Ongoing Proton Pump Inhibitor Therapy Research Articles

Real-time gastric juice analysis with EndoFaster for H. pylori diagnosis: a large, multicentre study.

Helicobacter pylori infection is the main cause of the most frequent gastroduodenal diseases. Because its prevalence is decreasing in developed countries, gastric biopsies are negative in several patients. By measuring ammonium in the gastric juice, EndoFaster allows to exclude H. pylori infection during endoscopy. This study aimed to assess the accuracy of device versions working with either 6 ml or 3 ml of gastric juice. This prospective study involved 12 endoscopic units. During endoscopy, EndoFaster testing was performed and standard five gastric biopsies were taken. The accuracy was calculated by considering histological assessment as the gold standard for H. pylori diagnosis. Gastric juice analysis was attempted in 1279 patients, but it failed in 131 (15.5%) and in 10 (2.3%), with the 6 ml and the 3 ml device, respectively (P < 0.001). Overall, EndoFaster detected H. pylori infection with an 86.3% sensitivity, 83.3% specificity, 52.7% positive predictive value, 96.6% negative predictive value and 83.8% accuracy. The performance was not affected either by ongoing proton pump inhibitor therapy or a previous H. pylori eradication. No significant difference in accuracy emerged between the two versions of the device. The novel version of the EndoFaster device operating with 3 ml gastric juice may be performed in virtually all patients, and it allows excluding H. pylori infection with a very high accuracy. Gastric biopsies can be avoided in a definite portion of cases without endoscopic lesions or other clinical indications.

Real-time determination of gastric juice pH with EndoFaster® for atrophic gastritis assessment

BackgroundIn patients with atrophic gastritis involving gastric body mucosa the pH value of gastric juice is distinctly increased, so that pH assessment would allow predict this precancerous lesion. We tested whether EndoFaster® − a device allowing real-time pH measure and H. pylori diagnosis – may optimize the need of taking gastric biopsies. MethodsIn this prospective, multicentre study, the accuracy of EndoFaster® for ruling out gastric atrophy involving corporal mucosa was assessed. Real-time pH and ammonium determination was performed by aspirating 3–6 ml gastric juice during endoscopy. Histology performed on 5 standard gastric biopsies was used as gold standard. ResultsA total of 1008 consecutive patients were observed in 12 centres. At histology, gastric body mucosa atrophy/metaplasia was detected in 65 (6.4%) cases, and a pH value >4.5 in the gastric juice was observed in 150 patients. The values of EndoFaster® performance in predicting the presence of atrophic gastritis were as follow: 51% sensitivity, 84% specificity, 18% PPV, 96% NPV, and 82% accuracy. The NPV value was not distinctly affected by neither ongoing proton pump inhibitor therapy nor H. pylori infection. By considering also data of ammonium concentrations, the values of EndoFaster® in detecting extensive atrophy on gastric mucosa were 74% sensitivity, 84% specificity, 24% PPV, 98% NPV, and 83% accuracy. ConclusionThe very high NPV of EndoFaster® might allow to safely rule out presence of atrophic gastritis, reducing the need of taking gastric biopsies in unselected patients managed in clinical practice

Optimizing the searching for H. pylori in clinical practice with EndoFasterⓇ

Background/AimH. pylori plays a major role in gastroduodenal diseases. Since its incidence is decreasing in developed countries, gastric biopsies were negative in several patients managed in clinical practice. We tested whether EndoFasterⓇ − a device allowing real-time H. pylori detection by gastric juice analysis – may optimize the need of biopsies. MethodsIn this prospective, multicentre study, the accuracy of EndoFasterⓇ for H. pylori detection was computed by using histology of gastric biopsies as a gold standard. ResultsData of 525 consecutive patients were available, including 90 (17.1%) patients with infection. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of EndoFasterⓇ were 87%, 84%, 53%, 97% and 85%, respectively. The overall accuracy of test was not affected neither by ongoing proton pump inhibitor therapy nor by previous eradication therapy. By using EndoFasterⓇ in our series, biopsy sampling could have been eventually avoided in a total of 279 patients, accounting for a reduction of 42.3%, accepting the risk of only 8 false negative cases. ConclusionsThe very high NPV of EndoFasterⓇ might allow to safely halve the need of taking gastric biopsies in unselected patients managed in clinical practice, avoiding an unavailing consume of health resources.

Helicobacter pylori and Upper Endoscopy in Systemic Sclerosis: A Cross-sectional Study in the Real World.

