Continuous Proton Pump Inhibitor Therapy Research Articles

Intermittent Versus Continuous Infusion Dosing of Intravenous Proton Pump Inhibitors for Upper Gastrointestinal Bleeding.

Proton pump inhibitor (PPI) continuous infusions or intermittent boluses are used for the treatment of upper gastrointestinal bleeding (UGIB). Intermittent boluses are easier to give and are of lower cost without affecting clinical outcomes. To compare the rate of rebleeding between intermittent bolus and continuous infusion PPI therapy. We performed a retrospective, multicenter review of patients with UGIB receiving either continuous or intermittent PPI therapy. During the study period, due to drug and supply shortages, each institution implemented policies preferring intermittent PPI bolus therapy. We performed bivariate and multivariable comparisons of the 2 treatment strategies, with the primary outcome of interest being incidence of rebleeding. Additional variables of interest included intensive care unit (ICU) and hospital lengths of stay, discharge disposition, and in-hospital mortality. Compared with intermittent bolus dosing (n = 209), patients receiving continuous infusion PPI (n = 237) were associated with a higher rate of rebleeding (33.8% vs 23.0%; P = 0.012); however, no difference was detected in multivariable analysis: adjusted odds ratio, 1.50 (95% confidence interval, 0.91-2.50). There was no difference in median hospital or ICU length of stay, discharge disposition, or in-hospital mortality. Correlatively, patients receiving continuous infusion therapy were more likely to have liver disease (29.1% vs 20.1%; P = 0.028), alcohol use disorder (28.3% vs 16.3.%; P = 0.003), history of lower gastrointestinal bleeding (6.4% vs 1.9%; P = 0.021), variceal bleeding (6.3 vs 2.4%, P = 0.045), and be admitted to the ICU (65.0% vs 32.5%, P = 0.00). Introduction of intermittent PPI bolus UGIB treatment via change in hospital policy was not associated with higher rates of rebleeding. However, continuous PPI therapy may have been perceived as more effective as it was used more commonly in high-risk patients.

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.

The effects of continuous proton pump inhibitor therapy on small intestinal bacterial overgrowth in elderly

Objective: Long-term proton pump inhibitor(PPI) therapy may increase the risk of small intestinal bacterial overgrowth(SIBO). Few studies on the effect of on-demand and continuous PPI therapy are available in elderly. To investigate the prevalence of SIBO and the effect of on-demand and continuous PPI therapy on SIBO in elderly. Methods: A total of 200 elderly outpatients admitted to Department of Gastroenterology at the Second Medical Center of PLA General Hospital were enrolled and divided into 3 groups: continuous PPI group, on-demand PPI group and control group. SIBO was diagnosed according to methane and hydrogen lactulose breath test (LBT).The prevalence of SIBO in the 3 groups was analyzed. Results: The prevalence of SIBO was 71.5% in 200 elderly. PPI therapy and diabetes mellitus (DM) were independent risk factors for SIBO. The prevalence of SIBO was 77.1% (108/140) in elderly who underwent long-term PPI therapy and 58.3% (35/60) in those without PPI therapy (P<0.01).The prevalence of SIBO was significantly higher in continuous PPI therapy group than that in on-demand PPI group and control group(88.6% vs. 65.7% and 58.3%, all P<0.01).However, no significant difference was found in the prevalence of SIBO between on-demand PPI group and control group (P>0.05). In elderly who underwent long-term PPI therapy, the prevalence of SIBO increased significantly if administration time was longer than 61 months. Conclusions: SIBO usually occurs in elderly patients who receive continuous PPI rather than on-demand use. If elderly require long-term PPI therapy, on demand administration is suggested as long as primary diseases are properly treated.

Skipping the Drip: Intravenous Proton Pump Inhibitor Bolus Therapy Leads to Poor Outcomes in High-Risk Bleeding.

