Proton Pump Inhibitor Regimens Research Articles

Heartburn Relief Is the Major Unmet Need for Drug Development in Gastroesophageal Reflux Disease: Threshold Value Analysis

Background and AimsHeartburn symptoms contribute to healthcare-seeking among patients with gastroesophageal reflux disease (GERD). Despite clinical guidance, management is often dictated by insurance restrictions. Several potassium-competitive acid blockers (PCABs) are under development as a new class of therapy. We performed economic analyses to align GERD drug development with the needs of gastroenterologists, insurers and patients in a value-based environment. MethodsA decision-analytic model was constructed to compare vonoprazan 20 mg daily (an example of a PCAB), common over-the-counter or prescription proton pump inhibitor regimens, and no treatment over a 1-year time horizon. Clinical responses were evaluated based on the proportions of heartburn-free days in a recent phase 3 multicenter trial. Healthcare utilization for persistent reflux symptoms was derived from national observational studies compared with healthy control subjects. Costs and quality-adjusted life years were reported. ResultsWithout insurance coverage for appropriate therapy, patients spend $4443 and insurers spend $3784 on average per year for inadequately treated GERD symptoms. Our model estimates that PCABs could save at least $3000 in annual costs to patients and insurers, could generate quality-adjusted life year gains (+0.06 per year), and could be cost-saving to insurers as a covered option at a price up to $8.57 per pill, if these drugs are able to demonstrate similar effectiveness to proton pump inhibitors in future trials evaluating heartburn relief and erosive esophagitis healing to regulators. Threshold prices reflect pricing after all pharmacy benefits manager rebates and discounts. DiscussionWe demonstrate that aiming GERD-related drug development toward heartburn relief appears critical to align cost-effective incentives for industry and insurers with those of patients and gastroenterologists.

First-line therapies for H. pylori infection in Italy: a pooled-data analysis.

Curing H. pylori infection remains challenging, and the use of most effective first-line therapy represents a therapeutic cornerstone. To monitor the efficacy of first-line therapies in Italy, we designed a systematic review with pooled- data analysis of data published in the last 15 years. The search was focused on standard regimens and adult patients. Studies that included modified therapy regimens, pediatric patients, case series with less than 5 patients, and those in language other than English were excluded. A total of 40 studies, with 74 therapeutic arms and 13,539 patients were evaluated. Among the 14-day triple therapies, the combination with proton pump inhibitor (PPI), clarithromycin and amoxicillin achieved the highest (77.9%) success rate, whilst the lowest success rate (62.7%) was observed following the 14-day PPI, clarithromycin and tinidazole regimen. The overall efficacy of triple therapies significantly decreased from 75.7% to 72.1% in the last decade. Sequential (88.3% on 3431 patients), concomitant (88.8% on 376 patients), and the bismuth-based quadruple therapy with three-in-one capsule, containing bismuth subcitrate potassium (140 mg), metronidazole (125 mg), tetracycline (125 mg) (90.4% on 999 patients) achieved similarly high eradication rates, but data on concomitant are still limited. The bismuth-based was associated with the higher (38.7%) incidence of side-effects. Data found that all triple therapies, irrespective of drug combination and therapy duration, should be abandoned in Italy due to their unacceptable low success rates. Monitoring the efficacy of standard first-line therapies in other countries could be clinically useful for both patients and clinicians.

S1292 Optimizing Endoscopy Procedure Documentation Improves Guideline Adherent Care in Upper Gastrointestinal Bleeding

