Maintenance Proton Pump Inhibitor Research Articles

Real-world Prescription Patterns and Patient Satisfaction Regarding Maintenance Therapy of Gastroesophageal Reflux Disease: An Observational, Cross-sectional, Multicenter Study.

Gastroesophageal reflux disease (GERD) is a common chronic gastrointestinal disorder that typically requires long-term maintenance therapy. However, little is known about patient preferences and satisfaction and real-world prescription patterns regarding maintenance therapy for GERD. This observational, cross-sectional, multicenter study involved patients from 18 referral hospitals in Korea. We surveyed patients who had been prescribed proton pump inhibitors (PPIs) for GERD for at least 90 days with a minimum follow-up duration of 1 year. The main outcome was overall patient satisfaction with different maintenance therapy modalities. A total of 197 patients were enrolled. Overall patient satisfaction, patient preferences, and GERD health-related quality of life scores did not significantly differ among the maintenance therapy modality groups. However, the on-demand therapy group experienced a significantly longer disease duration than the continuous therapy group. The continuous therapy group demonstrated a lower level of awareness of potential adverse effects associated with PPIs than the on-demand therapy group but received higher doses of PPIs than the on-demand therapy group. The prescribed doses of PPIs also varied based on the phenotype of GERD, with higher doses prescribed for non-erosive reflux disease than erosive reflux disease. Although overall patient satisfaction did not significantly differ among the different PPI maintenance therapy modality groups, awareness of potential adverse effects was significantly different between the on-demand and continuous therapy groups.

PD-18 Maintenance proton pump inhibitor usage and risk of colorectal cancer: A population-based Swedish cohort study

PD-18 Maintenance proton pump inhibitor usage and risk of colorectal cancer: A population-based Swedish cohort study

Appropriateness of Proton Pump Inhibitor Prescription Evaluated by Using Serological Markers.

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy.

Maintenance Proton Pump Inhibitor Use Associated with Increased All-Cause and Cause-Specific Mortality in Sweden

BackgroundProton pump inhibitor (PPI) use has increased over the last decades and has been associated with multiple adverse events and potentially even overall survival.AimsWe aimed to investigate the association between proton pump inhibitor maintenance use and all-cause and cause-specific mortality, addressing confounding by indication and duration of use.MethodsThis Swedish population-based cohort study included all adult (N = 935,236) PPI and histamine-2 receptor antagonist maintenance users (≥ 180 days use) during 2005–2014. Standardised mortality ratios (SMRs) and 95% confidence intervals were calculated for all-cause and cause-specific mortality comparing the risk among PPI/H2RA users to that of the Swedish background population, stratified by age, sex, calendar period, indication and duration of use. Multivariable Poisson regression models were used to compare PPI use to H2RA use, expressed as incidence rate ratios and 95% confidence intervals.ResultsPPI and histamine-2 receptor antagonist use were associated with an increased risk of all-cause mortality (SMR = 1.35; 1.34–1.36; SMR = 1.31; 1.27–1.36, respectively). The highest SMRs were found in the youngest age groups. In direct comparison, PPI use showed a higher mortality risk than histamine-2 receptor antagonist use (incidence rate ratios = 1.42; 1.38–1.46). PPIs were related to increased cancer (SMR = 1.21; 1.20–1.22), and cardiovascular mortality (SMR = 1.36; 1.35–1.37). Increased SMRs were observed for most indications. Longer duration of use was associated with a higher mortality among PPI users but not among histamine-2 receptor antagonist users.ConclusionMaintenance PPI use was associated with an increased risk of all-cause and cause-specific mortality, and the risk increased with prolonged duration.

On-demand Versus Continuous Maintenance Treatment of Gastroesophageal Reflux Disease With Proton Pump Inhibitors: A Systematic Review and Meta-analysis.

