Several proton pump inhibitor (PPI) dosing regimens that vary by strength and frequency (once [Qday] or twice [BID] daily) are available to treat gastroesophageal reflux disease (GERD). We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the impact of various PPI regimens on esophageal healing and GERD and heartburn symptoms. To identify relevant studies, we searched EMBASE and PubMed in January 2023, which yielded 1381 records. Eligible RCTs included those that enrolled adults diagnosed with GERD and compared different dosing regimens within the same PPI. The outcomes were esophageal healing and resolution of GERD and heartburn symptoms within 12 weeks (i.e. short-term) and > 12 weeks (i.e. long-term). Meta-analysis pooling of the odds ratios with 95% confidence intervals were estimated using the random-effects inverse-variance model. Overall, a total of 38 RCTs across 20 countries (N = 15,540 patients, mean age 50 years, 55% male) were included. Most PPI trials compared half standard dose Qday versus standard dose Qday or standard dose Qday versus double standard dose Qday. In general, when considering daily dosing, higher PPI strength significantly improved esophageal healing and relief of GERD symptoms both in the short- and long-term. Fewer trials compared Qday versus BID dosing; the impact of BID dosing on outcomes was inconsistent across the different PPI strength comparisons. In conclusion, this meta-analysis revealed that increasing PPI Qday dosages led to improved GERD outcomes. However, few studies compared Qday to BID dosing; as twice daily PPI usage is common in clinical practice, further studies are warranted to determine whether such dosing improves clinical outcomes.

Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE.

This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose.

A systematic review and network meta-analysis.

Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted.

In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline.

This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients.

The study protocol was registered with INPLASY (registration number INPLASY2023120053).

Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.

To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE).

Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups.

Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.

Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.

Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.

A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.

Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.

Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes.

We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset.

Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients.

Therapeutic outcome in gastroesophageal reflux disease (GERD) is commonly determined by both subjective and objective clinical endpoints. Clinicians frequently use symptom improvement as a key benchmark of clinical success, in conjunction with normalization of objective parameters such as esophageal acid exposure and inflammation. However, GERD therapeutic trials have demonstrated that a substantial number of patients rendered asymptomatic, whether through medical, surgical, or endoscopic intervention, continue to have persistent abnormal esophageal acid exposure and erosive esophagitis. The opposite has also been demonstrated in therapeutic trials, where patients remained symptomatic despite normalization of esophageal acid exposure and complete resolution of esophageal inflammation. Moreover, there is no substantive evidence that symptomatic response to antireflux treatment requires complete esophageal mucosal healing or normalization of esophageal acid exposure. Thus, it appears that a certain level of improvement in objective parameters is needed to translate into meaningful changes in symptoms and health-related quality of life of GERD patients. This supports the need to reconsider the commonly used "hard" clinical endpoints to evaluate therapeutic trials in GERD.

We aimed to evaluate whether adding a sustained-release (SR) formula of mosapride to proton-pump inhibitors (PPIs) would be more effective in controlling symptoms than PPI alone in patients with gastroesophageal reflux disease (GERD). Sixty patients with heartburn and/or regurgitation were randomly assigned to two groups: mosapride SR 15 mg combined with esomeprazole 20 mg once daily (ME group) and esomeprazole 20 mg once daily alone (E group). The primary endpoint was the complete-resolution rate of GERD symptoms after eight-week medication, and the secondary endpoints were the complete-resolution rate of GERD symptoms after four-week medication, symptom-improvement rates ≥ 50% after four- and eight-week medication, and change in reflux-disease-questionnaire (RDQ) and GERD-health-related quality-of-life (GERD-HRQL) scores from baseline at four- and eight-week medication. No significant differences in complete-symptom-resolution rates at eight weeks and four weeks or in the changes in RDQ and GERD-HRQL scores from baseline at four- and eight-week medication were observed between the ME and E groups. The symptom-improvement rate of ≥50% after four and eight weeks was comparable between both groups. Adding mosapride SR to esomeprazole in patients with GERD provides no additional benefits in controlling GERD symptoms.

Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD.

We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption.

Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs.

This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.

Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms.

To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed.

This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10.

Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment.

Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.

Gastroesophageal reflux disease (GERD) characterized by heartburn and/or regurgitation symptoms is one of the most common gastrointestinal disorders managed by gastroenterologists and primary care physicians. There has been an increase in GERD prevalence, particularly in North America and East Asia. Over the past three decades proton pump inhibitors (PPIs) have been the mainstay of medical therapy for GERD. However, recently there has been an increasing awareness amongst physicians and patients regarding the side effects of the PPI class of drugs. In addition, there has been a marked decline in the utilization of surgical fundoplication as well as a rise in the development of nonmedical therapeutic modalities for GERD. This review focuses on different management strategies for GERD, optimal management of refractory GERD with special focus on available endoluminal therapies and the future directions.

This study compared the effectiveness and acceptability of all Food and Drug Administration (FDA)-recommended dose proton pump inhibitors (PPIs) in erosive esophagitis (EE): Dexlansoprazole 60 mg, Esomeprazole 40 mg, Esomeprazole 20 mg, Pantoprazole 40 mg, Lansoprazole 30 mg, Rabeprazole 20 mg, Omeprazole 20 mg.

A systematic literature search was performed using PubMed, Embase, and Cochrane Library. Totally, 25 randomized controlled trials (RCTs) met study selection criteria and were incorporated in this network meta-analysis (NMA) study.

For the NMA, eligible RCTs of adults with EE verified by endoscopic examination were randomly assigned to the licensed PPIs at least 4 weeks of continuous therapy. The primary efficacy outcome was the endoscopic healing rates at 4 and 8 weeks. Heartburn relief rates were a secondary efficacy outcome. The rates of withdrawal were analyzed as a safety outcome. In comparison to the common comparator omeprazole 20 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [odds ratio (OR), 1.46 (95% confidence interval, 95% CI, 1.24-1.71)] and 8 weeks [1.58 (1.29-1.92)], and improved the heartburn relief rates [1.29 (1.07-1.56)]. In comparison to lansoprazole 30 mg, esomeprazole 40 mg provided significantly healing rates at 4 weeks [1.30 (1.10-1.53)] and 8 weeks [1.37 (1.13-1.67)], and improved the heartburn relief rates [1.29 (1.03-1.62)]. In terms of acceptability, only dexlansoprazole 60 mg had significantly more all-cause discontinuation than omeprazole 20 mg [1.54 (1.03-2.29)], pantoprazole 40 mg [1.68 (1.08-2.63)], and lansoprazole 30 mg [1.38 (1.02-1.88)].

