Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Indian Journal of Gastroenterology
Published in: Indian Journal of Gastroenterology 5/2023

12-09-2023 | Proton Pump Inhibitors | Guidelines

Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship

Authors: Amit Kumar Dutta, Abhinav Jain, Vaneet Jearth, Ramit Mahajan, Manas Kumar Panigrahi, Vishal Sharma, Mahesh Kumar Goenka, Rakesh Kochhar, Govind Makharia, Duvvur Nageshwar Reddy, Richard Kirubakaran, Vineet Ahuja, Neha Berry, Naresh Bhat, Usha Dutta, Uday Chand Ghoshal, Ajay Jain, Umesh Jalihal, V. Jayanthi, Ajay Kumar, Sandeep Nijhawan, Ujjal Poddar, G. N. Ramesh, Shivram P Singh, Showkat Zargar, Shobna Bhatia

Published in: Indian Journal of Gastroenterology | Issue 5/2023

Login to get access

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.
Literature
1.
Olbe L, Carlsson E, Lindberg P. A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole. Nat Rev Drug Discov. 2003;2:132–9.PubMedCrossRef
2.
Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11:27–37.PubMedCrossRef
3.
Hagymasi K, Mullner K, Herszenyi L, Tulassay Z. Update on the pharmacogenomics of proton pump inhibitors. Pharmacogenomics. 2011;12:873–88.PubMedCrossRef
4.
Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding the complications and risks. Nat Rev Gastroenterol Hepatol. 2017;14:697–710.PubMedCrossRef
5.
National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. wwwniceorguk/guidance/cg184 2014;CG184.
6.
Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol. 2018;16:800-8.e7.CrossRef
7.
Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016;65:1439–46.PubMedCrossRef
8.
Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs. 2000;32:1008–15.PubMed
9.
Schünemann H, Brożek J, Guyatt G, Oxman A, eds. GRADE handbook for grading quality of evidence and strength of recommendations. The GRADE Working Group, 2013 Updated October 2013; Available from: guidelinedevelopment.org/handbook
10.
11.
Arnoux A, Bailhache M, Tetard C, et al. Proton pump inhibitors are still overprescribed for hospitalized children. Arch Pediatr. 2022;29:258–62.PubMedCrossRef
12.
Blackett JW, Chen L, Li J, Wright JD, Freedberg DE. Inappropriateness of proton pump inhibitors after hospital discharge is associated with thirty-day hospital readmission. Dig Dis Sci. 2022;67:817–25.PubMedCrossRef
13.
Lassalle M, Le Tri T, Bardou M, et al. Use of proton pump inhibitors in adults in France: a nationwide drug utilization study. Curr Gastroenterol Rep. 2020;76:449–57.
14.
Muheim L, Signorell A, Markun S, et al. Potentially inappropriate proton-pump inhibitor prescription in the general population: a claims-based retrospective time trend analysis. Therap Adv Gastroenterol. 2021;14:1756284821998928.PubMedPubMedCentralCrossRef
15.
16.
Dries AM, Richardson P, Cavazos J, Abraham NS. Therapeutic intent of proton pump inhibitor prescription among elderly nonsteroidal anti-inflammatory drug users. Aliment Pharmacol Ther. 2009;30:652–61.PubMedCrossRef
17.
Perwaiz MK, Posner G, Hammoudeh F, et al. Inappropriate use of intravenous PPI for stress ulcer prophylaxis in an inner city community hospital. J Clin Med Res. 2010;2:215–9.PubMedPubMedCentral
18.
Schepisi R, Fusco S, Sganga F, et al. Inappropriate use of proton pump inhibitors in elderly patients discharged from acute care hospitals. J Nutr Health Aging. 2016;20:665–70.PubMedCrossRef
19.
Venkataraman R, Rashid M, Shrestha H. Inappropriate medication use and cost comparison analysis of proton pump inhibitors: evidence from an Indian tertiary care facility. Curr Drug Saf. 2020;15:147–55.PubMedCrossRef
20.
Yadav R, Bolia R, Bhat NK. Inappropriate prescribing of proton pump inhibitors in children: insights from a survey. Indian J Pediatr. 2021;88:1055.PubMedCrossRef
21.
Helgadottir H, Metz DC, Lund SH, et al. Study of gender differences in proton pump inhibitor dose requirements for GERD: a double-blind randomized trial. J Clin Gastroenterol. 2017;51:486–93.PubMedCrossRef
22.
Inadomi JM, McIntyre L, Bernard L, Fendrick AM. Step-down from multiple- to single-dose proton pump inhibitors (PPIs): a prospective study of patients with heartburn or acid regurgitation completely relieved with PPIs. Am J Gastroenterol. 2003;98:1940–4.PubMedCrossRef
23.
Pilotto A, Leandro G, Franceschi M. Ageing, Acid-Related Disease Study G. Short- and long-term therapy for reflux oesophagitis in the elderly: a multi-centre, placebo-controlled study with pantoprazole. Aliment Pharmacol Ther. 2003;17:1399–406.PubMedCrossRef
24.
van der Velden AW, de Wit NJ, Quartero AO, Grobbee DE, Numans ME. Pharmacological dependency in chronic treatment of gastroesophageal reflux disease: a randomized controlled clinical trial. Digestion. 2010;81:43–52.PubMedCrossRef
25.
Bjornsson E, Abrahamsson H, Simren M, et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006;24:945–54.PubMedCrossRef
26.
Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology. 2022;162:1334–42.PubMedCrossRef
27.
Bhatia SJ, Makharia GK, Abraham P, et al. Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology. Indian J Gastroenterol. 2019;38:411–40.PubMedCrossRef
28.
Eusebi LH, Ratnakumaran R, Yuan Y, Solaymani-Dodaran M, Bazzoli F, Ford AC. Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut. 2018;67:430–40.PubMedCrossRef
29.
Rai S, Kulkarni A, Ghoshal UC. Prevalence and risk factors for gastroesophageal reflux disease in the Indian population: A meta-analysis and meta-regression study. Indian J Gastroenterol. 2021;40:209–19.PubMedCrossRef
30.
Chowdhury SD, George G, Ramakrishna K, et al. Prevalence and factors associated with gastroesophageal reflux disease in southern India: A community-based study. Indian J Gastroenterol. 2019;38:77–82.PubMedCrossRef
31.
Katzka DA, Pandolfino JE, Kahrilas PJ. Phenotypes of gastroesophageal reflux disease: where Rome, Lyon, and Montreal meet. Clin Gastroenterol Hepatol. 2020;18:767–76.PubMedCrossRef
32.
Gyawali CP, Fass R. Management of gastroesophageal reflux disease. Gastroenterology. 2018;154:302–18.PubMedCrossRef
33.
Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: a meta-analysis. Gastroenterology. 1997;112:1798–810.PubMedCrossRef
34.
Sigterman KE, van Pinxteren B, Bonis PA, Lau J, Numans ME. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2013;2013:CD002095.PubMedPubMedCentral
35.
Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022;117:27–56.PubMedPubMedCentralCrossRef
36.