Background/AimsLong-term maintenance treatment of gastroesophageal reflux disease (GERD) is commonly used to prevent relapse of reflux symptoms; however, due to concerns about safety of long-term proton pump inhibitors (PPI) use, on-demand therapy is recommended as a long-term treatment modality. We compared the efficacy of on-demand and continuous PPI therapy for maintenance treatment of patients with GERD using meta-analysis.MethodsCore electronic databases were searched for randomized controlled trials comparing on-demand and continuous therapy in GERD patients. The primary outcome was treatment failure of maintenance therapy, and the secondary outcomes included symptomatic relief, patient satisfaction, and amount of PPI use.ResultsOverall, 11 studies were selected in the systematic review and meta-analysis. Compared with continuous PPI therapy, on-demand therapy showed similar outcomes for treatment failure (risk ratio, 1.26; 95% confidence interval [CI], 0.76-2.07), particularly in the non-erosive esophageal reflux disease and mild erosive reflux disease group (risk ratio, 1.48; 95% CI, 0.39-5.63). In studies including severe esophagitis patients, continuous PPI maintenance treatment was more effective (β, 0.127 [95% CI, 0.066-0.188]; P < 0.001). Severity of esophagitis was associated with higher efficacies of continuous maintenance therapy. The amount of daily PPI use was about half in the on-demand group compared to the continuous group (risk difference −0.52; 95% CI, −0.62-−0.42).ConclusionsOn-demand PPI therapy shows comparable efficacy to the continuous maintenance treatment in the non-erosive esophageal reflux disease and mild erosive reflux disease group, and can remarkably reduce the amount of PPI use. Therefore, on-demand therapy may be preferentially recommended in the maintenance treatment of GERD unaccompanied by severe esophagitis.

Association Between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: A Swedish Population-Based Cohort Study.

Biliary tract cancer is a group of highly aggressive malignant disorders, yet risk factors are poorly understood. In this study, we aim to assess whether prolonged use of proton pump inhibitors (PPIs) increases the risk of incident biliary tract carcinoma in a nation-wide population-based cohort in Sweden. Using nation-wide registries, we identified all adults who received maintenance PPIs (≥180days) according to the Swedish Prescribed Drug Register from 2005 through 2012. Data on incident biliary tract cancer were retrieved from the Swedish Cancer, Death and Outpatient Registers. Risk of biliary tract cancer in persons who received PPI treatment was compared with the general population of the corresponding age, sex, and calendar year yielding standardized incidence ratios (SIRs) with 95% CIs. Of 738,881 PPI users (median follow-up of 5.3years), 206 (0.03%) developed gallbladder cancer and 265 (0.04%) extrahepatic and 131 (0.02%) intrahepatic bile duct cancer corresponding to SIRs of 1.58 (95% CI, 1.37-1.81), 1.77 (95% CI, 1.56-2.00), and 1.88 (95% CI, 1.57-2.23), respectively. In sensitivity analyses restricted to persons without a history of gallstones or chronic liver or pancreatic diseases, SIRs were 1.36 (95% CI, 1.17-1.57) and 1.47 (95% CI, 1.19-1.80) for extra- and intrahepatic duct cancer, respectively. The risk remained higher than the corresponding general population with ≥5years of PPIs use, ruling out confounding by indication. In this study, long-term use of PPIs was associated with an increased risk of gallbladder, intrahepatic, and extrahepatic bile duct cancer compared with the general population.

Treatment strategies for reflux esophagitis including a potassium-competitive acid blocker: A cost-effectiveness analysis in Japan.