Background and AimThe aim of this study was to evaluate the impact of a change in our institute’s protocol from continuous intravenous (IV) proton pump inhibitor (PPI) therapy to bolus IV PPI therapy for the treatment of peptic ulcer-related bleeding on patient outcomes. Current guidelines recommend PPI therapy through high-dose IV bolus followed by continuous infusion for bleeding ulcers. Conflicting data have been reported regarding the practice shift to intermittent IV PPI therapy.MethodsA retrospective record review was conducted of patients treated at West Virginia University between 2017 and 2018 for peptic ulcer related bleeding who underwent endoscopy and had high-risk stigmata. Relevant variables were identified. Outcomes were compared between groups based on PPI strategy. The primary endpoint was any poor outcome defined as rebleeding, need for embolization or surgery, or mortality during hospital stay.ResultsA total of 130 patients were included, with a mean age of 62.18 years. Continuous PPI infusion was used in 39.23%, whereas bolus IV PPI was used 60.76%. Poor outcome was encountered in 11 (21.57%) patients in the continuous and 33 (41.77%) patients in the bolus group (p = 0.028). On multivariable analyses, bolus PPI strategy was independently linked to poor outcome (Wald’s odds ratio: 2.8; 95% CI: 1.21-6.84; p = 0.019) and an increased need for embolization/surgery (OR: 4.12, 95% CI: 1.14-19.99; p = 0.046).ConclusionsIV bolus therapy showed worse outcomes compared with continuous IV PPI therapy for patients with peptic ulcer bleeding with high-risk features. More robust data are needed before a practice shift to bolus PPI may be appropriate.

Association Between Acute Gastroenteritis and Continuous Use of Proton Pump Inhibitors During Winter Periods of Highest Circulation of Enteric Viruses

An increased risk of acute bacterial enteric infections has been reported among patients receiving proton pump inhibitor (PPI) therapy. The risk of acute gastroenteritis (AGE) of viral origin associated with continuous PPI exposure has been less studied. To investigate the association between continuous PPI therapy and AGE occurrence during winter epidemic periods when the circulation of enteric viruses is the highest. A matched cohort study was performed using a prospectively collected drug dispensing database from a large panel of community pharmacies in continental France. All patients recorded in the database during the 2015 to 2016 winter season, with documented age, sex, and use of an identifiable regular panel pharmacy, were eligible for the study. Each patient exposed to continuous PPI therapy was matched to 3 unexposed patients, according to year of birth, sex, and identifiable regular panel pharmacy. Analyses were performed between January 2017 and December 2018. Continuous PPI use during the 2015 to 2016 AGE winter epidemic. The occurrence of at least 1 AGE episode during the 2015 to 2016 AGE winter epidemic was the main outcome. Episodes of AGE were identified using a previously validated algorithm based on drug dispensing data. Relative risks of AGE were estimated using a multivariable log-binomial model adjusted for age, sex, and treatments for chronic conditions. There were 233 596 patients receiving PPI therapy (median [interquartile range] age, 71 [62-81] years; 55.8% female) and 626 887 matched patients not receiving PPI therapy (median [interquartile range] age, 70 [61-80] years; 56.3% female) included in the analyses. At least 1 AGE epidemic episode was identified in 3131 patients (1.3%) receiving PPI therapy and in 4327 patients (0.7%) not receiving PPI therapy. The adjusted relative risk of AGE for those receiving PPI therapy was 1.81 (95% CI, 1.72-1.90) for all ages considered, 1.66 (95% CI, 1.54-1.80) among those aged 45 to 64 years, 2.19 (95% CI, 1.98-2.42) among those aged 65 to 74 years, and 1.98 (95% CI, 1.82-2.15) among those aged 75 years and older. Continuous PPI therapy was associated with an increased risk of developing AGE during periods of highest circulation of enteric viruses. These findings support the hypothesis that PPI use is associated with an increased risk of enteric viral infections.