The standard-dose esomeprazole 40 mg had more superiority in mucosal erosion healing and heartburn relief. Esomeprazole 40 mg, pantoprazole 40 mg, esomeprazole 20 mg, and lansoprazole 30 mg showed more benefits in effectiveness and acceptability than other interventions.

Proton pump inhibitors (PPIs) are a class of medications that reduce acid secretion and are used for treating many conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease, and hypersecretory conditions (e.g. Zollinger-Ellison syndrome), and as part of the eradication therapy for Helicobacter pylori bacteria. However, approximately 25% to 70% of people are prescribed a PPI inappropriately. Chronic PPI use without reassessment contributes to polypharmacy and puts people at risk of experiencing drug interactions and adverse events (e.g. Clostridium difficile infection, pneumonia, hypomagnesaemia, and fractures).

To determine the effects (benefits and harms) associated with deprescribing long-term PPI therapy in adults, compared to chronic daily use (28 days or greater).

We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 10), MEDLINE, Embase, clinicaltrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). The last date of search was November 2016. We handsearched the reference lists of relevant studies. We screened 2357 articles (2317 identified through search strategy, 40 through other resources). Of these articles, we assessed 89 for eligibility.

We included randomized controlled trials (RCTs) and quasi-randomized trials comparing at least one deprescribing modality (e.g. stopping PPI or reducing PPI) with a control consisting of no change in continuous daily PPI use in adult chronic users. Outcomes of interest were: change in gastrointestinal (GI) symptoms, drug burden/PPI use, cost/resource use, negative and positive drug withdrawal events, and participant satisfaction.

Two review authors independently reviewed and extracted data and completed the risk of bias assessment. A third review author independently confirmed risk of bias assessment. We used Review Manager 5 software for data analysis. We contacted study authors if there was missing information.

The review included six trials (n = 1758). Trial participants were aged 48 to 57 years, except for one trial that had a mean age of 73 years. All participants were from the outpatient setting and had either nonerosive reflux disease or milder grades of esophagitis (LA grade A or B). Five trials investigated on-demand deprescribing and one trial examined abrupt discontinuation. There was low quality evidence that on-demand use of PPI may increase risk of 'lack of symptom control' compared with continuous PPI use (risk ratio (RR) 1.71, 95% confidence interval (CI) 1.31 to 2.21), thereby favoring continuous PPI use (five trials, n = 1653). There was a clinically significant reduction in 'drug burden', measured as PPI pill use per week with on-demand therapy (mean difference (MD) -3.79, 95% CI -4.73 to -2.84), favoring deprescribing based on moderate quality evidence (four trials, n = 1152). There was also low quality evidence that on-demand PPI use may be associated with reduced participant satisfaction compared with continuous PPI use. None of the included studies reported cost/resource use or positive drug withdrawal effects.

In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

  Symptomatic response to proton pump inhibitor (PPI) therapy in patients with non-erosive reflux disease (NERD) is often reported as lower than in patients with erosive reflux disease (ERD). However, the definition of NERD differs across clinical trials. This meta-analysis aims to estimate the rate of symptom relief in response to PPI in NERD patients.

MEDLINE (1966-2010), Cochrane Comprehensive Trial Register (1997-2010) and EMBASE (1985-2010) databases were searched and manual searches from studies' references were performed. Randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term PPI treatment. The primary outcome of selected studies was defined as complete or partial heartburn relief. Two reviewers independently extracted data and assessed study quality of selected articles. Random effects models and meta-regression were used to combine and analyze results.

The pooled estimate of complete relief of heartburn after 4 weeks of PPI therapy in patients with ERD was 0.72 (95% CI 0.69-0.74) (32 studies), vs 0.50 (0.43-0.57) (eight studies) in empirically treated patients, 0.49 (0.44-0.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.69-0.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive pH-test.

In well-defined NERD patients, the estimated complete symptom response rate after PPI therapy is comparable to the response rate in patients with ERD. The previously reported low response rate in studies with patients classified as NERD is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease.

Chronic consumption of proton pump inhibitors (PPIs) by patients with gastroesophageal reflux disease is very common, primarily because of their potent and profound effect on acid secretion that results in an unsurpassed rate of symptom resolution and esophageal healing. However, there have been a growing number of reports over the past few years about various side effects caused by chronic PPI treatment. Concerns have been raised by patients and physicians alike about the common practice of prescribing PPIs, often more than once daily, on a long-term basis. As a result, there has been a resurgence of interest in alternative therapeutic modalities for chronic PPI treatment. These include novel endoscopic and surgical techniques, as well as other available therapeutic strategies that are likely to be revisited, such as histamine-2-receptor antagonists, intermittent and on-demand PPI treatment, and antireflux surgery, among others.

Proton pump inhibitors (PPIs) are well established as first-line agents for the treatment of moderate-to-severe gastro-oesophageal reflux disease (GORD). Although all PPIs heal oesophageal lesions and provide symptomatic relief, breakthrough symptoms may occur as acidity levels rebound. Pantoprazole magnesium (pantoprazole-Mg) has a longer elimination half-life than pantoprazole sodium (pantoprazole-Na), resulting in prolonged drug exposure.

This study compares the clinical efficacy and safety of once-daily pantoprazole-Mg 40 mg with that of once-daily pantoprazole-Na 40 mg in the management of GORD.

This was a randomized, double-blind, controlled, multicentre study of non-inferiority design in outpatients with GORD. The study was conducted in 53 centres in Germany from 12 May 2003 to 18 September 2003. Male or female outpatients (aged ≥18 years) with endoscopically confirmed GORD stage I-III (according to the Savary-Miller classification modified by Siewert) were enrolled. Using a computer-generated randomization list, patients were randomized to treatment with pantoprazole-Mg 40 mg plus placebo or pantoprazole-Na 40 mg plus placebo, both given once daily for 4 or 8 weeks depending on healing of oesophagitis. The primary objective was endoscopic healing at 8 weeks.