IntroductionGastroesophageal reflux disease is a common condition, and proton pump inhibitors (PPIs) are the mainstays of treatment. However, concerns have been raised about the safety of PPIs. A potassium‐competitive acid blocker (P‐CAB), vonoprazan (VPZ), was recently introduced, which may provide clinical benefits. This study was performed to investigate the cost‐effectiveness of alternative long‐term strategies including continuous and discontinuous treatment with VPZ for the management of reflux esophagitis in Japan.MethodsA health state transition model was developed to capture the long‐term management of reflux esophagitis. Four different strategies were compared: (a) intermittent PPI using lansoprazole (LPZ); (b) intermittent P‐CAB; (c) maintenance PPI using LPZ; and (d) maintenance P‐CAB.ResultsIntermittent P‐CAB was the most cost‐effective, and the number of days for which medication was required with this strategy was fewest. Maintenance PPI was more efficacious, but more costly than intermittent P‐CAB. Maintenance P‐CAB was more efficacious, but more costly than maintenance PPI. Co‐payments were higher for maintenance PPI than for intermittent P‐CAB, and for maintenance P‐CAB than for maintenance PPI, which were considered reasonable for the majority of patients to improve symptoms.ConclusionsIntermittent P‐CAB appears to be the strategy of choice for the majority of reflux esophagitis patients in clinical practice. If a patient is not satisfied with the symptom control of the current strategy, switching to a more effective strategy appears to be a reasonable option for the majority of patients.

STAT6 Variants Associate With Relapse of Eosinophilic Esophagitis in Patients Receiving Long-term Proton Pump Inhibitor Therapy

Based on histologic features, variants in STAT6 are associated with a poor initial response to proton pump inhibitor (PPI) therapy in pediatric patients with eosinophilic esophagitis (EoE). We investigated whether these genetic variants are associated with a poor long-term response in children with EoE who initially responded to PPI therapy. We performed a prospective longitudinal cohort study of children ages 2 to 16 years who met the diagnostic criteria for EoE (≥15 eosinophils/high-power field [eos/hpf]), responded to 8 weeks of treatment with 2 mg/kg/d PPI (<15 eos/hpf), and whose dose then was reduced to 1 mg/kg/d PPI (maintenance therapy) for 1 year, at which point biopsy specimens were collected by endoscopy. Genomic DNA was isolated from formalin-fixed paraffin-embedded biopsy tissue and was genotyped for variants of STAT6. Remission of inflammation was assessed at eos/hpf thresholds of <15 and ≤5. Among 73 patients who received 1 mg/kg/d PPI maintenance therapy for 1 year, 13 patients (18%) had 6 to 14 eos/hpf, 36 patients (49%) had 5 or fewer eos/hpf, and 24 patients (33%) relapsed to EoE (≥15 eos/hpf). Carriage of any of 3 STAT6 variants in linkage disequilibrium (r2 ≥0.8; rs324011, rs167769, or rs12368672) was associated with a 2.3- to 2.8-fold increase in the odds of EoE relapse, and with a 2.8- to 4.1-fold increase in the odds of having 6 to 14 eos/hpf. For rs324011, the odds ratio [95% CI] for relapse was 2.77 [1.11, 6.92]; P= .029, and the odds ratio [95% CI] for having 6 to 14 eos/hpf was 3.06 [1.27, 7.36]; P= .012. Pediatric EoE patients who initially respond to PPI therapy and carry STAT6 variants rs324011, rs167769, or rs12368672 are at increased risk of relapse after 1 year of PPI maintenance therapy.

Long-term Treatment With Proton Pump Inhibitor Is Effective in Children With Eosinophilic Esophagitis