Laparoscopic transhiatal suture closure for spontaneous esophageal rupture: a case report

BackgroundSpontaneous esophageal rupture is a rare but serious disease with high mortality. Conservative treatment and endoscopic therapy have been reported, but surgical treatment is still a basic modality of therapy. In addition to thoracotomy, recent studies have reported treatment with thoracoscopic surgery and laparoscopic transhiatal repair. In this study, we report a patient who underwent laparoscopic transhiatal suture closure for spontaneous esophageal rupture with favorable postoperative course. We also discuss indication for laparoscopic surgery for spontaneous esophageal rupture.Case presentationA 70-year-old man visited our hospital with chief complaints of epigastric pain and vomitus niger. He was diagnosed with spontaneous esophageal rupture in the left wall of the lower esophagus by computed tomography and upper gastrointestinal (GI) series. At 11 h after the onset of symptoms, we performed laparoscopic transhiatal suture closure and lavage drainage. We performed transhiatal esophageal replacement using the 5-hole approach. We observed a perforation of 2 cm in diameter at the site of the rostral portion approximately 4 cm from the esophageal hiatus. All layers were closed with three stitches using 3–0 absorbable sutures. No perforation was observed in the thoracic cavity. The total operative time was 178 min, and total bleeding was 2 ml. He had no postoperative complications and was discharged on day 15 after the procedure. He received continuous proton pump inhibitor therapy as an outpatient. Healing cicatrization was found at the site of rupture by esophagogastroscopy. The patient was advised to improve his lifestyle and has shown no signs of recurrence over 2 years from the date of surgery.ConclusionsSimple closure of all the layers using laparoscopic transhiatal simple closure was useful in the treatment of esophageal rupture as a less invasive approach for patients who meet the following conditions: stable general condition, intrathoracic perforation, and the perforation site is identified as the lower esophagus by pre-operative examination.

Strategies for Effective Discontinuation of Proton Pump Inhibitors.

Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy. Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a "step-down" approach with the use of alternative medications may be effective. "On-demand therapy" provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators. A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.

Factors Associated with Potassium-Competitive Acid Blocker Non-Response in Patients with Proton Pump Inhibitor-Refractory Gastroesophageal Reflux Disease

Background/Aims: Approximately 20-40% of patients with gastroesophageal reflux disease (GERD) are refractory to proton pump inhibitor (PPI) treatment. The acid-inhibitory effect of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), is significantly greater when compared to the effect of PPIs. We investigated the efficacy of vonoprazan treatment for PPI-refractory GERD and factors associated with P-CAB non-response. Methods: We enrolled 277 GERD patients receiving continuous PPI therapy. Subjects completed a self-report questionnaire including the frequency scale for the symptoms of GERD (FSSG). Patients with PPI-refractory GERD received 20 mg of vonoprazan once daily for 8 weeks. After that, subjects completed the same questionnaire, and the results were used to identify P-CAB responders and non-responders. Results: Twenty-eight patients were identified as P-CAB responders and 26 were non-responders. Vonoprazan treatment significantly decreased scores of FSSG, nighttime symptom, and Athens Insomnia Scale. Multivariate analysis demonstrated co-existing functional dyspepsia (FD; OR 4.94) and the presence of sleep disturbances (OR 4.34) was associated with P-CAB non-response, whereas alcohol consumption was inversely associated. Conclusions: Vonoprazan treatment might be appropriate as a promising new strategy for PPI-refractory GERD. Co-existing FD, sleep disturbances, and alcohol abstinence were significantly associated with P-CAB non-response. Other therapeutic options should be considered in patients with these factors.