Jung HK, Tae CH, Song KH, et al. 2020 Seoul Consensus on the diagnosis and management of gastroesophageal reflux disease. J Neurogastroenterol Motil. 2021;27:453–81.PubMedPubMedCentralCrossRef
37.
Chen L, Chen Y, Li B. The efficacy and safety of proton-pump inhibitors in treating patients with non-erosive reflux disease: a network meta-analysis. Sci Rep. 2016;6:32126.PubMedPubMedCentralCrossRef
38.
39.
Yadlapati R, Gyawali CP, Pandolfino JE, Participants CGCC. AGA clinical practice update on the personalized approach to the evaluation and management of GERD: expert review. Clin Gastroenterol Hepatol. 2022;20:984-94.e1.CrossRef
40.
Kahrilas PJ, Jonsson A, Denison H, Wernersson B, Hughes N, Howden CW. Regurgitation is less responsive to acid suppression than heartburn in patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol. 2012;10:612–9.PubMedCrossRef
41.
Bell RCW. Management of regurgitation in patients with gastroesophageal reflux disease. Curr Opin Gastroenterol. 2020;36:336–43.PubMedCrossRef
42.
Fass R, Zerbib F, Gyawali CP. AGA clinical practice update on functional heartburn: Expert review. Gastroenterology. 2020;158:2286–93.PubMedCrossRef
43.
Gyawali CP, Kahrilas PJ, Savarino E, et al. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018;67:1351–62.PubMedCrossRef
44.
Kinoshita Y, Hongo M, Japan TSG. Efficacy of twice-daily rabeprazole for reflux esophagitis patients refractory to standard once-daily administration of PPI: the Japan-based TWICE study. Am J Gastroenterol. 2012;107:522–30.PubMedCrossRef
45.
Gralnek IM, Dulai GS, Fennerty MB, Spiegel BM. Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials. Clin Gastroenterol Hepatol. 2006;4:1452–8.PubMedCrossRef
46.
Zhang C, Kwong JS, Yuan RX, et al. Effectiveness and tolerability of different recommended doses of PPIs and H(2)RAs in GERD: network meta-analysis and GRADE system. Sci Rep. 2017;7:41021.PubMedPubMedCentralCrossRef
47.
Donnellan C, Sharma N, Preston C, Moayyedi P. Medical treatments for the maintenance therapy of reflux oesophagitis and endoscopic negative reflux disease. Cochrane Database Syst Rev. 2005;18:CD003245.
48.
Schindlbeck NE, Klauser AG, Berghammer G, Londong W, Muller-Lissner SA. Three year follow up of patients with gastrooesophageal reflux disease. Gut. 1992;33:1016–9.PubMedPubMedCentralCrossRef
49.
Marks RD, Richter JE, Rizzo J, et al. Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis. Gastroenterology. 1994;106:907–15.PubMedCrossRef
50.
Silvis SE, Farahmand M, Johnson JA, Ansel HJ, Ho SB. A randomized blinded comparison of omeprazole and ranitidine in the treatment of chronic esophageal stricture secondary to acid peptic esophagitis. Gastrointest Endosc. 1996;43:216–21.PubMedCrossRef
51.
Smith PM, Kerr GD, Cockel R, et al. A comparison of omeprazole and ranitidine in the prevention of recurrence of benign esophageal stricture restore investigator group. Gastroenterology. 1994;107:1312–8.PubMedCrossRef
52.
Singh S, Garg SK, Singh PP, Iyer PG, El-Serag HB. Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett’s oesophagus: a systematic review and meta-analysis. Gut. 2014;63:1229–37.PubMedCrossRef
53.
Shaheen NJ, Falk GW, Iyer PG, Gerson LB. Corrigendum: ACG clinical guideline: diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111:1077.PubMedPubMedCentralCrossRef
54.
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.PubMedPubMedCentralCrossRef
55.
Pace F, Tonini M, Pallotta S, Molteni P, Porro GB. Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken ‘on-demand.’ Aliment Pharmacol Ther. 2007;26:195–204.PubMedCrossRef
56.
Khan Z, Alastal Y, Khan MA, et al. 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.PubMedPubMedCentralCrossRef
57.
Rex DK, Johnson DA, Anderson JC, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol. 2009;104:739–50.PubMedCrossRef
58.
Faybush EM, Fass R. Gastroesophageal reflux disease in noncardiac chest pain. Gastroenterol Clin North Am. 2004;33:41–54.PubMedCrossRef
59.
60.
Cremonini F, Wise J, Moayyedi P, Talley NJ. Diagnostic and therapeutic use of proton pump inhibitors in non-cardiac chest pain: a metaanalysis. Am J Gastroenterol. 2005;100:1226–32.PubMedCrossRef
61.
Kim JH, Sinn DH, Son HJ, Kim JJ, Rhee JC, Rhee PL. Comparison of one-week and two-week empirical trial with a high-dose rabeprazole in non-cardiac chest pain patients. J Gastroenterol Hepatol. 2009;24:1504–9.PubMedCrossRef
62.
de Bortoli N, Nacci A, Savarino E, et al. How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related? World J Gastroenterol. 2012;18:4363–70.PubMedPubMedCentralCrossRef
63.
Hicks DM, Ours TM, Abelson TI, Vaezi MF, Richter JE. The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers. J Voice Offic J Voice Found. 2002;16:564–79.CrossRef
64.
Guo H, Ma H, Wang J. Proton pump inhibitor therapy for the treatment of laryngopharyngeal reflux: a meta-analysis of randomized controlled trials. J Clin Gastroenterol. 2016;50:295–300.PubMedCrossRef
65.
Naik RD, Vaezi MF. Extra-esophageal manifestations of GERD: who responds to GERD therapy? Curr Gastroenterol Rep. 2013;15:318.PubMedCrossRef
66.
Joshi AA, Chiplunkar BG, Bradoo RA. Assessment of treatment response in patients with laryngopharyngeal reflux. Indian J Otolaryngol Head Neck Surg. 2017;69:77–80.PubMedPubMedCentralCrossRef
67.
Shilpa C, Sandeep S, Chandresh S, Grampurohit A, Shetty TS. Laryngopharyngeal reflux and GERD: correlation between reflux symptom index and reflux finding score. Indian J Otolaryngol Head Neck Surg. 2019;71 Suppl 1:684–8.CrossRef
68.
Chang AB, Lasserson TJ, Gaffney J, Connor FL, Garske LA. Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults. Cochrane Database Syst Rev. 2011;2011:CD004823.PubMedPubMedCentral
69.
Kahrilas PJ, Howden CW, Hughes N, Molloy-Bland M. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest. 2013;143:605–12.PubMedCrossRef
70.
71.
Havemann BD, Henderson CA, El-Serag HB. The association between gastro-oesophageal reflux disease and asthma: a systematic review. Gut. 2007;56:1654–64.PubMedPubMedCentralCrossRef
72.
American Lung Association Asthma Clinical Research Centers, Mastronarde JG, Anthonisen NR, et al. Efficacy of esomeprazole for treatment of poorly controlled asthma. N Engl J Med. 2009;360:1487–99.PubMedCentralCrossRef
73.
Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ. Functional dyspepsia. Lancet. 2020;396:1689–702.PubMedCrossRef
74.
Ford AC, Marwaha A, Sood R, Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut. 2015;64:1049–57.PubMedCrossRef
75.
76.
77.
Moayyedi P, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017;112:988–1013.PubMedCrossRef
