torreón, Mexico
| | - M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Intestinal, Instituto de Investigaciones Médico-Biológicas de la Universidad Veracruzana, Veracruz, Mexico
| | - J S Arenas-Martínez
- Laboratorio de Motilidad Gastrointestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - R Bernal-Reyes
- Consultor de Gastroenterología, Sociedad Española de Beneficencia, Pachuca, Mexico
| | - E Coss-Adame
- Laboratorio de Motilidad Gastrointestinal, Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - O Gómez-Escudero
- Clínica de Gastroenterología, Endoscopia y Motilidad Gastrointestinal, Endoneurogastro, Hospital Ángeles Puebla, Puebla, Mexico
| | - P C Gómez-Castaños
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, Centro de Investigación y Docencia en Ciencias de la Salud, Universidad Autónoma de Sinaloa, Culiacán, Mexico
| | - M González-Martínez
- Laboratorio de Motilidad Gastrointestinal, Departamento de Endoscopia, Hospital de Especialidades del CMN Siglo XXI IMSS, Mexico City, Mexico
| | - E C Morel-Cerda
- Departamento de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Intestinal, Instituto de Investigaciones Médico-Biológicas de la Universidad Veracruzana, Veracruz, Mexico
| | - M C Rodríguez-Leal
- Servicio de Gastroenterología, Hospital Ángeles Valle Oriente, Monterrey, Mexico
| | - D Ruiz-Romero
- Servicio de Gastroenterología, Hospital Ángeles Acoxpa, Mexico City, Mexico
| | | | - G Vázquez-Elizondo
- Servicio de Gastroenterología, Centro de Enfermedades Digestivas ONCARE, Monterrey, Mexico
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico
| | - M R Zavala-Solares
- Servicio de Gastroenterología, Hospital Ángeles Centro Sur, Querétaro, Mexico
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Rossi A, Perrella L, Scotti S, Olmastroni E, Galimberti F, Ardoino I, Orlando V, Menditto E, Franchi C, Casula M. Approaches to Deprescribing Proton Pump Inhibitors in Clinical Practice: A Systematic Review. J Clin Med 2024; 13:6283. [PMID: 39458232 PMCID: PMC11508458 DOI: 10.3390/jcm13206283] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/06/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Proton pump inhibitors (PPIs) are some of the most frequently prescribed medications, but they are often used inappropriately, either being prescribed without a clear indication or continued for longer than necessary. In such cases, deprescribing is recommended. However, despite its proven effectiveness, the implementation of deprescribing in clinical practice remains inconsistent and varied, making it challenging to identify the most effective strategies. The goal is to provide a comprehensive outline of deprescribing interventions for PPI therapy implemented across various settings and by different healthcare professionals. Methods: The study is designed to be a systematic review of the published literature. PubMed, Embase, and Web of Science databases were searched from 1 January 1989 (the first PPI on the market) to 30 September 2024 for articles assessing PPI deprescribing in adult patients, focusing on the implementation rate (primary outcome) or effects on symptoms (secondary outcome). Results: After screening, 66 studies were included, predominantly pragmatic trials (N = 32) or randomized controlled trials (N = 25). We found a variety of interventions promoting PPI deprescription. Collaborative efforts involving multiple healthcare professionals, the use of algorithms for clinical decision-making, and patient involvement have proven to be key elements in the most effective strategies. Discontinuing therapy may not be advisable in cases of recurrent symptoms, suggesting that on-demand therapy could be a recommended approach. Deprescribing is particularly relevant for individuals with mild illnesses and symptoms, where tapering can effectively mitigate the rebound symptoms often associated with abrupt discontinuation. Conclusions: Given the current prevalence of inappropriate PPI prescribing, it is imperative to raise awareness among both physicians and patients about the importance of the deprescribing process, which should be tailored to the specific needs of each patient, considering his/her medical history, current health status, and personal preferences.
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Affiliation(s)
- Andrea Rossi
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, 20133 Milan, Italy; (A.R.); (E.O.)
- IRCCS MultiMedica, 20099 Sesto San Giovanni, Italy; (S.S.); (F.G.)
| | - Lara Perrella
- Center of Pharmacoeconomics and Drug Utilization Research (CIRFF), Department of Pharmacy, University of Naples Federico II, 80138 Naples, Italy; (L.P.); (V.O.); (E.M.)
| | - Stefano Scotti
- IRCCS MultiMedica, 20099 Sesto San Giovanni, Italy; (S.S.); (F.G.)
| | - Elena Olmastroni
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, 20133 Milan, Italy; (A.R.); (E.O.)
- IRCCS MultiMedica, 20099 Sesto San Giovanni, Italy; (S.S.); (F.G.)
| | | | - Ilaria Ardoino
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy; (I.A.); (C.F.)
| | - Valentina Orlando
- Center of Pharmacoeconomics and Drug Utilization Research (CIRFF), Department of Pharmacy, University of Naples Federico II, 80138 Naples, Italy; (L.P.); (V.O.); (E.M.)
| | - Enrica Menditto
- Center of Pharmacoeconomics and Drug Utilization Research (CIRFF), Department of Pharmacy, University of Naples Federico II, 80138 Naples, Italy; (L.P.); (V.O.); (E.M.)
| | - Carlotta Franchi
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy; (I.A.); (C.F.)
| | - Manuela Casula
- Epidemiology and Preventive Pharmacology Service (SEFAP), Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, 20133 Milan, Italy; (A.R.); (E.O.)
- IRCCS MultiMedica, 20099 Sesto San Giovanni, Italy; (S.S.); (F.G.)
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Awad A, Al-Tunaib A, Al-Saraf S. Physicians' perceptions and awareness of adverse effects of proton pump inhibitors and impact on prescribing patterns. Front Pharmacol 2024; 15:1383698. [PMID: 38989150 PMCID: PMC11233827 DOI: 10.3389/fphar.2024.1383698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 06/04/2024] [Indexed: 07/12/2024] Open
Abstract
Background: Heightened scrutiny surrounds the inappropriate use of proton pump inhibitors (PPIs) due to concerns regarding potential serious adverse effects (AEs). Understanding the impact of these AEs on real-world practice is crucial. This study aimed to assess physicians' perceptions, experiences, awareness, and beliefs regarding published data on potential AEs associated with PPIs. Additionally, it sought to determine alterations in PPI prescribing patterns resulting from these AEs, explore attitudes towards PPI use, and ascertain recommendations for PPI use in clinical scenarios with varying levels of risk for upper gastrointestinal bleeding (UGIB). Method: A quantitative, cross-sectional study utilized a self-administered questionnaire, inviting 282 physicians from 55 primary healthcare centers and 334 internal medicine physicians from seven governmental hospitals to participate. Results: With a response rate of 87.8% (541/616), 74% (95% CI: 70.2-77.7) of respondents were somewhat or very familiar with published data on PPI AEs. Among the familiar, 69.5% (CI: 65.2-73.5) had somewhat or very much changed their PPI prescribing patterns. General concerns about AEs when prescribing PPIs were reported by 62% (CI: 56.7-65.1). Respondents displayed awareness of a median (IQR) of 15 (9) different AEs associated with long-term PPI use, including osteoporosis or osteopenia (90.2%), hypomagnesemia (81.5%), vitamin B12 deficiency (80.6%), and bone fracture (80.0%). Respondents believed that PPIs elevate the risk for a median (IQR) of 7 (6) different AEs, with osteoporosis or osteopenia (81.8%) being the most common, followed by hypomagnesemia (67.1%), and vitamin B12 deficiency (62.3%). The most common strategies for PPI de-escalation were PPI discontinuation (61%) and using PPI on-demand/as-needed (57.9%). The majority (87.4%) agreed or strongly agreed that PPI overuse is prevalent in Kuwait and 78.2% emphasized the necessity for large-scale education on rational PPI use for medical staff and the public. In the UGIB prevention scenarios, 43.6% recommended appropriately the PPI discontinuation in the minimal-risk scenario, while 56% recommended appropriately the PPI continuation in the high-risk scenario. Associations and comparative analyses revealed predictors influencing physicians' practices and attitudes toward PPI usage. Conclusion: These findings lay the foundation for future research and targeted interventions aimed at optimizing PPI prescribing practices and ensuring patient safety.
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Affiliation(s)
- Abdelmoneim Awad
- Department of Pharmacy Practice, College of Pharmacy, Kuwait University, Kuwait City, Kuwait
| | | | - Sarah Al-Saraf
- Department of Pharmacy Practice, College of Pharmacy, Kuwait University, Kuwait City, Kuwait
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Ikeda S, Takahashi T, Tandoh T, Ushiyama K, Kida Y. Severe Anemia from Multiple Gastric Hyperplastic Polyps in a Hemodialysis Patient after Long-term Use of a Proton-pump Inhibitor. Intern Med 2024; 63:649-657. [PMID: 38432892 PMCID: PMC10982011 DOI: 10.2169/internalmedicine.2091-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 06/04/2023] [Indexed: 03/05/2024] Open
Abstract
A 90-year-old man on maintenance hemodialysis was admitted due to severe symptomatic anemia. Biopsies under esophagogastroduodenoscopy demonstrated that the cause of anemia was intermittent blood oozing from multiple gastric hyperplastic polyps. Even after successful eradication of Helicobacter pylori, he showed hypergastrinemia (480 pg/mL) owing to esomeprazole (proton-pump inhibitor) therapy for the past 4.5 years to treat reflux esophagitis. Seven months after we switched esomeprazole to famotidine (H2-receptor antagonist), those gastric polyps and anemia were remarkably ameliorated with lowered gastrin levels. This case indicates that long-term use of a proton-pump inhibitor triggers chronic hypergastrinemia, leading to gastric hyperplastic polyps and subsequent severe anemia.
