Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side ...effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro- duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called "inclusion complexes" that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a more rapid onset of action after oral administration and improved GI tolerability because of minimization of the drug gastric effects. One such drug, piroxicam-β-cyclodextrin (PBC), has been used in Europe for 25 years. Preclinical and clinical pharmacology of PBC do show that the β-cyclodextrin inclusion complex of piroxicam is better tolerated from the upper GI tract than free piroxicam, while retaining all the analgesic and anti-inflammatory properties of the parent compound. In addition, the drug is endowed with a quick absorption rate, which translates into a faster onset of analgesic activity, an effect confirmed in several clinical studies. An analysis of the available trials show that PBC has a GI safety profile, which is better than that displayed by uncomplexed piroxicam. Being an inclusion complex of piroxicam, whose CV safety has been pointed out by several observational studies, PBC should be viewed as a CV safe anti-inflmmatory compound and a GI safer alternative to piroxicam. As a consequence, it should be considered as a useful addition to our therapeutic armamentarium.
Objective To do a systematic review and meta-analysis of studies comparing sequential therapy for eradication of Helicobacter pylori with pre-existing and new therapies, thus providing a glimpse of ...eradication success worldwide.Design Systematic review and meta-analysis.Data sources Medline, Embase, and Cochrane Central Register of Controlled Trials up to May 2013; abstract books of major European, American, and Asian gastroenterological meetings.Study selection Randomised controlled trials in previously untreated adults, in which sequential therapy was compared with a pre-existing or new therapy.Results 46 randomised controlled trials were reviewed and analysed. 5666 patients were randomised to sequential therapy and 7866 to other (established and new) treatments. The overall eradication rate of sequential therapy was 84.3% (95% confidence interval 82.1% to 86.4%). Sequential therapy was superior to seven day triple therapy (relative risk 1.21, 95% confidence interval 1.17 to 1.25; I2=29.3%; number needed to treat 6 , 95% confidence interval 5% to 7%), marginally superior to 10 day triple therapy (1.11, 1.04 to 1.19; I2= 67.2%; NNT 10, 7 to 15), but not superior to 14 day triple therapy (1.00, 0.94 to 1.06; I2=54.3%), bismuth based therapy (1.01, 0.95 to 1.06; I2=21.1%), and non-bismuth based therapy (0.99, 0.94 to 1.05; I2=52.3%). Data on eradication according to pre-treatment antimicrobial susceptibility testing were available in eight studies, and sequential therapy was able to eradicate 72.8% (61.6% to 82.8%) of the strains resistant to clarithromycin.Conclusions Eradication rates with pre-existing and new therapies for H pylori are suboptimal. Regional monitoring of resistance rates should help to guide treatment, and new agents for treatment need to be developed.
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, 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.
Despite acid secretion being normal in the majority of patients with gastro‐esophageal reflux disease (GERD) or Barrett’s esophagus, acid inhibition represents the mainstay of treatment for both ...these conditions, with the aim of reducing the aggressive nature of the refluxate toward the esophageal mucosa. Proton pump inhibitors (PPIs) represent, therefore, the first choice medical treatment for GERD, in that they are able to provide an 80–85% healing rate for esophageal lesions, a 56–76% symptom relief and also reduce the incidence of complications, such as strictures as well as dysplasia and adenocarcinoma in Barrett’s esophagus. According to a widely quoted systematic review, compared to patients with erosive esophagitis, patients with non‐erosive reflux disease (i.e., NERD) display a reduced symptom relief with PPIs, with about 20% reduction of therapeutic gain. In this issue of NeuroGastroenterology & Motility, Weijenborg et al. address for the first time the PPI efficacy in subpopulations of patients with NERD. The study shows clearly that, when the diagnosis is accurately made by including a functional test, NERD patients respond to PPI therapy in a similar way to those with erosive disease. Although not as frequent as previously suggested, however, PPI‐refractory heartburn does exist. Some 20% (range: 15–27%) of correctly diagnosed and appropriately treated patients do not respond to PPI treatment at standard doses. Although the pathophysiology underlying PPI failure in GERD is complex and likely multifactorial, acid (be it the sole component of refluxate or not) still remains a major causative factor. A better and more predictable form of acid suppression should therefore be pursued.
Summary
Background The impact of constipation on quality of life (QoL) may vary in different cultural or national settings.
Aim We studied QoL in a multinational survey to compare different social ...and demographic groups with and without constipation (defined according to Rome III criteria) and to detect country‐specific differences among the groups studied.
Methods Health‐related QoL (HRQoL) was assessed with the Short Form 36 (SF‐36) questionnaire in 2870 subjects in France, Germany, Italy, UK, South Korea, Brazil and USA.
Results Respondents were mainly middle‐aged, married or living together and part‐ or full‐time employed. General health status, measured by the SF‐36 questionnaire, was significantly worse in the constipated vs. non‐constipated populations. Results were comparable in all countries. QoL scores correlated negatively with age. Constipated women reported more impaired HRQoL than constipated men. Brazilians were most affected by constipation as to their social functioning (35.8 constipated vs. 51.3 non‐constipated) and general health perception (29.4 constipated vs. 54.4 non‐constipated).
Conclusions There are significant differences in HRQoL between constipated and non‐constipated individuals and a significant, negative correlation between the number of symptoms and complaints and SF‐36 scores. The study detected a correlation of constipation with QoL and the influence of social and demographic factors on HRQoL in constipated people.
Linked Content
This article is linked to Gatta et al and Siddique and Moss papers. To view these articles visit https://doi.org/10.1111/apt.14597 and https://doi.org/10.1111/apt.14643.
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