Introduction: Upper GI bleeding (UGIB) is a common indication forced inpatient esophagogastroduodenoscopy (EGD). Outcomes afterwards are often dependent in part by guideline-based post-EGD care. Our aim was to optimize and standardize documentation post-EGD in UGIB to improve clinical care. Methods: National guidelines were used to build optimized etiology- and severity-specific note templates at an academic tertiary referral center. 39 attendings and 15 fellows completed a 10 minute training session in template content & use. We collected pre- and post-intervention on “minimal-standard” (MS) report documentation including patient disposition, diet, & medications. We also recorded documentation of rebleed precautions, and follow-up procedures. Health outcomes measured included guideline-based medication prescriptions, ordering of follow-up EGD if indicated, and clinical cessation of bleeding after discharge. Results: Pre-intervention demonstrated 54% and 36% of 108 patients received guideline-based inpatient and outpatient proton pump inhibitor (PPI), respectively. At baseline, 67.6% were referred for standard-of-care repeat EGD and only 36.1% of reports met MS report criteria. After template implementation, of 309 EGDs for UGIB over 6 months, the templates were used in 72% of cases. Workload was reduced by a mean of 33 “clicks,” 356 free text characters and 2 minutes per report (Figure 1, Panel A). There was a significant improvement in documentation of disposition (63.0% to 74.1%, p=0.028), appropriate PPI use(57.1% to 69.8%, p=0.035), rebleed (22.2% to 44.3%, p< 0.001) recommendations, and MS report completion (27.8% to 40.8%,p=0.016). There was significant improvement in inpatient PPI administered (53.6% to 73.6%, p< 0.001), discharge PPI prescription(35.7% to 54.0%, p=0.004), octreotide regimen(79.2% to 93.2%,p=0.048) and follow-up EGD orde r(67.6% to 86.7%, p< 0.001) (Table 1). Template usage (64%-79%), process (38%-50%) and outcome(67%-95%) metrics remained high over 6 months (Figure 1, Panel B & C). Inpatient PPI compliance(71.7% vs 63.4%; p=0.069) and follow-up EGD orders (85.7% vs 77.3%;p=0.028) were improved with template use. Conclusion: Our project leveraged endoscopy software to standardize efficient provider documentation, resulting in improved clinical care. Our intervention required minimal implementation cost, low burden of maintenance, and sustainability with high utilization rates over 6 months. Similar endoscopy templates can be applied to other health systems and endoscopic procedures to improve the quality of care.Table 1.: Process and outcome metrics pre- vs post- intervention. Statistical analysis using X2 testing.Figure 1.: Panel A: Sample endoscopy documentation template, Upper Gastrointestinal Bleed High Risk Non-Variceal Panel B: Process metrics pre- vs post-intervention of template usage (circle), minimal-standard non-variceal report (square), minimal-standard report (all etiologies) (diamond), and minimal-standard variceal report (triangle) Panel C: Outcome metrics pre- vs post-intervention of compliance with coordinated repeat EGD (circle), inpatient PPI regimen (square) and discharge PPI regimen (triangle).

Cost Analysis in Helicobacter pylori Eradication Therapy Based on a Database of Health Insurance Claims in Japan.

ObjectiveCost-benefit is an important consideration for Helicobacter pylori (H. pylori) eradication in Japan, where 1.5 million patients were reported to receive first-line eradication annually. This study aimed to identify the optimal cost-saving triple therapy regimen for H. pylori eradication in Japan.Materials and MethodsThis retrospective observational study used data from a large-scale, nationwide health insurance claims database (2015‒2018). Using success rates of first-line eradication, mean total costs of first-line and second-line eradications per patient were compared between regimens including a potassium-competitive acid blocker (P-CAB) or a proton pump inhibitor (PPI), and between two clarithromycin (CAM) doses (400 and 800 mg/day). Subgroup analyses by smoking habit or body mass index (BMI) were performed.ResultsAmong propensity score (age, gender, CAM dose, disease name)-matched patients (P-CAB regimen, n=22,002; PPI regimen, n=22,002), total costs were lower with the P-CAB than the PPI regimen (Japanese yen [JPY] 12,952 vs 13,146) owing to significantly higher first-line eradication rates with the P-CAB regimen (93.6% vs 79.7%; p<0.001). For both regimens, even among current smokers or patients with BMI ≥25 kg/m2, eradication rates did not differ by CAM dose, and total costs were approximately JPY1000 lower with CAM 400 mg/day than with CAM 800 mg/day.ConclusionHigh success rate of first-line eradication contributes to saving in total eradication costs by reducing costs of subsequent therapy, irrespective of patients’ smoking status or BMI class. The combination of more potent acid-inhibitory medicine and low-dose CAM may be the optimal regimen in terms of efficacy and cost-benefit in Japan.

Proton pump inhibitors associated acute kidney injury and chronic kidney disease: data mining of US FDA adverse event reporting system

Proton pump inhibitors (PPIs) were widely used. Observational studies suggested increasing risk of kidney injury in patients with PPIs treatment. We gathered six PPI regimens and adverse reports of acute kidney injury (AKI) and chronic kidney disease (CKD) based on US FDA Adverse Event Reporting System (FAERS) database from 2004 to 2019. We employed reporting odds ratio (ROR) to detect signals. Finally, we identified 3187 PPIs-associated AKI cases and 3457 PPIs-associated CKD cases. We detected significant signals between PPIs and AKI as well as CKD. The signal strength was stronger for CKD (ROR = 8.80, 95% CI 8.49–9.13) than AKI (ROR = 3.95, 95% CI 3.81–4.10), while dexlansoprazole performed stronger association for CKD (ROR = 34.94, 95% CI 30.89–39.53) and AKI (ROR = 8.18, 95% CI 7.04–9.51) than the other five PPIs. The median time from PPIs use to event occurrence was 23 days for AKI and 177 days for CKD. PPIs-associated AKI resulted larger proportion of death, life-threatening, hospitalization and disability events than PPIs-associated CKD. By mining the FAERS big data, we provided more information between PPIs use and the AKI and CKD events. PPIs rational use should be repeatedly stressed.