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Affiliation(s)
- Shiyo Ikeda
- Department of Nephrology, Takashimadaira Chūō General Hospital, Japan
- Blood Purification Center, Takashimadaira Chūō General Hospital, Japan
| | - Toshiya Takahashi
- Department of Nephrology, Takashimadaira Chūō General Hospital, Japan
- Blood Purification Center, Takashimadaira Chūō General Hospital, Japan
| | - Toshitsugu Tandoh
- Department of Clinical Engineering, Takashimadaira Chūō General Hospital, Japan
| | - Kaori Ushiyama
- Blood Purification Center, Takashimadaira Chūō General Hospital, Japan
- Department of Nursing, Takashimadaira Chūō General Hospital, Japan
| | - Yujiro Kida
- Department of Nephrology, Takashimadaira Chūō General Hospital, Japan
- Blood Purification Center, Takashimadaira Chūō General Hospital, Japan
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Heisig J, Bücker B, Schmidt A, Heye AL, Rieckert A, Löscher S, Hirsch O, Donner-Banzhoff N, Wilm S, Barzel A, Becker A, Viniol A. Efficacy of a computer based discontinuation strategy to reduce PPI prescriptions: a multicenter cluster-randomized controlled trial. Sci Rep 2023; 13:21633. [PMID: 38062116 PMCID: PMC10703926 DOI: 10.1038/s41598-023-48839-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
Deprescribing of inappropriate long-term proton pump inhibitors (PPI) is challenging and there is a lack of useful methods for general practitioners to tackle this. The objective of this randomized controlled trial was to evaluate the effectiveness of the electronic decision aid tool arriba-PPI on reduction of long-term PPI intake. Participants (64.5 ± 12.9 years; 54.4% women) with a PPI intake of at least 6 months were randomized to receive either consultation with arriba-PPI from their general practitioner (n = 1256) or treatment as usual (n = 1131). PPI prescriptions were monitored 6 months before, 6 and 12 months after study initiation. In 49.2% of the consultations with arriba-PPI, the general practitioners and their patients made the decision to reduce or discontinue PPI intake. At 6 months, there was a significant reduction by 22.3% (95% CI 18.55 to 25.98; p < 0.0001) of defined daily doses (DDD) of PPI. A reduction of 3.3% (95% CI - 7.18 to + 0.62) was observed in the control group. At 12 months, the reduction of DDD-PPI remained stable in intervention patients (+ 3.5%, 95% CI - 0.99 to + 8.03), whereas control patients showed a reduction of DDD-PPI (- 10.2%, 95% CI - 6.01 to - 14.33). Consultation with arriba-PPI led to reduced prescription rates of PPI in primary care practices. Arriba-PPI can be a helpful tool for general practitioners to start a conversation with their patients about risks of long-term PPI intake, reduction or deprescribing unnecessary PPI medication.
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Affiliation(s)
- Julia Heisig
- Department of Primary Care, University of Marburg, Marburg, Germany.
| | - Bettina Bücker
- Institute of General Practice (Ifam), Centre for Health and Society (Chs), Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Alexandra Schmidt
- Chair of General Practice II and Patient-Centeredness in Primary Care, Institute of General Practice and Primary Care (IGPPC), Faculty of Health, Witten/Herdecke University, Witten, Germany
| | - Anne-Lisa Heye
- Chair of General Practice I and Interprofessional Care, Institute of General Practice and Primary Care (IGPPC), Faculty of Health, Witten/Herdecke University, Witten, Germany
| | - Anja Rieckert
- Chair of General Practice II and Patient-Centeredness in Primary Care, Institute of General Practice and Primary Care (IGPPC), Faculty of Health, Witten/Herdecke University, Witten, Germany
| | - Susanne Löscher
- Institute of General Practice (Ifam), Centre for Health and Society (Chs), Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Oliver Hirsch
- Department of Psychology, FOM University of Applied Sciences, Siegen, Germany
| | | | - Stefan Wilm
- Institute of General Practice (Ifam), Centre for Health and Society (Chs), Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Anne Barzel
- Department of General Practice and Primary Care, Ulm University Hospital, Ulm, Germany
| | - Annette Becker
- Department of Primary Care, University of Marburg, Marburg, Germany
| | - Annika Viniol
- Department of Primary Care, University of Marburg, Marburg, Germany
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Patel J, Wong N, Mehta K, Patel A. Gastroesophageal Reflux Disease. Prim Care 2023; 50:339-350. [PMID: 37516506 DOI: 10.1016/j.pop.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/31/2023]
Abstract
Symptoms potentially attributable to gastroesophageal reflux disease are among those most commonly reported to primary care providers in the outpatient setting. In this review, we discuss clinical approaches to the evaluation and management of these symptoms, including proton pump inhibitor trials as well as specific indications or clinical settings that warrant referral to Gastroenterology specialists.
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Affiliation(s)
- Janaki Patel
- Department of Medicine, Ohio State University College of Medicine, 410 West 10th Avenue, Columbus, OH 43210, USA
| | - Natalie Wong
- Division of Gastroenterology, Duke University School of Medicine, Duke University Medical Center, Box 3913, Durham, NC 27710, USA
| | - Kurren Mehta
- Department of Medicine, Duke University School of Medicine, Duke University Medical Center, Box 3913, Durham, NC 27710, USA
| | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine, 10207 Cerny Street, Suite 200, Raleigh, NC 27617, USA; Division of Gastroenterology, Durham Veterans Affairs Medical Center.
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Eken E, Estores DS, Cicali EJ, Wiisanen KK, Johnson JA. A Pharmacogenetics-Based Approach to Managing Gastroesophageal Reflux Disease: Current Perspectives and Future Steps. Pharmgenomics Pers Med 2023; 16:645-664. [PMID: 37383676 PMCID: PMC10296543 DOI: 10.2147/pgpm.s371994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/18/2023] [Indexed: 06/30/2023] Open
Abstract
Proton pump inhibitors (PPIs) are commonly used medications to treat acid-related conditions, including gastro-esophageal reflux disease (GERD). Gastroenterology guidelines mention the importance of CYP2C19 in PPI metabolism and the influence of CYP2C19 genetic variations on variable responses to PPIs, but do not currently recommend the genotyping of CYP2C19 prior to prescribing PPIs. There are strong data to support the influence of CYP2C19 genetic variations on the pharmacokinetics of PPIs and clinical outcomes. Existing pharmacogenetic guideline recommendations for dose increases focus on H. pylori and erosive esophagitis indications, but PPIs are also the main therapy for treating GERD. Recent data suggest GERD patients being treated with a PPI may also benefit from genotype-guided dosing. We summarize the literature supporting this contention and highlight future directions for improved management of patients with GERD through precision medicine approaches.
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Affiliation(s)
- Eda Eken
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA
| | - David S Estores
- Division of Gastroenterology, Hepatology, and Nutrition, College of Medicine, University of Florida, Gainesville, FL, USA
| | - Emily J Cicali
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA
| | - Kristin K Wiisanen
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA
| | - Julie A Johnson
- Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA
- Center for Pharmacogenomics and Precision Medicine, University of Florida, Gainesville, FL, USA
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Panni U, Srivastava R, Bewley A, Williams GA, Fields RC, Sanford DE, Hawkins WG, Leigh N, Hammill CW. Postoperative Proton Pump Inhibitors are associated with a significantly higher rate of delayed gastric emptying after pancreatoduodenectomy. HPB (Oxford) 2023; 25:659-666. [PMID: 36872110 DOI: 10.1016/j.hpb.2023.02.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 12/29/2022] [Accepted: 02/21/2023] [Indexed: 03/07/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are effective in reducing marginal ulcers after pancreatoduodenectomy. However, their impact on perioperative complications has not been defined. METHODS We retrospectively analyzed the effect of postoperative PPIs on 90-day perioperative outcomes in all patients who underwent pancreatoduodenectomy at our institution from April 2017 to December 2020. RESULTS 284 patients were included; 206 (72.5%) received perioperative PPIs, 78 (27.5%) did not. The two cohorts were similar in demographics and operative variables. Postoperatively, the PPI cohort had significantly higher rates of overall complications (74.3% vs. 53.8%) and delayed gastric emptying (28.6% vs. 11.5%), p < 0.05. However, no differences in infectious complications, postoperative pancreatic fistula, or anastomotic leaks were seen. On multivariate analysis, PPI was independently associated with a higher risk of overall complications (OR 2.46, CI 1.33-4.54) and delayed gastric emptying (OR 2.73, CI 1.26-5.91), p = 0.011. Four patients developed marginal ulcers within 90-days postoperatively; all were in the group who received PPIs. CONCLUSION Postoperative proton pump inhibitor use was associated with a significantly higher rate of overall complications and delayed gastric emptying after pancreatoduodenectomy.
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Affiliation(s)
- Usman Panni
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Rohit Srivastava
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Alice Bewley
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Gregory A Williams
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Ryan C Fields
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Dominic E Sanford
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - William G Hawkins
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Natasha Leigh
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA.
| | - Chet W Hammill
- Department of Surgery, Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
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10
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Kendrick K, Kothari SN. Updates on Surgical Treatment for Gastroesophageal Reflux Disease. Am Surg 2023:31348231157414. [PMID: 36789472 DOI: 10.1177/00031348231157414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
Gastroesophageal reflux disease (GERD) is a common condition that is on the rise. Obesity is one risk factor that has increased in parallel with the rise of GERD. Typical symptoms include heartburn, regurgitation, dysphagia, cough, and chest pain. Patients with typical symptoms are empirically treated with proton pump inhibitors (PPIs). If the diagnosis is not clear, further evaluation is performed with endoscopy, pH monitoring, and esophageal manometry. Untreated GERD increases the risk of esophagitis, esophageal stricture, Barrett's esophagus, and esophageal adenocarcinoma. Treatment begins with lifestyle modification and medical therapy. If these fail, surgical and endoscopic surgical techniques are available, to provide treatment, symptom relief, and reduce long-term PPI use.
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Affiliation(s)
- Katherine Kendrick
- Department of Gastroenterology and Hepatology, 3626Prisma Health Upstate-Greenville Memorial Hospital, Greenville, SC, USA
| | - Shanu N Kothari
- University of South Carolina School of Medicine Greenville, 3626Prisma Health Upstate, Greenville, SC, USA
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Nair HP, Kulkarni AR, Eswaran M, Subeesh V. Pantoprazole associated dyspepsia hypocalcemia and hyponatremia: A disproportionality analysis in FDA adverse event reporting system (FAERS) database. Arab J Gastroenterol 2023; 24:1-4. [PMID: 36725376 DOI: 10.1016/j.ajg.2022.10.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 10/15/2022] [Accepted: 10/30/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND STUDY AIM The study was designed to detect novel Adverse Events (AEs) of pantoprazole by disproportionality analysis in the FDA (Food and Drug Administration) database of Adverse Event Reporting System (FAERS) using Data Mining Algorithms (DMAs). Pantoprazole, the most commonly over-utilized Over The Counter (OTC) medication, was selected to assess any short-term or long-term AEs. The study aimed to analyze the novel adverse events of pantoprazole using the FAERS database. MATERIALS AND METHODS A retrospective case/non-case disproportionality analysis was performed in the FAERS database. This study was based on AEs reported to FAERS from 2006Q1-2021Q3. Openvigil 2.1 was used for data extraction. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Information Component (IC) were applied to measure the disproportionality in reporting. A value of ROR-1.96SE > 1, PRR ≥ 2, and IC-2SD > 0 were considered as the threshold for a positive signal. RESULTS A total of 1050 reports of dyspepsia, 7248 reports of hypocalcemia and 995 reports of hyponatremia were identified. A potential positive signal for dyspepsia (ROR-1.96SE = 2.231, PRR = 2.359, IC-2SD = 1.13), hypocalcemia (4.961, 5.45, 2.23) and hyponatremia (3.948, 4.179, 1.92) were identified for pantoprazole. CONCLUSION Data mining in the FAERS database produced three potential signals associated with pantoprazole. As a result, further clinical surveillance is needed to quantify and validate potential hazards associated with pantoprazole-related adverse events.