The intent-to-treat (ITT) group consisted of 636 patients (322 receiving pantoprazole-Mg and 314 receiving pantoprazole-Na). Endoscopically confirmed healing of reflux oesophagitis after 8 weeks occurred in 87.3% (95% CI 83.1, 90.7) of patients receiving pantoprazole-Mg and 85.0% (95% CI 80.6, 88.8) of patients receiving pantoprazole-Na (ITT population). The lower bound of the 95% CI for the between-group treatment difference was -1.3, which was within the predefined margin of non-inferiority of -10% to 0%. Healing rates after 4 weeks were superior in the pantoprazole-Mg group (72.7% [95% CI 67.5, 77.5]) compared with the pantoprazole-Na group (66.2% [95% CI 60.7, 71.5]), and the one-sided (lower bound) of the 95% CI for the difference between healing rates for the two treatments was within the predefined non-inferiority margin of -10% to 0%. Both treatments had a similar effect on GORD healing in subgroups of patients based on baseline oesophagitis grade and Helicobacter pylori status. Pantoprazole-Mg had similar efficacy to pantoprazole-Na in relieving a broad range of GORD-related symptoms across the course of the study, although symptomatic relief at 4 weeks was numerically higher in the pantoprazole-Mg group than in the pantoprazole-Na group (statistical analyses were not performed). Both treatments were well tolerated; most adverse events were of mild or moderate severity and unrelated to the study medication, and there were no unexpected safety concerns.

Pantoprazole-Mg is clinically as effective and well tolerated as pantoprazole-Na in the treatment of GORD stages I-III, demonstrating non-inferiority for oesophageal healing at 8 weeks and superior healing rates at 4 weeks associated with high levels of symptomatic relief.

Approximately one-third of gastro-oesophageal reflux disease (GERD) patients demonstrate refractory symptoms following treatment with proton pump inhibitor (PPI) therapy.

To develop a refractory GERD score that can be applied to predict patients' healthcare utilisation.

We enrolled adults (≥18 years) with a diagnosis of GERD. Refractory GERD was evaluated on an 8-point scale where 1 point was given for each of the following criteria: doubling, addition, or switching of GERD medication dose, receipt of a GERD-related endoscopic procedure or surgery, or ≥3 GERD-related outpatient visits. Refractory GERD was defined as the presence of two or more points.

A total of 135,139 GERD patients (44% male) were analysed with a mean (±s.d.) age of 52.9 ± 15 years. The mean overall refractory GERD score was 1.12 ± 1.2 (range 0-8 on an 8-point scale); 31% of patients had refractory GERD with a mean score of 2.56 ± 0.82. Among patients with refractory GERD, 31% doubled their GERD medication, 28% added a new GERD medication, 60% switched GERD medications, 54% had a GERD-related procedure and 1% had a GERD-related surgery. Patients with refractory GERD were more likely to be female (59% vs. 55%, P < 0.001) and had a higher co-morbidity score (0.78 vs. 0.56, P < 0.001). The overall mean costs for refractory patients during the study period were significantly higher compared with treatment-responsive patients ($18,088 ± $36,220 vs. $11,044 ± $22,955, P < 0.001).

Refractory GERD was present in approximately one-third of the GERD patients. We created a GERD refractory score that could define need for increased anti-reflux therapy and predict higher healthcare resource utilisation.

The typical symptoms of gastroesophageal reflux disease (GERD) are heartburn and regurgitation. Extensive analysis has characterized heartburn and its responsiveness to proton pump inhibitor (PPI) therapy, but regurgitation has received relatively little attention. This study aimed to evaluate the response of regurgitation to PPI therapy in GERD trials.

Studies were identified by systematic searches in PubMed and Embase, as well as searching congress abstracts and the reference lists of Cochrane reviews.

Regurgitation was not an entry criterion or the primary end point in any of the 31 clinical trials reporting the response of regurgitation to PPI treatment in GERD. The definitions of regurgitation and responsiveness varied among trials and over half used investigator assessment of response. Owing to these inconsistencies, no meta-analysis was attempted. In seven placebo-controlled trials of PPI therapy, the therapeutic gain for regurgitation response averaged 17% relative to placebo and was >20% less than that observed for heartburn. Studies comparing PPIs with histamine-2 receptor antagonists or prokinetics found the comparator drug response similar to the placebo response rates seen in the placebo-controlled trials.

The therapeutic gain with PPIs over placebo or comparator agents for the relief of regurgitation is modest, and considerably lower than for heartburn. Thus, regurgitation is likely to be an important factor for determining incomplete response to PPI treatment in GERD. Future trials would benefit from using regurgitation as a primary end point, applying an unambiguous definition of the symptom and of a positive treatment response, and using a validated patient-reported instrument for regurgitation assessment.

The population prevalence of eosinophilic esophagitis (EoE) is ~7% in adults. Current American Gastroenterology Association guidelines recommend endoscopic biopsy (Bx) in patients with symptoms of dysphagia. We conducted a cost-effectiveness model to determine if endoscopic Bx is cost effective in patients with refractory gastroesophageal reflux disease (GERD) without dysphagia.

We designed a 5-year Markov model to compare costs and quality-adjusted life years for a cohort of 35-year-old patients with GERD refractory to proton pump inhibitor (PPI) therapy. We compared upper endoscopy (EGD) with and without Bx for EoE. We modeled that patients with EoE who did not undergo initial biopsy would wait 5 years until the diagnosis would be established via a second endoscopy with biopsy.