Different dose of new generation proton pump inhibitors for the treatment of Helicobacter pylori infection: A meta-analysis.

The evidence on whether high-dose new generation proton pump inhibitors (PPIs) including rabeprazole and esomeprazole achieve a higher eradication rate of Helicobacter pylori has not been assessed. The primary comparison was eradication and adverse events (AEs) rate of standard (esomeprazole 20 mg bid, rabeprazole 10 mg bid) versus high-dose (esomeprazole 40 mg bid, rabeprazole 20 mg bid) PPIs. Sub-analyses were performed to evaluate the eradication rate between Asians and Caucasians, clarithromycin-resistance (CAM-R) strains, and clarithromycin-sensitivity (CAM-S) strains of different dose PPIs. We conducted a literature search for randomized controlled trials comparing high-with standard-dose esomeprazole and rabeprazole for H. pylori eradication and AEs. A total of 12 trials with 2237 patients were included. The eradication rate of high-dose PPIs was not significantly superior to standard-dose PPIs regimens: 85.3% versus 84.2%, OR 1.09 (0.86–1.37), P = 0.47. The high dose induced more AEs than those of the standard dose, but didn’t reach statistical significance (OR 1.25, 95% CI: 0.99–1.56, P = 0.06). Subgroup analysis showed that the difference in eradication rate of PPIs between high- and standard-dose groups were not statistically significant both in Asians (OR 0.99, 95% CI 0.75–1.32, P = 0.97) and Caucasians (OR 1.27, 95% CI 0.84–1.92, P = 0.26). Furthermore, there were similar eradication rates in CAM-S (OR 1.2; 95% CI 0.58–2.5; P = 0.63) and CAM-R strains (OR 1.08; 95% CI 0.45–2.56; P = 0.87) between the standard-and high-dose groups. High and standard dosages of new generation of the PPIs showed similar H. pylori eradication rates and AEs as well as between Asian versus Caucasian populations, with or without clarithromycin-resistance. However, further studies are needed to confirm.

S2957 Chronic Mesenteric Ischemia: A Rarer Cause of Refractory Gastric Ulceration

INTRODUCTION: H. pylori and non-steroidal anti-inflammatory drug (NSAID) use are common causes of peptic ulcer disease (PUD). In cases of refractory PUD after addressing these factors and treatment with a proton pump inhibitor (PPI), mesenteric ischemia should be considered. CASE DESCRIPTION/METHODS: A 74 year-old male experienced a non-ST segment myocardial infarction, underwent drug eluding coronary stenting, and was initiated on clopidogrel and aspirin therapy. That admission, he developed epigastric abdominal pain and “dark stools”. H. pylori serology was positive, and he was treated with high dose pantoprazole and amoxicillin. Despite twice daily PPI and NSAID avoidance, his epigastric pain persisted, so EGD was performed, revealing superficial, non-bleeding ulcerations and erythema in the gastric body; biopsies showed reactive gastropathy and congestion without H. pylori. 2 weeks later he developed overt melena, and small bowel enteroscopy revealed gastric mucosa pallor and an adherent clot overlying a 1 cm oozing peptic ulcer along the greater curvature. The ulcer was successfully treated with epinephrine and hemostatic clips. His pain symptoms and bleeding resolved, though a surveillance EGD 12 weeks later revealed persistent smaller ulcers, flat pigmented spots, and congestion adjacent to site of the larger ulcer. Sucralfate thus was added to his PPI regimen. He remained asymptomatic until his clopidogrel was discontinued, shortly thereafter developing severe epigastric pain. Physical exam was unremarkable and labs were notable for lactate 1.6 mmol/dL, hemoglobin 12.2 g/d, and gastrin 169 pg/ml (on PPI). CT angiogram showed 90% stenosis at the superior mesenteric artery (SMA) origin, high grade stenosis of the celiac and inferior mesenteric arteries, and dilated bowel. Endovascular intervention was attempted, but revascularization failed due to extent of disease, leading to open mesenteric bypass graft from the external iliac artery to proximal SMA. His dyspeptic symptoms completely resolved at 1 month follow up. DISCUSSION: Chronic ischemia rarely causes PUD due to highly-vascularized gastric mucosa. However, in cases such as this with severe stenosis of the major branches of the aorta this rare complication may occur. Mesenteric ischemia is an important diagnosis to consider in patients with refractory gastric ulcers, especially in the setting of known atherosclerotic disease. Mesenteric ischemia and its associated symptoms and mucosal injury can be successfully managed by revascularization.Figure 1.: EGD with superficial, non-bleeding ulcerations and erythema in the gastric body.Figure 2.: CT angiogram with stenosis of the superior mesenteric artery.Figure 3.: CT angiogram with stenosis of the superior mesenteric artery.

