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Serra Prat M, Lavado Cuevas A, Bolibar Ribas I, Palomera Fanegas E, Almirall Pujol J. Development and validation of a risk score to predict community-acquired pneumonia occurrence in the adult population. Respir Investig 2025; 63:542-547. [PMID: 40288222 DOI: 10.1016/j.resinv.2025.04.012] [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: 01/17/2025] [Revised: 04/04/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025]
Abstract
BACKGROUND Community-acquired pneumonia (CAP) preventive strategies can benefit from a quantification of individual CAP risk. This study develops and validates a CAP Risk Score (CAP-RS) for the adult population to predict CAP occurrence in the next five years. METHODS The development phase was as follows: a population-based case-control study to identify potential CAP risk factors for inclusion in the CAP-RS after weighting according to odds ratios; development of a numerical scoring system for weighted risk factors; and establishment of cut-off points to discriminate between different risk levels. The validation phase consisted of a population-based case-control study and a retrospective cohort study (with 47 836 adults aged ≥18 years corresponding to three Maresme (Barcelona) primary care centres) followed up over a five-year period (2015-2019). RESULTS 786 new CAP cases were identified. 15 factors were included in the CAP-RS. Risk was higher in subjects with CAP than without CAP (4.5 vs 1.9; p < 0.001), and the association (OR) between the CAP-RS and the occurrence of CAP increased as the CAP-RS value increased. AUC-ROC was 0.67 (p < 0.001). Cut-offs were established at <1, <5, and <10 points as best discriminating between risk groups. Annual CAP incidence was 1.9, 3.1, 6.2, and 12.4 new cases/103 inhabitants for the no, moderately, severely, and very severely increased risk groups, respectively. Significant differences in CAP-free survival were observed between the four CAR-RS categories. CONCLUSIONS The 15-item CAP-RS, which stratifies risk with good validity, can aid in the design and implementation of preventive CAP strategies for adult populations.
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Affiliation(s)
- Mateu Serra Prat
- Research Unit, Consorci Sanitari del Maresme, Ctra. de Cirera 230, Mataró, 08304, Barcelona, Spain; Networked Biomedical Research Centre for Liver and Digestive Diseases (CIBEREHD), Madrid, Spain
| | - Angel Lavado Cuevas
- Information Management Unit, Consorci Sanitari del Maresme, Ctra. de Cirera 230, Mataró, 08304, Barcelona, Spain
| | - Ignasi Bolibar Ribas
- Department of Paediatrics, Obstetrics and Gynaecology and Preventive Medicine and Public Health, Autonomous University of Barcelona, Edifici M, Avinguda de Can Domenech, 08193, Bellaterra, Spain; Department of Clinical Epidemiology and Public Health, Hospital de la Santa Creu i Sant Pau, Pavelló 18 (Planta baixa), C/Sant Antoni M. Claret, 167, Barcelona, Spain; Institute of Biomedical Research Sant Pau (IIB Sant Pau), C/ Sant Quintí, 77-79, 08025, Barcelona, Spain; Networked Biomedical Research Centre for Epidemiology and Public Health (CIBERESP), Madrid, Spain.
| | | | - Jordi Almirall Pujol
- Networked Biomedical Research Centre for Respiratory Diseases (CIBERES), Madrid, Spain; Maresme Study Group for Community-Acquired Pneumonia (GEMPAC), Mataró, Barcelona, Spain
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Schulthess-Lisibach AE, Lüthold RV, Tombez C, Weir KR, Zangger M, Chan S, Jenal F, Roumet M, Mattmann Y, Bieri C, Aubert CE, Rodondi N, Zambrano Ramos SC, Trelle S, Neuner-Jehle S, Juillerat P, Barbier M, Inauen J, Streit S, Jungo KT, Vallejo-Yagüe E. DepRescribing inapprOpriate Proton Pump InhibiTors (DROPIT): study protocol of a cluster-randomised controlled trial in Swiss primary care. BMJ Open 2025; 15:e094495. [PMID: 39832992 PMCID: PMC11749314 DOI: 10.1136/bmjopen-2024-094495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/18/2024] [Indexed: 01/22/2025] Open
Abstract
OBJECTIVES Proton pump inhibitors (PPIs) are widely prescribed medications and commonly used for the treatment of gastric acid-related disorders. Nevertheless, PPIs are often overused leading to potential adverse effects and unnecessary healthcare costs. Deprescribing strategies have emerged to safely reduce or substitute inappropriate PPIs and optimise patient care in an evidence-based manner. This protocol describes a study to evaluate the effectiveness of a PPI deprescribing intervention in comparison to usual care in the Swiss primary care setting. DESIGN An open-label, cluster randomised controlled trial. SETTING Swiss primary care settings. PARTICIPANTS Included participants will be adults with inappropriate PPI treatment and will be recruited by general practitioners (GPs). Participants treated by the same GP constitute a cluster. Clusters are randomised 1:1 to either the intervention group or the control group. INTERVENTIONS The intervention components consist of deprescribing tools including educational material, decision aids for both participants and GPs, and additional trainings for GPs only. Patients in the control group will receive usual care. Data will be collected at baseline, 3-, 6-, 9- and 12-month follow-up time through online surveys or a phone call for both GPs and participants. PRIMARY AND SECONDARY OUTCOME MEASURES The first co-primary endpoint is the effectiveness of the deprescribing intervention measured by the change of prescribed PPI dose. The second co-primary endpoint is safety, which is measured with the Reflux Disease Questionnaire assessing change in gastrointestinal symptoms. There are several secondary endpoints, such as the total number of prescribed medications, occurrences of changes in prescription patterns, PPI discontinuation and cost-effectiveness. CONCLUSIONS The findings from this study will provide evidence on the effectiveness and safety of a PPI deprescribing intervention for patients and GPs. Successful implementation of our PPI deprescribing strategy has the potential to improve patient outcomes and lower costs. TRIAL REGISTRATION NUMBER NCT06129474.