Do sleeve gastrectomy and gastric bypass influence treatment with proton pump inhibitors 4 years after surgery? A nationwide cohort

BackgroundGastroesophageal reflux disease (GERD) is a common obesity-related co-morbidity that routinely is treated by continuous proton pump inhibitor (PPI) therapy. A number of concerns have been raised regarding the risk of de novo GERD or exacerbation of preexisting GERD after sleeve gastrectomy (SG). ObjectiveTo assess PPI use at 4 years after bariatric surgery. SettingFrench National Health Insurance. MethodsData were extracted from the French National Health Insurance database. All adult obese patients who had undergone gastric bypass (GBP) (n = 8250) or SG (n = 11,923) in 2011 in France were included. Patients were considered to be on continuous PPI therapy when PPIs were dispensed≥6 times per year. Logistic regression models were used to compute odds ratios for potential risk factors for PPI reimbursement 4 years after surgery. ResultsOverall, continuous use of PPIs increased from baseline to 4 years after SG and GBP, from 10.9% to 26.5% (P<.001) and from 11.4% to 21.9% (P<.001), respectively. Among patients who underwent PPI therapy before surgery, those who had undergone SG were more likely to continue PPI therapy 4 years after surgery compared with those who underwent GBP (72.7% versus 59.2%; P<.001). In multivariate analyses, the major risk factors for persistent continuous PPI treatment 4 years after surgery were the following: SG (odds ratio [OR] = 1.87; 95% confidence interval [CI] 1.55–2.25), higher body mass index (OR 1.85; 95% CI 1.35–2.5), and preoperative antidepressant treatment (OR 1.89; 95% CI 1.56–2.29). ConclusionAt a nationwide scale, continuous PPI treatment is used by 1 of 10 obese patients before bariatric surgery, but by 1 of 4 patients 4 years after surgery. SG compared with GBP, higher body mass index, and other coexisting conditions are the 3 major risk factors for medium-term continuous PPI therapy.

Non-Helicobacter pylori, Non-nonsteroidal Anti-inflammatory Drug Peptic Ulcer Disease

Non-Helicobacter pylori, non-NSAID peptic ulcer disease (PUD), termed idiopathic PUD, is increasing in Korea. Diagnosis is based on exclusion of common causes such as H. pylori infection, infection with other pathogens, surreptitious ulcerogenic drugs, malignancy, and uncommon systemic diseases with upper gastrointestinal manifestations. The clinical course of idiopathic PUD is delayed ulcer healing, higher recurrence, higher re-bleeding after initial ulcer healing, and higher mortality than the other types of PUD. Genetic predisposition, older age, chronic mesenteric ischemia, cigarette smoking, concomitant systemic diseases, and psychological stress are considered risk factors for idiopathic PUD. Diagnosis of idiopathic PUD should systematically explore all possible causes. Management of this disease is to treat underlying disease followed by regular endoscopic surveillance to confirm ulcer healing. Continuous proton pump inhibitor therapy is an option for patients who respond poorly to the standard ulcer regimen.

Low Prevalence of Hypomagnesemia in Long-term Recipients of Proton Pump Inhibitors in a Managed Care Cohort.

Chronic intake of proton pump inhibitors (PPI) has been associated with hypomagnesemia, but prevalence of PPI-associated hypomagnesemia is not known. We examined the prevalence of hypomagnesemia among long-term PPI recipients by using a large health maintenance organization database. We collected data on 10,167 participants eligible for chronic drug prescriptions from 2008 through 2013. Adult subjects receiving continuous PPI therapy for ≥ 6 months between 2008 and 2013 and ≥ 1 serum magnesium determination(s) were identified. Patients with any magnesium levels less than 1.6 mg/dL were selected for analysis; those with recognizable causes of altered magnesium homeostasis were excluded. Five hundred ninety participants received long-term PPIs, and 414 (70.2%) met the inclusion criteria for a total exposure of 2293 PPI-years (average, 5.7 years/subject). Of these patients, 57 (13.8%) had ≥ 1 low serum magnesium; 5 were no longer on PPIs, and 44 had other recognizable causes for hypomagnesemia (25 receiving diuretics, 8 with chronic diarrhea, 8 with chronic kidney disease, and 3 with malignancies). Of the 8 remaining patients (7 female; mean age, 71.2 ± 13.4 years; mean daily medications, 5.4 ± 1.1), mild hypomagnesemia (range, 1.2-1.5 mg/dL) was noted in 13.9% of 289 measurements. All 8 patients had normal serum levels of magnesium at their final measurement. In the absence of known precipitating factors, chronic PPI use does not appear to be associated with hypomagnesemia.