Evaluation of different proton pump inhibitors combined with bismuth quadruple regimens in Helicobacter pylori eradication.

To evaluate the efficacy and economics of different proton pump inhibitors (PPIs) combined with bismuth quadruple regimens for Helicobacter pylori (Hp) eradication, a retrospective analysis method was used to collect Hp-positive patients who were treated with a bismuth-containing quadruple regimen (PPIs + amoxicillin + furazolidone + colloid pectin bismuth) from the outpatient department of gastroenterology in our hospital from January to June 2017. A total of 1410 patients were included in the study and divided into four groups according to different PPIs: group A (pantoprazole sodium enteric-coated capsules, 352 cases), group B (esomeprazole magnesium enteric-coated tablets, 462 cases), group C (pantoprazole sodium enteric-coated tablets, 392 cases) and group D (rabeprazole sodium enteric-coated tablets, 204 cases). The eradication rate of Hp and cost-saving in each group were then compared. There were no significant differences of gender (P = 0.526) and age (P = 0.366) between each Hp treatment regimen. The eradication rates of groups A, B, C and D were 91.48%, 89.83%, 86.73% and 90.69%, respectively. No statistical differences of Hp eradication rates were observed between each group yet (P > 0.05). However, the cost of group A was the lowest. In the present study, the Hp eradication rates between different PPIs regimens were similar in treating Hp infection. Nevertheless, the point in favor of pantoprazole capsules is the slightly higher Hp eradication rate and lower drug cost than other PPIs, which provides a significant evidence for the clinical medication decision in treating Hp infection.

Acute kidney injury following the use of different proton pump inhibitor regimens: A real-world analysis of post-marketing surveillance data.

Recent evidence has concerned acute kidney injury (AKI) after the proton pump inhibitor (PPI) application. There are few real-world studies to compare the occurrences, clinical features, and prognosis of AKI related to various PPI regimens. We aimed to evaluate and compare the links between different PPIs and AKI in a large population by investigating the Food and Drug Administration Adverse Event Reporting System (FAERS) until recently. Disproportionality analysis and Bayesian analysis were used in data mining to screen the suspected AKI after different PPIs based on the FAERS from January 2004 to December 2019. The times to onset, fatality, and hospitalization rates of PPI-associated AKI were also investigated. We identified 19522 PPI-associated AKIs, which appeared to influence more middle-aged patients than elderly ones (53.04% vs 33.94%). Women were more affected than men (55.42% vs 44.58%). Lansoprazole appeared a stronger AKI association than other PPIs, based on the highest reporting odds ratio (reporting odds ratio=20.8, 95% confidence interval=20.16, 21.46), proportional reporting ratio (proportional reporting ratio=15.55, χ2 =73899.68), and empirical Bayes geometric mean (empirical Bayes geometric mean=15.15, 95% confidence interval=14.76). The median time to AKI onset was 446 (interquartile range [IQR] 16-2176) days after PPI administration. PPIs showed a significant difference in average time to AKI onset (P<0.001), with the shortest of 9 (IQR 3-25) days for rabeprazole and the longest of 1221 (IQR 96.5-2620) days for esomeprazole. PPI-associated AKI generally led to a 5.69% fatality rate and an 8.94% hospitalization rate. The highest death rate occurred in rabeprazole (15.35%). Based on the FAERS database, we profiled AKI related to various PPIs with more details in occurrences, clinical characteristics, and prognosis. Concern should be paid for PPIs when applied to patients with a tendency for AKI.

