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      Is Open Access

      Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression

      editorial
      1 , , 1 , 2 , 3 , 4 , for the SIF-AIGO-FIMMG Group, on behalf of the Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners
      BMC Medicine
      BioMed Central
      Proton pump inhibitors, Antisecretory drugs, Efficacy, Safety, Appropriateness, Acid-related diseases

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          Abstract

          Background

          The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications.

          Methods

          The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence.

          Results

          Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger–Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile.

          Conclusions

          Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy.

          Please see related Commentary: doi:10.1186/s12916-016-0724-1.

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          Most cited references418

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          Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.

          Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.
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            American College of Gastroenterology guideline on the management of Helicobacter pylori infection.

            Helicobacter pylori (H. pylori) remains a prevalent, worldwide, chronic infection. Though the prevalence of this infection appears to be decreasing in many parts of the world, H. pylori remains an important factor linked to the development of peptic ulcer disease, gastric malignanc and dyspeptic symptoms. Whether to test for H. pylori in patients with functional dyspepsia, gastroesophageal reflux disease (GERD), patients taking nonsteroidal antiinflammatory drugs, with iron deficiency anemia, or who are at greater risk of developing gastric cancer remains controversial. H. pylori can be diagnosed by endoscopic or nonendoscopic methods. A variety of factors including the need for endoscopy, pretest probability of infection, local availability, and an understanding of the performance characteristics and cost of the individual tests influences choice of evaluation in a given patient. Testing to prove eradication should be performed in patients who receive treatment of H. pylori for peptic ulcer disease, individuals with persistent dyspeptic symptoms despite the test-and-treat strategy, those with H. pylori-associated MALT lymphoma, and individuals who have undergone resection of early gastric cancer. Recent studies suggest that eradication rates achieved by first-line treatment with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin have decreased to 70-85%, in part due to increasing clarithromycin resistance. Eradication rates may also be lower with 7 versus 14-day regimens. Bismuth-containing quadruple regimens for 7-14 days are another first-line treatment option. Sequential therapy for 10 days has shown promise in Europe but requires validation in North America. The most commonly used salvage regimen in patients with persistent H. pylori is bismuth quadruple therapy. Recent data suggest that a PPI, levofloxacin, and amoxicillin for 10 days is more effective and better tolerated than bismuth quadruple therapy for persistent H. pylori infection, though this needs to be validated in the United States.
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              Is Open Access

              Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis

              Objective To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Design Network meta-analysis. Data sources Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. Study selection All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. Data extraction The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. Data synthesis 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Conclusions Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.
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                Author and article information

                Contributors
                +39 0521 903863 , scarpi@tin.it
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                9 November 2016
                9 November 2016
                2016
                : 14
                : 179
                Affiliations
                [1 ]Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Maggiore University Hospital, Cattani Pavillon, I-43125 Parma, Italy
                [2 ]Gastroenterology & Endoscopy Unit, Versilia Hospital, Azienda USL Toscana Nord Ovest, Lido di Camaiore, Italy
                [3 ]Division of Gastroenterology & Digestive Endoscopy, Nuovo Regina Elena Hospital, Rome, Italy
                [4 ]Division of Pharmacology, Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy
                Article
                718
                10.1186/s12916-016-0718-z
                5101793
                27825371
                8aec9630-a484-499e-826a-1ff1df11ebb8
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 August 2016
                : 14 October 2016
                Categories
                Guideline
                Custom metadata
                © The Author(s) 2016

                Medicine
                proton pump inhibitors,antisecretory drugs,efficacy,safety,appropriateness,acid-related diseases

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