78.
Singh SP, Ahuja V, Ghoshal UC, et al. Management of Helicobacter pylori infection: The Bhubaneswar consensus report of the Indian Society of Gastroenterology. Indian J Gastroenterol. 2021;40:420–44.PubMedCrossRef
79.
80.
Pinto-Sanchez MI, Yuan Y, Hassan A, Bercik P, Moayyedi P. Proton pump inhibitors for functional dyspepsia. Cochrane Database Syst Rev. 2017;11:CD011194.PubMed
81.
Talley NJ, Lauritsen K. The potential role of acid suppression in functional dyspepsia: the BOND, OPERA, PILOT, and ENCORE studies. Gut. 2002;50 Suppl 4:iv36–41.PubMed
82.
83.
Dutta AK, Rebekah G, Chowdhury SD, et al. A simple pre-endoscopy score for predicting risk of malignancy in patients with dyspepsia: A 5-year prospective study. Dig Dis Sci. 2018;63:3442–7.PubMedCrossRef
84.
Malfertheiner P, Megraud F, O’Morain CA, et al. Management of helicobacter pylori infection-the maastricht V/Florence consensus report. Gut. 2017;66:6–30.PubMedCrossRef
85.
Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of helicobacter pylori infection in adults. Gastroenterology. 2016;151:51-69.e14.PubMedCrossRef
86.
McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2012;36:414–25.PubMedCrossRef
87.
Dekkers CP, Beker JA, Thjodleifsson B, Gabryelewicz A, Bell NE, Humphries TJ. Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study. Aliment Pharmacol Ther. 1999;13:179–86.PubMedCrossRef
88.
Zhang J, Ge L, Hill M, et al. Standard-dose proton pump inhibitors in the initial non-eradication treatment of duodenal ulcer: systematic review, network meta-analysis, and cost-effectiveness analysis. Front Pharmacol. 2018;9:1512.PubMedCrossRef
89.
Dekkers CP, Beker JA, Thjodleifsson B, Gabryelewicz A, Bell NE, Humphries TJ. Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer–a European multicentre study. The European Rabeprazole Study Group. Aliment Pharmacol Ther. 1998;12:789–95.PubMedCrossRef
90.
Malfertheiner P, MÖssner J, Fischbach W, et al. Helicobacter pylori eradication is beneficial in the treatment of functional dyspepsia. Aliment Pharmacol Ther. 2003;18:615–25.PubMedCrossRef
91.
Yang M, He M, Zhao M, et al. Proton pump inhibitors for preventing non-steroidal anti-inflammatory drug induced gastrointestinal toxicity: a systematic review. Curr Med Res Opin. 2017;33:973–80.PubMedCrossRef
92.
Laine L, Barkun AN, Saltzman JR, Martel M, Leontiadis GI. ACG clinical guideline: upper gastrointestinal and ulcer bleeding. Am J Gastroenterol. 2021;116:899–917.PubMedCrossRef
93.
Javid G, Masoodi I, Zargar SA, et al. Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer. Am J Med. 2001;111:280–4.PubMedCrossRef
94.
Zargar SA, Javid G, Khan BA, et al. Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial. J Gastroenterol Hepatol. 2006;21:716–21.PubMedCrossRef
95.
Sreedharan A, Martin J, Leontiadis GI, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;2010:CD005415.PubMedPubMedCentral
96.
Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med. 2014;174:1755–62.PubMedPubMedCentralCrossRef
97.
Cheng HC, Wu CT, Chang WL, Cheng WC, Chen WY, Sheu BS. Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study. Gut. 2014;63:1864–72.PubMedCrossRef
98.
Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference. Gastroenterology. 2018;155:1022-33 e10.CrossRef
99.
Lucendo AJ, Arias A, Molina-Infante J. Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016;14:13-22. e1.PubMedCrossRef
100.
Rank MA, Sharaf RN, Furuta GT, et al. Technical review on the management of eosinophilic esophagitis: A report from the AGA Institute and the joint task force on allergy-immunology practice parameters. Gastroenterology. 2020;158:1789-810. e15.CrossRef
101.
Strossman N, Donovan K, Trovato A, et al. Exploring treatment options for eosinophilic esophagitis. Gastroenterol Insights. 2022;13:228–37.CrossRef
102.
Hirano I, Chan ES, Rank MA, et al. AGA institute and the joint task force on allergy-immunology practice parameters clinical guidelines for the management of eosinophilic esophagitis. Gastroenterology. 2020;158:1776–86.PubMedCrossRef
103.
Frandsen LT, Westmark S, Melgaard D, Krarup AL. Effectiveness of PPI treatment and guideline adherence in 236 patients with eosinophilic oesophagitis-results from the population-based DanEoE cohort shows a low complication rate. United Eur Gastroenterol J. 2021;9:910–8.CrossRef
104.
Laserna-Mendieta EJ, Casabona S, Guagnozzi D, et al. Efficacy of proton pump inhibitor therapy for eosinophilic oesophagitis in 630 patients: results from the EoE connect registry. Aliment Pharmacol Ther. 2020;52:798–807.PubMedCrossRef
105.
Gomez-Torrijos E, Garcia-Rodriguez R, Castro-Jimenez A, Rodriguez-Sanchez J, Mendez Diaz Y, Molina-Infante J. The efficacy of step-down therapy in adult patients with proton pump inhibitor-responsive oesophageal eosinophilia. Aliment Pharmacol Ther. 2016;43:534–40.PubMedCrossRef
106.
Gutierrez-Junquera C, Fernandez-Fernandez S, Cilleruelo ML, et al. High prevalence of response to proton-pump inhibitor treatment in children with esophageal eosinophilia. J Pediatr Gastroenterol Nutr. 2016;62:704–10.PubMedCrossRef
107.
King SB 3rd, Smith SC Jr, Hirshfeld JW Jr, et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice guidelines. J Am Coll Cardiol. 2008;51:172–209.PubMedCrossRef
108.
Hallas J, Dall M, Andries A, et al. Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ. 2006;333:726.PubMedPubMedCentralCrossRef
109.
Guo H, Ye Z, Huang R. Clinical outcomes of concomitant use of proton pump inhibitors and dual antiplatelet therapy: A systematic review and meta-analysis. Front Pharmacol. 2021;12:694698.PubMedPubMedCentralCrossRef
110.
Ray WA, Murray KT, Griffin MR, et al. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med. 2010;152:337–45.PubMedPubMedCentralCrossRef
111.
Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med. 2000;160:2093–9.PubMedCrossRef
112.
Luo PJ, Lin XH, Lin CC, et al. Risk factors for upper gastrointestinal bleeding among aspirin users: An old issue with new findings from a population-based cohort study. J Formos Med Assoc. 2019;118:939–44.PubMedCrossRef
113.
Lv M, Zheng X, Wu T, et al. A new score for predicting acute gastrointestinal bleeding in patients administered oral antiplatelet drugs. Front Pharmacol. 2020;11:571605.PubMedCrossRef
114.
Ng FH, Chan P, Kwanching CP, et al. Management and outcome of peptic ulcers or erosions in patients receiving a combination of aspirin plus clopidogrel. J Gastroenterol. 2008;43:679–86.PubMedCrossRef
115.