Proton pump inhibitors in Iranian population: from clinical regimens to pharmacogenomics

Proton pump inhibitors (PPIs) are one of the highly prescribed or over-the-counter available medications among Iranians, mainly to treat conditions such as helicobacter pylori infection, gastroesophageal reflux disease or frequent heartburn. In recent years, several reports have shown potential adverse effects of PPI administration among which cardiovascular adverse events, myocardial infarction and chronic kidney disease are considered as the greatest risks. Recent addition of proton pump inhibitors to the list of medications on Beers Criteria of Potentially Inappropriate Drugs has arisen significant concerns about their safety. This review aims at providing an up-to date overview of PPIs indications and their pharmacogenomics and pharmacokinetics in Iranian population. The focus of this review is on PPIs regimens in Iranian population and then it is compared with the reported studies performed on other ethnic groups around the world. An extensive review of the literature was carried out and data under various sections were identified using a computerized literature search via Pubmed, Web of Science, Google Scholar and some local search engines. All abstracts and full text articles were examined and most relevant papers were selected for inclusion in this review. Also several expert internalists were interviewed for their clinical experiences in this field.

Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibit Cag A and Vac A Oncoprotein of Helicobacter pylori: Probable Treatment of H. pylori Infections.

Helicobacter pylori infection is accountable for most of the peptic ulcer and intestinal cancers. Due to the uprising resistance towards H. pylori infection through the present and common proton pump inhibitors regimens, the investigation of novel candidates is the inevitable issue. Medicinal plants have always been a source of lead compounds for drug discovery. The research of the related effective enzymes linked with this gram-negative bacterium is critical for the discovery of novel drug targets. The aim of the study is to identify the best candidate to evaluate the inhibitory effect of thymoquinone and thymol against H. pylori oncoproteins, Cag A and Vac A in comparison to the standard drug, metronidazole by using a computational approach. The targeted oncoproteins, Cag A and Vac A were retrieved from RCSB PDB. Lipinski's rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa. The two compounds of N. sativa were further analyzed by molecular docking and MD simulation studies. The reported phytoconstituents, thymoquinone and thymol present in N. sativa were docked with H. pylori Cag A and Vac A oncoproteins. Structures of ligands were prepared using ChemDraw Ultra 10 software and then changed into their 3D PDB structures using Molinspiration followed by energy minimization by using software Discovery Studio client 2.5. The docking results revealed the promising inhibitory potential of thymoquinone against Cag A and Vac A with docking energy of -5.81 kcal/mole and -3.61kcal/mole, respectively. On the contrary, the inhibitory potential of thymol against Cag A and Vac A in terms of docking energy was -5.37 kcal/mole and -3.94kcal/mole as compared to the standard drug, metronidazole having docking energy of -4.87 kcal/mole and -3.20 kcal/mole, respectively. Further, molecular dynamic simulations were conducted for 5ns for optimization, flexibility prediction, and determination of folded Cag A and Vac A oncoproteins stability. The Cag A and Vac A oncoproteins-TQ complexes were found to be quite stable with the root mean square deviation value of 0.2nm. The computational approaches suggested that thymoquinone and thymol may play an effective pharmacological role to treat H. pylori infection. Hence, it could be summarized that the ligands thymoquinone and thymol bound and interacted well with the proteins Cag A and Vac A as compared to the ligand MTZ. Our study showed that all lead compounds had good interaction with Cag A and Vac A proteins and suggested them to be a useful target to inhibit H. pylori infection.

Endoscopic measurement of gastric pH associates with persistent acid reflux in patients treated with proton-pump inhibitors for gastroesophageal reflux disease.

