Nonsteroidal anti-inflammatory drugs (NSAIDs) can damage the gastrointestinal tract, causing widespread morbidity and mortality. Although mechanisms of damage involve the activities of prostaglandin-endoperoxide synthase 1 (PTGS1 or cyclooxygenase [COX] 1) and PTGS1 (COX2), other factors are involved. We review the mechanisms of gastrointestinal damage induction by NSAIDs via COX-mediated and COX-independent processes. NSAIDs interact with phospholipids and uncouple mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the gastrointestinal barrier. The resulting increase in intestinal permeability leads to low-grade inflammation. NSAID inhibition of COX enzymes, along with luminal aggressors, results in erosions and ulcers, with potential complications of bleeding, protein loss, stricture formation, and perforation. We propose a model for NSAID-induced damage to the gastrointestinal tract that includes these complex, interacting, and inter-dependent factors. This model highlights the obstacles for the development of safer NSAIDs.

There are many strongly held beliefs about constipation that are not evidence based. The purpose of this review is to address these beliefs concerning various aspects of constipation. There is no evidence to support the theory that diseases may arise via “autointoxication,” whereby poisonous substances from stools within the colon are absorbed. Dolichocolon, defined as an elongated colon, should not be seen as a cause of constipation. The role of sex hormones altering gut function during the menstrual cycle appears to be minimal. During pregnancy they may play a role in slowing gut transit. Hypothyroidism can cause constipation, but among patients presenting with constipation, hypothyroidism is rare. A diet poor in fiber should not be assumed to be the cause of chronic constipation. Some patients may be helped by a fiber-rich diet but many patients with more severe constipation get worse symptoms when increasing dietary fiber intake. There is no evidence that constipation can successfully be treated by increasing fluid intake unless there is evidence of dehydration. In the elderly constipation may correlate with decreased physical activity, but many cofactors are likely to play a role. Intervention programs to increase physical activity as part of a broad rehabilitation program may help. It is unlikely that stimulant laxatives at recommended doses are harmful to the colon. A proportion of patients with chronic constipation is dependent of laxatives to achieve satisfactory bowel function, but this is not the result of prior laxative intake. Tolerance to stimulant laxatives is uncommon. There is no indication for the occurrence of “rebound constipation” after stopping laxative intake. While laxatives may be misused, there is no potential for addiction.

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 .

Caustic injury of the upper gastrointestinal tract: A comprehensive review

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.