Consequences and Complications of Long Term Use of proton Pump Inhibitors

Proton Pump Inhibitors (PPIs) have become one of the most commonly prescribed category of drugs in both primary as well as tertiary care, commonly for gastric acid-related disorders. It is advised that no more than three 14-day treatment courses with PPIs should be used in one year. The two main indications for the long-term use of PPIs are gastro esophageal reflux disease and concomitant use with the maintenance dose of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). PPIs block the gastric H + ,K + -ATPase, inhibiting gastric acid secretion. If the drug is discontinued, there is a potential risk for rebound hypersecretion, creating a sort of dependency on the drug because the body is acclimated to having acid suppressed. The potential adverse effects relating to PPIs are Hypochlorhydria (11%- 24%) leading to pernicious anaemia and bone fractures(elevated risk after 7 years of continuous PPI therapy) and Hypergastrinemia (20%- 25%). Review of various literatures have shown that long-term PPI use is associated with upto fourfold increase in the risk of fundic gland polyps(upto 36%). Other potential consequences of chronic PPI use are malabsorption of key minerals (calcium and magnesium) in the body, increased risk of infections, cancer (5%-12%), severe drug interactions and birth defects. The most commonly seen infections with chronic PPI use are Enteric Infections and Community Acquired Pneumonia(CAP).A case-controlled study discovered an associated 2.5-fold risk of infection with concomitant PPI therapy. A population-based case-controlled study of7642 CAP cases identified, 11% were chronic PPI users. Another study found that 50% of chronic PPI users are more likely to develop CAP.Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from longterm therapy. In conclusion, based on the above evidences, pharmacists are poised to educate patients about the benefits and risks associated with chronic PPI use.

Proton pump inhibitors and helicobacter pylori-associated pathogenesis.

The fact that long-term use of proton pump inhibitors (PPIs) aggravates corpus atrophic gastritis in patients with Helicobacter pylori infection has been proven clinically and experimentally. Corpus atrophic gastritis is a known risk factor for gastric cancer. Therefore, gastric neoplasia might be associated with the long-term use of PPIs. One of the causes of worsening corpus atrophic gastritis, leading to the development of adenocarcinoma, might be bacterial overgrowth under conditions of hypochlorhydria. The production of potentially carcinogenic N-nitrosocompounds by nitrosating organisms under conditions of hypochlorhydria might be associated with carcinogenesis. Interactions between bile acids, pH, and H. pylori might also contribute to carcinogenicity, especially in patients with gastro-esophageal reflux disease (GERD). The concentration of soluble bile acids, which have bactericidal or chemorepellent properties toward H. pylori, in gastric contents is considerably higher in patients undergoing continuous PPI therapy than in healthy individuals with normal acid production. Under these circumstances, H. pylori might colonize the stomach body rather than the pyloric antrum. Hypergastrinemia induced by PPI administration might promote the development of gastric cancer. Because the main cause of corpus atrophic gastritis is H. pylori infection, and not PPI administration, H. pylori infection should be eradicated before starting long-term PPI therapy.

Review: In high-risk ulcers, intermittent and continuous PPI therapy do not differ for recurrent bleeding

Source Citation Sachar H, Vaidya K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: A systematic review and meta-analysis. JAMA Intern Med. 2014;174:1755-62. 25201154

Intermittent vs Continuous Proton Pump Inhibitor Therapy for High-Risk Bleeding Ulcers: Sachar H, Vaidya K, Laine L. JAMA Intern Med 2014;4056. [Epub ahead of print

Intermittent vs Continuous Proton Pump Inhibitor Therapy for High-Risk Bleeding Ulcers: Sachar H, Vaidya K, Laine L. JAMA Intern Med 2014;4056. [Epub ahead of print