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Affiliation(s)
| | | | | | - Kristie Rebecca Weir
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Syndey, New South Wales, Australia
| | - Martina Zangger
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
| | - Samantha Chan
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Flurina Jenal
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Marie Roumet
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Yvonne Mattmann
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
| | - Christof Bieri
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
| | - Carole Elodie Aubert
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
| | - Nicolas Rodondi
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland
| | | | - Sven Trelle
- Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Stefan Neuner-Jehle
- Institute of Primary Care, University of Zurich and University Hospital of Zurich, Zurich, Switzerland
- Center for Primary and Community Care, University of Luzern, Luzern, Switzerland
| | - Pascal Juillerat
- Gastroenterology, Clinic for Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Crohn and Colitis Center, Gasteroenterology Intesto, Bern and Fribourg, Switzerland
| | - Michaela Barbier
- Health Economics Facility, Departement of Public Health, University of Basel, Basel, Switzerland
- Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland
| | - Jennifer Inauen
- Institute of Psychology, University of Bern, Bern, Switzerland
| | - Sven Streit
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
| | - Katharina Tabea Jungo
- Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
- Center for Healthcare Delivery Sciences (C4HDS) and Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
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Harper S, Kartha M, Mealing S, Pavanello M, Bonavina L. The Economic Impact of Introducing RefluxStop for Refractory Gastroesophageal Reflux Disease on the Italian Healthcare System. PHARMACOECONOMICS - OPEN 2024; 8:935-943. [PMID: 39190268 PMCID: PMC11499547 DOI: 10.1007/s41669-024-00521-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/12/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a common ailment associated with troublesome symptoms. The standard of care in Italy involves initial treatment with proton pump inhibitor (PPI)-based medical management or laparoscopic Nissen fundoplication (LNF) for patients unwilling to continue or intolerant of long-term PPI therapy. RefluxStop is a novel medical device, intended for laparoscopic implantation, that has recently proven to be an efficacious and cost-effective treatment option for patients with GERD. This analysis aims to describe the short-term budget impact of introducing RefluxStop as a GERD treatment option within the Italian National Health Service (SSN). METHODS A model adherent to international best practice recommendations was developed to estimate the budget impact of introducing RefluxStop over a 5-year time horizon. Two scenarios were considered: one without RefluxStop (i.e., comprising PPI therapy, LNF, and magnetic sphincter augmentation using the LINX system); and one with RefluxStop (i.e., addition of RefluxStop to the three treatment options previously mentioned). Clinical benefits and costs associated with each intervention were included in the analysis. RESULTS Over 5 years, the introduction of RefluxStop resulted in avoidance of 95 surgical failures, 11 reoperations, and 64 endoscopic esophageal dilations. Introduction of RefluxStop resulted in an almost neutral impact on the existing budget with a 0.316% increase in the annual Italian SSN spending on GERD treatment. CONCLUSION Introduction of RefluxStop as a GERD treatment option in Italy is likely to be associated with substantial clinical benefits and a marginal budget impact.
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Affiliation(s)
- Sam Harper
- York Health Economics Consortium, York, UK
| | | | | | | | - Luigi Bonavina
- Division of General and Foregut Surgery, IRCCS Policlinico San Donato, University of Milan Medical School, Milan, Italy
- University of Milan Medical School, Milan, Italy
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Harper S, Kartha M, Mealing S, Lundell L. A cost-effectiveness analysis of RefluxStop against relevant therapeutic alternatives for chronic gastroesophageal reflux disease in Sweden. Expert Rev Pharmacoecon Outcomes Res 2024:1-13. [PMID: 39428644 DOI: 10.1080/14737167.2024.2417774] [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: 06/27/2024] [Accepted: 09/24/2024] [Indexed: 10/22/2024]
Abstract
INTRODUCTION The standard treatment for gastroesophageal reflux disease (GERD) is proton pump inhibitors (PPIs). In selected cases, Nissen fundoplication is offered as a surgical treatment option, but alternative endoscopic and minimally invasive surgical alternatives are emerging. RefluxStop is a new technology for the treatment of GERD. RESEARCH DESIGN AND METHODS A cost-effectiveness analysis of RefluxStop in comparison to PPI therapy and Nissen fundoplication in the Swedish healthcare setting was conducted using a Markov model and available comprehensive population and clinical trial-based long-term data. Benefits were measured in quality-adjusted life-years (QALYs). Uncertainty was determined by deterministic and probabilistic sensitivity analyses. RESULTS The base case incremental cost-effectiveness ratios (ICERs) for RefluxStop in comparison to PPIs and Nissen fundoplications were SEK 48,152 (€ 4,531) and SEK 62,966 (€ 5,925) per QALY gained, respectively. At a cost-effectiveness threshold of SEK 500,000 per QALY gained, RefluxStop has a high likelihood of being cost-effective, with probabilities of 96% and 100% against Nissen fundoplication and PPIs, respectively. The results of the model remained robust with sensitivity analysis. CONCLUSIONS RefluxStop may offer a highly cost-effective long-term treatment alternative for chronic GERD patients over lifelong PPI therapy, but also in comparison with laparoscopic Nissen fundoplication.
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Affiliation(s)
- Sam Harper
- York Health Economics Consortium, University of York, York, UK
| | | | - Stuart Mealing
- York Health Economics Consortium, University of York, York, UK
| | - Lars Lundell
- Division of Surgery and Oncology, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery, Odense University Hospital, Odense, Denmark
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Floria DE, Obeidat M, Kávási SB, Teutsch B, Veres DS, Hagymási K, Hegyi P, Drug VL, Erőss B. Systematic review and meta-analysis: proton pump inhibitors slightly decrease the severity of chronic cough. Sci Rep 2024; 14:11956. [PMID: 38796481 PMCID: PMC11127940 DOI: 10.1038/s41598-024-62640-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 05/20/2024] [Indexed: 05/28/2024] Open
Abstract
The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. We performed a meta-analysis to assess the effects of acid-suppressive medications in adults with non-specific chronic cough. The protocol was registered on PROSPERO (CRD42022368769). Placebo-controlled randomized trials evaluating the impact of acid-suppressive medications on persistent cough were included. The systematic search was performed on the 1st of November 2022 in three databases. A random-effects model was used for the calculations. The effect size was the standardized mean difference (SMD) with 95% confidence interval (CI). A total number of 11 double-blinded placebo-controlled randomized trials were included in the meta-analysis. Data showed that compared to placebo, PPIs decreased the severity of cough (SMD 0.33; CI 0.05; 0.61). Therapeutic response was not different in patients with non-specific chronic cough only, compared to those with laryngopharyngeal reflux. Prolonged treatment durations did not result in greater symptomatic improvement, with SMD 0.33 (CI - 0.22; 0.88), 0.31 (CI - 1.74; 2.35), 0.32 (CI - 0.29; 0.93) and 0.34 (CI - 0.16; 0.85), following 4, 6, 8 and 12 weeks of treatment, respectively. The pooled analysis of the improvement in quality of life with PPIs found an SMD of 0.39 (CI - 0.51; 1.29). PPIs mildly decrease the severity of non-specific chronic cough, irrespective of treatment duration.
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Affiliation(s)
- Diana-Elena Floria
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Grigore T. Popa University of Medicine and Pharmacy Iaşi, University Street 16, Iaşi, 700115, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Emergency Hospital Iaşi, Independence Boulevard 1, Iaşi, 700111, Romania
| | - Mahmoud Obeidat
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
| | - Sarolta Beáta Kávási
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Department of Surgery, Toldy Ferenc Hospital, Cegléd, Hungary
| | - Brigitta Teutsch
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
| | - Dániel Sándor Veres
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary
| | - Krisztina Hagymási
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Department of Surgery, Transplantation and Gastroenterology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
| | - Péter Hegyi
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
| | - Vasile-Liviu Drug
- Grigore T. Popa University of Medicine and Pharmacy Iaşi, University Street 16, Iaşi, 700115, Romania
- Institute of Gastroenterology and Hepatology, Saint Spiridon Emergency Hospital Iaşi, Independence Boulevard 1, Iaşi, 700111, Romania
| | - Bálint Erőss
- Centre for Translational Medicine, Semmelweis University, Üllői Út 26, Budapest, 1085, Hungary.
