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. 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. 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. 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 .

Summary: Background: Small intestinal bacterial overgrowth (SIBO) is a heterogeneous syndrome, characterised by an increased number and/or abnormal type of bacteria in the small bowel. Over the past decades, rifaximin has gained popularity for this indication despite its use is not evidence based.Aim: To perform a systematic review and meta‐analysis to summarise evidence about the efficacy and safety of rifaximin to eradicate SIBO in adult patients.Methods: MEDLINE, EMBASE, CCRCT, Scopus and Web of Science were searched from inception to March 16, 2015 for RCTs and observational studies. Furthermore, abstract books of major European, American and Asian gastroenterological meetings were also examined.Results: Thirty‐two studies involving 1331 patients were included. The overall eradication rate according to intention‐to‐treat analysis was 70.8% (95% CI: 61.4–78.2; I² = 89.4%) and to per protocol analysis 72.9% (95% CI: 65.5–79.8; I² = 87.5%). Meta‐regression identified three covariates (drug dose, study design and co‐therapy) independently associated with an increased eradication rate. The overall rate of adverse events was 4.6% (95% CI: 2.3–7.5; I² = 63.6%). In the subset of studies (n= 10) allowing the analysis, improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7% (95% CI: 44.7–86.9; I² = 91.3%).Conclusions: Rifaximin treatment seems to be effective and safe for the treatment of SIBO. However, the quality of the available studies is generally poor. Well‐designed RCTs are needed to substantiate these findings and to establish the optimal regimen.

Eradication rates with triple therapy (TT) for Helicobacter pylori infection have declined to unacceptable levels. Sequential therapy (ST) is a novel treatment that has shown promise in several controlled trials. Our aim was to assess the efficacy of ST in adults and children compared with that of TT by performing a systematic review and meta-analysis. We performed an electronic search of the following: Cochrane Trial Register (until Issue 4, 2008), MEDLINE (1966 to 21 October 2008), EMBASE (1980 to 21 October 2008), and abstracts from the major US, European, and Asian gastroenterology conferences. Randomized controlled trials (RCTs) and controlled clinical trials with a parallel group design comparing the ST with a TT lasting at least 7 days were used. Ten RCTs enrolled 3,006 adult patients and the odds ratio (OR) for eradication of H. pylori with ST compared with TT was 2.99 (95% confidence interval (CI): 2.47–3.62), giving a number needed to treat (NNT) of 6 (95% CI: 5–7) favoring ST. There was no publication bias. The OR for eradication with ST compared with 10-day TT was 2.92 (95% CI: 1.95–4.38), yielding an NNT of 8 (95% CI: 6–12), favoring ST. In patients with clarithromycin resistance, the OR for eradication with ST was 10.21 (95% CI: 3.01–34.58) compared with TT, but the numbers studied are small. Three RCTs enrolled 260 children and adolescents, and the OR for eradication was 1.98 (95% CI: 0.96–4.07). There was no difference in the rate of side effects between the ST and the TT (OR, 1.01; 95% CI: 0.78–1.30). ST appears to be better than TT in the eradication of H. pylori. This is a promising therapy, but further trials are needed in other European countries and North America before it can be recommended as a first-line treatment.

F1000Prime Recommended Article: Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy.

Summary: Background : Eradication rates of Helicobacter pylori with standard triple therapy are disappointing, and studies from several countries confirm this poor performance.Aim : To assess the eradication rate of a new sequential treatment regimen compared with conventional triple therapy for the eradication of H. pylori infection.Methods : One thousand and forty‐nine dyspeptic patients were studied prospectively. H. pylori‐infected patients were randomized to receive 10‐day sequential therapy [rabeprazole (40 mg daily) plus amoxicillin (1 g twice daily) for the first 5 days, followed by rabeprazole (20 mg), clarithromycin (500 mg) and tinidazole (500 mg) twice daily for the remaining 5 days] or standard 7‐day treatment [rabeprazole (20 mg), clarithromycin (500 mg) and amoxicillin (1 g) twice daily]. H. pylori status was assessed by histology, rapid urease test and ¹³C‐urea breath test at baseline and 6 weeks or more after completion of treatment.Results : Higher eradication rates were found with the sequential regimen compared to the standard regimen (intention‐to‐treat: 92% vs. 74%, P < 0.0001; per protocol: 95% vs. 77%, P < 0.0001). Higher eradication rates were also seen in patients with peptic ulcer disease and non‐ulcer dyspepsia. In both treatments, compliance was similar (> 90%), as was the rate of side‐effects, which were mild.Conclusions : This 10‐day sequential treatment regimen achieves high eradication rates in peptic ulcer disease and non‐ulcer dyspepsia.

Background and aims: The incidence of gastric cancer in Japan is four times higher than in the UK. It usually arises in a stomach with corpus predominant or pangastritis that has undergone extensive atrophy and intestinal metaplasia. We hypothesised that a Japanese population would have a more severe gastritis with a corpus predominant or pangastritis pattern and a greater degree of atrophy and intestinal metaplasia than that found in the UK. To test this we designed a comparative trial. Methods: A total of 252 age matched consecutive patients were recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21 patients were prospectively selected from each decennial, between the ages of 20–80 years. All had epigastric discomfort as their predominant symptom. Patients with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies were examined by two histopathologists using the updated Sydney system. Helicobacter pylori infection was assessed by histology and culture of biopsies and enzyme linked immunosorbent assay and immunoblot of plasma. Results: Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese patients (χ ² test, p = 0.04). In those patients with gastritis, corpus predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the UK (χ ² test, p = 0.003) Atrophy and intestinal metaplasia were more extensive and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph activity were also greater, especially in the corpus (Mann-Whitney U test, p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (χ ² test, p = 1) Japanese gastritis patients were positive for H pylori . Using a previously described “gastric cancer risk index” among H pylori positive patients, there were significantly more Japanese than UK subjects with a “high risk” score. Conclusion: In Japanese as opposed to English patients, gastritis is more prevalent and severe with more corpus predominant atrophy and intestinal metaplasia. These differences may partially explain the higher incidence of gastric cancer in Japan.