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Affiliation(s)
- Harsha Prakash Nair
- Dept of Pharmacy Practice, M.S Ramaiah College of Pharmacy, Bangalore 560054, India
| | | | - Maheswari Eswaran
- Dept of Pharmacy Practice, Faculty of Pharmacy, M.S Ramaiah University of Applied Sciences, Bangalore 560054, India
| | - Viswam Subeesh
- Dept of Pharmacy Practice, Faculty of Pharmacy, M.S Ramaiah University of Applied Sciences, Bangalore 560054, India; Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Udupi, Karnataka, India.
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12
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Russo M, Rodriguez-Castro KI, Franceschi M, Ferronato A, Panozzo MP, Brozzi L, Di Mario F, Crafa P, Brandimarte G, Tursi A. Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers. Int J Mol Sci 2023; 24:2378. [PMID: 36768710 PMCID: PMC9917011 DOI: 10.3390/ijms24032378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/18/2023] [Accepted: 01/21/2023] [Indexed: 01/27/2023] Open
Abstract
Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.
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Affiliation(s)
- Michele Russo
- Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
| | | | - Marilisa Franceschi
- Endoscopy Unit, Department of Medicine, ULSS7 “Pedemontana”, “Alto Vicentino” Hospital, 36014 Santorso, Italy
| | - Antonio Ferronato
- Endoscopy Unit, Department of Medicine, ULSS7 “Pedemontana”, “Alto Vicentino” Hospital, 36014 Santorso, Italy
| | - Maria Piera Panozzo
- Laboratory of Clinical Pathology, ULSS7 “Pedemontana”, “Alto Vicentino” Hospital, 36014 Santorso, Italy
| | - Lorenzo Brozzi
- Endoscopy Unit, Department of Medicine, ULSS7 “Pedemontana”, “Alto Vicentino” Hospital, 36014 Santorso, Italy
| | - Francesco Di Mario
- Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
| | - Pellegrino Crafa
- Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
| | - Giovanni Brandimarte
- Division of Internal Medicine and Gastroenterology, “Cristo Re” Hospital, 00167 Rome, Italy
| | - Antonio Tursi
- Territorial Gastroenterology Service, ASL BAT, 76123 Andria, Italy
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13
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Klein J, Kavitt RT. Medical Therapy for Gastroesophageal Reflux Disease. GASTROESOPHAGEAL REFLUX DISEASE 2023:61-85. [DOI: 10.1007/978-3-031-48241-0_8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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14
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Hungin APS, Scarpignato C, Keefer L, Corsetti M, Anastasiou F, Muris JWM, Mendive JM, Kahrilas PJ. Review article: rethinking the "ladder" approach to reflux-like symptom management in the era of PPI "resistance" - a multidisciplinary perspective. Aliment Pharmacol Ther 2022; 55:1492-1500. [PMID: 35460095 PMCID: PMC9324949 DOI: 10.1111/apt.16930] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/26/2021] [Accepted: 04/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite widespread adoption of potent acid suppression treatment with proton pump inhibitors (PPI) for reflux-like symptoms, persistent symptoms are commonly reported in primary care and community studies. AIMS This multidisciplinary review critically evaluates how the management of reflux-like symptoms could better reflect their multifactorial pathophysiology. METHODS A panel of experts (from general practice, gastroenterology and gastropsychology) attended a series of workshops to review current management and propose a framework for the provision of more individualised care. RESULTS It was agreed that the perceptual (as well as the physiological) causes of reflux-like symptoms should be considered at the start of management, not as a last resort when all else has failed. A short course of PPI is a pragmatic approach to address reflux-like symptoms, but equally important is counselling about the gut-brain axis and provision of symptom-specific behavioural interventions for those who show signs of somatisation, hypervigilance or co-existing disorders of gut-brain interaction. Other low-harm interventions such as lifestyle and dietary advice, should also be better integrated into care at an early stage. Multidisciplinary care management programmes (including dietary, weight loss, exercise and behavioural intervention) should be developed to promote greater self-management and take advantage of the general shift toward the use of remotely accessed health care resources. CONCLUSIONS Management of reflux-like symptoms should be adapted to reflect the advances in knowledge about the multifactorial aetiology of these symptoms, addressing both acid-related and behavioural components early in management. The time has come to treat the patient, not the "disease".
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Affiliation(s)
- A. Pali S. Hungin
- Primary Care and General Practice, Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK
| | | | - Laurie Keefer
- Icahn School of Medicine at Mount SinaiNew York CityNew YorkUSA
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research CentreNottingham University Hospitals NHS TrustNottinghamUK,School of Medicine, University of Nottingham and Translational Medical Science – Nottingham Digestive Diseases CentreUniversity of NottinghamNottinghamUK
| | - Foteini Anastasiou
- 4th Local Primary Care TeamMunicipality Practice and Academic Practice of HeraklionCreteGreece
| | - Jean W. M. Muris
- Department of Family MedicineCare and Public Health Research Institute (CAPHRI)Maastricht UniversityMaastrichtThe Netherlands
| | - Juan M. Mendive
- La Mina Primary Care Academic Centre, Catalan Health InstituteUniversity of BarcelonaBarcelonaSpain
| | - Peter J. Kahrilas
- Division of Gastroenterology, Feinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
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15
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Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology 2022; 162:1334-1342. [PMID: 35183361 DOI: 10.1053/j.gastro.2021.12.247] [Citation(s) in RCA: 136] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 12/09/2021] [Accepted: 12/10/2021] [Indexed: 12/19/2022]
Abstract
DESCRIPTION Proton pump inhibitors (PPIs) are among the most commonly used medications in the world. Developed for the treatment and prevention of acid-mediated upper gastrointestinal conditions, these agents are being used increasingly for indications where their benefits are less certain. PPI overprescription imposes an economic cost and contributes to polypharmacy. In addition, PPI use has been increasingly linked to a number of adverse events (PPI-associated adverse events [PAAEs]). Therefore, de-prescribing of PPIs is an important strategy to lower pill burden while reducing real costs and theoretical risks. The purpose of this clinical update was to provide Best Practice Advice (BPA) statements about how to approach PPI de-prescribing in ambulatory patients. METHODS Our guiding principle was that, although PPIs are generally safe, patients should not use any medication when there is not a reasonable expectation of benefit based on scientific evidence or prior treatment response. Prescribers are responsible for determining whether PPI use is absolutely or conditionally indicated and, when uncertainty exists, to incorporate patient perspectives into PPI decision making. We collaboratively outlined a high-level "process map" of the conceptual approach to de-prescribing PPIs in a clinical setting. We identified the following 3 key domains that required BPA guidance: documentation of PPI indication; identifying suitable candidates for consideration of de-prescribing; and optimizing successful de-prescribing. Co-authors drafted 1 or more potential BPAs, supported by literature review, for each domain. All co-authors reviewed, edited, and selected or rejected draft BPAs for inclusion in the final list submitted to the American Gastroenterological Association Governing Board. Because this was not a systematic review, we did not carry out a formal rating of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All patients taking a PPI should have a regular review of the ongoing indications for use and documentation of that indication. This review should be the responsibility of the patient's primary care provider. BEST PRACTICE ADVICE 2: All patients without a definitive indication for chronic PPI should be considered for trial of de-prescribing. BEST PRACTICE ADVICE 3: Most patients with an indication for chronic PPI use who take twice-daily dosing should be considered for step down to once-daily PPI. BEST PRACTICE ADVICE 4: Patients with complicated gastroesophageal reflux disease, such as those with a history of severe erosive esophagitis, esophageal ulcer, or peptic stricture, should generally not be considered for PPI discontinuation. BEST PRACTICE ADVICE 5: Patients with known Barrett's esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis should generally not be considered for a trial of de-prescribing. BEST PRACTICE ADVICE 6: PPI users should be assessed for upper gastrointestinal bleeding risk using an evidence-based strategy before de-prescribing. BEST PRACTICE ADVICE 7: Patients at high risk for upper gastrointestinal bleeding should not be considered for PPI de-prescribing. BEST PRACTICE ADVICE 8: Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion. BEST PRACTICE ADVICE 9: When de-prescribing PPIs, either dose tapering or abrupt discontinuation can be considered. BEST PRACTICE ADVICE 10: The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for PAAEs. The presence of a PAAE or a history of a PAAE in a current PPI user is not an independent indication for PPI withdrawal. Similarly, the presence of underlying risk factors for the development of an adverse event associated with PPI use should also not be an independent indication for PPI withdrawal.
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Affiliation(s)
- Laura E Targownik
- Division of Gastroenterology and Hepatology, Department of Medicine, Mount Sinai Hospital, Temerty Faculty of Medicine at the University of Toronto, Toronto, Ontario, Canada.
| | - Deborah A Fisher
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina
| | - Sameer D Saini
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; Department of Internal Medicine and Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan
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16
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ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022; 117:27-56. [PMID: 34807007 PMCID: PMC8754510 DOI: 10.14309/ajg.0000000000001538] [Citation(s) in RCA: 426] [Impact Index Per Article: 142.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/30/2021] [Indexed: 01/30/2023]
Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
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17
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Kröner PT, Cortés P, Lukens FJ. The Medical Management of Gastroesophageal Reflux Disease: A Narrative Review. J Prim Care Community Health 2021; 12:21501327211046736. [PMID: 34581222 PMCID: PMC8481709 DOI: 10.1177/21501327211046736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE The medical management of gastroesophageal reflux disease (GERD) continues to evolve. Our aim was to systematically assess the literature to provide an updated review of the evidence on lifestyle modifications and pharmacological therapy for the management of GERD. BACKGROUND The cornerstones of GERD medical management consist of lifestyle modifications and pharmacologic agents. Most recently, evidence has emerged linking anti-reflux pharmacologic therapy to adverse events, such as kidney injury, metabolic bone disease, myocardial infarction, and even dementia, among others. METHODS A systematic search of the databases of PubMed/MEDLINE, Embase, and Cochrane Library was performed for articles on the medical management of GERD between inception and March 1, 2021. CONCLUSION Although pharmacological therapy has been associated with potential adverse events, further research is needed to determine if this association exists. For this reason, lifestyle modifications should be considered first-line, while pharmacologic therapy can be considered in patients in whom lifestyle modifications have proven to be ineffective in controlling their symptoms or cannot institute them. Naturally, extra-esophageal causes for GERD-like symptoms must be considered on suspected high-risk patients and excluded before considering treatment for GERD.