- Institute for Translational Medicine, University of Pécs, Pécs, Hungary.
- Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary.
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Kakiuchi T, Obata S, Koji A, Minematsu N, Fuchigami M, Fukuta A, Tajiri T, Yoshiura M. Case Report: The importance of early intervention for gastroesophageal reflex disease caused by hiatal hernia. Front Pediatr 2024; 12:1305585. [PMID: 38803638 PMCID: PMC11128614 DOI: 10.3389/fped.2024.1305585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 04/30/2024] [Indexed: 05/29/2024] Open
Abstract
Background Gastroesophageal reflux (GER) disease (GERD) is a condition wherein GER causes troublesome symptoms that can affect daily functioning and/or clinical complications within the esophagus or other systems. To avoid this, patients with GERD often require treatment; hence, it is important to distinguish GER from GERD. Patients with GERD exhibiting alarm signs should be examined early to differentiate it from GER and treated accordingly. Herein, we present a case of GERD caused by a hiatal hernia that required surgical intervention for esophagial cicatrical stenosis despite oral treatment. We also discussed how to choose the appropriate acid suppressants for GERD. Case presentation A 1-year-old boy was referred to our hospital for repeated vomiting and poor weight gain. He received histamine 2 receptor antagonists (H2RAs) that contributed slightly to the decreased frequency of vomiting and aided weight gain; however, he soon stopped gaining weight and had bloody vomit. His upper gastrointestinal series revealed hiatal hernia, a 24 h impedance pH monitoring test indicated abnormal values for acid reflux, and esophagogastroduodenoscopy (EGD) revealed esophagitis. He was subsequently diagnosed with GERD associated with hiatal hernia. A proton pump inhibitor (PPI) was intravenously administered to him, following which his medication was changed to a potassium-competitive acid blocker (P-CAB). Thereafter, his vomiting episodes significantly decreased and his weight increased. However, 6 months after starting P-CAB, his vomiting episodes suddenly increased in frequency. EGD revealed the presence esophageal stricture due to scarring from GERD. He was then treated via laparoscopic fundoplication, gastrostomy, and esophageal balloon dilation. Thereafter, his vomiting episodes stopped and food intake improved, leading to weight gain. Conclusion It is essential to identify the cause of GERD early and take an appropriate treatment approach depending on the cause of GERD with alarm signs. Further, as a drug therapy for GERD as a clear acid mediated disease or in children with alarm signs, PPIs or P-CAB should be used from the beginning instead of H2RAs.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Satoshi Obata
- Department of Pediatric Surgery, Graduate School of Medicine Sciences, Kyushu University, Fukuoka, Japan
| | - Azusa Koji
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Nobuya Minematsu
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Maho Fuchigami
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Atsuhisa Fukuta
- Department of Pediatric Surgery, Graduate School of Medicine Sciences, Kyushu University, Fukuoka, Japan
| | - Tatsuro Tajiri
- Department of Pediatric Surgery, Graduate School of Medicine Sciences, Kyushu University, Fukuoka, Japan
| | - Masato Yoshiura
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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Menichelli D, Gazzaniga G, Del Sole F, Pani A, Pignatelli P, Pastori D. Acute upper and lower gastrointestinal bleeding management in older people taking or not taking anticoagulants: a literature review. Front Med (Lausanne) 2024; 11:1399429. [PMID: 38765253 PMCID: PMC11099229 DOI: 10.3389/fmed.2024.1399429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 04/11/2024] [Indexed: 05/21/2024] Open
Abstract
Acute upper and lower gastrointestinal (GI) bleeding may be a potentially life-threatening event that requires prompt recognition and an early effective management, being responsible for a considerable number of hospital admissions. Methods. We perform a clinical review to summarize the recent international guidelines, helping the physician in clinical practice. Older people are a vulnerable subgroup of patients more prone to developing GI bleeding because of several comorbidities and polypharmacy, especially related to an increased use of antiplatelet and anticoagulant drugs. In addition, older patients may have higher peri-procedural risk that should be evaluated. The recent introduction of reversal strategies may help the management of GI bleeding in this subgroup of patients. In this review, we aimed to (1) summarize the epidemiology and risk factors for upper and lower GI bleeding, (2) describe treatment options with a focus on pharmacodynamics and pharmacokinetics of different proton pump inhibitors, and (3) provide an overview of the clinical management with flowcharts for risk stratification and treatment. In conclusion, GI is common in older patients and an early effective management may be helpful in the reduction of several complications.
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Affiliation(s)
- Danilo Menichelli
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
- Department of General Surgery and Surgical Specialty Paride Stefanini, Sapienza University of Rome, Rome, Italy
| | - Gianluca Gazzaniga
- Department of Medical Biotechnology and Translational Medicine, Postgraduate School of Clinical Pharmacology and Toxicology, Università degli Studi di Milano, Milan, Italy
| | - Francesco Del Sole
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Arianna Pani
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Pasquale Pignatelli
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Daniele Pastori
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
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Palmowski L, von Busch A, Unterberg M, Bergmann L, Schmitz S, Schlüter A, Peters J, Adamzik M, Rahmel T. Timely Cessation of Proton Pump Inhibitors in Critically Ill Patients Impacts Morbidity and Mortality: A Propensity Score-Matched Cohort Study. Crit Care Med 2024; 52:190-199. [PMID: 38240505 PMCID: PMC10793775 DOI: 10.1097/ccm.0000000000006104] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
OBJECTIVE Proton pump inhibitors (PPIs) are among the drugs most commonly used in critically ill patients. Although mainly applied temporarily for stress ulcer prophylaxis, their application is frequently not terminated. Potential adverse effects of PPI treatment could impact the outcome in case of unnecessary and, therefore, avoidable long-term continuation. We tested the hypotheses that nonindicated PPI therapy continued beyond hospital discharge is associated with increased morbidity, rehospitalization rate, and mortality. DESIGN Nationwide retrospective cohort study considering critically ill patients treated on German ICUs between January, 2017, and December, 2018 with a 2-year follow-up. SETTING A total of 591,207 patient datasets of a German healthcare insurer were screened. PATIENTS We identified 11,576 ICU patients who received PPI therapy for the first time during their index ICU stay without having an indication for its continuation. INTERVENTIONS The cohort was stratified into two groups: 1) patients without further PPI therapy and 2) patients with continuation of PPI therapy beyond 8 weeks after hospital discharge. MEASUREMENTS AND MAIN RESULTS Frequency of predescribed adverse events associated with PPI therapy, 1-year rehospitalization rate, and 2-year mortality were determined. The proportion of patients with continued PPI therapy without an objectifiable indication was 41.7% (4,825 of 11,576 patients). These patients had a 27% greater risk of pneumonia (odds ratio [OR] 1.27; 95% CI, 1.15-1.39; p < 0.001) and a 17% greater risk of cardiovascular events (OR 1.17; 95% CI, 1.08-1.26; p < 0.001). Continued PPI therapy was associated with a 34% greater risk of rehospitalization (OR 1.34; 95% CI, 1.23-1.47) and a nearly 20% greater 2-year mortality risk (hazard ratio 1.17; 95% CI, 1.08-1.27; p = 0.006). CONCLUSIONS These data demonstrate that an unnecessary continuation of PPI therapy after hospital discharge may significantly impact morbidity and mortality. To avoid potentially harmful overuse of a PPIs, intensivists should ensure timely cessation of a temporarily indicated PPI therapy.
