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      Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

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          Abstract

          Objective

          To determine the effectiveness of management strategies for uninvestigated dyspepsia.

          Design

          Systematic review and network meta-analysis.

          Data sources

          Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019.

          Eligibility criteria for selecting studies

          Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months).

          Results

          The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design.

          Conclusions

          “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms.

          Systematic review registration

          PROSPERO registration number CRD42019132528.

          Related collections

          Most cited references51

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          ACG and CAG Clinical Guideline: Management of Dyspepsia

          We have updated both the American College of Gastroenterology (ACG) and the Canadian Association of Gastroenterology (CAG) guidelines on dyspepsia in a joint ACG/CAG dyspepsia guideline. We suggest that patients ≥60 years of age presenting with dyspepsia are investigated with upper gastrointestinal endoscopy to exclude organic pathology. This is a conditional recommendation and patients at higher risk of malignancy (such as spending their childhood in a high risk gastric cancer country or having a positive family history) could be offered an endoscopy at a younger age. Alarm features should not automatically precipitate endoscopy in younger patients but this should be considered on a case-by-case basis. We recommend patients <60 years of age have a non-invasive test Helicobacter pylori and treatment if positive. Those that are negative or do not respond to this approach should be given a trial of proton pump inhibitor (PPI) therapy. If these are ineffective tricyclic antidepressants (TCA) or prokinetic therapies can be tried. Patients that have an endoscopy where no pathology is found are defined as having functional dyspepsia (FD). H. pylori eradication should be offered in these patients if they are infected. We recommend PPI, TCA and prokinetic therapy (in that order) in those that fail therapy or are H. pylori negative. We do not recommend routine upper gastrointestinal (GI) motility testing but it may be useful in selected patients.
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            Complications of Proton Pump Inhibitor Therapy.

            Safety issues associated with proton pump inhibitors (PPIs) have recently attracted widespread media and lay attention. Gastroenterologists are frequently asked about the appropriateness of PPI therapy for specific patients. Furthermore, some patients may have had PPI therapy discontinued abruptly or inappropriately due to safety concerns. Faced with such a wide variety of potentially serious adverse consequences, prescribers need to evaluate the evidence objectively to discern the likelihood that any reported association might actually be causal. Here, we review many of the proposed adverse consequences of PPI therapy and apply established criteria for the determination of causation. We also consider the potential contribution of residual confounding in many of the reported studies. Evidence is inadequate to establish causal relationships between PPI therapy and many of the proposed associations. Residual confounding related to study design and the over-extrapolation of quantitatively small estimates of effect size have probably led to much of the current controversy about PPI safety. In turn, this has caused unnecessary concern among patients and prescribers. The benefits of PPI therapy for appropriate indications need to be considered along with the likelihood of the proposed risks. Patients with a proven indication for a PPI should continue to receive it in the lowest effective dose. PPI dose escalation and continued chronic therapy in those unresponsive to initial empiric therapy is discouraged.
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              Effect of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: An Updated Systematic Review and Meta-analysis

              Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective.
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                Author and article information

                Contributors
                Role: senior assistant professor
                Role: clinical research fellow
                Role: professor of medicine
                Role: professor and honorary consultant gastroenterologist
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2019
                11 December 2019
                : 367
                : l6483
                Affiliations
                [1 ]Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
                [2 ]Leeds Gastroenterology Institute, St James’s University Hospital, Leeds, UK
                [3 ]Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
                [4 ]Division of Gastroenterology and Hepatology, Department of Medicine, University of Tennessee College of Medicine, Memphis, TN, USA
                Author notes
                Correspondence to: A C Ford Leeds Gastroenterology Institute, St James’s University Hospital, Leeds LS9 7TF, UK alexf12399@ 123456yahoo.com (or @alex_ford12399 on Twitter)
                Author information
                http://orcid.org/0000-0001-6371-4359
                Article
                eusl050524
                10.1136/bmj.l6483
                7190054
                31826881
                3a2f1951-4003-4a9c-ae7e-bedd17741b6b
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 07 November 2019
                Categories
                Research

                Medicine
                Medicine

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