To evaluate the long-term efficacy and safety of proton pump inhibitors (PPIs) in pediatric eosinophilic esophagitis (EoE).One hundred and nine children between 1 month and 15 years of age with esophageal symptoms and EoE were recruited at 2 pediatric hospitals in Madrid between February 2013 and August 2017. All patients were treated with esomeprazole for 8 weeks, and 72 (66%) achieved histologic remission. Of the 72, 57 children were enrolled in this 1-year study.This was a prospective study of 57 children (73.7% boys, median age 11 years) with EoE who reached complete or partial histologic remission after an 8-week esomeprazole trial (1 mg/kg per dose, twice daily). Esomeprazole was continued at 1 mg/kg per day (max 40 mg daily) for 1 year. Patients were closely monitored every 3 months for symptom recurrence, clinical outcomes, and adverse events. Follow-up endoscopy was performed at 1 year or before, if symptoms recurred. Complete histologic remission was defined as ≤5 eosinophils per high-power field, and partial remission was defined as >5 and <15 eosinophils per high-power field. Patients were not treated with concomitant dietary restrictions or topical steroids.After 12 months of PPI maintenance therapy, histologic remission continued in 70.1% (n = 40) of children. Long-term remission was observed more frequently in children with initial complete histologic remission compared with those with partial remission (81% vs 50%, P = .014). There were no other clinical, endoscopic, or histologic data to predict remission on PPI therapy. Eleven of 12 children (91.6%) who remained on esomeprazole at a lower maintenance dose (0.5 mg/kg per day) for an additional 12 months also sustained histologic remission. Five children developed adverse events on esomeprazole (0.7–2 mg/kg per day), including diarrhea, urticaria, and headache. All adverse events self-resolved or improved by substituting for another PPI.Long-term PPI therapy is safe and effective for the treatment of pediatric EoE. At 1 year follow-up, 70% of children with PPI-responsive EoE remained in histologic and clinical remission on a low-dose maintenance regimen. Patients with complete histologic remission after an 8-week trial of PPI were more likely to maintain histologic remission with maintenance PPI.This is a landmark prospective study supporting the use of PPI therapy for the long-term treatment of EoE in a subset of pediatric patients. Seventy percent efficacy after 12 months of PPI is comparable or higher than reported remission rates for alternative EoE therapies, such as dietary restriction or swallowed corticosteroids. Future studies will need to compare therapies and determine if PPI dose escalation can lead to improved remission rates.

Contemporary Approaches to the Treatment of Gastroesophageal Reflux Disease

Aim:to describe existing approaches to the treatment of gastroesophageal reflux disease (GERD) in accordance with the requirements of evidence-based medicine, as well as to discuss controversial issues in the management of GERD patients.Key findings.Nonmedical GERD treatment should be based on the reduction of body weight by decreasing the calorie intake and its proper distribution throughout the day, as well as by increasing the level of physical activity. Proton-pump inhibitors (PPIs) are used as the main class of drugs for reflux esophagitis and non-erosive reflux disease (NERD), as well as in cases when the disease is characterized by certain specific features (e.g., the presence of night symptoms) and extraesophageal manifestations. The efficacy of PPI treatment may depend on the genetic polymorphism of the CYP2C19 cytochrome. Rabeprazole is characterized by a predominantly non-enzymatic pathway, providing a more stable pharmacokinetics profile, which is less dependent on the CYP2C19 polymorphism. The duration of the initial and maintenance PPI course is determined by the GERD form. Long-term PPI maintenance therapy is indicated for erosive esophagitis. In the presence of Barrett’s esophagus, this measure is considered from the standpoint of cancer prevention.Conclusion.The use of PPIs is considered to be the key approach in the drug treatment of GERD. The choice of a PPI is based on factors that determine the efficacy and safety of such drugs, namely the rate of the onset of acid suppressive effects, the intensity of acid suppressive effects, the time of the onset of GERD clinical remission, the dependence on the CYP2C19 genetic polymorphism, the absence of significant interaction with other drugs, as well as the presence of pleiotropic effects.

On-Demand Therapy with Proton Pump Inhibitors for Maintenance Treatment of Nonerosive Reflux Disease or Mild Erosive Esophagitis: A Systematic Review and Meta-Analysis.