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Affiliation(s)
- Lars Palmowski
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Alexander von Busch
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Matthias Unterberg
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Lars Bergmann
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Stefanie Schmitz
- Abteilung I - Kranken und Pflegeversicherung, Knappschaft, Bochum, Germany
| | - Andreas Schlüter
- Hauptverwaltung, Knappschaft Kliniken GmbH, Recklinghausen, Germany
| | | | - Michael Adamzik
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Tim Rahmel
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
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Harper S, Grodzicki L, Mealing S, Gemmill E, Goldsmith P, Ahmed A. Budget Impact of RefluxStop™ as a Treatment for Patients with Refractory Gastro-oesophageal Reflux Disease in the United Kingdom. JOURNAL OF HEALTH ECONOMICS AND OUTCOMES RESEARCH 2024; 11:1-7. [PMID: 38222857 PMCID: PMC10787539 DOI: 10.36469/001c.90924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 12/07/2023] [Indexed: 01/16/2024]
Abstract
Background: Gastro-oesophageal reflux disease (GORD) is a common condition associated with heartburn and regurgitation. Standard of care for GORD patients in the UK involves initial treatment with proton pump inhibitors (PPIs) and laparoscopic antireflux surgery in patients unwilling to continue or intolerant of long-term PPI treatment. Recently, RefluxStop™, a novel, implantable medical device, has proven to be an efficacious and cost-effective treatment for patients with GORD. The current analysis aimed to describe the budget impact of introducing RefluxStop™ within National Health Service (NHS) England and Wales. Objectives: To estimate the more immediate, short-term clinical and economic effects of introducing RefluxStop™ as a therapeutic option for patients with GORD treated within NHS England and Wales. Methods: A model adherent to international best practice guidelines was developed to estimate the budget impact of introducing RefluxStop™ over a 5-year time horizon, from an NHS perspective. Two hypothetical scenarios were considered, one without RefluxStop™ (comprising PPI treatment, laparoscopic Nissen fundoplication, and magnetic sphincter augmentation using the LINX® system) and one with RefluxStop™ (adding RefluxStop™ to the aforementioned treatment options). Clinical benefits and costs associated with each intervention were included in the analysis. Results: Over 5 years, introducing RefluxStop™ allowed the avoidance of 347 surgical failures, 39 reoperations, and 239 endoscopic esophageal dilations. The financial impact of introducing RefluxStop™ was £3 029 702 in year 5, corresponding to a 1.68% increase in annual NHS spending on GORD treatment in England and Wales. Discussion: While the time horizon was too short to capture some of the adverse events of PPIs and complications of GORD, such as the development of Barrett's esophagus or esophageal cancer, the use of RefluxStop™ was associated with a substantial reduction in surgical complications, including surgical failures, reoperations, and endoscopic esophageal dilations. This favorable clinical profile resulted in cost offsets for the NHS and contributed to the marginal budget impact of RefluxStop™ estimated in the current analysis. Conclusions: Introducing RefluxStop™ as a treatment option for patients with GORD in England and Wales may be associated with clinical benefits at the expense of a marginal budget impact on the NHS.
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Affiliation(s)
- Sam Harper
- York Health Economics Consortium, York, UK
| | | | | | | | - Paul Goldsmith
- Central Manchester University Hospital NHS Foundation Trust, Manchester, UK
| | - Ahmed Ahmed
- Department of Surgery and CancerImperial College London, London, UK
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10
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Harper S, Kartha M, Mealing S, Borbély YM, Zehetner J. Cost-effectiveness of the RefluxStop device for management of refractory gastroesophageal reflux disease in Switzerland. J Med Econ 2024; 27:805-815. [PMID: 38820006 DOI: 10.1080/13696998.2024.2362564] [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: 05/03/2024] [Accepted: 05/29/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND One of the most prevalent conditions in Western societies is gastroesophageal reflux disease (GERD). In Switzerland, the standard treatment for GERD is proton pump inhibitor (PPI)-based medical management, but surgical options such as Nissen fundoplication and magnetic sphincter augmentation (MSA) are available. RefluxStop is a novel device that offers an alternative solution. The purpose of this report is to evaluate the cost-effectiveness of RefluxStop compared to PPIs and existing surgical treatments. METHODS A model (Markov) was developed using the Swiss healthcare payer perspective with a lifetime horizon, 1-month cycle length, and a 3% annual discount rate for costs and benefits. Adverse events specific to treatment arms were incorporated, and benefits were measured in quality-adjusted life-years (QALYs). Clinical efficacy data for RefluxStop was obtained from its CE mark study, and comparator treatments were based on published literature. Deterministic and probabilistic sensitivity analyses were used to explore uncertainty. Since there are no head-to-head studies between RefluxStop and PPI therapy, Nissen fundoplication, or MSA, a limitation of this study is the use of naïve, indirect comparison of clinical effectiveness between the studied treatment options. RESULTS Higher QALYs and lower costs were provided by RefluxStop compared to Nissen fundoplication and the MSA system. The incremental cost-effectiveness ratio (ICER) for RefluxStop was CHF 2,116 in comparison to PPI-based medical management. At a cost-effectiveness threshold of CHF 100,000 per QALY gained, the probability of RefluxStop being cost-effective was high, with probabilities of 100%, 97%, and 100% against PPI-based medical management, Nissen fundoplication, and MSA, respectively. The robustness of the analysis was provided by deterministic and probabilistic sensitivity analyses. CONCLUSION This cost-effectiveness analysis demonstrates that there is a high likelihood of RefluxStop being a cost-effective treatment modality in adults with GERD when compared with other treatment options available in Switzerland.