In patients with refractory GERD without dysphagia, endoscopic Bx for EoE was associated with an incremental cost-effectiveness ratio (ICER) of $51,420 per quality of life year (QALY). The upper endoscopy with biopsy arm cost $12,490 per patient and was associated with 4.080 QALYs, compared with EGD without Bx arm that cost $12,280 and was associated with 4.076 QALYs. The ICER was <$50,000 per QALY when the prevalence of EoE exceeded 8%, or the time of missed diagnosis was 6 years or greater. The biopsy arm was also cost effective if the QALY associated with symptomatic GERD was ≤0.93, cost of 3-month course of PPI therapy ≥$770 cost of fluticasone <$650, probability of EoE resolved on PPI ≤25%, symptom resolution on fluticasone ≥70%, cost endoscopy with biopsy ≤$520, or the cost of endoscopy without biopsy exceeded $300.

Upper endoscopy with Bx for EoE appears to be a cost-effective approach in patients when the prevalence of EoE is 8% or greater.

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.

Gastro-esophageal reflux disease (GERD) is a chronic condition, with 50-80% of patients experiencing recurrence within one year following completion of initial treatment. The present study aimed to estimate recurrence rate and treatment response in GERD patients treated with proton pump inhibitor.

A total of 207 symptomatic GERD patients, which were confirmed by endoscopy from July 2008 till January 2009, were enrolled. They were divided into non-erosive reflux disease (NERD) group and erosive reflux disease (ERD) group by endoscopic findings. Patients were treated with lansoprazole 15 mg (NERD group) or 30 mg (ERD group) once daily for 8 weeks. The presence of symptoms was assessed in each patient at baseline and post-treatment using a questionnaire. Subsequent symptomatic recurrence on the cessation of therapy in each improved patients was checked by telephone survey or outpatient interview.

Ninety-four patients and 113 patients were first diagnosed with NERD and ERD, respectively. The mean post-treatment follow-up period was 24.4+/-8.5 weeks. Recurrence rate was 40.0% (NERD, 43.8%; ERD, 37.1% (p=0.224)). Recurrence time was 10.1+/-5.8 weeks (NERD 9.6 weeks; ERD, 10.6 weeks (p=0.444)). Regarding the symptom improvement after 8 week therapy with lansoprazole, 89.4% (NERD, 85.1%; ERD, 92.9% (p=0.056)) of total patients were symptomatically improved.

Forty percentage of GERD patients recurred within 6 months following the completion of 8 week therapy with lansoprazole. Recurrence rate, recurrence time, and rate of symptom improvement were not significantly different between NERD group treated with half dose and ERD group treated with full dose lansoprazole.

Oesophagitis arises when reflux of acid from the stomach into the oesophagus causes mucosal inflammation. It is a common problem and a systematic review on the optimum treatment would be useful.

To assess the effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing reflux symptoms or both. To compare adverse effects with the different treatments.

We searched MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials and the National Research Register until December 2004 and reference lists of articles. We also contacted manufacturers and researchers in the field.

Randomised controlled trials assessing the healing of oesophagitis or reflux symptoms or both. Treatment involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in comparison to another treatment regimen or to placebo for 2 and 12 weeks.

Two reviews independently assessed trial quality and extracted data.

We included 134 trials involving 35,978 oesophagitis participants. Five RCTs evaluated standard dose of PPI versus placebo in 965 participants. There was a statistically significant benefit of taking standard dose PPI therapy compared to placebo in healing of oesophagitis (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA versus placebo evaluating 1241 participants. There was statistically significant benefit of taking H2RA compared to placebo in healing of oesophagitis (RR 0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus placebo in 198 participants. There was no statistically significant benefit of taking prokinetic therapy compared to placebo in healing of oesophagitis (RR 0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was statistically significant benefit of taking PPI therapy compared to H2RA or H2RA plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59).

PPI therapy is the most effective therapy in oesophagitis but H2RA therapy is also superior to placebo. There is a paucity of evidence on prokinetic therapy but no evidence that it is superior to placebo.

This randomized, double-blind, controlled study examined whether lafutidine is superior to placebo and non-inferior to famotidine in terms of healing rates as assessed by endoscopy in Japanese patients with mild reflux esophagitis. Safety and improvement in symptoms of heartburn were also assessed.

Patients with an endoscopic diagnosis of grade A or B reflux esophagitis according to the Los Angeles classification were randomly assigned to receive lafutidine (20 mg/day), famotidine (40 mg/day), or placebo for 8 weeks.

Of the 584 patients enrolled in the study, 447 were diagnosed to have grade A or B reflux esophagitis by the Endoscopic Assessment Committee. Healing rates at 8 weeks were 71.0% (115/162) in the lafutidine group, 61.4% (86/140) in the famotidine group, and 9.7% (14/145) in the placebo group. Lafutidine was thus demonstrated to be superior to placebo and non-inferior to famotidine. As compared with placebo, lafutidine significantly improved symptoms of heartburn.

Lafutidine has a high endoscopic healing rate and improves symptoms of heartburn in patients with mild reflux esophagitis. Lafutidine is considered a promising treatment option for mild reflux esophagitis.

We investigated the 5-year clinical course in a cohort of patients with typical reflux symptoms and negative endoscopy. Prospective follow-up was conducted in patients with non-erosive reflux disease (NERD) for at least 5 years after initial evaluation with esophageal pH monitoring and upper gastrointestinal endoscopy. Within the last year of follow-up, reflux symptoms occurred in 27 of the 30 patients (90%). Twenty-five of twenty-seven symptomatic patients (93%) were on acid suppression therapy. The majority of our patients (70%) remained unchanged regarding their endoscopic status over 5 years. Progression to erosive esophagitis occurred in four patients with Los Angeles (LA) A (13%), three patients with LA B (10%), and two patients with LA C (7%). The presence of pathological acid exposure did not alter the presence of reflux symptoms over 5 years. Disease progression to erosive esophagitis occurred more frequently in patients with pathological acid exposure than those without pathological acid exposure (P= 0.025). Most NERD patients have symptoms and require acid suppression therapy 5 years after their initial diagnosis. Initial pathological acid exposure does not influence the use of acid suppression; however, it does influence the progression of NERD within 5 years of follow-up.