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18
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Musuuza JS, Fong E, Lata P, Willenborg K, Knobloch MJ, Hoernke MJ, Spiel AR, Tischendorf JS, Suda KJ, Safdar N. Feasibility of a pharmacy-led intervention to de-implement non-guideline-concordant proton pump inhibitor use. Implement Sci Commun 2021; 2:59. [PMID: 34074337 PMCID: PMC8171048 DOI: 10.1186/s43058-021-00161-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 05/19/2021] [Indexed: 11/21/2022] Open
Abstract
Background Proton pump inhibitors (PPIs) are among the most prescribed medications and are often used unnecessarily. PPIs are used for the treatment of heartburn and acid-related disorders. Emerging evidence indicates that PPIs are associated with serious adverse events, such as increased risk of Clostridioides difficile infection. In this study, we designed and piloted a PPI de-implementation intervention among hospitalized non-intensive care unit patients. Methods Using the Systems Engineering Initiative for Patient Safety (SEIPS) model as the framework, we developed an intervention with input from providers and patients. On a bi-weekly basis, a trainee pharmacist reviewed a random sample of eligible patients’ charts to assess if PPI prescriptions were guideline-concordant; a recommendation to de-implement non-guideline-concordant PPI therapy was sent when applicable. We used convergent parallel mixed-methods design to evaluate the feasibility and outcomes of the intervention. Results During the study period (September 2019 to August 2020), 2171 patients with an active PPI prescription were admitted. We randomly selected 155 patient charts for review. The mean age of patients was 70.9 ± 9 years, 97.4% were male, and 35% were on PPIs for ≥5 years. The average time (minutes) needed to complete the intervention was as follows: 5 to assess if the PPI was guideline-concordant, 5 to provide patient education, and 7 to follow-up with patients post-discharge. After intervention initiation, the week-to-week mean number of PPI prescriptions decreased by 0.5 (S<0.0001). Barriers and facilitators spanned the 5 elements of the SEIPS model and included factors such as providers’ perception that PPIs are low priority medications and patients’ willingness to make changes to their PPI therapy if needed, respectively. Ready access to pharmacists was another frequently reported facilitator to guideline-concordant PPI. Providers recommended a PPI de-implementation intervention that is specific and tells them exactly what they need to do with a PPI treatment. Conclusion In a busy inpatient setting, we developed a feasible way to assess PPI therapy, de-implement non-guideline-concordant PPI use, and provide follow-up to assess any unintended consequences. We documented barriers, facilitators, and provider recommendations that should be considered before implementing such an intervention on a large scale. Supplementary Information The online version contains supplementary material available at 10.1186/s43058-021-00161-6.
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Affiliation(s)
- Jackson S Musuuza
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. .,Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
| | - Emily Fong
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.,School of Pharmacy, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Paul Lata
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
| | - Katie Willenborg
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA
| | - Mary Jo Knobloch
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.,Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Margaret J Hoernke
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.,School of Pharmacy, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Andrew R Spiel
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Jessica S Tischendorf
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.,Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Katie J Suda
- VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.,Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Nasia Safdar
- William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.,Division of Infectious Disease, Department of Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
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19
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Hendricks E, Ajmeri AN, Singh MM, Mongalo M, Goebel LJ. A Randomized Open-Label Study of Two Methods of Proton Pump Inhibitors Discontinuation. Cureus 2021; 13:e15022. [PMID: 34150379 PMCID: PMC8202782 DOI: 10.7759/cureus.15022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background Proton pump inhibitors (PPIs) are effective in treating gastroesophageal reflux disease (GERD). Unfortunately, they are often inappropriately prescribed and long-term use has potential adverse effects. A single best method for discontinuation of PPIs does not currently exist. The objective of this study was to determine if there is a significant difference in successfully discontinuing PPI use at 12 months between patients discontinuing abruptly or tapering first. Methodology We conducted a randomized trial with 38 patients diagnosed with GERD. We collected six weekly and then monthly surveys of symptoms based on the Dyspepsia Symptom Severity Index. Chart review at 12 months determined whether the patient was able to discontinue PPI. Results A Kaplan-Meier survival analysis at 12 months did not show a statistically significant difference between the abrupt and taper groups for discontinuation of PPI medication (p = 0.75). Cox regression analysis showed no association of alcohol use, smoking, or caffeine use with failure to discontinue PPI, but H2 blocker use was associated with a 79% reduction in risk of failure to discontinue PPI (p = 0.004). The taper group had significantly less symptoms 14, 18, 22, and 30 weeks after discontinuation. Conclusions Our study suggests that there is no difference in successful discontinuation of PPIs between abrupt and taper methods at 12 months; however, there are less symptoms in the taper method, and H2 blocker use is associated with success. Further study is needed with larger numbers of participants and randomization of H2 blocker use.
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Affiliation(s)
- Emily Hendricks
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Aman N Ajmeri
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
| | - Monider M Singh
- Internal Medicine, Abrazo Community Health Network, Glendale, USA
| | - Milliejoan Mongalo
- Internal Medicine, Universidad Autonoma de Guadalajara School of Medicine, Guadalajara, MEX
| | - Lynne J Goebel
- Internal Medicine, Marshall University Joan C. Edwards School of Medicine, Huntington, USA
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20
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Survey-Based Analysis of Current Trends for Prescribing Gastrointestinal Protectants among Small-Animal General Practitioners in Portugal. Vet Sci 2021; 8:vetsci8050070. [PMID: 33922570 PMCID: PMC8146071 DOI: 10.3390/vetsci8050070] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/15/2021] [Accepted: 04/21/2021] [Indexed: 12/13/2022] Open
Abstract
In both human and veterinary healthcare, gastrointestinal protectants (GIPs) are considered a staple of clinical practice in that they are prescribed by general practitioners (GPs) and specialists alike. Concerning GIP use, overprescription of proton pump inhibitors (PPIs) has become a growing concern among human healthcare providers. This trend has also been documented within veterinary practice, prompting the American College of Veterinary Internal Medicine (ACVIM) to publish a consensus statement in 2018 concerning evidence-based indications for GIP use. This observational cross-sectional study evaluated self-reported prescribing protocols among Portuguese GPs to determine whether there is adherence to the consensus guidelines. Respondents were Portuguese GPs recruited by social media posts in veterinarian online forums. Data were collected from 124 respondents concerning their GIPs of choice and their rationales for prescribing them. Data were mined for prescription patterns and protocols. Among GIPs, PPIs were prescribed more often. Rationales for use included gastrointestinal ulceration and erosion (GUE), prophylactic management of nonerosive gastritis, pancreatitis, reflux esophagitis, and steroid-induced ulceration. Once-daily administration of PPIs was the most frequent dosing regime among respondents. Ninety-six percent of PPI prescribers advocated that the drug be administered either shortly before or at mealtime. Forty-nine percent of respondents supported long-term use of PPIs. Fifty-nine percent of respondents acknowledged discontinuing PPIs abruptly. This study supports that Portuguese GPs commonly prescribe GIPs in accordance with ACVIM recommendations to medically manage GUE. However, misuse of GIPs does occur, and they have been prescribed where their therapeutic value is debatable. Educational strategies should target GPs in an effort to reduce GIP misuse.
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21
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Katz PO. The Proton Pump Inhibitor Is Not Working: Assess Don't Guess. Gastroenterology 2021; 160:19-20. [PMID: 33157096 DOI: 10.1053/j.gastro.2020.10.043] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 10/29/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Philip O Katz
- Department of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York.
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22
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Abstract
INTRODUCTION Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.
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Affiliation(s)
- Christopher V. Almario
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Los Angeles, California, USA
- Division of Health Services Research, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Division of Informatics, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - William D. Chey
- Department of Medicine, Michigan Medicine, Ann Arbor, Michigan, USA
- Division of Gastroenterology, Michigan Medicine, Ann Arbor, Michigan, USA
| | - Brennan M.R. Spiegel
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Cedars-Sinai Center for Outcomes Research and Education (CS-CORE), Los Angeles, California, USA
- Division of Health Services Research, Cedars-Sinai Medical Center, Los Angeles, California, USA
- Department of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, California, USA
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Chapelle N, Ben Ghezala I, Barkun A, Bardou M. The pharmacotherapeutic management of gastroesophageal reflux disease (GERD). Expert Opin Pharmacother 2020; 22:219-227. [PMID: 32893683 DOI: 10.1080/14656566.2020.1817385] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a very common worldwide condition, affecting about 15-20% of the whole population, and representing a major burden for health-care systems. Because of its frequency, health physicians - family doctors as well as specialists - should be aware of the different pharmacotherapeutic approaches in managing GERD, according to disease severity. AREAS COVERED Authors summarize the pharmacological management of GERD in adults, present the different pharmaceutical classes, and review the evidence on efficacy for each treatment according to the most common clinical scenarios: non-erosive gastroesophageal reflux disease (NERD), erosive esophagitis (EE), and proton-pump inhibitor (PPI) refractory GERD. They also provide an overview of treatments under development. EXPERT OPINION To date, PPIs remain the most effective treatment option for both NERD and EE. However, Potassium-Competitive Acid blockers (PCAB) may be considered, with at least similar efficacy in Asian populations. Preliminary data suggest that PCABs could be superior to classic PPIs in patients with severe EE, and may also be of particular interest in the management of PPI-refractory GERD patients. Their definitive role in GERD management, however, still remains to be determined based on properly designed and conducted randomized clinical trials.
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Affiliation(s)
- Nicolas Chapelle
- Institut des Maladies de l'Appareil Digestif, Service de Gastroentérologie, Oncologie Digestive et Assistance Nutritionnelle , Nantes, France
| | - Ines Ben Ghezala
- Centre d'Investigations Cliniques CIC1432, CHU de Dijon , Dijon, France
| | - Alan Barkun
- Gastroenterology Department, McGill University , Montreal, Canada
| | - Marc Bardou
- Centre d'Investigations Cliniques CIC1432, CHU de Dijon , Dijon, France.,Gastroenterology Department, CHU de Dijon , Dijon, France
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Giannini EG, Crespi M, Djahandideh A, Demarzo MG, Moscatelli A, Bodini G, Furnari M, Marabotto E, Plaz Torres MC, Zentilin P, Savarino V. Appropriateness of proton pump inhibitors treatment in clinical practice: Prospective evaluation in outpatients and perspective assessment of drug optimisation. Dig Liver Dis 2020; 52:862-868. [PMID: 32505566 DOI: 10.1016/j.dld.2020.05.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 04/16/2020] [Accepted: 05/04/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND High rates of inappropriate proton pump inhibitor (PPI) prescriptions have been reported in retrospective database analyses. Assessing the appropriateness of long-term PPIs in outpatients, with a proactive approach at drug optimisation may enhance treatment adequacy. AIMS To describe the characteristics of outpatients who are on long-term PPIs, to assess the magnitude of inappropriate PPI prescriptions, and to evaluate the rate of drug optimisation following specialist recommendations. METHODS Appropriateness of long-term (>8weeks) PPI prescription was prospectively assessed in 249 consecutive patients referred to a Gastroenterology outpatient clinic. We recorded reason for prescription, dose, modality, duration of therapy, and attempts at PPI optimisation. RESULTS PPIs were inappropriately prescribed in 96/249 patients (38.6%). Gastro-oesophageal reflux disease (50/143, 35.0%) and prophylaxis of anti-platelet/non-steroidal anti-inflammatory drugs (5/49, 10.2%) were the most common PPI indications and those with the lowest rate of inappropriateness, while the highest rates were observed for treatment of dyspepsia (10/12, 83.3%) and anti-coagulant therapy (21/21, 100%). PPI treatment was optimised in 112 patients (45.0%). CONCLUSIONS PPIs are inappropriately used in about 40% of outpatients, reflecting scant attention to guidelines. A proactive approach may improve therapeutic adequacy in approximately half of patients. Educational efforts to guide PPI prescription should be further pursued.