Background Proton pump inhibitors (PPIs) are widely used for the long-term management of gastroesophageal reflux disease (GERD). However, concerns about the cost and/or inconvenience of continuous maintenance PPI treatment have led to the evaluation of various alternative approaches. Aim To assess the effectiveness of on-demand PPI therapy in the maintenance treatment of nonerosive reflux disease (NERD) or mild erosive esophagitis (EE). Methods We searched MEDLINE, EMBASE, Web of Science, and Cochrane Library from inception until October 2, 2017, for randomized controlled trials (RCTs) comparing on-demand PPI versus placebo or daily PPI in the management of NERD or mild EE (Savary-Miller grade 1). Discontinuation of therapy during the trial was used as a surrogate for patient dissatisfaction and failure of symptomatic control. We calculated pooled odds ratios (OR) to evaluate the efficacy of on-demand PPI treatment. Separate analyses were conducted for studies comparing on-demand PPI with daily PPI and with placebo. Subgroup analysis was done based on NERD studies alone and on studies of both NERD and mild EE. These were analyzed using a random effects model. Results We included 10 RCTs with 4574 patients. On-demand PPI was superior to daily PPI (pooled OR = 0.50; 95% confidence interval (CI) = 0.35, 0.72). On subgroup analysis in NERD patients only, pooled OR was 0.44 (0.29, 0.66). In studies including patients with NERD and mild EE, pooled OR was 0.76 (0.36, 1.60). For studies comparing on-demand PPI with placebo, pooled OR was 0.21 (0.15, 0.29); subgroup analyses of studies evaluating NERD only and studies conducted in NERD and mild EE showed similar results (pooled OR was 0.22 (0.13, 0.36) and 0.18 (0.11, 0.31), resp.). Conclusions On-demand PPI treatment is effective for many patients with NERD or mild EE. Although not FDA-approved, it may be adequate for those patients whose symptoms are controlled to their satisfaction.

Long‐term Treatment With Proton Pump Inhibitors Is Effective in Children With Eosinophilic Esophagitis

Proton pump inhibitor (PPI)-responsive eosinophilic esophagitis (EoE) is frequently observed in children, but data on long-term treatment are scarce. The objective of this study is to evaluate the long-term efficacy and safety of PPIs in children with EoE. This prospective study enrolled children with EoE and histological remission to an 8-week esomeprazole trial (1 mg/kg/dose, twice daily). Esomeprazole was maintained at 1 mg/kg/day for 1 year. Symptom recurrence and adverse events were monitored and a follow-up endoscopy was performed at 12 months. Complete histological remission was defined as ≤5 eosinophils/high-power field (eos/hpf), and partial histological remission as >5 and <15 eos/hpf. Patients had no concomitant dietary restrictions or topical steroid. Fifty-seven children were included. Histological remission on maintenance PPI therapy was present in 40 children (70.1%; 95% CI 56.5-81.5). Long-term remission rate was higher in children with initial complete histological remission than in those with partial remission (81% vs 50%, P = 0.014). Forty-nine children (86%) remained asymptomatic. Pretreatment clinical and histological findings and median PPI dose/kg/day were similar between relapsers and nonrelapsers. Eleven out of 12 children (91.6%) receiving esomeprazole 0.5 mg · kg · day for 12 additional months remained in remission. Mild and transient side effects without requiring PPI avoidance were observed in 5 children. Up to 70% of children with PPI-responsive EoE remain in histological and clinical remission on a low-dose maintenance treatment at 1-year follow-up, with adequate safety profile. Complete histological remission to an 8-week PPI trial was associated with higher probability of histological remission on maintenance therapy.

Maintenance proton pump inhibition therapy and risk of oesophageal cancer

BackgroundThe association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication. MethodsThis population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005–2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population. The different indications for maintenance PPI therapy were analysed separately. ResultsAmong all individuals using maintenance PPI therapy, the overall SIR of oesophageal adenocarcinoma was 3.93 (95% CI 3.63–4.24). The SIRs of adenocarcinoma were increased also among individuals without gastro-oesophageal reflux disease who used PPIs for indications not associated with any increased risk of oesophageal adenocarcinoma. For example, the SIRs among participants using maintenance PPI therapy because of maintenance treatment with non-steroidal anti-inflammatory drugs and aspirin were 2.74 (95% CI 1.96–3.71) and 2.06 (95% CI 1.60–2.60), respectively. The SIRs of oesophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for oesophageal adenocarcinoma. ConclusionIn conclusion, the long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution.