In an 8-week, multicenter, randomized, double-blind study, we evaluated the efficacy and tolerability of pantoprazole (0.3mg/kg [low dose (LD)], 0.6 mg/kg [medium dose (MD)], and 1.2 mg/kg [high dose (HD)]) for delayed-release oral suspension (granules) in patients 1 to 5 years with documented symptoms of gastroesophageal reflux disease (GERD) and endoscopic evidence of reflux-related erosive esophagitis (EE) or histologic esophagitis (HE) consistent with GERD. Patients with HE were randomly assigned to LD, MD, or HD, and patients with EE, to MD or HD. A daily eDiary captured 5 individual GERD symptoms. A total of 60 patients (56 HE, 4 EE) were randomized. Mean weekly GERD symptom score (WGSS, sum of weekly mean frequency scores for 5 individual GERD symptoms) for the modified intention-to-treat HE population at the final week was improved with LD ( P < .001), MD (P = .063), and HD (P < 0.001) (paired t-tests). Patients with EE were healed at week 8. Adverse event incidences did not increase with dose.

There appears to be a significant placebo response rate in clinical trials for gastro-oesophageal reflux disease. Little is known about the determinants and the circumstances associated with placebo response in the treatment of gastro-oesophageal reflux disease (GERD).

To estimate the magnitude of the placebo response rate in randomized controlled trials for GERD and to identify factors that influence this response.

A meta-analysis of randomized, double-blind, placebo-controlled trials, published in English language, which included >20 patients with GERD, treated with either a proton pump inhibitor or H(2)-receptor antagonist for at least 2 weeks. Medline, Cochrane and EMBASE databases were searched, considering only studies that reported a global response for 'heartburn'.

A total of 24 studies included 9989 patients with GERD. The pooled odds ratio (OR) for response to active treatment vs. placebo was 3.71 (95% CI: 2.78-4.96). The pooled estimate of the overall placebo response was 18.85% (range 2.94%-47.06%). Patients with erosive oesophagitis had a non-significantly lower placebo response rate than patients without it (11.87% and 18.31%, respectively; P = 0.246). Placebo response was significantly lower in studies of PPI therapy vs. studies of H(2) RAs (14.51% vs. 24.69%, respectively; P = 0.05).

The placebo response rate in randomized controlled trials for GERD is substantial. A lower placebo response was associated with the testing of PPIs, but not the presence of erosive oesophagitis.

The objective of this study was to assess the efficacy of pantoprazole in infants with gastroesophageal reflux disease (GERD).

Infants ages 1 through 11 months with GERD symptoms after 2 weeks of conservative treatment received open-label (OL) pantoprazole 1.2 mg x kg(-1) x day(-1) for 4 weeks followed by a 4-week randomized, double-blind (DB), placebo-controlled, withdrawal phase. The primary endpoint was withdrawal due to lack of efficacy in the DB phase. Mean weekly GERD symptom scores (WGSSs) were calculated from daily assessments of 5 GERD symptoms. Safety was assessed.

One hundred twenty-eight patients entered OL treatment, and 106 made up the DB modified intent-to-treat population. Mean age was 5.1 months (82% full-term, 64% male). One third of patients had a GERD diagnostic test before OL study entry. WGSSs at week 4 were similar between groups. WGSSs decreased significantly from baseline during OL therapy (P < 0.001), when all patients received pantoprazole. The decrease in WGSSs was maintained during the DB phase in both treatment groups. There was no difference in withdrawal rates due to lack of efficacy (pantoprazole 6/52; placebo 6/54) or time to withdrawal during the DB phase. The greatest between-group difference in WGSS was slightly worse with placebo at week 5 (P = 0.09), mainly due to episodes of arching back (P = 0.028). No between-group differences in adverse event frequency were noted. Serious adverse events in 8 patients were considered unrelated to treatment.

Pantoprazole significantly improved GERD symptom scores and was well tolerated. However, during the DB treatment phase, there were no significant differences noted between pantoprazole and placebo in withdrawal rates due to lack of efficacy.

The results of clinical trials with proton pump inhibitors (PPIs) are usually based on the Hetzel-Dent (HD), Savary-Miller (SM), or Los Angeles (LA) classifications to describe the severity and assess the healing of erosive oesophagitis. However, it is not known whether these classifications are comparable. The aim of this study was to review systematically the literature to compare the healing rates of erosive oesophagitis with PPIs in clinical trials assessed by the HD, SM, or LA classifications.

A recursive, English language literature search in PubMed and Cochrane databases to December 2006 was performed. Double-blind randomized control trials comparing a PPI with another PPI, an H2-RA or placebo using endoscopic assessment of the healing of oesophagitis by the HD, SM or LA, or their modified classifications at 4 or 8 weeks, were included in the study. The healing rates on treatment with the same PPI(s), and same endoscopic grade(s) were pooled and compared between different classifications using Fisher's exact test or chi2 test where appropriate.

Forty-seven studies from 965 potential citations met inclusion criteria. Seventy-eight PPI arms were identified, with 27 using HD, 29 using SM, and 22 using LA for five marketed PPIs. There was insufficient data for rabeprazole and esomeprazole (week 4 only) to compare because they were evaluated by only one classification. When data from all PPIs were pooled, regardless of baseline oesophagitis grades, the LA healing rate was significantly higher than SM and HD at both 4 and 8 weeks (74, 71, and 68% at 4 weeks and 89, 84, and 83% at 8 weeks, respectively). The distribution of different grades in study population was available only for pantoprazole where it was not significantly different between LA and SM subgroups. When analyzing data for PPI and dose, the LA classification showed a higher healing rate for omeprazole 20 mg/day and pantoprazole 40 mg/day (significant at 8 weeks), whereas healing by SM classification was significantly higher for omeprazole 40 mg/day (no data for LA) and lansoprazole 30 mg/day at 4 and 8 weeks. The healing rate by individual oesophagitis grade was not always available or robust enough for meaningful analysis. However, a difference between classifications remained.

There is a significant, but not always consistent, difference in oesophagitis healing rates with the same PPI(s) reported by the LA, SM, or HD classifications. The possible difference between grading classifications should be considered when interpreting or comparing healing rates for oesophagitis from different studies.