Proton-pump inhibitors (PPIs) are the mainstay of gastroesophageal reflux disease (GERD) treatment, however, up to 30% of patients have a poor symptomatic response. PH-impedance is the gold standard to assess whether this is due to persistent acid reflux. We aimed to characterize clinical predictors of persistent esophageal acid reflux on PPIs including gastric pH measured during endoscopy. We prospectively recruited patients with GERD and/or Barrett's esophagus (BE) on PPIs. All patients completed a symptom questionnaire (RDQ) and underwent gastroscopy with gastric pH analysis, immediately followed by ambulatory 24-hour pH-impedance. We used a modified cut-off of 1.3% for pathological esophageal acid exposure time (AET). Multiple linear regression model was used to analyze the correlation between AET and predictive variables. We recruited 122 patients, of which 92 (75.4%) were included in the final analysis [44 male (47.8%), median age 53 years (IQR: 43-66)]. Forty-four patients (47.8%) had persistent acid reflux with a median total AET of 2.2 (IQR1.2-5.0), as compared to 0.1 (IQR 0.0-0.2) in patients without persistent reflux (n=48; P<.001). There was no difference in age, gender, BMI, PPI-regimen, diagnosis of hiatus hernia or BE, and severity of symptoms between patients with normal and abnormal AET. Median gastric pH was significantly lower in patients with abnormal AET (5.8 vs 6.6, P=0.032) and it correlated with the total AET (P=.045; R2=12.0%). With a pH cut-off of 5.05, single point endoscopic gastric pH analysis had an area under the ROC curve (AUC) of 63.0% (95%CI 51.3-74.7) for prediction of pathological esophageal AET. Symptoms and clinical characteristics are not useful to predict persistent acid reflux in patients on PPIs. One-point gastric pH correlates with 24-hour esophageal AET and could guide clinicians to assess response to PPIs, however, its utility needs validation in larger studies.

588 Skipping the Drip: Intravenous Bolus Proton Pump Inhibitor Therapy Produces Similar Outcomes to Continuous Infusions With Less Healthcare Resource Utilization

INTRODUCTION: Continuous proton pump inhibitor (PPI) infusions remain the most commonly employed therapeutic strategy for administration of PPIs in upper gastrointestinal (GI) bleeding. Recent data has pointed towards non-inferiority of intravenous (IV) bolus regimens, but real-world data is lacking. Cost effectiveness and resource utilization data is also unavailable and projections made by estimation have shown low potential for cost savings. METHODS: A retrospective cohort study to evaluate the impact of a shift in institutional practice from PPI infusions to bolus was conducted. As part of a quality improvement initiative, an electronic medical record-based order set was employed; this involved an IV PPI twice daily for 72 hours subsequently defaulting to an oral regimen. After obtaining institutional review board (IRB) approval, patients admitted with upper GI bleeding at our institution from January 2017 to December 2018 were identified with relevant ICD 10 codes. All patients with peptic ulcer disease as the cause of bleeding were included and divided into two groups on the basis of PPI administration strategy. Clinical and resource utilization outcomes were compared between the two groups. Univariate and multivariable analyses were performed to assess independent associations. RESULTS: Of the 368 patients included the mean age was 62.68 years (SD: 5.3 years) and 170 (46.1%) were male. On univariate analysis, age, gender, smoking status, use of anticoagulants, and PPI administration strategy were not associated with inpatient mortality, readmissions, re-bleeding at 3, 7 and 30 days, need for endoscopic hemostatic therapy and need for re-intervention or surgery (all P values &gt; 0.05). Multivariable logistic regression revealed that smoking (OR 2.12 95% CI 1.13- 3.70), anticoagulation use (OR: 2.27 95% CI 1.17- 4.62) and age (OR: 1.03, 95% CI 1.01-1.04) were significantly associated with in-hospital packed red blood cell transfusions. Bolus PPI use was associated with less pharmacy cost of drug calculated per patient, earlier de-escalation to oral PPI, and shorter hospital stay (P &lt; 0.05). CONCLUSION: Our real world, tertiary care experience ascertains non-inferiority of IV bolus PPI regimen compared to continuous infusion for acid suppression therapy in managing upper GI bleeds. The use of simpler bolus regimens can result in a decrease in healthcare resource utilization. A practice shift to such a regimen can therefore serve as a good quality improvement initiative in health care settings.

Clinical management of eosinophilic esophagitis – a nationwide survey among gastroenterologists in Germany

Eosinophilic esophagitis (EoE) is an increasingly recognized immune-mediated esophageal disease and a common cause for dysphagia and food bolus obstruction. The aim of this study was to evaluate the current clinical management of EoE among adult gastroenterologists in Germany. We performed a cross-sectional study of 1393 adult gastroenterologists using a questionnaire containing 22 questions to general, diagnostic, and therapeutic aspects of EoE. The self-administered online survey was conducted between November 2017 and February 2018. Data capture and analysis was performed using SurveyMonkey. The overall responder rate was 29.6 %. More than half of the responders (54.9 %) felt to observe a significant increase of EoE patients. The EREFS score was mostly either unknown (44.3 %) or not routinely used (52.2 %). If EoE was suspected, most responders obtained multiple esophageal biopsies (n = 3 - 4: 35.7 %; n > 4: 61.6 %). The preferred primary treatment was proton pump inhibitors (PPI) in 37.2 % and topical steroids in 35.0 % of responders. PPI regimens were highly diverse, with only half of responders using high-dose PPI regimens. Allergy testing was often initiated (always 25.4 %, sometimes 48.9 %). The most common dietary therapy was 6-food elimination diet (52 %), followed by allergy test-directed diets (16 %) and 2-food elimination diet (16.5 %). The majority of responders indicated a need for long-term treatment (i. e., 23 % of responders in > 50 % their patients and 47.7 % of responders in 25 - 50 % of their patients). Among gastroenterologists in Germany, substantial variation in the adherence to published EoE guidelines appears to exist. This indicates the need for intensified education and national guidelines in order to optimize and harmonize the clinical management of EoE patients.