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Affiliation(s)
- Sam Harper
- York Health Economics Consortium, York, UK
| | | | | | - Yves M Borbély
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
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11
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Dutta AK, Jain A, Jearth V, Mahajan R, Panigrahi MK, Sharma V, Goenka MK, Kochhar R, Makharia G, Reddy DN, Kirubakaran R, Ahuja V, Berry N, Bhat N, Dutta U, Ghoshal UC, Jain A, Jalihal U, Jayanthi V, Kumar A, Nijhawan S, Poddar U, Ramesh GN, Singh SP, Zargar S, Bhatia S. Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship. Indian J Gastroenterol 2023; 42:601-628. [PMID: 37698821 DOI: 10.1007/s12664-023-01428-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
Proton pump inhibitors (PPIs) have been available for over three decades and are among the most commonly prescribed medications. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need for PPI stewardship to promote the use of PPIs for appropriate indication and duration. With this objective, the Indian Society of Gastroenterology has formulated guidelines on the rational use of PPIs. The guidelines were developed using a modified Delphi process. This paper presents these guidelines in detail, including the statements, review of literature, level of evidence and recommendations. This would help the clinicians in optimizing the use of PPIs in their practice and promote PPI stewardship.
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Affiliation(s)
- Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College and Hospital, Vellore, 632 004, India.
| | | | - Vaneet Jearth
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Ramit Mahajan
- Dayanand Medical College and Hospital, Ludhiana, 141 001, India
| | | | - Vishal Sharma
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | | | | | - Govind Makharia
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | | | - Richard Kirubakaran
- Center of Biostatistics and Evidence Based Medicine, Vellore, 632 004, India
| | - Vineet Ahuja
- All India Institute of Medical Sciences, New Delhi, 110 029, India
| | - Neha Berry
- BLK Institute of Digestive and Liver Disease, New Delhi, 201 012, India
| | - Naresh Bhat
- Aster CMI Hospital, Bengaluru, 560 092, India
| | - Usha Dutta
- Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Uday Chand Ghoshal
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | - Ajay Jain
- Choithram Hospital and Research Center, Indore, 452 014, India
| | | | - V Jayanthi
- Sri Ramachandra Medical College, Chennai, 600 116, India
| | - Ajay Kumar
- Institute of Digestive and Liver Diseases, BLK - Max Superspeciality Hospital, New Delhi, 201 012, India
| | | | - Ujjal Poddar
- Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226 014, India
| | | | - Shivram P Singh
- Kalinga Gastroenterology Foundation, Cuttack, 753 001, India
| | - Showkat Zargar
- Department of Gastroenterology, Sher-i-Kashmir Institute of Medical Sciences, Kashmir, 190 011, India
| | - Shobna Bhatia
- Sir H N Reliance Foundation Hospital, Mumbai, 400 004, India
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12
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Maret-Ouda J, Panula J, Santoni G, Xie S, Lagergren J. Proton pump inhibitor use and risk of pneumonia: a self-controlled case series study. J Gastroenterol 2023; 58:734-740. [PMID: 37314495 PMCID: PMC10366235 DOI: 10.1007/s00535-023-02007-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 06/01/2023] [Indexed: 06/15/2023]
Abstract
BACKGROUND Recent research indicates that use of proton pump inhibitors (PPIs) is associated with pneumonia, but existing evidence is inconclusive because of methodological issues. This study aimed to answer whether PPI-use increases risk of pneumonia while taking the methodological concerns of previous research into account. METHODS This population-based and nationwide Swedish study conducted in 2005-2019 used a self-controlled case series design. Data came from national registries for medications, diagnoses, and mortality. Conditional fixed-effect Poisson regression provided incidence rate ratios (IRR) with 95% confidence intervals (CI) for pneumonia comparing PPI-exposed periods with unexposed periods in the same individuals, thus controlling for confounding. Analyses were stratified by PPI-treatment duration, sex, age, and smoking-related diseases. Use of histamine type-2 receptor antagonists (used for the same indications as PPIs) and risk of pneumonia was analysed for assessing the validity and specificity of the results for PPI-therapy and pneumonia. RESULTS Among 519,152 patients with at least one pneumonia episode during the study period, 307,709 periods of PPI-treatment occurred. PPI-use was followed by an overall 73% increased risk of pneumonia (IRR 1.73, 95% CI 1.71-1.75). The IRRs were increased across strata of PPI-treatment duration, sex, age, and smoking-related disease status. No such strong association was found between histamine type-2 receptor antagonist use and risk of pneumonia (IRR 1.08, 95% CI 1.02-1.14). CONCLUSIONS PPI-use seems to be associated with an increased risk of pneumonia. This finding highlights a need for caution in using PPIs in individuals with a history of pneumonia.
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Affiliation(s)
- John Maret-Ouda
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
| | - Joni Panula
- Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Giola Santoni
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Shaohua Xie
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
- School of Cancer and Pharmaceutical Sciences, King's College London, London, UK.
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13
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Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J 2023; 59:115-127. [PMID: 37303818 PMCID: PMC10248387 DOI: 10.4068/cmj.2023.59.2.115] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 05/03/2023] [Accepted: 05/04/2023] [Indexed: 06/13/2023] Open
Abstract
Proton Pump Inhibitors are used widely to manage many gastric acid-related conditions such as gastroesophageal disease, gastritis, esophagitis, Barrett's esophagus, Zollinger-Ellison syndrome, peptic ulcer disease, nonsteroidal anti-inflammatory drug-associated ulcers, and Helicobacter pylori eradication, around the globe. This review article focuses on adverse effects associated with the long-term use of proton pump inhibitors. Various observational studies, clinical trials, and meta-analyses have established the adverse effects associated with the long-term use of proton pump inhibitors including renal disorders (acute interstitial nephritis, acute kidney injury, chronic kidney disease, and end-stage renal disease), cardiovascular risks (major adverse cardiovascular events, myocardial infarction, stent thrombosis, and stroke), fractures, infections (Clostridium difficile infection, community-acquired pneumonia, and Coronavirus disease 2019), micronutrient deficiencies (hypomagnesemia, anemia, vitamin B12 deficiency, hypocalcemia, hypokalemia), hypergastrinemia, cancers (gastric cancer, pancreatic cancer, colorectal cancer, hepatic cancer), hepatic encephalopathy, and dementia. Clinicians including prescribers and pharmacists should be aware of the adverse effects of taking proton pump inhibitors for an extended period of time. In addition, the patients taking proton pump inhibitors for long-term should be monitored for the listed adverse effects. The American Gastroenterological association recommends a few non-pharmacological measures and the use of histamine 2 blockers to lessen gastrointestinal symptoms of gastroesophageal reflex disease and the utilization of proton pump inhibitors treatment if there is a definitive indication. Additionally, the American Gastroenterological association's Best Practice Advice statements emphasize deprescribing when there is no clear indication for proton pump inhibitors therapy.