Proton pump inhibitor use may not prevent high‐grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: a nationwide study of 9883 patients

Proton pump inhibitors (PPI) may potentially modify and decrease the risk for development of oesophageal adenocarcinoma in Barrett's oesophagus (BO). To investigate if the intensity and adherence of PPI use among all patients with BO in Denmark affected the risk of oesophageal adenocarcinoma. We performed a nationwide case-control study in Denmark among 9883 patients with a new diagnosis of BO. All incident oesophageal adenocarcinomas and high-grade dysplasias were identified, and risk ratios were estimated on the basis of prior use of PPIs. Sex- and age-matched BO patients without dysplasia or malignancies in a 10:1 ratio were used for comparison. Conditional logistic regression was used for analysis, adjusting for low-grade dysplasia, gender and medication. We identified 140 cases with incident oesophageal adenocarcinomas and/or high-grade dysplasia, with a median follow-up time of 10.2years. The relative risk of oesophageal adenocarcinoma or high-grade dysplasia was 2.2 (0.7-6.7) and 3.4 (95% CI: 1.1-10.5) in long-term low- and high-adherence PPI users respectively. No cancer-protective effects from PPI's were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia. This could partly be due to confounding by indication or a true negative effect from PPIs. Until the results from future studies hopefully can elucidate the association further, continuous PPI therapy should be directed at symptom control and additional modalities considered as aid or replacement.

Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD.

The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). Diluted human plasma and bile acids have been found to be significant chemoattractants and chemorepellents, respectively, for the bacillus H. pylori. Although only taurine conjugates, with a pKa of 1.8-1.9, are soluble in an acidic environment, glycine conjugates, with a pKa of 4.3-5.2, as well as taurine-conjugated bile acids are soluble in the presence of PPI therapy. Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface. H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors

To determine if the observed paracellular sucrose leak in Barrett's esophagus patients is due to their proton pump inhibitor (PPI) use. The in vivo sucrose permeability test was administered to healthy controls, to Barrett's patients and to non-Barrett's patients on continuous PPI therapy. Degree of leak was tested for correlation with presence of Barrett's, use of PPIs, and length of Barrett's segment and duration of PPI use. Barrett's patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was observed in Barrett's patients who ceased PPI use for 7 d. Although initial introduction of PPI use (in a PPI-naïve population) results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spontaneous decline in leak. The sucrose leak observed in Barrett's patients showed no correlation to the amount of Barrett's tissue present in the esophagus. Although future research is needed to determine the degree of paracellular leak in actual Barrett's mucosa, the relatively high degree of leak observed with in vivo sucrose permeability measurement of Barrett's patients reflects their PPI use and not their Barrett's tissue per se.

A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial

ObjectiveTo evaluate the efficacy and tolerability of add-on treatment with lesogaberan (AZD3355), a novel reflux inhibitor, in patients with persistent gastro-oesophageal reflux disease (GORD) symptoms despite proton pump inhibitor (PPI)...

Guidelines for the Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. In the last decade, GERD has been increasing in Korea. Seventeen consensus statements for the treatment of GERD were developed using the modified Delphi approach. Acid suppression treatments, such as proton pump inhibitors (PPIs), histmine-2 receptor antagonists and antacids are effective in the control of GERD-related symptoms. Among them, PPIs are the most effective medication. Standard dose PPI is recommended as the initial treatment of erosive esophagitis (for 8 weeks) and non-erosive reflux disease (at least for 4 weeks). Long-term continuous PPI or on-demand therapy is required for the majority of GERD patients after the initial treatment. Anti-reflux surgery can be considered in well selected patients. Prokinetic agents and mucosal protective drugs have limited roles. Twice daily PPI therapy can be tried to control extra-esophageal symptoms of GERD. For symptomatic patients with Barrett's esophagus, long-term treatment with PPI is required. Further studies are strongly needed to develop better treatment strategies for Korean patients with GERD.