Esophageal Squamous Papilloma: An Interesting Find in a Patient Presenting With Dysphagia

Esophageal squamous papilloma (ESP) is an uncommon tumor of the esophagus occurring in 0.01% to 0.45% of those undergoing endoscopy. The etiology of these lesions has not been clearly defined, however, suggested contributing factors include chronic mucosal irritation, human papilloma virus (HPV), and direct mucosal trauma. These benign tumors are usually asymptomatic, however, patient can present with dysphagia and dyspepsia. We present a case of ESP in a patient presenting with dysphagia. We present a case of a 67-year-old female with ongoing complaint of dysphagia and odynophagia. Last esophagogastroduodenoscopy (EGD) was 2 years prior showed LA Grade C esophagitis. The patient had been well maintained on proton pump inhibitor (PPI) therapy until this presentation. The patient states that dysphagia and odynophagia have been progressing over the last year, despite the use of PPI twice daily dosing. It was recommended by the patients' primary gastroenterologist that she undergo endoscopic evaluation. An EGD was completed that revealed no evidence of esophagitis, however, it showed a polypoid lesion at the gastroesophageal junction (Figure 1). Superficial cold forceps biopsies of the lesion were collected, pathology revealed benign polypoid esophageal mucosa. Patient was referred to our advanced endoscopy center for an endoscopic ultrasound (EUS) and possible endoscopic mucosal resection (EMR). Endosonographic evaluation revealed a 15mm deep mucosal based lesion (Figure 2). EMR using band ligation was successfully performed and specimen sent for pathology. Pathology confirmed squamous papilloma (Figure 3). As this is a benign lesion, mucosal resection was the treatment and a follow up EGD several months later confirmed adequate resection without regrowth. The patient is doing well on maintenance PPI therapy. ESP is an uncommon benign tumor that is usually asymptomatic but can present with dysphagia, dyspepsia, and abdominal discomfort. ESP are usually small in size ranging from 2mm to 6mm, commonly affecting patients aged 43 to 50 years old. Our case presented a rare finding of ESP in patient presenting with ongoing dysphagia. The clinical significance of ESP has not been well established. Long-term longitudinal studies would be valuable in helping to establish clinical significance as well as malignant potential of ESPs to better clarify the role of surveillance and management of these lesions.Figure: Polypoid lesion at the gastro-esophageal junction.Figure: Endosonographic examination revealed a deep mucosa based lesion.Figure: Low power magnification of squamous cell papilloma: papillary fronds of thickened squamous epithelium.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy.

AIMTo elucidate the factors associated with residual gastroesophageal reflux disease (GERD) symptoms in patients receiving proton pump inhibitor (PPI) maintenance therapy in clinical practice.METHODSThe study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed.RESULTSThe FSSG scores ranged from 1 to 28 points (median score: 7.5 points), and 19 patients (48.7%) had a score of 8 points or more. The patients’ GSRS scores were significantly correlated with their FSSG scores (correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers (RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers (total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients (total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01).CONCLUSIONApproximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