Intravenous (IV) proton-pump inhibitors (PPIs) are potent gastric acid suppressing agents, and their use is popular in clinical practice. Both IV and oral PPIs have similarly short half-lives, and their effects on acid secretion are similar, thus their dosing and dosage intervals appear to be interchangeable. The possible exception is when sustained high pHs are required to promote clot stabilization in bleeding peptic ulcers. Continuous infusion appears to be the only form of administration that reliably achieves these high target pHs. IV PPI is indicated in the treatment of high-risk peptic ulcers, complicated gastroesophageal reflux, stress-induced ulcer prophylaxis, Zollinger-Ellison syndrome, and whenever it is impossible or impractical to give oral therapy. The widespread use of PPIs has been controversial. IV PPIs have been linked to the development of nosocomial pneumonia in the intensive care setting and to spontaneous bacterial peritonitis in cirrhotic patients. This review discusses the use of IV PPI in different clinical scenarios, its controversies, and issues of appropriate use.

Combined multi-channel intra-luminal impedance and pH (Mll-pH) monitoring can detect gastro-esophageal reflux and identify acid and non-acid reflux (NAR) events. It can be used for patients with persistent symptoms who are having proton pump inhibitor (PPI) therapy. The aim of this study is to determine the frequency of acid reflux and NAR and to establish their relationship with persistent reflux symptoms in Japanese patients with non-erosive reflux disease (NERD) who are on a double-dose of PPI therapy.

Thirteen patients with NERD, with persistent reflux symptoms, despite taking PPI at least twice daily, were included in this study. Twenty-four-hour combined Mll-pH monitoring was carried out on all patients and reflux episodes were detected by impedance channels, located at 3, 5, 7, 9, 15 and 17 cm above the lower esophageal sphincter (LES) and classified into acid reflux and NAR, based on pH data from 5 cm above the LES. A positive symptom index (SI) was declared, if at least half of the symptoms were preceded by reflux episodes within 5 min.

A total of 916 liquid reflux episodes were detected, and a total of 171 symptoms were recorded. Eight (4.7%) of 171 symptoms were related to acid reflux, and 68 (39.8%) were related to NAR. Seven (53.8%) patients had a positive SI and in these seven patients, a total of 79 symptoms were recorded. 5 (6.3%) of the 79 symptoms were related to acid reflux and 44 (55.7%) were related to NAR.

Persistent reflux symptoms, in SI-positive patients with NERD on double-dose PPI therapy, are more likely to be associated with primarily non-acid reflux.

There has been no report on the response to proton pump inhibitor (PPI) therapy and on-demand or the relapse rate of non-erosive reflux disease (NERD) and erosive oesophagitis in Korea.

To compare the risk factors, clinical symptoms and PPI responses between patients with erosive oesophagitis and NERD patients.

A survey was performed prospectively in the erosive oesophagitis (205 patients) and NERD group (200 patients). Clinical symptoms, risk factors and PPI responses were analysed. On-demand therapy and the relapse rate of GERD symptoms were investigated during a one-year follow-up.

BMI > or = 25 (OR 3.0, 95% CI 1.1-8.3), alcohol use (OR 2.9, 95% CI 1.0-8.3), hiatal hernia (OR 5.0, 95% CI 1.2-20) and triglyceride > or =150 mg/dL (OR 4.0, 95% CI 1.7-10) were more common in the erosive oesophagitis group than in the NERD group by multivariate analysis. The ratio of oesophageal to extra-oesophageal symptoms was higher in the erosive oesophagitis group compared with the NERD group (P < 0.001). The PPI response rates at 8 weeks were different (P = 0.02); refractory rates were higher in the NERD group (16.7%) compared with the erosive oesophagitis group (6.0%). However, there was no significant difference between the two groups in on-demand therapy or the relapse rate.

These results suggest that the underlying pathogenic mechanisms of erosive oesophagitis and NERD are distinct.

The Clinical Outcomes Research Initiative database was used to evaluate ethnic trends in complicated reflux disease and suspected Barrett's esophagus among various racial groups.

Endoscopic findings for procedures performed January 2000-December 2005 for any indication and for reflux-related indications were reviewed by racial group.

Of 280,075 procedures examined, Hispanics were the most likely to have esophagitis (Hispanic 19.6%, white 17.3%, black 15.8%, Asian/Pacific Islander 9.5%, P-value<0.0001), and white subjects were most likely to have suspected BE (white 5.0%, Hispanic 2.9%, Asian/Pacific Islander 1.8%, black 1.5%, P-value<0.0001). Endoscopies performed for reflux-related indications had similar trends for esophagitis and esophageal stricture. Among reflux/Barrett's screening procedures adjusted for age and gender, Hispanics were most likely to have esophagitis (OR=1.28, P-value<0.0001) compared to Caucasians.

Our results demonstrate an association of suspected Barrett's esophagus and stricture with white patients and esophagitis with Hispanic patients. These findings need to be followed-up with further study.

Dexlansoprazole MR employs a dual delayed-release delivery system that extends drug exposure and prolongs pH control compared with lansoprazole.

To assess the efficacy and safety of dexlansoprazole MR in healing erosive oesophagitis (EO).

Patients in two identical double-blind, randomized controlled trials (n = 4092) received dexlansoprazole MR 60 or 90 mg or lansoprazole 30 mg once daily. Week 8 healing was assessed using a closed testing procedure--first for non-inferiority, then superiority, vs. lansoprazole. Secondary endpoints included week 4 healing and week 8 healing in patients with moderate-to-severe disease (Los Angeles Classification grades C and D). Life-table and crude rate analyses were performed. Symptoms and tolerability were assessed.

Dexlansoprazole MR achieved non-inferiority to lansoprazole, allowing testing for superiority. Using life-table analysis, dexlansoprazole MR healed 92-95% of patients in individual studies vs. 86-92% for lansoprazole; the differences were not statistically significant (P > 0.025). Using crude rate analysis, dexlansoprazole MR 90 mg was superior to lansoprazole in both studies and 60 mg was superior in one study. Week 4 healing was > 64% with all treatments in both studies. In an integrated analysis of 8-week healing in patients with moderate-to-severe EO, dexlansoprazole MR 90 mg was superior to lansoprazole. All treatments effectively relieved symptoms and were well tolerated.

Dexlansoprazole MR is highly effective in healing EO and offers benefits over lansoprazole, particularly in moderate-to-severe disease.