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14
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Zhang D, Wang Z, Ma L, Xu L, Fan S, Su Y, Shi X, Hu J, Zhao S, Li W, Linghu E, Yan L. Local injection of adipose-derived mesenchymal stem cells in silk fibroin solution on the regeneration of lower esophageal sphincter in an animal model of GERD. Front Cell Dev Biol 2023; 11:993741. [PMID: 37077418 PMCID: PMC10106618 DOI: 10.3389/fcell.2023.993741] [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: 07/14/2022] [Accepted: 03/09/2023] [Indexed: 04/05/2023] Open
Abstract
Presently, various tissue engineering methods using adult stem cells and biomaterials are being confirmed to regenerate vessels, cardiac muscle, bladder, and intestines. However, there are few studies about the repair of the lower esophageal sphincter (LES) may help alleviate the symptoms of gastroesophageal reflux disease (GERD). This study aims to determine whether Adipose-Derived Stem Cells (ADSCs) combined with regenerated silk fibroin (RSF) solution could regenerate the LES. In vitro, the ADSCs were isolated, identified, and then cultured with an established smooth muscular induction system. In vivo, in the experimental groups, CM-Dil labeled ADSCs or induced ADSCs mixed with RSF solution were injected into the LES of rats after the development of the animal model of GERD respectively. The results showed that ADSCs could be induced into smooth muscular-like cells with the expression of h-caldesmon, calponin, α-smooth muscle actin, and a smooth muscle-myosin heavy chain in vitro. In vivo, the thickness of LES in the experiment rats was much thicker than those in the controlled groups. This result indicated that ADSCs mixed with RSF solution might contribute to the regeneration of the LES, thus reducing the occurrence of GERD.
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Affiliation(s)
- Daxu Zhang
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Zhanbo Wang
- Department of Pathology, Chinese PLA General Hospital, Beijing, China
| | - Lianjun Ma
- Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Lijuan Xu
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Suna Fan
- State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, China
| | - Yinan Su
- Department of Hepatobiliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Xiaonan Shi
- The Second Medical Center and National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Jingjing Hu
- The Second Medical Center and National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Shuo Zhao
- The Second Medical Center and National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - WeiLong Li
- The Second Medical Center and National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Enqiang Linghu
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li Yan
- The Second Medical Center and National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
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15
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Han CT, Islam MM, Poly TN, Lu YC, Lin MC. A Meta-Analysis of Proton Pump Inhibitor Use and the Risk of Acute Kidney Injury: Geographical Differences and Associated Factors. J Clin Med 2023; 12:jcm12072467. [PMID: 37048551 PMCID: PMC10095047 DOI: 10.3390/jcm12072467] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/11/2023] [Accepted: 03/16/2023] [Indexed: 04/14/2023] Open
Abstract
Proton pump inhibitors (PPIs) are widely prescribed in medical practice for the treatment of several gastrointestinal disorders. Previous epidemiology studies have reported the association between PPI use and the risk of AKI, although the magnitude of the association between PPIs and the risk of acute kidney injury (AKI) remains uncertain. Therefore, we conducted a meta-analysis to determine the relationship between PPI therapy and the risk of AKI. We systematically searched for relevant articles published before January 2023 on PubMed, Scopus, and Web of Science. In addition, we conducted a manual search of the bibliographies of potential articles. Two independent reviewers examined the appropriateness of all studies for inclusion. We pooled studies that compared the risk of AKI with PPI against their control using a random effect model. The search criteria based on PRISMA guidelines yielded 568 articles. Twelve observational studies included 2,492,125 individuals. The pooled adjusted RR demonstrated a significant positive association between PPI therapy and the risk of AKI (adjusted RR 1.75, 95% CI: 1.40-2.19, p < 0.001), and it was consistent across subgroups. A visual presentation of the funnel plot and Egger's regression test showed no evidence of publication bias. Our meta-analysis indicated that persons using PPIs exhibited an increased risk of AKI. North American individuals had a higher risk of AKI compared to Asian and European individuals. However, the pooled effect from observational studies cannot clarify whether the observed association is a causal effect or the result of some unmeasured confounding factors. Hence, the biological mechanisms underlying this association are still unclear and require further research.
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Affiliation(s)
- Cheng Ta Han
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Md Mohaimenul Islam
- International Center for Health Information Technology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Tahmina Nasrin Poly
- International Center for Health Information Technology, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
| | - Yu-Chun Lu
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Ming-Chin Lin
- Department of Neurosurgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
- Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
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16
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Sintusek P, Mutalib M, Thapar N. Gastroesophageal reflux disease in children: What's new right now? World J Gastrointest Endosc 2023; 15:84-102. [PMID: 37034973 PMCID: PMC10080553 DOI: 10.4253/wjge.v15.i3.84] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/15/2023] [Accepted: 02/08/2023] [Indexed: 03/16/2023] Open
Abstract
Gastroesophageal reflux (GER) in children is very common and refers to the involuntary passage of gastric contents into the esophagus. This is often physiological and managed conservatively. In contrast, GER disease (GERD) is a less common pathologic process causing troublesome symptoms, which may need medical management. Apart from abnormal transient relaxations of the lower esophageal sphincter, other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense, impaired esophageal and gastric motility and clearance, as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia. The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation. Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD. The following review focuses on up-to-date information regarding of the pathogenesis, diagnostic evaluation and management of GERD in children.
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Affiliation(s)
- Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit (TPGHAI), Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital and Thai Red Cross, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Bangkok, Thailand
| | - Mohamed Mutalib
- Department of Paediatric Gastroenterology, Pediatric and Gastroenterology Services, Evelina London Children’s Hospital, London SE1 7EH, United Kingdom
| | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland 4101, Australia
- School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia
- Woolworths Centre for Child Nutrition Research, Queensland University of Technology, Brisbane, Queensland 4101, Australia
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17
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De Luca D, Alonso A, Autilio C. Bile acids-induced lung injury: update of reverse translational biology. Am J Physiol Lung Cell Mol Physiol 2022; 323:L93-L106. [DOI: 10.1152/ajplung.00523.2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The presence of bile acids in lung tissue is associated with some clinical features observed in various medical specialties, but it took time to understand that these are due to a "bile acid-induced lung injury" since specific translational studies and cross-disciplinary awareness were lacking. We used a reverse translational approach to update and summarize the current knowledge about the mechanisms of bile acid-induced lung injury. This has been done in a cross-disciplinary fashion since these conditions may occur in patients of various age and in different medical fields. We here define these clinical conditions, then we review the physiopathology of these conditions and the animal models used to mimic them and, finally, their pathobiology. Mechanisms of bile acid-induced lung injury have been partially clarified overtime and are represented by: 1) the interaction with secretory phospholipase A2 pathway, 2) the effect on surfactant function and structure, 3) the biological effects on inflammation and local immunity, 4) the direct cellular toxicity. These mechanisms are schematically illustrated and histological comparisons between ARDS induced by bile acids and other triggers are also provided. Based on these mechanisms we propose possible direct therapeutic applications and, finally, we discuss further research steps to improve the understanding of processes that generate pathological clinical conditions.