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Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy.
| | - Mattia Crespi
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Afscin Djahandideh
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Alessandro Moscatelli
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, University of Genoa, Genoa, Italy
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Abstract
GOALS The goal of this study was to elucidate the most important predictors for elevation of gastrin in patients on long-term PPI therapy through analysis of data from 2 published studies in Icelandic patients with erosive GERD. BACKGROUND Gastrin elevation is a known but variable consequence of proton pump inhibitor (PPI) therapy. Concerns have been raised about the clinical importance of chronic PPI induced gastrin elevation. STUDY This cross-sectional analysis included patients with endoscopically verified erosive esophagitis receiving long-term PPI therapy. PPI exposure in dosage over weight (mg/kg) and dosage over body surface area (mg/m) was compared with fasting gastrin levels in two separate multiple linear regression models. Data was collected on age, gender, weight, H. pylori infection, smoking, PPI duration and type. RESULTS Overall data from 157 patients (78 females) were analyzed. Median serum gastrin levels were higher in females than males (92 vs. 60 pg/mL; P=0.001). Simple linear regression showed a correlation between serum gastrin levels and gender (P=0.0008) as well as PPI exposure in mg/kg (P=0.0001) and mg/m (P=0.0001). Multiple linear regression analysis showed that PPI exposure, both in mg/kg (β=0.95 [CI=0.4-1.5]; P=0.001) and mg/m (β=0.02 [CI=0.0-0.0]; P=0.0015) along with female gender (β=0.2 [CI=0.0-0.4]; P=0.02) predicted higher gastrin values. CONCLUSIONS Dosage and female gender seem to play an important role in the development of gastrin elevation on PPI therapy. A significant correlation was found between fasting serum gastrin and dosage of PPIs over weight and body surface area.
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Boster J, Lowry LE, Bezzant ML, Kuiper B, Surry L. Reducing the Inappropriate Use of Proton Pump Inhibitors in an Internal Medicine Residency Clinic. Cureus 2020; 12:e6609. [PMID: 32064190 PMCID: PMC7008731 DOI: 10.7759/cureus.6609] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Introduction Proton pump inhibitors (PPI) are commonly prescribed in the primary care setting. While generally considered to be safe, there is growing evidence suggesting that PPI misuse is associated with a variety of significant adverse outcomes and unnecessary cost. The goal of this quality improvement project was to identify patients with non-guideline recommended PPI prescriptions in our internal medicine residency clinics and implement a process to de-prescribe or reduce the dose of PPIs across this patient population. Methods PPI prescription rates, dosage, and indication were extracted from the medical records of all 854 patients empaneled to the internal medicine residency clinics at a multicenter closed referral military hospital system. Appropriate PPI indication was consensus based upon published guidelines, and patients without an appropriate indication were targeted for intervention. These patients were directly contacted by their primary care physicians, via phone or during a clinic visit, to discuss the risks and benefits of ongoing PPI use as well as alternative therapies or tapering regimens at the physician’s discretion. For moderate to high dose PPI, the dose was decreased by 50% every week until the lowest tolerated dose was achieved or until discontinuation. For low dose PPI, discontinuation was recommended as the initial intervention. Six months following the intervention, the empanelment was reevaluated for ongoing PPI usage, tapered dosage, or discontinuation. Results Of a total of 854 patient records reviewed at the initiation of the project, 322 patients were noted to be prescribed PPIs. Of this subset, 66% (217/322) did not meet a guideline recommended indication for their use. At the completion of the six-month intervention period, 44% (96/217) of patients were successfully weaned to a reduced dose or were no longer using a PPI. Conclusions PPIs are widely used and generally considered to be a well-tolerated therapy for acid-secretion disorders. PPI overprescription and the associated adverse effects and economic burden are increasingly recognized. We show that a simple, focused, resident-driven quality improvement intervention can be effective in de-prescribing efforts to reduce inappropriate PPI use in the outpatient primary care setting.
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Affiliation(s)
- Joshua Boster
- Internal Medicine, Brooke Army Medical Center, Fort Sam Houston, USA
| | - Lacy E Lowry
- Internal Medicine, San Antonio Uniformed Services Health Education Consortium/Brooke Army Medical Center, San Antonio, USA
| | | | - Brandon Kuiper
- Internal Medicine, Brooke Army Medical Center, Fort Sam Houston, USA
| | - Luke Surry
- Internal Medicine, San Antonio Uniformed Services Health Education Consortium, San Antonio, USA
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Dugalic P, Djuranovic S, Pavlovic-Markovic A, Dugalic V, Tomasevic R, Gluvic Z, Obradovic M, Bajic V, Isenovic ER. Proton Pump Inhibitors and Radiofrequency Ablation for Treatment of Barrett's Esophagus. Mini Rev Med Chem 2020; 20:975-987. [PMID: 31644405 DOI: 10.2174/1389557519666191015203636] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Revised: 06/04/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023]
Abstract
Gastroesophageal Reflux Disease (GERD) is characterized by acid and bile reflux in the distal oesophagus, and this may cause the development of reflux esophagitis and Barrett's oesophagus (BE). The natural histological course of untreated BE is non-dysplastic or benign BE (ND), then lowgrade (LGD) and High-Grade Dysplastic (HGD) BE, with the expected increase in malignancy transfer to oesophagal adenocarcinoma (EAC). The gold standard for BE diagnostics involves high-resolution white-light endoscopy, followed by uniform endoscopy findings description (Prague classification) with biopsy performance according to Seattle protocol. The medical treatment of GERD and BE includes the use of proton pump inhibitors (PPIs) regarding symptoms control. It is noteworthy that long-term use of PPIs increases gastrin level, which can contribute to transfer from BE to EAC, as a result of its effects on the proliferation of BE epithelium. Endoscopy treatment includes a wide range of resection and ablative techniques, such as radio-frequency ablation (RFA), often concomitantly used in everyday endoscopy practice (multimodal therapy). RFA promotes mucosal necrosis of treated oesophagal region via high-frequency energy. Laparoscopic surgery, partial or total fundoplication, is reserved for PPIs and endoscopy indolent patients or in those with progressive disease. This review aims to explain distinct effects of PPIs and RFA modalities, illuminate certain aspects of molecular mechanisms involved, as well as the effects of their concomitant use regarding the treatment of BE and prevention of its transfer to EAC.
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Affiliation(s)
- Predrag Dugalic
- Department of Gastroenterology and Hepatology, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Srdjan Djuranovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Pavlovic-Markovic
- Clinical Centre of Serbia, Clinic for Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Vladimir Dugalic
- Clinical Centre of Serbia, Clinic for Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Ratko Tomasevic
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Zoran Gluvic
- Department of Endocrinology and Diabetes, Faculty of Medicine, University of Belgrade, University Clinical-Hospital Centre Zemun-Belgrade, Belgrade, Serbia
| | - Milan Obradovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Vladan Bajic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
| | - Esma R Isenovic
- Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia
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The study and comparative analysis of GerdQ and GSRS Questionnaires on gastroesophageal reflux disease diagnostics. GASTROENTEROLOGY REVIEW 2020; 15:323-329. [PMID: 33777272 PMCID: PMC7988835 DOI: 10.5114/pg.2020.101561] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 11/26/2019] [Indexed: 12/13/2022]
Abstract
Introduction Clinical questionnaires have some limitations compared to instrumental diagnosis of gastroesophageal reflux disease (GERD), but clinical diagnosis of GERD based on typical symptoms is pragmatic and well-established by societal guidelines. Aim To study the diagnostic value and provide comparative analysis of GerdQ and GSRS questionnaires regarding the GERD diagnostics based on a comparison of the questionnaires with the results of intraluminal oesophageal impedance-pH monitoring in Ukraine. Material and methods Twenty-eight patients (11 men and 17 women with a mean age of 47 ±2.4 years and a mean body mass index of 25.6 ±1.1 kg) filled in the GerdQ and GSRS questionnaires and underwent 24-hour multichannel intraluminal oesophageal impedance-pH monitoring. Results The GerdQ questionnaire showed a significantly strong correlation between the total score of the questionnaire and the key indicators of 24-hour impedance-pH monitoring: AET (rs = 0.793), acid reflux episodes (rs = 0.796), and liquid reflux episodes (rs = 0.730). Correlation of reflux syndrome according to the GSRS questionnaire was established between the acid reflux episodes (rs = 0.530), the episodes of all fluid refluxes (rs = 0.598), and AET (rs = 0.560), but the strength of the correlation relationships is weaker. The GerdQ questionnaire showed a sensitivity of 78.6%, specificity of 92.9%, and accuracy (diagnostic efficiency) of 85.7%. Conclusions The use of the GerdQ questionnaire for the diagnosis of GERD is optimal in everyday practice for deciding whether to prescribe “ex juvantibus” therapy or whether to use instrumental examination methods (upper endoscopy, oesophageal pH monitoring, oesophageal impedance-pH monitoring).
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Odenthal DR, Philbrick AM, Harris IM. Successful deprescribing of unnecessary proton pump inhibitors in a primary care clinic. J Am Pharm Assoc (2003) 2019; 60:100-104. [PMID: 31601478 DOI: 10.1016/j.japh.2019.08.012] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2019] [Revised: 07/25/2019] [Accepted: 08/27/2019] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The objective of this study was to determine the rate of successful deprescribing of unnecessary proton pump inhibitors (PPIs) after implementation of a clinical pharmacist- managed program that included detailed tapering instructions, patient education, and follow-up. SETTING The setting was a family medicine clinic in St. Paul, MN, in an underserved community. PRACTICE DESCRIPTION Eligible patients were taking a long-term PPI for gastroesophageal reflux disease without esophagitis, or without a clear indication. Each morning, the clinical pharmacist generated a report in the electronic medical record that identified patients with appointments who were currently prescribed a PPI. After chart review, the pharmacist determined if patients were candidates for PPI deprescribing. If so, a focused visit with these patients was conducted. PRACTICE INNOVATION A unique pharmacist-managed PPI tapering schedule was developed and implemented to deprescribe unnecessary PPI therapy in a family medicine clinic. EVALUATION Eligible patients were seen by the pharmacist and initiated on a PPI taper. After 8 weeks, the patients who were initiated on a PPI taper were evaluated to determine if they successfully discontinued the PPI completely, decreased the dose or frequency, or were unsuccessful at tapering the PPI. RESULTS Of the patients assessed (N = 126), 60% were excluded, 19% were unable to be seen, and 21% were willing to attempt the taper and discontinue their PPI. Of the 22 patients who initiated PPI deprescribing, 19 (86%) successfully discontinued their PPI completely, 2 (9%) decreased the dose or frequency, and 1 (5%) was unable to decrease or discontinue their PPI. This success rate of PPI discontinuation was higher than that in previous studies in primary care settings (31%-66%). CONCLUSION Deprescribing long-term PPI therapy can be successful in a family medicine clinic when implementing a clinical pharmacist-managed program that includes detailed tapering instructions, patient education, and follow-up.
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Why differences between New York and New Delhi matter in approach to gastroesophageal reflux disease. Indian J Gastroenterol 2019; 38:371-377. [PMID: 31768894 DOI: 10.1007/s12664-019-00987-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Bhatia SJ, Makharia GK, Abraham P, Bhat N, Kumar A, Reddy DN, Ghoshal UC, Ahuja V, Rao GV, Devadas K, Dutta AK, Jain A, Kedia S, Dama R, Kalapala R, Alvares JF, Dadhich S, Dixit VK, Goenka MK, Goswami BD, Issar SK, Leelakrishnan V, Mallath MK, Mathew P, Mathew P, Nandwani S, Pai CG, Peter L, Prasad AVS, Singh D, Sodhi JS, Sud R, Venkataraman J, Midha V, Bapaye A, Dutta U, Jain AK, Kochhar R, Puri AS, Singh SP, Shimpi L, Sood A, Wadhwa RT. Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology. Indian J Gastroenterol 2019; 38:411-440. [PMID: 31802441 DOI: 10.1007/s12664-019-00979-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 07/17/2019] [Indexed: 02/06/2023]
Abstract
The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H2 receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.
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Affiliation(s)
- Shobna J Bhatia
- Seth GS Medical College and KEM Hospital, Mumbai, 400 012, India.
| | | | - Philip Abraham
- P D Hinduja Hospital and MRC, and Hinduja Heathcare Surgical, Mumbai, 400 016, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Ajay Kumar
- Fortis Escorts Liver and Digestive Diseases Institute, Delhi, 110 025, India
| | | | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - G Venkat Rao
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India
| | | | - Amit K Dutta
- Christian Medical College, Vellore, 632 004, India
| | - Abhinav Jain
- Seth GS Medical College and KEM Hospital, Mumbai, 400 012, India
| | - Saurabh Kedia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Rohit Dama
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India
| | - Rakesh Kalapala
- Asian Institute of Gastroenterology, Hyderabad, 500 082, India
| | | | | | - Vinod Kumar Dixit
- Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221 005, India
| | | | - B D Goswami
- Gauhati Medical College, Dispur Hospitals, Guwahati, 781 032, India
| | - Sanjeev K Issar
- JLN Hospital and Research Center, Bhilai Steel Plant, Bhilai, 490 009, India
| | | | | | | | - Praveen Mathew
- Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, 560 066, India
| | | | - Cannanore Ganesh Pai
- Kasturba Medical College, Manipal Academy of Higher Education, Manipal, 576 104, India
| | | | - A V Siva Prasad
- Institute of Gastroenterology, Visakhapatnam, 530 002, India
| | | | | | - Randhir Sud
- Medanta - The Medicity, Gurugram, 122 001, India
| | | | - Vandana Midha
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | - Amol Bapaye
- Deenanath Mangeshkar Hospital and Research Center, Pune, 411 004, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ajay K Jain
- Choithram Hospital and Research Centre, Indore, 452 014, India
| | - Rakesh Kochhar
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | | | - Ajit Sood
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
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Habu Y. Vonoprazan versus Lansoprazole for the Initial Treatment of Reflux Esophagitis: A Cost-effectiveness Analysis in Japan. Intern Med 2019; 58:2427-2433. [PMID: 31178490 PMCID: PMC6761357 DOI: 10.2169/internalmedicine.2535-18] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Accepted: 03/10/2019] [Indexed: 12/22/2022] Open
Abstract
Objective Gastroesophageal reflux disease (GERD) is a highly prevalent disorder that negatively affects patients' quality of life and reduces their work productivity. The medical expenses associated with the treatment of GERD are the highest among all digestive diseases. Current guidelines recommend the administration of a standard dose of proton pump inhibitor (PPI) for eight weeks as an initial GERD treatment. However, there is growing concern regarding the safety of PPI treatment. Recently, a novel potassium-competitive acid blocker (P-CAB), vonoprazan (VPZ), was approved for the treatment of reflux esophagitis in Japan and may provide clinical benefits in GERD treatment. This study was conducted to evaluate the cost-effectiveness of a P-CAB, VPZ vs. a PPI, lansoprazole (LPZ), for the acute medical treatment of reflux esophagitis. Methods A clinical decision analysis was performed using a Markov chain approach to compare VPZ to LPZ in the acute treatment of reflux esophagitis in Japan. Results The P-CAB strategy was superior to the PPI strategy in terms of cost-effectiveness (direct cost per patient to achieve clinical success) and the number of days for which medication was required. Sensitivity analyses revealed that this superiority was robust within the plausible range of probabilities. This remained true even when the healing rates in cases of mild esophagitis were applied. Conclusion The P-CAB strategy was consistently superior to the conventional PPI strategy using the original LPZ in terms of cost-effectiveness and the number of days for which medication was required. Thus, VPZ appears to be the drug of choice for the acute medical treatment of reflux esophagitis.
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Affiliation(s)
- Yasuki Habu
- Department of Gastroenterology, Saiseikai-Noe Hospital, Japan
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33
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Abstract
There is increasing concern among patients and health care providers about the associations between PPI use and a multitude of potential adverse outcomes. Therefore, clinicians need to have a rational approach both to identifying PPI users who may not have an ongoing indication for their use and on how to encourage discontinuation of unnecessary PPI use. In this paper, we will provide a detailed review of the specific indications where the benefits of ongoing PPI use is of questionable value and will review the evidence on how to maximize the likelihood of being able to successfully discontinue PPI use while minimizing symptom recurrence.
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Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis JM, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García ES. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:344-356. [PMID: 31239096 DOI: 10.1016/j.rgmx.2019.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/26/2019] [Accepted: 04/30/2019] [Indexed: 06/09/2023]
Abstract
Proton pump inhibitors are the reference standards for the treatment of acid-related diseases. Acid suppression in gastroesophageal reflux disease is associated with a high rate of mucosal cicatrization, but symptom response differs among endoscopic phenotypes. Extraesophageal manifestations have a good clinical response in patients that present with abnormal acid exposure (diagnostic test) in the esophagus. Proton pump inhibitors have shown their effectiveness for reducing symptom intensity in nighttime reflux and sleep disorders, improving quality of life and work productivity. That can sometimes be achieved through dose modifications by splitting or increasing the dose, or through galenic formulation. Proton pump inhibitors are not exempt from controversial aspects related to associated adverse events. Technological development is directed at improving proton pump inhibitor performance through increasing the half-life, maximum concentration, and area under the curve of the plasma concentrations through galenic formulation, as well as creating safer and more tolerable drugs. The present review is focused on the mechanisms of action, pharmacokinetic properties, and technological advances for increasing the pharmacologic performance of a proton pump inhibitor.
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Affiliation(s)
- S Sobrino-Cossío
- Hospital Ángeles del Pedregal, Ciudad de México, México; Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México.
| | - O Teramoto-Matsubara
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Centro Médico ABC, Ciudad de México, México
| | - G Mateos-Pérez
- Hospital Ángeles del Pedregal, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J M Abdo-Francis
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J Tawil
- Departamento de Trastornos Funcionales Digestivos, Gedyt-Gastroenterología Diagnóstica y Terapéutica, Buenos Aires, Argentina
| | - C Olguín-Ramírez
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México
| | - A Orozco-Gamiz
- Gastrolab Laboratorio de Fisiología Gastrointestinal, Guadalajara, Jalisco, México
| | - E S Galvis-García
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
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Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis J, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García E. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Klenzak S, Danelisen I, Brannan GD, Holland MA, van Tilburg MAL. Management of gastroesophageal reflux disease: Patient and physician communication challenges and shared decision making. World J Clin Cases 2018; 6:892-900. [PMID: 30568943 PMCID: PMC6288517 DOI: 10.12998/wjcc.v6.i15.892] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/16/2018] [Accepted: 11/24/2018] [Indexed: 02/05/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a common upper esophageal condition and typical symptoms can include heartburn and sensation of regurgitation while atypical symptoms include chronic cough, asthma, hoarseness, dyspepsia and nausea. Typically, diagnosis is presumptive given the presence of typical and atypical symptoms and is an indication for empiric therapy. Treatment management can include lifestyle modifications and/or medication therapy with proton pump inhibitor (PPI) class being the preferred and most effective. Complete symptom resolution is not always achieved and long-term PPI therapy can put patients at risk for serious side effects and needless expense. The brain-gut connection and hypervigilance plays an important role in symptom resolution and treatment success, especially in the case of non-PPI responders. Hypervigilance is a combination of increased esophageal sensory sensitivity in combination with exaggerated threat perception surrounding esophageal symptoms. Hypervigilance requires a different approach to GERD managements, where continued PPI therapy and surgery are usually not recommended. Rather, helping physicians and patients understand the brain-gut connection can guide and improve care. Education and reassurance should be the main pillars or treatment. However, it is important not to suggest the symptoms are due to anxiety alone, this often leads to patient dissatisfaction. Patient dissatisfaction with treatment reveals the need for a more patient-centered approach to GERD management and better communication between patients and providers. Shared decision making (SDM) with the incorporation of patient-reported outcomes (PRO) promotes patient adherence and satisfaction. SDM is a joint discussion between clinician and patient in which a mutually shared solution is explored for GERD symptoms. For SDM to work the physician needs to capture patients’ perceptions which may not be obtained in the standard interview. This can be done through the use of PROs which promote a dialogue with patients about their symptoms and treatment priorities in the context of the SDM patient encounter. SDM could potentially help in the management of patient expectations for GERD treatment, ultimately positively impacting their health-related quality of life.