Proton pump inhibitors (PPIs) have become the mainstay of treatment for and prevention of many serious gastrointestinal diseases. Laboratory and clinical evidence suggests that the increase in gastric pH caused by PPIs may be linked to increased bacterial colonization of the stomach and may predispose patients to an increased risk for respiratory infections.

To examine the association between PPI treatment and respiratory infections.

A literature search was conducted using PubMed, MEDLINE and Cochrane databases of randomized, placebo-controlled trials evaluating the efficacy of PPIs. Studies that listed and quantified the specific adverse events of 'respiratory infection' or 'upper respiratory infection' (or equivalent), and compared their rates between PPIs and placebo were included. The chi(2) analysis was used to calculate the significance of association in individual studies and a meta-analysis of the selected studies was performed.

Of 7457 studies initially identified and 70 relevant randomized, controlled trials (RCTs) selected, seven studies met the inclusion criteria. A total of 16 comparisons for chi(2) analysis were possible given the multiple dosage arms used in several studies. PPIs included in the studies were esomeprazole, rabeprazole, pantoprazole and omeprazole. More than one-half of the studies showed a trend toward an association between PPI use and respiratory infections, although the majority of the studies failed to show a significant correlation. A single study using high-dose esomeprazole (40 mg) showed a significant association -4.3% rate of respiratory infections in the active group compared with 0% in the placebo group (P<0.05). Meta-analysis showed a trend toward an association between PPIs and respiratory infections, although it failed to reach significance (OR 1.42, 95% CI 0.86 to 2.35; P=0.17).

Although a trend was evident in both a chi(2) analysis of individual studies and a meta-analysis, the present review and meta-analysis failed to show a conclusive association between PPIs and respiratory infections. Very few RCTs actively sought out respiratory infections, which excluded the majority of RCTs identified. A well-structured, placebo-controlled prospective study would be needed to determine whether a true association between PPIs and respiratory infections exists.

Antisecretory therapies that raise intragastric pH provide the best healing of the esophageal mucosal damage that occurs in gastroesophageal reflux disease. Continuous maintenance therapy is also effective to reduce the likelihood of recurrence of esophagitis and control symptoms in the long term. Proton pump inhibitor (PPI) therapy is an effective approach for healing esophagitis and controlling symptoms. Endoscopic and surgical treatments may provide an option for patients who are refractory to PPIs in whom reflux has been clearly demonstrated. Long-term antireflux medication is often needed after surgical treatment because of persisting or recurrent pathologic reflux and symptoms. An alternative approach to controlling transient lower esophageal sphincter relaxations, such as the GABA-B agonists, deserves further study.

Gastro-oesophageal reflux disease (GORD) is one of the most common gastrointestinal diseases in the Western world and imposes a heavy burden on society. Although its prevalence in Asia is much lower, there is evidence that this is rapidly rising in Asia. The reported population prevalence of GORD in Eastern Asia ranges from 2.5% to 6.7% for at least weekly symptoms of heartburn and/or acid regurgitation. In general, Asians tend to have a milder spectrum of the disease. Most Asian patients have non-erosive GORD; erosive oesophagitis is less commonly seen than in the Western population. Complicated GORD, such as oesophageal stricture and Barrett's oesophagus, is seldom encountered. The mechanisms of GORD may be different in the Chinese population compared with the Western population. Chest pain is the most predominant extra-oesophageal manifestation of GORD in China, whereas an association with asthma has been shown in Japanese patients. The prevalence of GORD appears to be increasing and possible factors for GORD in Asian populations include Helicobacterpylori infection, obesity and increasing dietary fat intake. The adoption of a Western lifestyle in many developing Asian countries may account for the increasing prevalence of GORD. Proton pump inhibitors remain the most effective medical treatment for GORD. GORD will undoubtedly be a great challenge to clinicians both in primary care and in gastroenterology practice in the Asia-Pacific region in the coming years.

Reflux esophagitis is a common disease. Erosive reflux esophagitis is a more advanced stage of reflux esophagitis. Although death from reflux disease is uncommon, significant morbidity and mortality from complications, such as esophageal ulcer, stricture, and cancer, are not uncommon. Proton pump inhibitors are the popular medication for reflux esophagitis. The objective of this study was to determine the efficacy and safety of continuous intravenous infusion of pantoprazole in the treatment of severe erosive esophagitis.

From February 2005 to November 2006, all patients with grade 4 erosive reflux esophagitis were screened for the study. Eligible patients were randomized into two groups. Each patient in the study group received intravenous pantoprazole 80 mg loading dose over 5 min, followed by 8 mg/h intravenous infusion for 72 h, then 40 mg orally once a day for 4 days. Each patient in the control group received 40 mg pantoprazole intravenously once a day for 72 h, then orally once a day for 4 days. A second endoscopic gastrointestinal examination (EGD) was performed on treatment days 6-8 (+/-1 day if day 7 was on a weekend) to document any healing of esophagitis in either the study or the control group.

In the study group, severe erosive esophagitis healed completely in three patients and significantly in the other three by the time of the second endoscopy. In the control group, severe erosive esophagitis healed partially in five patients, and no improvement was seen at all in one patient by the time of second endoscopy. The difference in the intervention between those two groups was statistically different (P = 0.015). There were no significant complications in either group.

Severe erosive esophagitis can be completely healed in a few days if pantoprazole is given intravenously and continuously for 72 h. It is safe to give pantoprazole intravenously and continuously for treatment of severe erosive esophagitis.

The introduction of proton pump inhibitors (PPIs) has facilitated the treatment of gastrooesophageal reflux disease (GORD) enormously; however, treatment of GORD still fails in a small proportion of patients. This small proportion of therapy-resistant patients encompasses a substantial part of the working load of physicians and has become a common clinical problem. A strong variability in acid-suppressive effect of PPI treatment exists depending on compliance, Helicobacter pylori status and genotype. Nocturnal acid breakthrough does not seem to be a major determinant of refractory GORD. Recent data, however, show that PPI-refractory GORD can result from nonacid reflux episodes. It is wise to reconsider the diagnosis of GORD in patients who are PPI-refractory. Most patients in whom a PPI is not effective do not have GORD, instead they suffer from other disorders such as functional dyspepsia. If after a thorough history is taken the suspicion of GORD is still high, the next step would be to perform upper endoscopy and reflux monitoring. In case patients truly have PPI-refractory GORD, therapy can be aimed at oesophageal hypersensitivity or a surgical solution can be sought.