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Affiliation(s)
- Daniele De Luca
- Division of Pediatrics and Neonatal Critical Care, Paris Saclay University Hospital, Clamart, Paris, France
- Physiopathology and Therapeutic Innovation Unit-INSERM U999, Paris Saclay University, Le Plessis Robinson, France
| | - Alejandro Alonso
- Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research, Institut-Hospital, Complutense University, Madrid, Spain
| | - Chiara Autilio
- Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research, Institut-Hospital, Complutense University, Madrid, Spain
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18
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Franciosi JP, Mougey EB, Dellon ES, Gutierrez-Junquera C, Fernandez-Fernandez S, Venkatesh RD, Gupta SK. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy 2022; 15:281-302. [PMID: 35250281 PMCID: PMC8892718 DOI: 10.2147/jaa.s274524] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 01/14/2022] [Indexed: 12/11/2022] Open
Abstract
Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE.
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Affiliation(s)
- James P Franciosi
- Division of Gastroenterology, Nemours Children’s Hospital, Orlando, FL, USA
- College of Medicine, University of Central Florida, Orlando, FL, USA
- Correspondence: James P Franciosi, Division of Gastroenterology, Nemours Children’s Hospital, 6535 Nemours Parkway, Orlando, FL, 32827, USA, Email
| | - Edward B Mougey
- Center for Pharmacogenomics and Translational Research, Nemours Children’s Health System, Jacksonville, FL, USA
| | - Evan S Dellon
- Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Carolina Gutierrez-Junquera
- Pediatric Gastroenterology Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Autonomous University of Madrid, Madrid, Spain
| | | | - Rajitha D Venkatesh
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children’s Hospital, Columbus, OH, USA
| | - Sandeep K Gupta
- Section of Pediatric Gastroenterology, Hepatology and Nutrition, Riley Hospital for Children, Indiana University School of Medicine and Community Health Network, Indianapolis, IN, USA
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Yang BR, Lee J, Kim MG. The risk of pulmonary adverse drug reactions of rebamipide and other drugs for acid-related diseases: An analysis of the national pharmacovigilance database in South Korea. J Dig Dis 2022; 23:118-123. [PMID: 34965009 PMCID: PMC9304304 DOI: 10.1111/1751-2980.13075] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 12/20/2021] [Accepted: 12/28/2021] [Indexed: 12/11/2022]
Abstract
OBJECTIVE The objective of this case/non-case study was to detect rebamipide-related pulmonary adverse events (AE) compared with other drugs for acid-related disorders based on population-level data. METHODS From 2009 to 2018, AE reports on drugs for acid-related disorders, which are anatomical therapeutic chemical code A02B drugs, in the Korea Adverse Events Reporting System (KAERS) database were examined. The reporting odds ratio (ROR) was calculated, and the odds of reporting pulmonary AE for rebamipide and all other A02B drugs were compared. Furthermore, a stratified analysis according to patients' age and sex was conducted. RESULTS Altogether 13 (0.05%) and 157 (0.11%) cases of pulmonary AE were reported for rebamipide and all other A02B drugs, respectively. The risk of reporting pulmonary AE was significantly lower for rebamipide than for all other A02B drugs (ROR 0.49, 95% confidence interval [CI] 0.28-0.87). The number of reports of pulmonary AE for rebamipide was significantly higher among patients aged ≥65 years than those aged <65 years (ROR 19.36, 95% CI 2.50-149.97). CONCLUSIONS Rebamipide was less often reported for pulmonary AE. However, healthcare professionals need to be aware of the risk of pulmonary AE in elderly patients.
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Affiliation(s)
- Bo Ram Yang
- College of PharmacyChungnam National UniversityDaejeonRepublic of Korea
| | - Jae‐Young Lee
- College of PharmacyChungnam National UniversityDaejeonRepublic of Korea
| | - Myeong Gyu Kim
- College of PharmacyEwha Womans UniversitySeoulRepublic of Korea,Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea
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20
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Kang SJ, Jung HK, Tae CH, Kim SY, Lee KJ. On-demand Versus Continuous Maintenance Treatment of Gastroesophageal Reflux Disease With Proton Pump Inhibitors: A Systematic Review and Meta-analysis. J Neurogastroenterol Motil 2022; 28:5-14. [PMID: 34980685 PMCID: PMC8748841 DOI: 10.5056/jnm21095] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/30/2021] [Accepted: 08/10/2021] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Long-term maintenance treatment of gastroesophageal reflux disease (GERD) is commonly used to prevent relapse of reflux symptoms; however, due to concerns about safety of long-term proton pump inhibitors (PPI) use, on-demand therapy is recommended as a long-term treatment modality. We compared the efficacy of on-demand and continuous PPI therapy for maintenance treatment of patients with GERD using meta-analysis. Methods Core electronic databases were searched for randomized controlled trials comparing on-demand and continuous therapy in GERD patients. The primary outcome was treatment failure of maintenance therapy, and the secondary outcomes included symptomatic relief, patient satisfaction, and amount of PPI use. Results Overall, 11 studies were selected in the systematic review and meta-analysis. Compared with continuous PPI therapy, on-demand therapy showed similar outcomes for treatment failure (risk ratio, 1.26; 95% confidence interval [CI], 0.76-2.07), particularly in the non-erosive esophageal reflux disease and mild erosive reflux disease group (risk ratio, 1.48; 95% CI, 0.39-5.63). In studies including severe esophagitis patients, continuous PPI maintenance treatment was more effective (β, 0.127 [95% CI, 0.066-0.188]; P < 0.001). Severity of esophagitis was associated with higher efficacies of continuous maintenance therapy. The amount of daily PPI use was about half in the on-demand group compared to the continuous group (risk difference −0.52; 95% CI, −0.62-−0.42). Conclusions On-demand PPI therapy shows comparable efficacy to the continuous maintenance treatment in the non-erosive esophageal reflux disease and mild erosive reflux disease group, and can remarkably reduce the amount of PPI use. Therefore, on-demand therapy may be preferentially recommended in the maintenance treatment of GERD unaccompanied by severe esophagitis.