Moukarbel GV, Signorovitch JE, Pfeffer MA, et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J. 2009;30:2226–32.PubMedCrossRef
116.
Barada K, Karrowni W, Abdallah M, Shamseddeen W, Sharara AI, Dakik HA. Upper gastrointestinal bleeding in patients with acute coronary syndromes: clinical predictors and prophylactic role of proton pump inhibitors. J Clin Gastroenterol. 2008;42:368–72.PubMedCrossRef
117.
Nikolsky E, Mehran R, Dangas G, et al. Development and validation of a prognostic risk score for major bleeding in patients undergoing percutaneous coronary intervention via the femoral approach. Eur Heart J. 2007;28:1936–45.PubMedCrossRef
118.
Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4:e004587.PubMedPubMedCentralCrossRef
119.
Miller CS, Dorreen A, Martel M, Huynh T, Barkun AN. Risk of gastrointestinal bleeding in patients taking non-vitamin K antagonist oral anticoagulants: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2017;15.1674-683.e3.PubMedCrossRef
120.
Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMedCrossRef
121.
Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.PubMedCrossRef
122.
Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.PubMedCrossRef
123.
Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.PubMedCrossRef
124.
Bang CS, Joo MK, Kim BW, et al. The role of acid suppressants in the prevention of anticoagulant-related gastrointestinal bleeding: a systematic review and meta-analysis. Gut Liver. 2020;14:57–66.PubMedCrossRef
125.
Ray WA, Chung CP, Murray KT, et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology. 2016;151:1105-12 e10.CrossRef
126.
Komen J, Pottegard A, Hjemdahl P, et al. Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds. Heart. 2022;108:613–8.PubMedCrossRef
127.
Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138:1093–100.PubMedCrossRef
128.
Ahn HJ, Lee SR, Choi EK, et al. Protective effect of proton-pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis. Brit J Clin Pharmacol. 2022;88:4676–87.CrossRef
129.
Chen WC, Chen YH, Hsu PI, et al. Gastrointestinal hemorrhage in warfarin anticoagulated patients: incidence, risk factor, management, and outcome. Biomed Res Int. 2014;2014:463767.PubMedPubMedCentral
130.
Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin Drug Saf. 2017;16:673–85.PubMedCrossRef
131.
Abrignani MG, Gatta L, Gabrielli D, et al. Gastroprotection in patients on antiplatelet and/or anticoagulant therapy: a position paper of National Association of Hospital Cardiologists (ANMCO) and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO). Eur J Intern Med. 2021;85:1–13.PubMedCrossRef
132.
Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994;236:619–32.PubMedCrossRef
133.
Messer J, Reitman D, Sacks HS, Smith H Jr, Chalmers TC. Association of adrenocorticosteroid therapy and peptic-ulcer disease. N Engl J Med. 1983;309:21–4.PubMedCrossRef
134.
135.
Dayton MT, Kleckner SC, Brown DK. Peptic ulcer perforation associated with steroid use. Arch Surg. 1987;122:376–80.PubMedCrossRef
136.
Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis Ann Intern Med. 1991;115:787–96.PubMedCrossRef
137.
Larkai EN, Smith JL, Lidsky MD, Graham DY. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal anti-inflammatory drug use. Am J Gastroenterol. 1987;82:1153–8.PubMed
138.
Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000;284:1247–55.PubMed
139.
Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000;343:1520–8.PubMedCrossRef
140.
Walan A, Bader JP, Classen M, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med. 1989;320:69–75.PubMedCrossRef
141.
Agrawal NM, Campbell DR, Safdi MA, Lukasik NL, Huang B, Haber MM. Superiority of lansoprazole vs ranitidine in healing nonsteroidal anti-inflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-associated gastric ulcer study group. Arch Intern Med. 2000;160:1455–61.PubMedCrossRef
142.
Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) study group. N Engl J Med. 1998;338:727–34.PubMedCrossRef
143.
Scheiman JM, Yeomans ND, Talley NJ, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101:701–10.PubMedCrossRef
144.
Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;4:CD002296.
145.
Endo H, Sakai E, Taniguchi L, et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc. 2014;80:826–34.PubMedCrossRef
146.
Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-inflammatory drug-induced small bowel injury: a randomized, placebo-controlled trial. Clin Gastroenterol Hepatol. 2016;14:809-15. e1.CrossRef
147.
Zhang X, Xiao X, Chen PR, Li YN, Lv XH, Yang JL. Proton pump inhibitors increase the risk of nonsteroidal anti-inflammatory drug-related small-bowel injury: a systematic review with meta-analysis. Clin Transl Gastroenterol. 2023;14:e00588.PubMedPubMedCentralCrossRef
148.
Saeed M, Bass S, Chaisson NF. Which ICU patients need stress ulcer prophylaxis? Cleve Clin J Med. 2022;89:363–7.PubMedCrossRef
149.
Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833–45.PubMedCrossRef
150.
Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330:377–81.PubMedCrossRef
151.
Alhazzani W, Alshamsi F, Belley-Cote E, et al. Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials. Intensive Care Med. 2018;44:1–11.PubMedCrossRef
152.
Barbateskovic M, Marker S, Granholm A, et al. Stress ulcer prophylaxis with proton pump inhibitors or histamin-2 receptor antagonists in adult intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med. 2019;45:143–58.PubMedCrossRef
153.
Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165–228.PubMedPubMedCentralCrossRef
154.
Marik PE, Vasu T, Hirani A, Pachinburavan M. Stress ulcer prophylaxis in the new millennium: a systematic review and meta-analysis. Crit Care Med. 2010;38:2222–8.PubMedCrossRef
155.
Azab M, Doo L, Doo DH, et al. Comparison of the hospital-acquired Clostridium difficile infection risk of using proton pump inhibitors versus histamine-2 receptor antagonists for prophylaxis and treatment of stress ulcers: a systematic review and meta-analysis. Gut Liver. 2017;11:781–8.PubMedPubMedCentralCrossRef
156.
Krag M, Marker S, Perner A, et al. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med. 2018;379:2199–208.PubMedCrossRef
157.
PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group, et al. Effect of stress ulcer prophylaxis with proton pump inhibitors vs histamine-2 receptor blockers on in-hospital nortality among ICU patients receiving invasive mechanical ventilation: the PEPTIC randomized clinical trial. JAMA. 2020;323:616–26.CrossRef