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Affiliation(s)
- Scott Klenzak
- Department of Psychiatry, Cape Fear Valley Health System, Fayetteville, NC 28304, United States
| | - Igor Danelisen
- School of Osteopathic Medicine, Campbell University, Lillington, NC 27546, United States
| | - Grace D Brannan
- School of Osteopathic Medicine, Campbell University, Lillington, NC 27546, United States
| | - Melissa A Holland
- College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, United States
| | - Miranda AL van Tilburg
- College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, United States
- Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, United States
- University of Washington, Seattle, WA 98105, United States
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Bytzer P. Deprescribing proton pump inhibitors: why, when and how. Med J Aust 2018; 209:436-438. [PMID: 30404592 DOI: 10.5694/mja18.00674] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 07/31/2018] [Indexed: 11/17/2022]
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On-Demand Therapy with Proton Pump Inhibitors for Maintenance Treatment of Nonerosive Reflux Disease or Mild Erosive Esophagitis: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2018; 2018:6417526. [PMID: 30158966 PMCID: PMC6109549 DOI: 10.1155/2018/6417526] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 06/30/2018] [Accepted: 07/10/2018] [Indexed: 12/14/2022] Open
Abstract
Background Proton pump inhibitors (PPIs) are widely used for the long-term management of gastroesophageal reflux disease (GERD). However, concerns about the cost and/or inconvenience of continuous maintenance PPI treatment have led to the evaluation of various alternative approaches. Aim To assess the effectiveness of on-demand PPI therapy in the maintenance treatment of nonerosive reflux disease (NERD) or mild erosive esophagitis (EE). Methods We searched MEDLINE, EMBASE, Web of Science, and Cochrane Library from inception until October 2, 2017, for randomized controlled trials (RCTs) comparing on-demand PPI versus placebo or daily PPI in the management of NERD or mild EE (Savary-Miller grade 1). Discontinuation of therapy during the trial was used as a surrogate for patient dissatisfaction and failure of symptomatic control. We calculated pooled odds ratios (OR) to evaluate the efficacy of on-demand PPI treatment. Separate analyses were conducted for studies comparing on-demand PPI with daily PPI and with placebo. Subgroup analysis was done based on NERD studies alone and on studies of both NERD and mild EE. These were analyzed using a random effects model. Results We included 10 RCTs with 4574 patients. On-demand PPI was superior to daily PPI (pooled OR = 0.50; 95% confidence interval (CI) = 0.35, 0.72). On subgroup analysis in NERD patients only, pooled OR was 0.44 (0.29, 0.66). In studies including patients with NERD and mild EE, pooled OR was 0.76 (0.36, 1.60). For studies comparing on-demand PPI with placebo, pooled OR was 0.21 (0.15, 0.29); subgroup analyses of studies evaluating NERD only and studies conducted in NERD and mild EE showed similar results (pooled OR was 0.22 (0.13, 0.36) and 0.18 (0.11, 0.31), resp.). Conclusions On-demand PPI treatment is effective for many patients with NERD or mild EE. Although not FDA-approved, it may be adequate for those patients whose symptoms are controlled to their satisfaction.
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Kim J, Blackett JW, Jodorkovsky D. Strategies for Effective Discontinuation of Proton Pump Inhibitors. Curr Gastroenterol Rep 2018; 20:27. [PMID: 29767318 DOI: 10.1007/s11894-018-0632-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy. RECENT FINDINGS Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a "step-down" approach with the use of alternative medications may be effective. "On-demand therapy" provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators. A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.
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Affiliation(s)
- Judith Kim
- Division of Digestive and Liver Diseases, Columbia University Medical Center, 161 Fort Washington Ave Suite 862, New York, NY, 10032, USA
| | - John W Blackett
- Division of Digestive and Liver Diseases, Columbia University Medical Center, 161 Fort Washington Ave Suite 862, New York, NY, 10032, USA
| | - Daniela Jodorkovsky
- Division of Digestive and Liver Diseases, Columbia University Medical Center, 161 Fort Washington Ave Suite 862, New York, NY, 10032, USA.
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Abstract
Proton pump inhibitors (PPIs) are among the most widely used class of drugs prescribed over the long term in all of clinical medicine with 8-10% of ambulatory adults have been prescribed a PPI in the past 30 days. However, numerous studies have raised doubts about the long term safety of PPI use. The purpose of this review is threefold: (i) To provide an overview of the current evidence demonstrating associations between PPI use and adverse health outcomes and the likelihood of the associations being causal (Why?); (ii) To be able to identify long-term PPI users in whom the intensity of PPI therapy could be reduced or in whom PPIs could be eliminated outright (Who?); and (iii) To provide strategies on how to reduce or stop chronic PPI therapy while maintaining symptom control and reducing the risk for symptom or upper GI disease recurrence (How?).
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Affiliation(s)
- Laura Targownik
- Section of Gastroenterology, Department of Internal Medicine, Max Rady School of Medicine at University of Manitoba, Winnipeg, Manitoba, Canada
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Avraham O, Biglow M. Implementation of Proton Pump Inhibitor Deprescription Protocol in Geriatric Residents. Ann Pharmacother 2018; 52:747-753. [PMID: 29473423 DOI: 10.1177/1060028018759747] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Deprescribing is a recommended intervention to reduce morbidity and mortality caused by polypharmacy in older residents. However, a lack of definite deprescription guidelines and evidence of clinically meaningful outcomes complicates or precludes the practicality of such an approach. OBJECTIVE The objective of the present pilot study is to establish and implement a stepwise taper protocol that can potentially minimize overuse of proton pump inhibitors in a safe, effective, and feasible manner in the nursing home. METHODS Proton pump inhibitor dosage was reduced by half every 3 weeks until the lowest dose was reached; thereafter, the frequency was changed to every other day for 3 weeks, if tolerated. Subsequently, histamine receptor antagonists replaced proton pump inhibitors and followed the same deprescription regimen until discontinuation. Patient-specific interventions also included reassessment of therapeutic agents and dosage forms for more tolerable alternatives to facilitate deprescription efforts and minimize gastric ulceration or discomfort. RESULTS The pilot study enrolled 10 patients (average age 65.6 years, medication burden 16.8 units, and antisecretory duration 37.5 months). Physicians accepted >95% of interventions, and 90% of patients achieved cessation at 12 weeks. Post cessation, none of the patients needed antacid, prokinetic, or antisecretory agents at 4 weeks. Difficulties in order interpretation and transcription among nurses as well as order entry and calculations among pharmacists were noted. CONCLUSIONS The present pilot study added to the growing body of evidence that gradual deprescription of antisecretory medications is feasible. Nonetheless, the pilot design precludes any conclusions about safety and efficacy of the intervention.
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Kurlander JE, Kolbe M, Rubenstein JH, Richardson CR, Heisler M, Weissman A, De Vries R, Saini SD. Internists' Perceptions of Proton Pump Inhibitor Adverse Effects and Impact on Prescribing Practices: Results of a Nationwide Survey. Gastroenterology Res 2018; 11:11-17. [PMID: 29511400 PMCID: PMC5827896 DOI: 10.14740/gr944w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 12/27/2017] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Observational studies have linked proton pump inhibitors (PPIs) with serious adverse effects. The study aimed to evaluate internists' perceptions of PPI harms and effects on prescribing. METHODS This was an online survey of a representative sample of the American College of Physicians in 2013. We queried familiarity with and concern about PPI adverse effects (1 - 7 Likert-type scales, anchored by "not at all" and "extremely"). We also asked how frequently (often, sometimes, rarely, or never) participants used any of three "de-escalation" strategies to stop or reduce PPIs because of concern about adverse effects: reducing patients' PPI dose, switching to H2 blocker, or discontinuing PPI. We used multivariable logistic regression to evaluate associations between sometimes/often using any PPI de-escalation strategy and gender, time in practice, familiarity, and concern. RESULTS The response rate was 53% (487/914). Seventy percent were male, median time in practice was 11 - 15 years, and most practiced general medicine (58%). Ninety-nine percent reported at least some familiarity with reported adverse effects (mean 4.9, standard deviation (SD) 1.0), and 98% reported at least some concern (mean 4.6, SD 1.3). Sixty-three percent reported sometimes/often reducing the PPI dose, 52% switching to H2 blocker, and 44% discontinuing PPI. In multivariable analysis, familiarity with adverse effects (OR 1.66 (1.31 - 2.10) for 1-point increase, P < 0.001) and concern (OR 2.14 (1.76 - 2.61) for 1-point increase, P < 0.001) were independently associated with de-escalation. Gender and time in practice had no effects. CONCLUSION Almost all internists report awareness and concern about PPI adverse effects, and most are de-escalating PPIs as a result. Research on which approach is most effective for which patients is critically important.
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Affiliation(s)
- Jacob E. Kurlander
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Veterans Affairs Ann Arbor Health Care System, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
| | - Mark Kolbe
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Joel H. Rubenstein
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- VA Ann Arbor Center for Clinical Management Research, Ann Arbor, MI, USA
| | - Caroline R. Richardson
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Michele Heisler
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- VA Ann Arbor Center for Clinical Management Research, Ann Arbor, MI, USA
| | - Arlene Weissman
- Research Center, American College of Physicians, Philadelphia, PA, USA
| | - Raymond De Vries
- Center for Bioethics and Social Sciences in Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Sameer D. Saini
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
- Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
- VA Ann Arbor Center for Clinical Management Research, Ann Arbor, MI, USA
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Gyawali CP, Fass R. Management of Gastroesophageal Reflux Disease. Gastroenterology 2018; 154:302-318. [PMID: 28827081 DOI: 10.1053/j.gastro.2017.07.049] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Revised: 07/29/2017] [Accepted: 07/31/2017] [Indexed: 02/06/2023]
Abstract
Management of gastroesophageal reflux disease (GERD) commonly starts with an empiric trial of proton pump inhibitor (PPI) therapy and complementary lifestyle measures, for patients without alarm symptoms. Optimization of therapy (improving compliance and timing of PPI doses), or increasing PPI dosage to twice daily in select circumstances, can reduce persistent symptoms. Patients with continued symptoms can be evaluated with endoscopy and tests of esophageal physiology, to better determine their disease phenotype and optimize treatment. Laparoscopic fundoplication, magnetic sphincter augmentation, and endoscopic therapies can benefit patients with well-characterized GERD. Patients with functional diseases that overlap with or mimic GERD can also be treated with neuromodulators (primarily antidepressants), or psychological interventions (psychotherapy, hypnotherapy, cognitive and behavioral therapy). Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.
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Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, Esophageal and Swallowing Center, Case Western Reserve University, MetroHealth Medical Center, Cleveland, Ohio.