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Affiliation(s)
- Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Chung Hyun Tae
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Seung Young Kim
- Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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21
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Baré M, Lleal M, Ortonobes S, Gorgas MQ, Sevilla-Sánchez D, Carballo N, De Jaime E, Herranz S. Factors associated to potentially inappropriate prescribing in older patients according to STOPP/START criteria: MoPIM multicentre cohort study. BMC Geriatr 2022; 22:44. [PMID: 35016636 PMCID: PMC8751453 DOI: 10.1186/s12877-021-02715-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 12/10/2021] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVES The objectives of the present analyses are to estimate the frequency of potentially inappropriate prescribing (PIP) at admission according to STOPP/START criteria version 2 in older patients hospitalised due to chronic disease exacerbation as well as to identify risk factors associated to the most frequent active principles as potentially inappropriate medications (PIMs). METHODS A multicentre, prospective cohort study including older patients (≥65) hospitalized due to chronic disease exacerbation at the internal medicine or geriatric services of 5 hospitals in Spain between September 2016 and December 2018 was conducted. Demographic and clinical data was collected, and a medication review process using STOPP/START criteria version 2 was performed, considering both PIMs and potential prescribing omissions (PPOs). Primary outcome was defined as the presence of any most frequent principles as PIMs, and secondary outcomes were the frequency of any PIM and PPO. Descriptive and bivariate analyses were conducted on all outcomes and multilevel logistic regression analysis, stratified by participating centre, was performed on the primary outcome. RESULTS A total of 740 patients were included (mean age 84.1, 53.2% females), 93.8% of them presenting polypharmacy, with a median of 10 chronic prescriptions. Among all, 603 (81.5%) patients presented at least one PIP, 542 (73.2%) any PIM and 263 (35.5%) any PPO. Drugs prescribed without an evidence-based clinical indication were the most frequent PIM (33.8% of patients); vitamin D supplement in older people who are housebound or experiencing falls or with osteopenia was the most frequent PPO (10.3%). The most frequent active principles as PIMs were proton pump inhibitors (PPIs) and benzodiazepines (BZDs), present in 345 (46.6%) patients. This outcome was found significantly associated with age, polypharmacy and essential tremor in an explanatory model with 71% AUC. CONCLUSIONS PIMs at admission are highly prevalent in these patients, especially those involving PPIs or BZDs, which affected almost half of the patients. Therefore, these drugs may be considered as the starting point for medication review and deprescription. TRIAL REGISTRATION NUMBER NCT02830425.
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Affiliation(s)
- Marisa Baré
- Institutional Committee for the Improvement of Clinical Practice Adequacy, Consorci Corporació Sanitària Parc Taulí, Parc Taulí 1, 08208, Sabadell, Catalonia, Spain. .,Health Services Research on Chronic Patients Network (REDISSEC), Sabadell, Spain.
| | - Marina Lleal
- Institutional Committee for the Improvement of Clinical Practice Adequacy, Consorci Corporació Sanitària Parc Taulí, Parc Taulí 1, 08208, Sabadell, Catalonia, Spain
| | - Sara Ortonobes
- Pharmacy Department, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | - Maria Queralt Gorgas
- Health Services Research on Chronic Patients Network (REDISSEC), Sabadell, Spain.,Pharmacy Department, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
| | | | - Nuria Carballo
- Pharmacy Department, Consorci Parc de Salut MAR, Barcelona, Spain
| | | | - Susana Herranz
- Acute Geriatric Unit, Consorci Corporació Sanitària Parc Taulí, Sabadell, Spain
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22
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Xun X, Yin Q, Fu Y, He X, Dong Z. Proton Pump Inhibitors and the Risk of Community-Acquired Pneumonia: An Updated Meta-analysis. Ann Pharmacother 2021; 56:524-532. [PMID: 34425689 DOI: 10.1177/10600280211039240] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Some studies suggested an increased risk of community-acquired pneumonia (CAP) among proton pump inhibitors (PPI) users. However, the published evidence is inadequate to define the association between PPI use and the risk of CAP. OBJECTIVE The aims of our meta-analysis were to systematically assess the association between the risk of CAP and PPI use in adults to reduce the adverse effects of PPI and ensure the safety of medication for patients. METHODS A comprehensive literature search was conducted, published between January 1, 2004, and February 1, 2021. The primary outcome was the incidence of CAP. This meta-analysis was performed using odds ratios (ORs) with 95% CIs as effective measures; 13 studies including 2 098 804 patients were enrolled in our meta-analysis. RESULTS Our study revealed that the incidence of CAP was higher in PPI users than non -PPI users [OR = 1.37 (95% CI = 1.22-1.53)], especially for PPI duration < 30 days [OR = 1.49 (95% CI = 1.34-1.66)]. Compared with non-PPI use, PPI use increased the incidence of CAP in the stroke disease population [OR = 1.52 (95% CI = 1.33-1.75)], but not in the liver disease population [OR = 1.13 (95% CI = 0.98-1.30)]. CONCLUSIONS AND RELEVANCE Using PPI could increase the risk of CAP when compared to not using PPI. PPI use increased the incidence of CAP in patients with stroke. Clinicians and clinical pharmacists should weigh the benefits before medication and strictly control the indication of the prescription, so as to reduce adverse reactions.
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Affiliation(s)
- Xuejiao Xun
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Qifan Yin
- Hebei General Hospital, Shijiazhuang, Hebei Province, China.,Hebei Medical University First Affiliated Hospital, Shijiazhuang, Hebei Province, China
| | - Yuhao Fu
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Xueru He
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Zhanjun Dong
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
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23
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Yang L, Qi J, Chen W, Guo Q, Xie R, Zhao Z, Qin S, Liu A, Den M, Fan C, Bai J, Lin H, Guo H, Yang S. Low-dose PPI to prevent bleeding after ESD: A multicenter randomized controlled study. Biomed Pharmacother 2021; 136:111251. [PMID: 33450486 DOI: 10.1016/j.biopha.2021.111251] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 12/27/2020] [Accepted: 01/03/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. METHODS This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. RESULTS 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3-9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9-9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (-4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). CONCLUSION The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs.
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Affiliation(s)
- Li Yang
- Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing, China
| | - Jian Qi
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Hubei, China
| | - Weiqing Chen
- Department of Gastroenterology, Chongqing University Cancer Hospital, Chongqing, China
| | - Qinghong Guo
- Department of Gastroenterology, the First Hospital of Lanzhou University, Gansu, China
| | - Rui Xie
- Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Guizhou, China
| | - Zhifeng Zhao
- Department of Gastroenterology, the Fourth Affiliated Hospital of China Medical University, Liaoning, China
| | - Shanyu Qin
- Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Aiming Liu
- Department of Gastroenterology, Fuling Central Hospital, Chongqing, China
| | - Mingming Den
- Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan, China
| | - Chaoqiang Fan
- Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing, China
| | - Jianyin Bai
- Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing, China
| | - Hui Lin
- Department of Epidemiology, Army Medical University, Chongqing, China
| | - Hong Guo
- Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing, China.
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital of Army Medical University, Chongqing, China.
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24
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Abstract
IMPORTANCE Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries. OBSERVATIONS GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established. CONCLUSIONS AND RELEVANCE The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.
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Affiliation(s)
- John Maret-Ouda
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
- Centre for Clinical Research Sormland, Uppsala University, Eskilstuna, Sweden
| | - Sheraz R Markar
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden
- School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom
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25
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Koyyada A. Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations. Therapie 2020; 76:13-21. [PMID: 32718584 DOI: 10.1016/j.therap.2020.06.019] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 06/16/2020] [Accepted: 06/16/2020] [Indexed: 02/07/2023]
Abstract
The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (B12 and C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.
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Affiliation(s)
- Arun Koyyada
- GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam, 530045 Andhra Pradesh, India.
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