Rifabutin Triple Therapy is Effective in Patients With Multidrug-resistant Strains of Helicobacter pylori.

Eradicating Helicobacter pylori continues to be a challenge, and no treatment regimen is uniformly successful in all treated patients. Triple therapy with rifabutin and amoxicillin is a successful rescue therapy after consecutive treatment failures. We designed this study to test the efficacy of 12-day rifabutin-based triple therapy in patients infected with multidrug-resistant strains. Consecutive patients with dyspeptic symptoms after at least 1 antibiotic therapy course for H. pylori infection harboring triple-resistant (clarithromycin, metronidazole, levofloxacin) strains were enrolled. They received triple therapy with esomeprazole 40 mg bid, amoxicillin 1 g bid, and rifabutin 150 mg od for 12 days. Patients who failed rifabutin therapy were treated empirically on the basis of the judgment of the treating physician. A total of 254 out of 756 tested patients were found to be infected with a triple-resistant H. pylori strains after at least 1 antibiotic therapy course. Overall, the infection was eradicated in 213 patients, corresponding to a cure rate of 82.9% (95% CI, 78.3-87.5) by intention-to-treat analysis and 88.7% (95% CI, 84.7-92.7) at per-protocol analysis. In multivariate analysis, no factor was identified as an independent predictor of bacterial eradication. There is no current standard for the growing population of patients with multidrug-resistant strains of H. pylori. The 12-day low-dose rifabutin/high-dose proton pump inhibitor regimen is a safe and reliable option for patients infected with triple-resistant strains.

Efficacy and safety of twice-daily rabeprazole maintenance therapy for patients with reflux esophagitis refractory to standard once-daily proton pump inhibitor: the Japan-based EXTEND study

BackgroundRabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks.MethodsPatients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52.ResultsIn total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry.ConclusionsIn the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration.ClinicalTrials.gov number: NCT02135107.

Limited effectiveness with a 10‐day bismuth‐containing quadruple therapy (Pylera®) in third‐line recue treatment for Helicobacter pylori infection. A real‐life multicenter study

Helicobacter pylori antibiotic resistance is an increasing problem worldwide. Pylera® may be an option as salvage therapy. To assess the effectiveness, safety, and tolerance of Pylera® as a third-line in clinical practice. This was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori-infected individuals treated with Pylera® and a proton-pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI-clarithromycin-amoxicillin as first-line and to levofloxacin-amoxicillin-PPI as second-line therapy. Eradication was tested 4-8weeks after Pylera® using a C13 -urea breath test. Treatment-related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases. A questionnaire on patient satisfaction was completed in the last visit. Of 103 subjects fulfilling the selection criteria, 101 were included in the intention-to-treat (ITT) analysis and 97 in the per-protocol (PP) analysis. A 10day course was prescribed in all patients. Esomeprazole 40mg b.i.d. was the most used PPI regimen (ITT=94.1%). Ninety-seven individuals (ITT=96.04%) completed more than 90% of the treatment. Overall eradication rates were ITT=80.2% (95% confidence interval [CI]: 72.3%-88.1%) and PP=84.4% (95% CI: 76.8%-91.8%). One or more TRAEs were experienced by 67.3% (95% CI: 57.7%-75.7%), all mild or moderate. TRAEs and the number of pills were the main complaints. In an area of high antibiotic resistance to H. pylori, 10-day Pylera® plus double-dose PPI emerged as an alternative as third-line therapy, although not achieving optimal eradication rates. TRAEs were common but were neither severe nor did they condition compliance.