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Wahking RA, Steele RL, Hanners RE, Lockwood SM, Davis KW. Outcomes From a Pharmacist - led Proton Pump Inhibitor Stewardship Program at a Single Institution. Hosp Pharm 2017; 53:59-67. [PMID: 29434389 DOI: 10.1177/0018578717747192] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background: Proton pump inhibitors (PPIs) are effective medications for acid-related disorders; however, they are also overused and may be associated with several adverse effects. A PPI stewardship program was implemented at one institution to combat the overuse of PPIs. Objective: The purpose of this study is to evaluate the effectiveness of an inpatient PPI stewardship program in reducing PPI use, both during hospitalization and upon discharge. Methods: This was a retrospective cohort study of all patients admitted to an internal medicine service at a single institution from March 14, 2016, to August 14, 2016, with an intervention by the PPI stewardship team. The primary objective was to determine the percentage of patients who tolerated inpatient and outpatient PPI discontinuation, or dose de-escalations upon discharge. Secondary objectives included the identification of risk factors for intolerance of PPI discontinuation, the occurrence of gastrointestinal (GI) complications after PPI discontinuation, and the percentage of patients who required "as needed" acid suppressive therapy (AST) with an antacid or histamine-2 receptor antagonist (H2RA) to control their symptoms while hospitalized. Results: During the study time period, 537 patients with an active outpatient prescription for a PPI were admitted to an internal medicine team with 41.0% (n = 220) not meeting criteria for inpatient continuation. Of these patients, 95.9% (n = 211) tolerated inpatient PPI discontinuation, with 83.4% (n = 176) not requiring any "as needed" AST during hospitalization. Upon discharge, 57.1% patients (n = 24 of 42) tolerated PPI discontinuation at 3 months, while 81.8% patients (n = 18 of 22) tolerated PPI dose de-escalations at 3 months. Risk factors for intolerance of inpatient PPI discontinuation were a higher body mass index (BMI) (33.7 vs 30.3 kg/m2, P = .046) and longer length of stay (7.0 vs 4.0 days, P = .03), while longer duration of PPI use (9.0 vs 5.5 years, P = 0.03) was identified as a risk factor for intolerance of outpatient PPI discontinuation. One patient experienced reflux esophagitis 2 months after PPI discontinuation. Conclusion: A PPI stewardship program at a single institution resulted in the reduction of inappropriate PPI use in both the inpatient and outpatient settings.
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Affiliation(s)
| | - Randal L Steele
- Lexington Veterans Affairs Medical Center, Lexington, KY, USA
| | | | - Sean M Lockwood
- Lexington Veterans Affairs Medical Center, Lexington, KY, USA.,University of Kentucky College of Medicine, Lexington, KY, USA
| | - Kelly W Davis
- Lexington Veterans Affairs Medical Center, Lexington, KY, USA
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Reeve E, Moriarty F, Nahas R, Turner JP, Kouladjian O'Donnell L, Hilmer SN. A narrative review of the safety concerns of deprescribing in older adults and strategies to mitigate potential harms. Expert Opin Drug Saf 2017; 17:39-49. [PMID: 29072544 DOI: 10.1080/14740338.2018.1397625] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
INTRODUCTION As with prescribing or continuing medications, deprescribing brings with it the potential for harm as well as benefit. Uncertainty and avoidance of harm has been reported as a barrier to deprescribing in practice and may contribute to continuation of inappropriate medications. AREAS COVERED This narrative review covers four main safety concerns/potential harms of deprescribing in older adults: adverse drug withdrawal events, return of medical condition(s), reversal of drug-drug interactions and damage to the doctor-patient relationship. These are discussed in relation to medications in general, with some examples of medication classes used to illustrate the potential safety concerns. The majority of these harms can be minimized or even prevented by using a patient-centered, structured deprescribing process with planning, tapering and close monitoring during, and after medication withdrawal. EXPERT OPINION More research is needed into the safety concerns of deprescribing, however, avenues exist during drug development and post-marketing surveillance to gain knowledge on this topic. Questions remain about when it is suitable to discontinue certain medications/medication classes and there is uncertainty about the harms and benefits of both medication continuation and discontinuation in complex older adults.
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Affiliation(s)
- Emily Reeve
- a Cognitive Decline Partnership Centre, Ageing and Pharmacology, Kolling Institute of Medical Research, School of Medicine , University of Sydney , St Leonards , NSW , Australia.,b Geriatric Medicine Research , Dalhousie University Faculty of Medicine , Halifax , NS , Canada.,c Faculty of Health Professions - College of Pharmacy , Dalhousie University , Halifax , NS , Canada
| | - Frank Moriarty
- d HRB Centre for Primary Care Research, Department of General Practice , Royal College of Surgeons in Ireland , Dublin , Ireland
| | - Rayan Nahas
- e Departments of Aged Care and Clinical Pharmacology , Royal North Shore Hospital , Saint Leonards , NSW , Australia
| | - Justin P Turner
- f Centre de recherché , Universite de Montreal Institut universitaire de geriatrie de Montreal , Montreal , QC , Canada.,g Faculte de pharmacie , Universite de Montreal , Montreal , QC , Canada
| | - Lisa Kouladjian O'Donnell
- a Cognitive Decline Partnership Centre, Ageing and Pharmacology, Kolling Institute of Medical Research, School of Medicine , University of Sydney , St Leonards , NSW , Australia.,e Departments of Aged Care and Clinical Pharmacology , Royal North Shore Hospital , Saint Leonards , NSW , Australia
| | - Sarah N Hilmer
- a Cognitive Decline Partnership Centre, Ageing and Pharmacology, Kolling Institute of Medical Research, School of Medicine , University of Sydney , St Leonards , NSW , Australia.,e Departments of Aged Care and Clinical Pharmacology , Royal North Shore Hospital , Saint Leonards , NSW , Australia
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Abstract
PURPOSE OF REVIEW Proton pump inhibitor (PPI) use in gastroesophageal reflux disease (GERD) has been redefined, in light of recent advances highlighting GERD phenotypes that respond to PPIs, and fresh revelations of potential risks of long-term PPI therapy. RECENT FINDINGS Erosive esophagitis predicts excellent response to PPI therapy, but non-erosive reflux disease (NERD) with abnormal reflux parameters on ambulatory reflux monitoring also demonstrates a similar response. In contrast, response is suboptimal in the absence of abnormal reflux parameters. In this setting, if an alternate appropriate indication for PPI therapy does not coexist, risks may outweigh benefits of PPI therapy. Adverse events from long-term PPI therapy continue to be reported, most based on association rather than cause-and-effect. Appropriate indications need to be established before embarking on long-term PPI therapy. Future research will define true risks of long-term PPI therapy, and develop alternate management options for acid peptic diseases.
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Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, 660 S. Euclid Ave, Campus Box 8124, St. Louis, MO, 63110, USA.
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Lin RJ, Sridharan S, Smith LJ, Young VN, Rosen CA. Weaning of proton pump inhibitors in patients with suspected laryngopharyngeal reflux disease. Laryngoscope 2017; 128:133-137. [DOI: 10.1002/lary.26696] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Revised: 03/20/2017] [Accepted: 04/24/2017] [Indexed: 12/12/2022]
Affiliation(s)
- R. Jun Lin
- the University of Pittsburgh Voice Center, Division of Laryngology, Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Shaum Sridharan
- Department of Otolaryngology-Head and Neck Surgery; Georgetown University; Washington DC U.S.A
| | - Libby J. Smith
- the University of Pittsburgh Voice Center, Division of Laryngology, Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
| | - VyVy N. Young
- the University of Pittsburgh Voice Center, Division of Laryngology, Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Clark A. Rosen
- the University of Pittsburgh Voice Center, Division of Laryngology, Department of Otolaryngology, University of Pittsburgh School of Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
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Lee C, Lo A, Ubhi K, Milewski M. Outcome after Discontinuation of Proton Pump Inhibitors at a Residential Care Site: Quality Improvement Project. Can J Hosp Pharm 2017; 70:215-223. [PMID: 28680175 DOI: 10.4212/cjhp.v70i3.1661] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Increased prescribing of proton pump inhibitors (PPIs) in the past few decades can be attributed mainly to long-term use of this type of therapy. Recent evidence indicates signals of harm associated with long-term use of PPIs, such as increased risk of Clostridium difficile infection, recurrence of C. difficile infection, and fracture. A few studies have assessed the effectiveness of step-down management of patients receiving long-term PPI therapy in ambulatory care settings. However, it is unknown whether PPIs can be discontinued in older people without return of gastrointestinal symptoms. OBJECTIVES To determine the proportion of residents receiving long-term PPI therapy who were able to discontinue the drug without experiencing gastrointestinal symptoms warranting recommencement of the PPI or initiation of a histamine-2 receptor antagonist. METHODS The records of residents who had been taking a PPI for longer than 6 months at a single residential care site were audited by one pharmacist to determine the PPI indication. For residents who fit the criteria for discontinuation (no indication for long-term PPI therapy, not currently experiencing gastrointestinal symptoms, no previous trial of PPI discontinuation without success, and no anxiety when medications are discontinued), the pharmacist faxed a recommendation to discontinue PPI therapy without tapering to the physicians' offices. For cases in which the recommendation was accepted, 3 pharmacists followed the residents weekly for 8 weeks to assess whether gastrointestinal symptoms returned. RESULTS The pharmacist identified 28 residents who fit the criteria, and the recommendation to discontinue therapy was accepted for 27. At 8 weeks after the intervention, 19 (70%) of these residents were still asymptomatic and did not require re-initiation of medications to manage their gastrointestinal symptoms. CONCLUSIONS These results support discontinuation of long-term PPI therapy for older people who fit the criteria for discontinuation. The study provided limited evidence to support the use of tapering. However, tapering can be used to identify the lowest effective dose and may increase patient comfort with deprescribing. Further research is needed to determine the effects of and best approaches to PPI discontinuation in older populations.
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Affiliation(s)
- Candy Lee
- BScPharm, is a Pharmacist with Ridge Meadows Hospital, Maple Ridge, British Columbia
| | - Anita Lo
- BScPharm, PharmD, is a Clinical Pharmacy Specialist with Baillie House, Ridge Meadows Hospital, Maple Ridge, British Columbia
| | - Kiran Ubhi
- BSP, PharmD, is a Clinical Pharmacy Specialist with Baillie House, Ridge Meadows Hospital, Maple Ridge, British Columbia
| | - Michael Milewski
- MD, is the Medical Director at Baillie House, Ridge Meadows Hospital, Maple Ridge, British Columbia
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Boghossian TA, Rashid FJ, Thompson W, Welch V, Moayyedi P, Rojas‐Fernandez C, Pottie K, Farrell B, Cochrane Upper GI and Pancreatic Diseases Group. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst Rev 2017; 3:CD011969. [PMID: 28301676 PMCID: PMC6464703 DOI: 10.1002/14651858.cd011969.pub2] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures). OBJECTIVES To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater). SEARCH METHODS We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility. SELECTION CRITERIA We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information. MAIN RESULTS The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects. AUTHORS' CONCLUSIONS In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.
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Affiliation(s)
- Taline A Boghossian
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Farah Joy Rashid
- The Ottawa HospitalDepartment of Pharmacy501 Smyth RoadOttawaONCanadaK1H 8L6
| | - Wade Thompson
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Vivian Welch
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
| | - Paul Moayyedi
- McMaster UniversityDepartment of Medicine, Division of Gastroenterology1200 Main Street WestRoom 4W8EHamiltonONCanadaL8N 3Z5
| | - Carlos Rojas‐Fernandez
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
| | - Kevin Pottie
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
| | - Barbara Farrell
- University of OttawaBruyère Research Institute43 rue Bruyere StRoom 730DOttawaONCanadaK1N 5C8
- University of WaterlooSchool of Pharmacy10 Victoria St S.Room 7004KitchenerONCanadaN2G 1C5
- University of OttawaFamily Medicine75 Bruyere StOttawaONCanadaK1N 5C8
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