PTH-041 Per Oral Endoscopic Myotomy: First UK Experience

Introduction Per-oral endoscopic myotomy (POEM) has been adopted as a minimally invasive treatment option for achalasia. The first case of POEM was performed at King’s College Hospital in late 2013. Here we present our initial case series with video demonstration of technique. Methods Prospective data was collected for consecutive patients undergoing POEM including demographics, procedure technique, the use of Endoluminal Functional Lumen Imaging Probe (EndoFLIP) and adverse events. Follow up data at 3 months and 12–24 months post-POEM including Eckardt scores and lower oesophageal sphincter integrated resting pressure (IRP-4s) were compared with pre-POEM findings. Post-POEM Gastro-oesophageal Reflux Health-Related Quality of Life scale (GORD-HQL) was recorded. Statistical analysis was achieved using Wilcoxon matched-pairs signed rank test. Results POEM was performed in 33 patients (12 F, age 49.5±13.25 years). Pre-operative high-resoloution manometry confirmed type II achalasia in all patients. 19 patients had previous treatment (Botulinum n = 8, Pneumatic dilatation n = 10, Heller myotomy n = 5, POEM n = 1, >1 treatment n = 2). Median pre-POEM Eckardt Score 8, range 3–12. Median gastric and oesophageal myotomy was 3 cm (range 2–4) and 12 cm (range 5–16) respectively with a selective circular myotomy in all cases and a posterior approach in n = 5. There was significant reduction in post-operative Eckardt score at 3 months Median 0, range 0–6 (p EndoFLIP Intra-operative EndoFLIP measurements before and after myotomy have been implemented to aid confirmation of adequate myotomy (Figure 3). Adverse Events One patient underwent single clip displacement and was replaced at gastroscopy day 1 post POEM. There were no cases of perforation, infection or major bleeding. Gastro-oesophageal reflux Post-POEM GORD-HQL score was collected in 26 patients with a median score of 2.5, range 0–31. Two cases of reflux (positive 24 hr pH at 3 months) were identified and successfully managed with maintenance proton pump inhibitor. Conclusion POEM was performed successfully in 33 patients in whom 57.5% had prior endoscopic or surgical treatment representing a potentially more challenging patient population. This study is in line with international consortia and ASGE findings1 that POEM is a safe and efficacious procedure for the treatment of achalasia for both short term and sustained symptomatic benefit. Reference 1 Stavropoulos S, Desilets D, Fuchs KH et al; Per-oral endoscopic myotomy white paper summary; Gastrointestinal Endoscopy. 2014;1:1–15. Disclosure of Interest None Declared

Inulin significantly improves serum magnesium levels in proton pump inhibitor-induced hypomagnesaemia.

Proton pump inhibitors (PPI) are among the most widely prescribed drugs to treat gastric acid-related disorders. PPI-induced hypomagnesaemia, a defect in intestinal absorption of Mg(2+) , can be a severe side effect of chronic PPI use. To restore serum Mg(2+) concentrations in PPI-induced hypomagnesaemia patients by dietary supplementation with inulin fibres. Eleven patients with PPI-induced hypomagnesaemia and 10 controls were treated with inulin (20 g/day). Each trial consisted of two cycles of 14-day inulin treatment followed by a washout period of 14 days. Patients continued to use their PPI. Serum Mg(2+) levels served as the primary endpoint. Inulin significantly enhanced serum Mg(2+) levels from 0.60 to 0.68 mmol/L in PPI-induced hypomagnesaemia patients, and from 0.84 to 0.93 mmol/L in controls. As a consequence 24 h urinary Mg(2+) excretion was significantly increased in patients with PPI-induced hypomagnesaemia (0.3-2.2 mmol/day). Symptoms related to hypomagnesaemia, including muscle cramps and paraesthesia, were reduced during intervention with inulin. Inulin increases serum Mg(2+) concentrations under PPI maintenance in patients with PPI-induced hypomagnesaemia.

Updated Beers Criteria: A more comprehensive guide to medication safety in older adults

P from all practice settings are likely familiar with the American Geriatric Society’s (AGS) Beers Criteria of Potentially Inappropriate Drugs, last published in 20121 and recently revised and updated in 2015.2 The AGS Beers Criteria—Beers Criteria for short—have proven useful in identifying drugs to potentially avoid in older adults, to reduce adverse drug events and drug-related problems, and to improve medication selection and overall medication safety in older adults. The Beers Criteria are designed for use in any clinical setting and can also be used as an educational quality measure and research tool. The latest version of the Beers Criteria uses a more comprehensive, systematic review and grading of evidence.