Efficacy of proton pump inhibitors for patients with duodenal ulcers: A pairwise and network meta-analysis of randomized controlled trials

Background/Aim:To compare the efficacy and tolerance of different proton pump inhibitors (PPIs) in different doses for patients with duodenal ulcers.Materials and Methods:An electronic database was searched to collect all randomized clinical trials (RCTs), and a pairwise and network meta-analysis were performed.Results:A total of 24 RCTs involving 6188 patients were included. The network meta-analysis showed that there were no significant differences for the 4-week healing rate of duodenal ulcer treated with different PPI regimens except pantoprazle 40 mg/d versus lansoprazole 15 mg/d [Relative risk (RR) = 3.57; 95% confidence interval (CI) = 1.36–10.31)] and lansoprazole 30 mg/d versus lansoprazole 15 mg/d (RR = 2.45; 95% CI = 1.01–6.14). In comparison with H2 receptor antagonists (H2 RA), pantoprazole 40 mg/d and lansoprazole 30 mg/d significantly increase the healing rate (RR = 2.96; 95% CI = 1.78–5.14 and RR = 2.04; 95% CI = 1.13–3.53, respectively). There was no significant difference for the rate of adverse events between different regimens, including H2 RA for a duration of 4-week of follow up.Conclusion:There was no significant difference for the efficacy and tolerance between the ordinary doses of different PPIs with the exception of lansoprazle 15 mg/d.

Timing or Dosing of Intravenous Proton Pump Inhibitors in Acute Upper Gastrointestinal Bleeding Has Low Impact on Costs.

High-dose intravenous proton pump inhibitors (PPIs) post endoscopy are recommended in non-variceal upper gastrointestinal bleeding (UGIB), as they improve outcomes of patients with high-risk lesions. Determine the budget impact of using different PPI regimens in treating non-variceal UGIB, including pre- and post-endoscopic use, continuous infusion (high dose), and intermittent bolus (twice daily) dosing. A budget impact analysis using a decision model informed with data from the literature adopting a US third party payer's perspective with a 30-day time horizon was used to determine the total cost per patient (US$2014) presenting with acute UGIB. The base-case employing high-dose pre- and post-endoscopic IV PPI was compared with using only post-endoscopic PPI. For each, continuous or intermittent dosing regimens were assessed with associated incremental costs. Deterministic and probabilistic sensitivity analyses were performed. The overall cost per patient is $11,399 when high-dose IV PPIs are initiated before endoscopy. The incremental costs are all inferior in alternate-case scenarios: $106 less if only post-endoscopic high-dose IVs are used; with intermittent IV bolus dosing, the savings are $223 if used both pre and post endoscopy and $191 if only administered post endoscopy. Subgroup analysis suggests cost savings in patients with clean-base ulcers who are discharged early after endoscopy. Results are robust to sensitivity analysis. The incremental costs of using different IV PPI regimens are modest compared with total per patient costs.

Rifabutin-based high-dose proton-pump inhibitor and amoxicillin triple regimen as the rescue treatment for Helicobacter pylori.

BackgroundRifabutin has been known to be effective in multidrug-resistant Helicobacter pylori-harboring patients undergoing treatment failure for H. pylori infection.AimTo evaluate the efficacy of 7-day treatment regimen consisting rifabutin daily but increasing the dose of amoxicillin and lansoprazole in patients who have failed first and second eradication and to assess the side effect profiles in South Korea.MethodsFrom December 2007 to May 2013, 59 H. pylori-infected patients with two previous eradication failures were enrolled for this study prospectively. The eligible patients were randomly assigned to either group A or B. Group A received lansoprazole 30 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days, whereas group B received lansoprazole 60 mg bid, amoxicillin 1.0 g tid and rifabutin 150 mg bid during 7 days.ResultsIn group A, H. pylori eradication was achieved in 25 (78.1%) of the 32 patients in the ITT analysis and in 25 (80.6%) of the 31 patients in the PP analysis. In group B, H. pylori eradication was achieved in 26 (96.3%) of the 27 patients in the ITT analysis and in 27 (100%) of the 26 patients in the PP analysis. There was statistically significant difference between the two groups in terms of the eradication rates in PP analysis (p = .047), whereas a marginally statistical significance was found in terms of the eradication rates in ITT analysis (p = .051). Reported side effects were mild, and treatment was well tolerated. No major changes in physical examination or in standard laboratory parameters were observed after treatment.ConclusionsRifabutin-based high-dose proton-pump inhibitor (PPI)-combined therapy as empirical rescue treatment is more effective than standard dose PPI-combined rifabutin-based therapy, safe and best tolerable in third-line therapy in the Korean population. The key to successful rescue therapy with rifabutin–amoxicillin–PPI regimen may be to increase doses of PPI.