Since the publication of the Asia-Pacific GERD consensus in 2004, more data concerning the epidemiology and management of gastroesophageal reflux disease (GERD) have emerged. An evidence based review and update was needed.

A multidisciplinary group developed consensus statements using the Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded.

GERD is increasing in frequency in Asia. Risk factors include older age, male sex, race, family history, higher socioeconomic status, increased body mass index, and smoking. Symptomatic response to a proton pump inhibitor (PPI) test is diagnostic in patients with typical symptoms if alarm symptoms are absent. A negative pH study off therapy excludes GERD if a PPI test fails. The role for narrow band imaging, capsule endoscopy, and wireless pH monitoring has not yet been undefined. Diagnostic strategies in Asia must consider coexistent gastric cancer and peptic ulcer. Weight loss and elevation of head of bed improve reflux symptoms. PPIs are the most effective medical treatment. On-demand therapy is appropriate for nonerosive reflux disease (NERD) patients. Patients with chronic cough, laryngitis, and typical GERD symptoms should be offered twice daily PPI therapy after excluding non-GERD etiologies. Fundoplication could be offered to GERD patients when an experienced surgeon is available. Endoscopic treatment of GERD should not be offered outside clinical trials.

Further studies are needed to clarify the role of newer diagnostic modalities and endoscopic therapy. Diagnostic strategies for GERD in Asia must consider coexistent gastric cancer and peptic ulcer. PPIs remain the cornerstone of therapy.

Proton pump inhibitors (PPI) are a significant part of therapy for most acid-related diseases including gastroesophageal reflux disease, peptic ulcer disease and acute gastrointestinal bleeding. Pantoprazole is one of several available proton pump inhibitor agents and provides dose-dependent control of gastric acid secretion. Pantoprazole has indications in gastroesophageal reflux disease and peptic ulcer disease, along with indications as co-therapy in the eradication of Helicobacter pylori infection and in the control of the acid secretion associated with the Zollinger-Ellison syndrome, as well as in NSAID ulcer prevention. Pantoprazole is available in both oral and intravenous formulations. It is effective across all age groups, although only indicated in adults (and adolescents in Europe). It has been approved for use in over 100 countries and has been used for over 13 years. Pantoprazole has an excellent safety profile and a low potential for drug-drug interactions. While still widely prescribed, pantoprazole and the other branded proton pump inhibitors are under considerable market pressure from the less expensive but similarly effective generic and over-the-counter formulations of omeprazole.

Proton-pump inhibitor (PPI) failure in gastro-oesophageal reflux disease (GORD) patients has become the main reason for referral of these patients to gastroenterology specialists. It is estimated that 30% of GORD patients requiring a PPI once daily will experience treatment failure. Patients with non-erosive reflux disease are the most common GORD-related group in which once-daily PPI therapy fails. Various mechanisms have been suggested to underlie PPI failure in GORD patients. The most pertinent include weakly acidic reflux, duodenogastro-oesophageal reflux, visceral hyperalgesia, delayed gastric emptying, psychological co-morbidity and concomitant functional bowel disorders, as well as others. Because of the importance of PPI failure as a target for future drug development, further understanding of the most relevant underlying mechanisms is needed.

Several studies suggest that older adults with gastroesophageal reflux disease (GERD) are more likely to develop complications, including erosive esophagitis, but it is unclear whether erosive esophagitis is more difficult to treat in older patients. The purpose of this study was to determine if adults > or = 65 years with erosive esophagitis are more difficult to treat than younger adults. The study was a post hoc analysis of two double-blind, randomized, multicenter trials of patients with erosive esophagitis. Patients received pantoprazole 40 mg once daily, nizatidine 150 mg twice daily or placebo. Patients were evaluated for endoscopic healing at 4 and 8 weeks. Patients recorded typical reflux symptoms using a daily diary to note presence or absence of symptoms. Results showed that 44, 13 and 11 patients > or = 65 years and 210, 69, and 71 patients < 65 received pantoprazole 40 mg daily, nizatidine 150 mg twice daily, or placebo, respectively. Eighty-six percent (86%[76%, 97% CI]) of older and 83% (78%, 88% CI) of younger pantoprazole-treated patients were healed at 8 weeks; 46% (19%, 73% CI) and 35% (24%, 46% CI) of nizatidine-treated and 27% (1%, 54% CI) and 34% (23%, 45% CI) of placebo-treated were healed at 8 weeks. Median time to persistent absence of GERD-related symptoms was similar for older and younger patients treated with pantoprazole. We conclude that older patients with erosive esophagitis do not appear to have more difficult-to-treat disease. Erosive esophagitis is effectively healed and GERD symptoms are controlled in older patients using pantoprazole 40 mg daily.

Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease that can progress to major complications. Affected patients have poorer health-related quality of life than the general population. As GERD requires continued therapy to prevent relapse and complications, most patients with erosive esophagitis require long-term acid suppressive treatment. Thus GERD results in a significant cost burden and poor health-related quality of life. The effective treatment of GERD provides symptom resolution and high rates of remission in erosive esophagitis, lowers the incidence of GERD complications, improves health-related quality of life, and reduces the cost of this disease. Proton pump inhibitors are accepted as the most effective initial and maintenance treatment for GERD. Oral pantoprazole is a safe, well tolerated and effective initial and maintenance treatment for patients with nonerosive GERD or erosive esophagitis. Oral pantoprazole has greater efficacy than histamine H(2)-receptor antagonists and generally similar efficacy to other proton pump inhibitors for the initial and maintenance treatment of GERD. In addition, oral pantoprazole has been shown to improve the quality of life of patients with GERD and is associated with high levels of patient satisfaction with therapy. GERD appears to be more common and more severe in the elderly, and pantoprazole has shown to be an effective treatment for this at-risk population.