Adherence to 2013 ACG Guidelines for Proton Pump Inhibitor Weaning in GERD

Introduction: The current American College of Gastroenterology (ACG) guidelines recommend an 8-week course of PPIs as the therapy of choice for symptom relief in Gastroesophageal Reflux Disease (GERD). Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett's esophagus.The purpose of the study is observance of ACG guidelines in primary care settings for weaning patients with GERD from proton pump inhibitors (PPIs). Methods: A retrospective chart review study was conducted in a primary care physician group of six physicians. One hundred consecutive patients on PPIs were selected with the ICD-9 code for GERD, in the period from March 2013 to May 2014 and another 100 consecutive patient in a follow up study in the period from June 2014 to April 2015. Demographic data, body mass index (BMI), duration of PPI usage and weaning trial data were gathered and analyzed. Results: During the first study period from March 2013 to May 2014, 9 patients (9%) underwent weaning trials. Of these 9 patients, 4 (44%) were weaned off completely, 2 were weaned to a lower dose and 3 were switched to an Histamine-2 (H2) blocker. Two patients failed weaning and resumed same PPI. In the second follow up study period from June 2014 to April 2015, 16 patients (16%) underwent weaning trials. Of these 16 patients, 9 (56%) were weaned off completely, 1 (6.25%) switched to another PPI and 4 (25%) were switched to H2 blocker.Though an increase in the number of attempted weaning was noted after a year of publication of the recommendations it was not statistically significant (p value is 0.1989). Conclusion: ACG guidelines for selecting patients for long term maintenance PPI therapy in GERD are not well implemented in the primary care setting. Weaning off PPI is not attempted in most patients started on therapy. A relatively limited distribution and generalized unawareness of these recent guidelines are possible reasons. Increased dissemination and publication is needed for adequate adherence of these guidelines

Long-term proton pump inhibitor (PPI) use and the development of gastric pre-malignant lesions.

Proton pump inhibitors (PPIs) are the most effective drugs to reduce gastric acid secretion. PPIs are one of the most commonly prescribed classes of medications worldwide. Apart from short-term application, maintenance therapy with PPIs is recommended and increasingly used in certain diseases, such as Zollinger-Ellison syndrome and gastro-oesophageal reflux disease, especially for people with erosive oesophagitis or Barrett's oesophagus. Although PPIs are generally safe, their efficacy and safety of long-term use remains unclear. The question of whether the long-term use of PPIs could promote the development of gastric pre-malignant lesions has been widely investigated, but results are inconsistent. Limited insight on this problem leads to a dilemma in decision making for long-term PPI prescription. To compare the development or progression of gastric pre-malignant lesions, such as atrophic gastritis, intestinal metaplasia, enterochromaffin-like (ECL) cell hyperplasia, and dysplasia, in people taking long-term (six months or greater) PPI maintenance therapy. We searched the following databases (from inception to 6 August 2013): the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL. In addition, we searched the reference lists of included trials and contacted experts in the field. We searched for randomised controlled trials (RCTs) in adults (aged 18 years or greater) concerning the effects of long-term (six months or greater) PPI use on gastric mucosa changes, confirmed by endoscopy or biopsy sampling (or both). Two review authors independently performed selection of eligible trials, assessment of trial quality, and data extraction. We calculated odds ratios (OR) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CI). We included seven trials (1789 participants). Four studies had high risk of bias and the risk of bias in the other three trials was unclear. In addition, it was difficult to assess possible reporting bias. We pooled 1070 participants from four RCTs to evaluate corporal atrophy development revealing an insignificantly increased OR of 1.50 (95% CI 0.59 to 3.80; P value = 0.39; low-quality evidence) for long-term PPI users relative to non-PPI users. In five eligible trials, corporal intestinal metaplasia was assessed among 1408 participants, also with uncertain results (OR 1.46; 95% CI 0.43 to 5.03; P value = 0.55; low-quality evidence). However, by pooling data of 1705 participants from six RCTs, our meta-analysis showed that participants with PPI maintenance treatment were more likely to experience either diffuse (simple) (OR 5.01; 95% CI 1.54 to 16.26; P value = 0.007; very-low-quality evidence) or linear/micronodular (focal) ECL hyperplasia (OR 3.98; 95% CI 1.31 to 12.16; P value = 0.02; low-quality evidence) than controls. No participant showed any dysplastic or neoplastic change in any included studies. There is presently no clear evidence that the long-term use of PPIs can cause or accelerate the progression of corpus gastric atrophy or intestinal metaplasia, although results were imprecise. People with PPI maintenance treatment may have a higher possibility of experiencing either diffuse (simple) or linear/micronodular (focal) ECL cell hyperplasia. However, the clinical importance of this outcome is currently uncertain.