158.
ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis.. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm. 1999;56:347–79.
159.
Vanbiervliet G, Giudicelli-Bornard S, Piche T, et al. Predictive factors of bleeding related to post-banding ulcer following endoscopic variceal ligation in cirrhotic patients: a case-control study. Aliment Pharmacol Ther. 2010;32:225–32.PubMedCrossRef
160.
Lin L, Cui B, Deng Y, Jiang X, Liu W, Sun C. The efficacy of proton pump inhibitor in cirrhotics with variceal bleeding: a systemic review and meta-analysis. Digestion. 2021;102:117–27.PubMedCrossRef
161.
de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VIIF. Baveno VII - renewing consensus in portal hypertension. J Hepatol. 2022;76:959–74.PubMedCrossRef
162.
Gralnek IM, Camus Duboc M, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2022;54:1094–120.PubMedCrossRef
163.
Lee HJ, Lee H, Oh SH, et al. Chronic kidney disease (CKD) patients are exposed to more proton pump inhibitor (PPI)s compared to non-CKD patients. PloS One. 2018;13:e0203878.PubMedPubMedCentralCrossRef
164.
Kawaguchi Y, Mine T, Kawana I, et al. Gastroesophageal reflux disease in hemodialysis patients. Tokai J Exp Clin Med. 2009;34:48–52.PubMed
165.
Grant CH, Gillis KA, Lees JS, Traynor JP, Mark PB, Stevens KI. Proton pump inhibitor use and progression to major adverse renal events: a competing risk analysis. QJM. 2019;112:835–40.PubMedCrossRef
166.
167.
Liabeuf S, Lambert O, Metzger M, et al. Adverse outcomes of proton pump inhibitors in patients with chronic kidney disease: the CKD-REIN cohort study. Br J Clin Pharmacol. 2021;87:2967–76.PubMedCrossRef
168.
Chavez-Tapia NC, Tellez-Avila FI, Garcia-Leiva J, Valdovinos MA. Use and overuse of proton pump inhibitors in cirrhotic patients. Med Sci Monit. 2008;14:CR468–72.PubMed
169.
Garcia-Saenz-de-Sicilia M, Sanchez-Avila F, Chavez-Tapia NC, et al. PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis. World J Gastroenterol. 2010;16:5869–73.PubMedPubMedCentralCrossRef
170.
Alhumaid S, Al Mutair A, Al Alawi Z, et al. Proton pump inhibitors use and risk of developing spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis. Gut Pathog. 2021;13:17.PubMedPubMedCentralCrossRef
171.
Dam G, Vilstrup H, Watson H, Jepsen P. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology. 2016;64:1265–72.PubMedCrossRef
172.
Yu T, Tang Y, Jiang L, Zheng Y, Xiong W, Lin L. Proton pump inhibitor therapy and its association with spontaneous bacterial peritonitis incidence and mortality: a meta-analysis. Dig Liver Dis. 2016;48:353–9.PubMedCrossRef
173.
Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroent Hepatol. 2013;28:235–42.CrossRef
174.
Khan MA, Kamal S, Khan S, Lee WM, Howden CW. Systematic review and meta-analysis of the possible association between pharmacological gastric acid suppression and spontaneous bacterial peritonitis. Eur J Gastroenterol Hepatol. 2015;27:1327–36.PubMedCrossRef
175.
Xu HB, Wang HD, Li CH, et al. Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in cirrhotic patients: a systematic review and meta-analysis. Genet Mol Res. 2015;14:7490–501.PubMedCrossRef
176.
Wang J, Wu Y, Bi Q, Zheng X, Zhang J, Huang W. Adverse outcomes of proton pump inhibitors in chronic liver disease: a systematic review and meta-analysis. Hepatol Int. 2020;14:385–98.PubMedCrossRef
177.
Mak LY, Fung J. Proton pump inhibitors in chronic liver disease: accomplice or bystander? Hepatol Int. 2020;14:299–301.PubMedCrossRef
178.
De Roza MA, Kai L, Kam JW, et al. Proton pump inhibitor use increases mortality and hepatic decompensation in liver cirrhosis. World J Gastroenterol. 2019;25:4933–44.PubMedPubMedCentralCrossRef
179.
Tsai CF, Chen MH, Wang YP, et al. Proton pump inhibitors increase risk for hepatic encephalopathy in patients with cirrhosis in a population study. Gastroenterology. 2017;152:134–41.PubMedCrossRef
180.
Li DK, Chung RT. Use of proton pump inhibitors in chronic liver diseases. Clin Liver Dis (Hoboken). 2017;10:148–51.PubMedCrossRef
181.
182.
de la Iglesia-Garcia D, Huang W, Szatmary P, et al. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis. Gut. 2017;66:1354–5.PubMed
183.
Phillips ME, Hopper AD, Leeds JS, et al. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol. 2021;8:e000643.PubMedPubMedCentralCrossRef
184.
Bruno MJ, Rauws EA, Hoek FJ, Tytgat GN. Comparative effects of adjuvant cimetidine and omeprazole during pancreatic enzyme replacement therapy. Dig Dis Sci. 1994;39:988–92.PubMedCrossRef
185.
Heijerman HG, Lamers CB, Bakker W, Dijkman JH. Improvement of fecal fat excretion after addition of omeprazole to pancrease in cystic fibrosis is related to residual exocrine function of the pancreas. Dig Dis Sci. 1993;38:1–6.PubMedCrossRef
186.
Nakamura T, Takebe K, Kudoh K, et al. Effects of pancreatic digestive enzymes, sodium bicarbonate, and a proton pump inhibitor on steatorrhoea caused by pancreatic diseases. J Int Med Res. 1995;23:37–47.PubMedCrossRef
187.
Sander-Struckmeier S, Beckmann K, Janssen-van Solingen G, Pollack P. Retrospective analysis to investigate the effect of concomitant use of gastric acid-suppressing drugs on the efficacy and safety of pancrelipase/pancreatin (CREON(R)) in patients with pancreatic exocrine insufficiency. Pancreas. 2013;42:983–9.PubMedCrossRef
188.
Vecht J, Symersky T, Lamers CB, Masclee AA. Efficacy of lower than standard doses of pancreatic enzyme supplementation therapy during acid inhibition in patients with pancreatic exocrine insufficiency. J Clin Gastroenterol. 2006;40:721–5.PubMedCrossRef
189.
Brown A, Hughes M, Tenner S, Banks PA. Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis. Am J Gastroenterol. 1997;92:2032–5.PubMed
190.
Shafiq N, Rana S, Bhasin D, et al. Pancreatic enzymes for chronic pancreatitis. Cochrane Database Syst Rev. 2009;4:CD006302.
191.
Yaghoobi M, McNabb-Baltar J, Bijarchi R, Cotton PB. Pancreatic enzyme supplements are not effective for relieving abdominal pain in patients with chronic pancreatitis: meta-analysis and systematic review of randomized controlled trials. Can J Gastroenterol Hepatol. 2016;2016:8541839.PubMedPubMedCentral
192.
Gardner TB, Adler DG, Forsmark CE, Sauer BG, Taylor JR, Whitcomb DC. ACG clinical guideline: Chronic pancreatitis. Am J Gastroenterol. 2020;115:322–39.PubMedCrossRef
193.
Litalien C, Theoret Y, Faure C. Pharmacokinetics of proton pump inhibitors in children. Clin Pharmacokinet. 2005;44:441–66.PubMedCrossRef
194.