A role for Helicobacter pylori in triggering systemic sclerosis (SSc) has been proposed, but data are conflicting. In previous studies, infection has been generally searched for by using serology. We designed this study to assess H. pylori prevalence in SSc patients with histology of gastric mucosa, considered the criterion standard for infection diagnosis. This cross-sectional study enrolled 30 SSc patients who complained of upper gastrointestinal symptoms. All underwent upper endoscopy with gastric biopsies. Endoscopic alterations were recorded, and gastric mucosa biopsies were used for both histological examination and searching for H. pylori. The role for proton-pump inhibitor (PPI) therapy was considered. Fisher exact test was used for statistical analysis. Data of 28 SSc patients were available, 14 with ongoing PPI therapy. Helicobacter pylori infection at histology was detected in 14.3% patients, and it equally occurred in patients with or without PPI therapy. Erosive esophagitis/Barrett esophagus was detected in 26.6% of cases. Among patients with PPI therapy, 30% received half dose only. The prevalence of intestinal metaplasia was low (14.3%). Endoscopic esophageal alterations were significantly more frequent in those patients showing anti-Scl70 antibody positivity. This study showed that prevalence of H. pylori is very low in SSc patients, so that it seems not having a role in triggering SSc. Management of gastroesophageal diseases in SSc patients needs to be improved, and looking to the autoimmune profile may be of help. Thus, collaboration between rheumatologist and gastroenterologist is highly recommended.

Ambulatory Reflux Monitoring Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial

Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P= .04). Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Prevalence of lesions detected at upper endoscopy: An Italian survey

BackgroundPrevalence of gastroduodenal lesions is changing in the last decades. Prevalence of Helicobacter pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitor (PPI) therapy may be involved in such a phenomenon. We assessed gastroduodenal lesions prevalence in a nationwide study. Materials and methodsConsecutive patients who underwent upper endoscopy for the first time in 24 Italian centres between January 2012 and 31 March 2012 were enrolled. Prevalence of gastric ulcer (GU), duodenal ulcer (DU), gastric erosions (GE), duodenal erosions (DE), gastric polyp (GP), Barrett's oesophagus (BE), and neoplasia was assessed. ResultsOverall, 1054 (M/F: 388/666; Mean age: 57.5±5years) patients were enrolled. H. pylori infection was detected in 356 (33.9%) patients, 358 (34%) were taking NSAIDs, and 532 (50.5%) PPIs. PPI therapy was associated with a significantly lower H. pylori detection rate (27.8% vs 39.8%; OR: 0.6, 95% CI 0.45–0.77; P<0.001). GU, DU, GE, DE, GP and BE were detected in 17 (1.6%), 13 (1.2%), 150 (14.2%), 50 (4.7%), 51 (4.8%) and 17 (1.6%), respectively. Moreover, 3 (0.3%) distal gastric cancers were observed. H. pylori infection remained the most prevalent factor for all gastroduodenal lesions, but gastric polyp. One third of patients with GU and GE were taking only NSAIDs therapy. ConclusionsThe prevalence of peptic ulcer was very low (<3%), with a similar rate between DU and GU. As many as half patients were on ongoing PPI therapy. Such a therapy could affect both the detection rate of H. pylori infection and the real prevalence of gastroduodenal lesions.

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors.

To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease (GERD) and the response to proton pump inhibitor (PPI) therapy. Retrospectively, 683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement (pH/MII) were analyzed. All patients had previously undergone standard PPI treatment (e.g., pantoprazole 40 mg/d or comparable). Four hundred sixty patients were at least 10 d off PPIs (group A), whereas 223 patients were analyzed during their ongoing PPI therapy (group B). In addition, all patients completed a standardized symptom- and lifestyle-based questionnaire, including the therapeutic response to previous PPI trials on a 10-point scale. Uni- and multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs. In group A, positive predictors (PPs) for response in empirical PPI trials were typical GERD symptoms (heartburn and regurgitation), a positive symptom index (SI) and pathological results in pH/MII, along with atypical symptoms, including hoarseness and fullness. In group B, regular alcohol consumption was associated with the therapeutic response. The PPs for pathological results in pH/MII in group A included positive SI, male gender, obesity, heartburn and regurgitation. In group B, the PPs were positive SI and vomiting. Analyzing for positive SI, the PPs were pathological pH and/or MII, heartburn regurgitation, fullness, nausea and vomiting in group A and pathological pH and/or MII in group B. Anamnestic parameters (gender, obesity, alcohol) can predict PPI responses. In non-obese, female patients with non-typical reflux symptoms, pH/MII should be considered instead of empirical PPIs.

Efficacy and safety of lesogaberan in gastro-oesophageal reflux disease: a randomised controlled trial

ObjectiveLesogaberan (AZD3355) is a novel γ-aminobutyric acid B-type receptor agonist designed to treat gastro-oesophageal reflux disease (GERD) by inhibiting transient lower oesophageal sphincter relaxations. A randomised, double-blind, placebo-controlled, multi-centre phase...

Burden of Gastro-Oesophageal Reflux Disease in Patients with Persistent and Intense Symptoms Despite Proton Pump Inhibitor Therapy

Research on the negative impact of gastro-oesophageal reflux disease (GORD) on the health-related quality of life (HR-QOL) and resource utilization of patients with persistent and intense GORD symptoms despite proton pump inhibitor (PPI) therapy is lacking. The aim of this study was to describe the population of patients with GORD with persistent moderate-to-severe symptoms despite ongoing PPI therapy, and to compare their HR-QOL and healthcare resource use with patients with low GORD symptom load during ongoing PPI therapy. In this post hoc analysis of the 2007 National Health and Wellness Survey (NHWS), PPI-compliant (≥22 days with PPI use in the past month) European (France, Germany and the UK) and US respondents with physician-diagnosed GORD were stratified into those with persistent and intense GORD symptoms, those with low symptom load, or an intermediate group. 5672 PPI-compliant respondents were identified (persistent and intense symptoms, n = 1741; low symptom load, n = 1805; intermediate group, n = 2126). Respondents with persistent and intense symptoms had poorer HR-QOL than patients with a low symptom load, but none of the differences were statistically significant. Respondents with persistent and intense symptoms also reported lower work productivity (all countries; significant difference [p < 0.01] only in the US), greater activity impairment (all countries; significant difference [p < 0.01] only in the US) and more hours missed from work due to health problems (US, UK and Germany; significant difference [p < 0.01] only in the US). In the UK and US, respondents with persistent and intense symptoms reported significantly more visits to both primary-care physicians and specialists than respondents with a low symptom load (all p < 0.01). Additionally, US respondents with persistent and intense symptoms reported significantly more emergency room visits (p < 0.01). The 2007 NHWS gives support to the hypothesis that persistent and intense GORD symptoms despite PPI therapy have a significant and negative impact on both HR-QOL and healthcare resource utilization. These findings outline the need for new treatment options for symptomatic GORD patients taking PPI therapy.

Weakly acidic refluxes have a major role in the pathogenesis of proton pump inhibitor‐resistant reflux oesophagitis

In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied. To assess reflux parameters by impedance-pH monitoring in PPI-resistant reflux oesophagitis. Impedance-pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high-dose PPI therapy of at least 8-week duration. Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively. Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra-gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring results.

High-Dose Esomeprazole for Treatment of Symptomatic Refractory Gastroesophageal Reflux Disease – A Prospective pH-Metry/Impedance-Controlled Study

Background/Aims: Combined pH-metry/multichannel intraluminal impedance (pH/MII) measurement enables to measure gastroesophageal reflux despite ongoing proton pump inhibitor therapy. The aim of our study was to evaluate the influence of an escalating medical anti-reflux therapy with 40 mg esomeprazole, 80 mg esomeprazole and 80 mg esomeprazole plus baclofen for the treatment of refractory pathological reflux as determined by pH/MII. Methods: Symptomatic patients under 40 mg esomeprazole were screened by pH/MII. Patients with normal values in pH/MII were excluded; all others received 2 × 40 mg esomeprazole for another 4 weeks. Thereafter, the treatment effect was controlled by pH/MII. In the case of persistent pathological reflux, therapy was further escalated by adding baclofen and controlled after 3 months by pH/MII. Results: 45/138 (32.6%) patients showed pathological pH/MII despite ongoing therapy with 40 mg esomeprazole. In these, a significant reduction in liquid/mixed reflux events was observed after administering 2 × 40 mg (mean: 118.3 vs. mean: 66.6; p < 0.001), and pH/MII turned to normal in 32/45 (71.1%). Baclofen was additionally administered to 7/13 patients, which did not lead to a remarkable reduction in reflux events. Conclusion: In patients with abnormal pH/MII and persistent symptoms under 40 mg esomeprazole, we observed a significant reduction in liquid/mixed reflux events after increasing proton pump inhibitor dose up to 80 mg esomeprazole. Further escalation of therapy with baclofen has shown inconclusive results.

Proton-pump inhibitor therapy and the development of dysplasia in patients with Barrett's oesophagus.

To examine whether proton-pump inhibitor (PPI) therapy influences the incidence and progression of dysplasia in patients with Barrett's oesophagus. Review of prospective data on patients undergoing surveillance with regular endoscopy and biopsy at a private endoscopy centre in Canberra, ACT, between 1981 and 2001. 350 patients diagnosed with Barrett's oesophagus. PPI therapy was progressively introduced into clinical practice from late 1989. Once begun, PPI therapy was ongoing, with no attempt to reduce the dose. Relationship between development of dysplasia or adenocarcinoma and delay between diagnosis with Barrett's oesophagus and starting PPI therapy was determined by Cox regression analyses, stratified by year of enrollment. Age, sex, presence of macroscopic markers (severe oesophagitis, nodularity, Barrett's ulcer, stricture) and use of aspirin or non-steroidal anti-inflammatory drugs were considered as confounding factors in the regression analyses. The 350 patients had 1422 surveillance endoscopies, with a median follow-up of 4.7 years. Patients who delayed using a PPI for 2 years or more after diagnosis with Barrett's oesophagus had 5.6 times (95% CI, 2.0-15.7) the risk of developing low-grade dysplasia at any given time as those who used a PPI in the first year. Similar results were found for the risk of developing high-grade dysplasia or adenocarcinoma (hazard ratio, 20.9; 95% CI, 2.8-158). Use of ongoing PPI therapy appeared beneficial in the prevention of dysplasia and adenocarcinoma in patients with Barrett's oesophagus. We suggest that all patients with this condition, even those with no oesophagitis or symptoms, should be encouraged to continue long term PPI therapy.