Ward RM, Kearns GL. Proton pump inhibitors in pediatrics : mechanism of action, pharmacokinetics, pharmacogenetics, and pharmacodynamics. Paediatr Drugs. 2013;15:119–31.PubMedPubMedCentralCrossRef
195.
Haddad I, Kierkus J, Tron E, et al. Maintenance of efficacy and safety of rabeprazole in children with endoscopically proven GERD. J Pediatr Gastroenterol Nutr. 2014;58:510–7.PubMedCrossRef
196.
Haddad I, Kierkus J, Tron E, et al. Efficacy and safety of rabeprazole in children (1–11 years) with gastroesophageal reflux disease. J Pediatr Gastroenterol Nutr. 2013;57:798–807.PubMedCrossRef
197.
Tolia V, Gilger MA, Barker PN, Illueca M. Healing of erosive esophagitis and improvement of symptoms of gastroesophageal reflux disease after esomeprazole treatment in children 12 to 36 months old. J Pediatr Gastroenterol Nutr. 2015;60 Suppl 1:S31–6.PubMedCrossRef
198.
Tolia V, Youssef NN, Gilger MA, Traxler B, Illueca M. Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study. J Pediatr Gastroenterol Nutr. 2015;60 Suppl 1:S24–30.PubMedCrossRef
199.
200.
Mohan N, Matthai J, Bolia R, et al. Diagnosis and management of gastroesophageal reflux disease in children: recommendations of Pediatric Gastroenterology Chapter of Indian Academy of Pediatrics, Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition (ISPGHAN). Indian Pediatr. 2021;58:1163–70.PubMedCrossRef
201.
Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric gastroesophageal reflux clinical practice guidelines: Joint recommendations of the North American society for pediatric gastroenterology, hepatology, and nutrition and the European society for pediatric gastroenterology, hepatology, and nutrition. J Pediatr Gastroenterol Nutr. 2018;66:516–54.PubMedPubMedCentralCrossRef
202.
Poddar U. Diagnosis and management of gastroesophageal reflux disease (GERD): an Indian perspective. Indian Pediatr. 2013;50:119–26.PubMedCrossRef
203.
Le Thi TG, Werkstetter K, Kotilea K, et al. Management of Helicobacter pylori infection in paediatric patients in Europe: results from the EuroPedHp Registry. Infection. 2023;51:921–34.PubMedCrossRef
204.
Levy EI, Salvatore S, Vandenplas Y, de Winter JP. Prescription of acid inhibitors in infants: an addiction hard to break. Eur J Pediatr. 2020;179:1957–61.PubMedCrossRef
205.
O’Reilly D, Conway R, O’Connor L, Fitzpatrick P. Use of anti-reflux medications in infants under 1 year of age: a retrospective drug utilization study using national prescription reimbursement data. Eur J Pediatr. 2020;179:1963–7.PubMedCrossRef
206.
207.
Dipasquale V, Cicala G, Spina E, Romano C. A narrative review on efficacy and safety of proton pump inhibitors in children. Front Pharmacol. 2022;13:839972.PubMedPubMedCentralCrossRef
208.
van der Pol RJ, Smits MJ, van Wijk MP, Omari TI, Tabbers MM, Benninga MA. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: a systematic review. Pediatrics. 2011;127:925–35.PubMedCrossRef
209.
Lightdale JR, Gremse DA; Section on Gastroenterology, Hepatology, and Nutrition. Gastroesophageal reflux: management guidance for the pediatrician. Pediatrics. 2013;131:e1684–95.PubMedCrossRef
210.
Meyer A, Fermaut M, Drouin J, Carbonnel F, Weill A. Drug use for gastrointestinal symptoms during pregnancy: a French nationwide study 2010–2018. PloS One. 2021;16:e0245854.PubMedPubMedCentralCrossRef
211.
Gill SK, O’Brien L, Einarson TR, Koren G. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol. 2009;104:1541–5; quiz 1540, 1546.PubMedCrossRef
212.
Matok I, Levy A, Wiznitzer A, Uziel E, Koren G, Gorodischer R. The safety of fetal exposure to proton-pump inhibitors during pregnancy. Dig Dis Sci. 2012;57:699–705.PubMedCrossRef
213.
Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med. 2010;363:2114–23.PubMedCrossRef
214.
Li CM, Zhernakova A, Engstrand L, Wijmenga C, Brusselaers N. Systematic review with meta-analysis: the risks of proton pump inhibitors during pregnancy. Aliment Pharmacol Ther. 2020;51:410–20.PubMedCrossRef
215.
Acar S, Keskin-Arslan E, Uysal N, Karadas B, Kaplan YC. Letter: safety of proton pump inhibitors during pregnancy. Aliment Pharmacol Ther. 2020;52:739.PubMedCrossRef
216.
Mei Li C, Brusselaers N. Letter: safety of proton pump inhibitors during pregnancy-authors’ reply. Aliment Pharmacol Ther. 2020;52:740–1.PubMedCrossRef
217.
Lai T, Wu M, Liu J, et al. Acid-suppressive drug use during pregnancy and the risk of childhood asthma: a meta-analysis. Pediatrics. 2018;141:e20170889.PubMedCrossRef
218.
219.
Looijer-van Langen M, Veldhuyzen van Zanten S. Does the evidence show that prokinetic agents are effective in healing esophagitis and improving symptoms of GERD? Open Med. 2007;1:e181–3.PubMedPubMedCentral
220.
Ren LH, Chen WX, Qian LJ, Li S, Gu M, Shi RH. Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis. World J Gastroenterol. 2014;20:2412–9.PubMedPubMedCentralCrossRef
221.
Xi L, Zhu J, Zhang H, Muktiali M, Li Y, Wu A. The treatment efficacy of adding prokinetics to PPIs for gastroesophageal reflux disease: a meta-analysis. Esophagus. 2021;18:144–51.PubMedCrossRef
222.
Fock KM, Talley N, Goh KL, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett’s oesophagus. Gut. 2016;65:1402–15.PubMedCrossRef
223.
Harris J, Chorath K, Balar E, et al. Clinical practice guidelines on pediatric gastroesophageal reflux disease: a systematic quality appraisal of international guidelines. Pediatr Gastroenterol Hepatol Nutr. 2022;25:109–20.PubMedPubMedCentralCrossRef
224.
Hong SH, Lee EK, Shin JY. Proton-pump inhibitors and the risk of Clostridium difficile-associated diarrhea in high-risk antibiotics users: a population-based case-crossover study. Pharmacoepidemiol Drug Saf. 2019;28:479–88.PubMedCrossRef
225.
Anjewierden S, Han Z, Foster CB, Pant C, Deshpande A. Risk factors for Clostridium difficile infection in pediatric inpatients: a meta-analysis and systematic review. Infect Control Hosp Epidemiol. 2019;40:420–6.PubMedCrossRef
226.
Kaur S, Vaishnavi C, Prasad KK, Ray P, Kochhar R. Comparative role of antibiotic and proton pump inhibitor in experimental Clostridium difficile infection in mice. Microbiol Immunol. 2007;51:1209–14.PubMedCrossRef
227.
Singh G, Haileselassie Y, Briscoe L, et al. The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial. Clin Nutr ESPEN. 2022;47:70–7.PubMedCrossRef
228.
Belei O, Olariu L, Dobrescu A, Marcovici T, Marginean O. Is it useful to administer probiotics together with proton pump inhibitors in children with gastroesophageal reflux? J Neurogastroenterol Motil. 2018;24:51–7.PubMedPubMedCentralCrossRef
229.
Hegar B, Hutapea EI, Advani N, Vandenplas Y. A double-blind placebo-controlled randomized trial on probiotics in small bowel bacterial overgrowth in children treated with omeprazole. J Pediatr (Rio J). 2013;89:381–7.PubMedCrossRef
230.
Soubra L, Issa M. Prescribing of proton pump inhibitors for gastrointestinal bleeding prophylaxis in the Lebanese outpatient setting: patterns, compliance with guidelines and risks. Int J Pharm Pract. 2019;27:386–92.PubMedCrossRef
231.
de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ. 1999;319:1106–9.PubMedCrossRef
232.
Ross SB, Aperia B, Beck-Friis J, Jansa S, Wetterberg L, Aberg A. Inhibition of 5-hydroxytryptamine uptake in human platelets by antidepressant agents in vivo. Psychopharmacology (Berl). 1980;67:1–7.PubMedCrossRef
233.
Nochaiwong S, Ruengorn C, Awiphan R, et al. Use of serotonin reuptake inhibitor antidepressants and the risk of bleeding complications in patients on anticoagulant or antiplatelet agents: a systematic review and meta-analysis. Ann Med. 2022;54:80–97.PubMedCrossRef
234.
Iwagami M, Tomlinson LA, Mansfield KE, Douglas IJ, Smeeth L, Nitsch D. Gastrointestinal bleeding risk of selective serotonin reuptake inhibitors by level of kidney function: a population-based cohort study. Br J Clin Pharmacol. 2018;84:2142–51.PubMedPubMedCentralCrossRef
235.
Anglin R, Yuan Y, Moayyedi P, Tse F, Armstrong D, Leontiadis GI. Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis. Am J Gastroenterol. 2014;109:811–9.PubMedCrossRef
236.
Jiang HY, Chen HZ, Hu XJ, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2015;13:42-50. e3.PubMedCrossRef
237.
Carvajal A, Ortega S, Del Olmo L, et al. Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study. PloS One. 2011;6:e19819.PubMedPubMedCentralCrossRef
238.
Vidal X, Ibanez L, Vendrell L, Conforti A, Laporte JR. Spanish-Italian collaborative group for the epidemiology of gastrointestinal B. Risk of upper gastrointestinal bleeding and the degree of serotonin reuptake inhibition by antidepressants: a case-control study. Drug Saf. 2008;31:159–68.PubMedCrossRef
239.
Yuan Y, Tsoi K, Hunt RH. Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding? Am J Med. 2006;119:719–27.PubMedCrossRef
240.
Gjestad C, Westin AA, Skogvoll E, Spigset O. Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline. Ther Drug Monit. 2015;37:90–77.PubMedPubMedCentralCrossRef
241.
Assimon MM, Pun PH, Al-Khatib SM, et al. Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis. Pharmacoepidemiol Drug Saf. 2022;31:670–9.PubMedPubMedCentralCrossRef
242.
Elliott SN, McKnight W, Davies NM, MacNaughton WK, Wallace JL. Alendronate induces gastric injury and delays ulcer healing in rodents. Life Sci. 1998;62:77–91.PubMedCrossRef
243.
Marshall JK. The gastrointestinal tolerability and safety of oral bisphosphonates. Expert Opinion Drug Safety. 2002;1:71–8.CrossRef
244.
Marshall JK, Thabane M, James C. Randomized active and placebo-controlled endoscopy study of a novel protected formulation of oral alendronate. Dig Dis Sci. 2006;51:864–8.PubMedCrossRef
245.
Thomson AB, Marshall JK, Hunt RH, et al. 14 day endoscopy study comparing risedronate and alendronate in postmenopausal women stratified by Helicobacter pylori status. J Rheumatol. 2002;29:1965–74.PubMed
246.
Modi A, Siris ES, Steve Fan CP, Sajjan S. Gastrointestinal events among patients initiating osteoporosis therapy: a retrospective administrative claims database analysis. Clin Ther. 2015;37:1228–34.PubMedCrossRef
247.
Itoh S, Sekino Y, Shinomiya K, Takeda S. The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis. J Bone Miner Metab. 2013;31:206–11.PubMedCrossRef
248.
Yang SD, Chen Q, Wei HK, et al. Bone fracture and the interaction between bisphosphonates and proton pump inhibitors: a meta-analysis. Int J Clin Exp Med. 2015;8:4899–910.PubMedPubMedCentral
249.
Hafiz RA, Wong C, Paynter S, David M, Peeters G. The risk of community-acquired enteric infection in proton pump inhibitor therapy: systematic review and meta-analysis. Ann Pharmacother. 2018;52:613–22.PubMedCrossRef
250.
Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102:2047–56; quiz 2057.PubMedCrossRef
251.
Le Bastard Q, Al-Ghalith GA, Gregoire M, et al. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment Pharmacol Ther. 2018;47:332–45.PubMedCrossRef
252.
Lin CY, Cheng HT, Kuo CJ, et al. Proton pump inhibitor-induced gut dysbiosis increases mortality rates for patients with Clostridioides difficile infection. Microbiol Spectr. 2022;10:e0048622.PubMedCrossRef
253.
Cao F, Chen CX, Wang M, et al. Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection. J Hosp Infect. 2018;98:4–13.PubMedCrossRef
254.
Mehta P, Nahass RG, Brunetti L. Acid suppression medications during hospitalization as a risk factor for recurrence of Clostridioides difficile infection: systematic review and meta-analysis. Clin Infect Dis. 2021;73:e62–8.PubMedCrossRef
255.
Pranata R, Huang I, Lawrensia S, et al. Proton pump inhibitor on susceptibility to COVID-19 and its severity: a systematic review and meta-analysis. Pharmacol Rep. 2021;73:1642–9.PubMedPubMedCentralCrossRef
256.
Fatima K, Almas T, Lakhani S, et al. The use of proton pump inhibitors and COVID-19: a systematic review and meta-analysis. Trop Med Infect Dis. 2022;7:37.PubMedPubMedCentralCrossRef
257.
Ghoshal UC, Sachdeva S, Ghoshal U, et al. Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association. Indian J Gastroenterol. 2022;41:483–507.PubMedPubMedCentralCrossRef
258.
Revaiah PC, Kochhar R, Rana SV, et al. Risk of small intestinal bacterial overgrowth in patients receiving proton pump inhibitors versus proton pump inhibitors plus prokinetics. JGH Open. 2018;2:47–53.PubMedPubMedCentralCrossRef
259.
Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: A meta-analysis. Clin Gastroenterol Hepatol. 2013;11:483–90.PubMedCrossRef
260.
Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018;33:331–42.PubMedCrossRef
261.
Sierra F, Suarez M, Rey M, Vela MF. Systematic review: proton pump inhibitor-associated acute interstitial nephritis. Aliment Pharmacol Ther. 2007;26:545–53.PubMedCrossRef
262.
Yang Y, George KC, Shang WF, Zeng R, Ge SW, Xu G. Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies. Drug Design Dev Ther. 2017;11:1291–9.CrossRef
263.
Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol. 2014;10:193–207.PubMedCrossRef
264.
265.
266.
Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3:E166–71.PubMedPubMedCentralCrossRef
267.
Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016;27:339–47.PubMedCrossRef
268.
Poly TN, Islam MM, Yang HC, Wu CC, Li YJ. Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporos Int. 2019;30:103–14.PubMedCrossRef
269.
Yang J, Zhou TJ, Yang J, Bao DN. Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies. Curr Gastroenterol Rep. 2022;78:365–73.
270.
Liu J, Li X, Fan L, et al. Proton pump inhibitors therapy and risk of bone diseases: an update meta-analysis. Life Sci. 2019;218:213–23.PubMedCrossRef
271.
Hoff M, Skovlund E, Skurtveit S, et al. Proton pump inhibitors and fracture risk. The HUNT study, Norway. Osteoporos Int. 2020;31:109–18.PubMedCrossRef
272.
Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157:682-91. e2.CrossRef
273.
274.
Srinutta T, Chewcharat A, Takkavatakarn K, et al. Proton pump inhibitors and hypomagnesemia: a meta-analysis of observational studies. Medicine. 2019;98:e17788.PubMedPubMedCentralCrossRef
275.
Park CH, Kim EH, Roh YH, Kim HY, Lee SK. The association between the use of proton pump inhibitors and the risk of hypomagnesemia: a systematic review and meta-analysis. PloS One. 2014;9:e112558.PubMedPubMedCentralCrossRef
276.
Park SH, Lee SH, Lee JS, et al. Changes in serum magnesium concentration after use of a proton pump inhibitor in patients undergoing percutaneous coronary intervention. Kidney Res Clin Pract. 2015;34:98–102.PubMedPubMedCentralCrossRef
277.
278.
279.
Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95:1002–7.PubMedCrossRef
280.
Jung SB, Nagaraja V, Kapur A, Eslick GD. Association between vitamin B12 deficiency and long-term use of acid-lowering agents: a systematic review and meta-analysis. Internal Med J. 2015;45:409–16.CrossRef
281.
Choudhury A, Jena A, Jearth V, et al. Vitamin B12 deficiency and use of proton pump inhibitors: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 2023;17:479–87.PubMedCrossRef
282.
Qorraj-Bytyqi H, Hoxha R, Sadiku S, et al. Proton pump inhibitors intake and iron and vitamin B12 status: a prospective comparative study with a follow up of 12 months. Open Access Maced J Med Sci. 2018;6:442–6.PubMedPubMedCentralCrossRef
283.
Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr Gastroenterol Rep. 2010;12:448–57.PubMedPubMedCentralCrossRef
284.
Sharma VR, Brannon MA, Carloss EA. Effect of omeprazole on oral iron replacement in patients with iron deficiency anemia. South Med J. 2004;97:887–9.PubMedCrossRef
285.
Stewart CA, Termanini B, Sutliff VE, et al. Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment Pharmacol Ther. 1998;12:83–98.PubMedCrossRef
286.
Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86–91.PubMedCrossRef
287.
Ali MD. Proton pump inhibitors’ use and risk of iron deficiency anaemia: a systematic review and meta-analysis. Curr Rev Clin Exp Pharmacol. 2023;18:158–66.PubMedCrossRef
288.
Serfaty-Lacrosniere C, Wood RJ, Voytko D, et al. Hypochlorhydria from short-term omeprazole treatment does not inhibit intestinal absorption of calcium, phosphorus, magnesium or zinc from food in humans. J Am Coll Nutr. 1995;14:364–8.PubMedCrossRef
289.
Wright MJ, Sullivan RR, Gaffney-Stomberg E, et al. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res. 2010;25:2205–11.PubMedPubMedCentralCrossRef
290.
Graziani G, Badalamenti S, Como G, et al. Calcium and phosphate plasma levels in dialysis patients after dietary Ca-P overload Role of gastric acid secretion. Nephron. 2002;91:474–9.PubMedCrossRef
291.
Graziani G, Como G, Badalamenti S, et al. Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects. Nephrol Dial Transplant. 1995;10:1376–80.PubMed
292.
O’Connell MB, Madden DM, Murray AM, Heaney RP, Kerzner LJ. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;11:778–81.CrossRef
293.
Hussain S, Singh A, Zameer S, et al. No association between proton pump inhibitor use and risk of dementia: evidence from a meta-analysis. J Gastroenterol Hepatol. 2020;35:19–28.PubMedCrossRef
294.
Khan MA, Yuan Y, Iqbal U, et al. No association linking short-term proton pump inhibitor use to dementia: systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2020;115:671–8.PubMedCrossRef
295.
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. 2022;56:524–32.PubMedCrossRef
296.
Nguyen PA, Islam M, Galvin CJ, et al. Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia. Int J Qual Health Care. 2020;32:292–9.PubMedCrossRef
297.
Wang CH, Ma MH, Chou HC, et al. High-dose vs non-high-dose proton pump inhibitors after endoscopic treatment in patients with bleeding peptic ulcer: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2010;170:751–8.PubMedCrossRef
298.
Huber MA, Nadella S, Cao H, et al. Does chronic use of high dose proton pump inhibitors increase risk for pancreatic cancer? Pancreas. 2022;51:1118–27.PubMedCrossRef
299.
Zhang ML, Fan YX, Meng R, et al. Proton pump inhibitors and cancer risk: an umbrella review and meta-analysis of observational studies. Am J Clin Oncol. 2022;45:475–85.PubMedCrossRef
Metadata
Title
Guidelines on optimizing the use of proton pump inhibitors: PPI stewardship
Authors
Amit Kumar Dutta
Abhinav Jain
Vaneet Jearth
Ramit Mahajan
Manas Kumar Panigrahi
Vishal Sharma
Mahesh Kumar Goenka
Rakesh Kochhar
Govind Makharia
Duvvur Nageshwar Reddy
Richard Kirubakaran
Vineet Ahuja
Neha Berry
Naresh Bhat
Usha Dutta
Uday Chand Ghoshal
Ajay Jain
Umesh Jalihal
V. Jayanthi
Ajay Kumar
Sandeep Nijhawan
Ujjal Poddar
G. N. Ramesh
Shivram P Singh
Showkat Zargar
Shobna Bhatia
Publication date
12-09-2023
Publisher
Springer India
Published in
Indian Journal of Gastroenterology / Issue 5/2023
Print ISSN: 0254-8860
Electronic ISSN: 0975-0711
DOI
https://doi.org/10.1007/s12664-023-01428-7

Other articles of this Issue 5/2023

Indian Journal of Gastroenterology 5/2023 Go to the issue

Original Article

Combination of antimicrobials for non-specific isolated terminal ileal abnormalities - A randomized clinical trial

Original Article

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn’s disease: A cohort study from northern India

Research Letter

Occasional constipation—Understanding a common but overlooked problem!

Image

Double infection in Crohn’s disease

Original Article

Differences in Coronavirus disease - 19 vaccination related side effects in patients with ulcerative colitis and Crohn’s disease in Japan

SYSTEMATIC REVIEW and META-ANALYSIS

Prevalence of hepatic encephalopathy in patients with non-cirrhotic portal hypertension: A systematic review and meta-analysis
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits