Weeks Of Proton Pump Inhibitor Research Articles

Submucosal Clustered Brownish Microvessels Based on NBI Endoscopy: A Characteristic of LPR.

This study aimed to analyze the characteristics of laryngopharyngeal reflux (LPR) by using narrow band imaging (NBI) endoscopy. A prospective study. A large-volume practice with tertiary care providers. A total of 67 patients with suspected LPR who underwent 24-hour multichannel intraluminal impedance-pH monitoring were included from June 2020 to March 2022. Manifestations of NBI endoscopy included submucosal clustered brownish microvessels (CBMs), spotted brownish microvessels, and no special microvessels; the latter 2 formed the non-CBM group. The manifestations of all patients and their changes were observed after 8 weeks of proton pump inhibitor and symptomatic treatment for patients with LPR, and symptomatic treatment for patients without LPR. According to the results of 24-hour multichannel intraluminal impedance-pH monitoring, the incidence of submucosal CBMs was significantly higher in patients with LPR (30 cases) than in those without LPR (37 cases, P < .001), particularly in the posterior cricoid area (P < .001). Besides Reflux Finding Score, the incidence of signs such as subglottic edema and vocal fold edema was significantly higher in the CBM group than the non-CBM group (P < .05). Finally, 22 patients with LPR (91.7%) and only 2 patients without LPR (28.6%) underwent a transformation from CBMs to spotted brownish microvessels after continuous medication for 8 weeks in the CBM group (χ2 = 15.916, P < .001), while no significant change was observed in patients with or without LPR in the non-CBM group (P > .05). Submucosal CBMs in the posterior cricoid area under NBI endoscopy may be a characteristic of LPR.

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response. This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks. Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01). This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Reliability and responsiveness of endoscopic disease activity assessment in eosinophilic esophagitis

Endoscopic outcomes have become important measures of eosinophilic esophagitis (EoE) disease activity, including as an endpoint in randomized controlled trials (RCTs). We evaluated the operating properties of endoscopic measures for use in EoE RCTs. Modified Research and Development/University of California Los Angeles appropriateness methods and a panel of 15 international EoE experts identified endoscopic items and definitions with face validity that were used in a 2-round voting process to define simplified (all items graded as absent or present) and expanded versions (additional grades for edema, furrows, and/or exudates) of the EoE Endoscopic Reference Score (EREFS). Inter- and intrarater reliability of these instruments (expressed as intraclass correlation coefficients [ICC]) were evaluated using paired endoscopy video assessments of 2 blinded central readers in patients before and after 8 weeks of proton pump inhibitors, swallowed topical corticosteroids, or dietary elimination. Responsiveness was measured using the standardized effect size (SES). The appropriateness of 41 statements relevant to EoE endoscopic activity (endoscopic items, item definitions and grading, and other considerations relevant for endoscopy) was considered. The original and expanded EREFS demonstrated moderate-to-substantial inter-rater reliability (ICCs of .472-.736 and .469-.763, respectively) and moderate-to-almost perfect intrarater reliability (ICCs of .580-.828 and .581-.828, respectively). Strictures were least reliably assessed (ICC, .072-.385). The original EREFS was highly responsive (SES, 1.126 [95%confidence interval {CI}, .757-1.534]), although both expanded versions of EREFS, scored based on worst affected area, were numerically most responsive to treatment (expanded furrows: SES, 1.229 [95% CI, .858-1.643]; all items expanded: SES, 1.252 [95% CI, .880-1.667]). The EREFS and its modifications were not more reliably scored by segment and also not more responsive when proximal and distal EREFSs were summed. EREFS and its modifications were reliable and responsive, and the original or expanded versions of the EREFS may be preferred in RCTs. Disease activity scored based on the worst affected area optimizes reliability and responsiveness.

Development and Psychometric Assessment of a Self-evaluation Questionnaire for Gastroesophageal Reflux Disease

Background/AimsThere is uncertainty about how to measure outcomes reported by patients in gastroesophageal reflux disease (GERD). This study was conducted to develop an instrument and to determine of the definition of respondent for a patient reported outcomes to assess the efficacy of a treatment used for GERD treatment.MethodsA structural process has developed a self-evaluation questionnaire for GERD (SEQ-GERD); health-related quality of life questionnaire for GERD (GERD-QOL) was translated through cross-cultural validation. Two-week reproducibility was evaluated and construct validity was assessed by correlating the SEQ-GERD with the Patient Assessment of Gastrointestinal Disorders (PAGI-SYM), the reflux disease questionnaire (RDQ), and GERD-QOL. Changes in SEQ-GERD scores were compared to assess the discriminative validity following 4 weeks of proton pump inhibitor administration.ResultsA total of 83 Korean patients were included (mean age 46 ± 14 years, females 61.4%). The internal consistency of the 19-item SEQ-GERD was good (alpha = 0.60–0.94) and the test–retest reliability was high (intra-class correlation coefficient = 0.67–0.95). The SEQ-GERD highly correlated with the GERD domain of the PAGI-SYM (correlation coefficient r = 0.894, P < 0.001), the RDQ-GERD (r = 0.877, P < 0.001), and GERD-QOL (r =−0.536, P < 0.05). SEQ-GERD scores significantly varied according to the overall treatment effectiveness scale of drug responsiveness and significantly decreased after drug treatment (mean differences according to the overall treatment effectiveness scale, P = 0.020).ConclusionThis study supports that SEQ-GERD is reliable and valid, and can be used to evaluate the treatment response in patients with GERD.

Is It Useful to Administer Probiotics Together With Proton Pump Inhibitors in Children With Gastroesophageal Reflux?

Background/AimsGastroesophageal reflux disease (GERD) is a frequent condition diagnosed in children and treated with proton pump inhibitors (PPI). Long-term PPI administration can alter intestinal bacterial population by suppressing the gastric acid barrier and may cause diarrhea. The aim of this study is to evaluate the prevalence of small intestinal bacterial overgrowth assessed by glucose hydrogen breath test among children that received 12 weeks of PPI with or without probiotics (Lactobacillus reuteri DSM 17938) associated, compared to controls.MethodsGlucose hydrogen breath test was performed before PPI treatment and after 12 weeks of PPI treatment to 128 consecutive children with GERD (1–18 years old) and a control group (120 healthy children). The children with GERD were randomized into 2 groups: placebo group (64 who received PPI and placebo for 12 weeks) and probiotics group (64 who received PPI and probiotics for 12 weeks).ResultsAfter 12 weeks of treatment, dysbiosis was detected among 56.2% of children from placebo group (36/64), compared to 6.2% of children from the probiotics group (4/64, P < 0.001). Bacterial overgrowth was detected in 5% of controls (6/120). Probiotics group had a lower prevalence of dysbiosis, similar to controls (P = 0.740).ConclusionProbiotics administration decreased the rate of dysbiosis among children treated with PPI.

Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis

ABSTRACTObjective: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countriesMethod: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest.Results: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation.Conclusion: Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis

Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Dysphagia in Gastroesophageal Reflux Disease (Gerd)

Abstract Introduction. Dysphagia is considered an alarm symptom, raising the question of stricture or malignancy. We sought to determine the prevalence and severity of dysphagia and correlation with severity of gastroesophageal reflux disease and its response to therapy. Methods. A total of 642 patients with endoscopically confirmed erosive esophagitis (Los Angeles grades AD). Esophagitis was classified as mild (grade A or B) or severe (grade C or D). Results. At baseline, of 642 patients 37% had dysphagia, 43% had severe esophagitis, and 35% mild esophagitis (odds ratio, 1.39; 95% confidence interval, 1.27-1.51, p&lt;0.001). Dysphagia resolved in 73% of patients after 4 weeks of proton pump inhibitor (PPI) treatment. Resolution of dysphagia was associated with a mean healing rate of 87% acrossall treatments. Seventeen percent of patients reported persistent dysphagia, and in these patients the healing rates were decreased significantly (mean 72%; p&lt;0.0001). Conclusions. Dysphagia is common in patients with erosive esophagitis but is not a reliable clinical predictor of severe erosive esophagitis. Dysphagia resolved with PPI therapy in most cases, but persistent dysphagia may indicate failed healing.

Early Referral for Esophageal pH Monitoring Is More Cost-Effective Than Prolonged Empiric Trials of Proton-Pump Inhibitors for Suspected Gastroesophageal Reflux Disease

IntroductionThe most cost-effective diagnostic algorithm for gastroesophageal reflux disease (GERD) remains controversial. We hypothesized that prompt referral for esophageal pH monitoring is more cost-effective than prolonged empiric courses of proton-pump inhibitors (PPIs). DiscussionA cost model was created based on a cohort of 100 patients with possible GERD who underwent pH monitoring. The additional costs incurred from pH monitoring were compared to the potential savings from avoiding unnecessary PPI usage in patients with a negative pH study. The costs of PPI therapy reach equivalence with pH monitoring after 6.4 to 23.7 weeks, depending on the PPI regimen. A total of 21,411 weeks of PPIs were prescribed beyond the recommended 8-week trial, of which 32 % were for patients who had a negative 24-h pH monitoring study. If the sensitivity of pH monitoring was 96 %, early referral for pH monitoring would have saved between $1,197 and $6,303 per patient over 10 years. This strategy remains cost-effective as long as the sensitivity of pH monitoring is above 35 %. Prompt referral for pH monitoring after a brief empiric PPI trial is a more cost-effective strategy than prolonged empiric PPI trials for patients with both esophageal and extraesophageal GERD symptoms.

A Case-Control Study of Esomeprazole plus Rebamipide vs. Omeprazole plus Rebamipide on Post-ESD Gastric Ulcers

ObjectivesEndoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. There is no report about the efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing comparing with omeprazole plus rebamipide.Methods:We reviewed the medical records of patients who underwent ESD for gastric neoplasia. We conducted a case-control study to compare the healing rates within 4 weeks effected by esomeprazole plus rebamipide (group E) and omeprazole plus rebamipide (group O). The sizes of the artificial ulcers were divided into normal-sized or large-sized.Results:The baseline characteristics did not differ significantly between the two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7% of patients after 4 weeks of treatment in the group E and O, respectively. In large-sized artificial ulcers, the healing rate of stage S1 in group E is significantly higher than that in group O in 4 weeks.(25% VS 0%:P = 0.02)Conclusions:The safety and efficacy profiles of esomeprazole plus rebamipide and omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.

The Management and Endoscopic Outcomes of Dyspepsia in Low-Risk Patients

Purpose: Dyspepsia is frequently encountered by primary care providers (PCP) and gastroenterologists (GI). Upper endoscopy (EGD) may be useful in the management of dyspepsia. Current published guidelines state that low-risk patients (age≤55 and without “alarm features”) should receive empiric proton pump inhibitor (PPI) treatment for 4-8 weeks and H. pylori (HP) testing/treatment prior to EGD. The rates of adherence to dyspepsia practice guidelines by both PCP and GI are unclear. Furthermore, EGD outcomes of low-risk dyspeptic patients as defined by current guidelines have not been assessed. The aims of this study are to evaluate dyspepsia management and guideline adherence prior to EGD referral in low-risk patients by PCP and GI, and to assess EGD outcomes among this population. Methods: This was a retrospective cohort study of patients who underwent EGD for dyspepsia over a 6-month period at a tertiary care center. Subjects with age>55, “alarm features” (weight loss, dysphagia, vomiting, signs of bleeding, or family history of upper gastrointestinal cancer), and other indications for EGD (anemia, odynophagia, abnormal imaging, malabsorption, or prior abnormal EGD) were excluded. Patient medical records were reviewed for demographic data, clinical history, PPI use and HP status prior to EGD, and results from EGD and pathology. Adequacy of PPI trial and HP testing prior to EGD were compared between PCP- and GI-referred patients using Chi-Squared test. Results: 1296 EGD were performed during the study period with 378 (29.2%) being referred for dyspepsia. Among dyspeptic patients, 124 (32.8%) met criteria for inclusion in the study. Prior to EGD, a significant proportion of low-risk patients did not receive adequate trial of PPI (Table 1). Notably, 53 (42.7%) patients did not receive at least 4 weeks of PPI and 44 (35.5%) were not tested for HP. Rates of guideline adherence were similar between PCP and GI referrals. Among this low-risk group, gastritis (n=47, 46.8%) was the most common EGD finding, while ulcers (n=5, 4%), Barrett's esophagus (n=2, 1.6%), and malignancy (n=0) were rare.Table 1: No Caption available.Conclusion: Adherence to practice guidelines for dyspepsia was low for both PCP and GI. Among low-risk patients (age≤55 and without alarm features), 42.7% did not receive at least 4 weeks of PPI treatment and 35.5% were not tested for HP prior to EGD referral. Within this population, significant findings on EGD were rare, supporting the use of current guidelines.

Clinical trial: rebamipide promotes gastric ulcer healing by proton pump inhibitor after endoscopic submucosal dissection—a randomized controlled study

Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. We examined the efficacy of a combination therapy of PPI and rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing. Patients were randomly assigned to either the PPI and rebamipide therapy or the PPI alone. Sixty-two consecutive patients with gastric tumors gave informed consent for enrolling in the study. In all cases, the estimated size of the post-ESD ulcer was larger than 20 mm. Oral administration of the drug was started on the 2nd day post-ESD and continued to the 28th day. All patients received the assigned pharmaceuticals and adhered well to the treatment regimen for 28 days. The endpoint ulcers reached S1 (scar stage) in 11/31 (36%) patients in the PPI-only group and in 21/31 (68%) in the combination group (P = 0.010). The combination of PPI plus rebamipide was more effective than the PPI alone for treating ulcers larger than 20 mm within 4 weeks after ESD.

Should Patients with Severe Reflux Esophagitis Undergo Repeat Endoscopy After 8 to 12 Weeks of Proton Pump Inhibitor (PPI) Therapy to Exclude Underlying Barrettʼs Esophagus (BE)? Preliminary Results from Two Prospective Trials

Purpose: Retrospective reports have suggested that 5-25% of patients with reflux esophagitis (RE) at baseline, who undergo repeat esophagogastroduodenoscopy (EGD) following PPI therapy, have concomitant BE—most short in segment length. Given the retrospective nature of these reports, it is not clear how many patients had intestinal metaplasia of the cardia misdiagnosed as BE. We are recruiting subjects with RE into 2 prospective studies, each with different primary aims. A uniting secondary aim is to assess the prevalence of suspected and unsuspected BE in patients with RE treated with PPI therapy for 8-12 weeks. Methods: Subjects from two studies were pooled for this analysis. Study A's primary aim is to assess the role of compliance in GERD symptom resolution in subjects with Los Angeles (LA) grades B, C and D RE. Follow-up EGD was left to the discretion of the primary physician. Study B's primary aim is to compare the percent of subjects with LA grades C and D RE who achieve resolution after 8 weeks PPI treatment (morning vs. bedtime dosing). Follow-up EGD was mandatory. Endoscopists were not informed of the subject's participation in a research study. Subjects previously diagnosed with BE were excluded from this analysis. Results: Study A recruited 50 subjects [25 (50%) male, mean age 56 (SD 15), B=40, C=5, D=5], of whom 10 [4 (40%) male, mean age 58 (SD 15), B=7, C=1, D=2] had a follow-up EGD. To date, Study B has recruited 57 subjects of which 45 [31 (69%) male, mean age 56.8 (SD 13), C=27, D=18] have undergone a follow-up EGD. Thus, 55 subjects (B=7, C=28, D=20, BMI 31.5) have undergone baseline and follow-up EGD after 8-12 weeks PPI therapy and are the subjects of this analysis. Five (C=3, D=2) of 55 (9%) subjects were newly diagnosed with biopsy-proven BE at follow-up EGD [overall 2 (40%) male; mean age 55 (SD 11); BMI 35.3, short (< 3 cm) N=4 (2 male, lengths ranging from islands to 2 cm); long (>3 cm) N=1 (0 male, 5 cm). In 5 (100%) cases, BE was unexpected. The BMI of the 50 RE subjects who did not have BE at follow up EGD was 31.3 (p=0.16). Conclusion: In this prospective study, 10% of subjects with LA grade C or D RE had concomitant BE that could not be recognized during the initial endoscopy in the setting of diffuse inflammation. Unsuspected BE was not found in subjects with LA grade B RE. Subjects with RE and BE tended to be more obese than subjects with RE alone, although this finding did not achieve statistical significance. These prospective results suggest that patients with severe LA grade C or D disease undergo repeat EGD after 8 to 12 weeks of PPI therapy to exclude underlying BE. Disclosure: Dr Alexander - Consulting Meritigae Pharmacia and Wyeth; Research Funding - Merck, Novartis, and Glaxo Smith Kline. Dr Howden - Consultant - Santarus and Takeda, Speakers Bureau - Santarus and Takeda. Dr Romero - Grant/Research Support and Consultant, Santarus, makers of omeprazole/sodium bicarbonate (Zegerid), and Grant/Research Support and Consultant, AstraZeneca, makers of esomeprazole (Nexium). No disclosures for: Drs Jung, Francis, Arora, Grothe, Enders, Dabade, Murray, Farrugia, Kane, Buttar, Crowell, Locke, Wong Kee Song, Wang, Prasad, Sharma, Namasivayam, and Achem, and Mrs Geno, Fredericksen, and Diehl. This research was supported by an industry grant from AstraZeneca funded Study A in this abstract. They supplied esomeprazole. Santarus funded Study B in this abstract. They supplied omeprazole/sodium bicarbonate. Note, they are both referred to as PPI therapy. The names of their products are not described in the abstract.

Small Bowel Injury by Low-Dose Enteric-Coated Aspirin and Treatment With Misoprostol: A Pilot Study

With capsule endoscopy, the ulcerogenic effect of low-dose enteric-coated aspirin on the small bowel and the therapeutic effect of misoprostol on intestinal injury were evaluated. Eleven patients who developed gastric ulcers while undergoing low-dose enteric-coated aspirin therapy were enrolled. They continued aspirin therapy while taking proton pump inhibitors (PPIs) for 8 weeks to heal the gastric ulcers. Then misoprostol 200 microg 4 times a day was administered instead of PPIs for 8 weeks. When the patients could not tolerate misoprostol as a result of side effects, they received another 8 weeks of PPI therapy. Capsule endoscopy performed after 8 weeks of PPI treatment identified red spots and mucosal breaks in 100% (11/11) and 90.9% (10/11) of patients, respectively. In 7 patients who completed the study protocol, misoprostol significantly decreased the median number of red spots and mucosal breaks, with complete disappearance of mucosal breaks in 4 patients. Intestinal lesions tended not to heal in 3 patients who discontinued misoprostol. Low-dose enteric-coated aspirin frequently damages the small intestine, and misoprostol is effective in the treatment of aspirin-induced enteropathy.

Systematic review: rebound acid hypersecretion after therapy with proton pump inhibitors

The occurrence and the clinical relevance of rebound acid hypersecretion after discontinuation of proton pump inhibitors is unclear. To perform a systematic review of rebound acid hypersecretion after discontinuation of proton pump inhibitors. PubMed, Embase and Central were searched up to October 2005 with indexed terms. Eight studies were included, sample size was 6-32. The studies used both basal and stimulated acid output as parameters to study rebound acid hypersecretion and assessed these at different time points and with variable methods. Five studies (including four randomized studies) did not find any evidence for rebound acid hypersecretion after proton pump inhibitor therapy. Of the remaining three studies, the duration of proton pump inhibitor therapy was the longest and two of these studies were the only to assess Helicobacter pylori status of their study subjects. These two studies suggested that rebound acid hypersecretion may occur in H. pylori-negatives after 8 weeks of proton pump inhibitors. Studies that have investigated rebound acid hypersecretion after cessation of proton pump inhibitor treatment are heterogenic in design, methods and outcome. There is some evidence from uncontrolled trials for an increased capacity to secrete acid in H. pylori-negative subjects after 8 weeks of treatment. There is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy.

Dysphagia in patients with erosive esophagitis: Prevalence, severity, and response to proton pump inhibitor treatment

Background & Aims: Dysphagia is considered an alarm symptom, raising the question of stricture or malignancy. We sought to determine the prevalence and severity of dysphagia in patients with uncomplicated erosive esophagitis and its response to therapy. Methods: A total of 11,945 patients with endoscopically confirmed erosive esophagitis (Los Angeles grades A—D) participated in 5 double—blind, randomized, clinical trials evaluating the efficacy of up to 8 weeks of treatment with either once—daily esomeprazole 40 mg (n = 5068), esomeprazole 20 mg (n = 1243), omeprazole 20 mg (n = 3018), or lansoprazole 30 mg (n = 2616). The severity of dysphagia (4-point scale) was rated at baseline and at week 4. Esophagitis was classified as mild (grade A or B) or severe (grade C or D). Results: At baseline, 4449 of 11,945 patients (37%) had dysphagia—43% of patients with severe esophagitis, and 35% of patients with mild esophagitis (odds ratio, 1.39; 95% confidence interval, 1.27–1.51, P < 0.001). Dysphagia resolved in 83% of patients after 4 weeks of proton pump inhibitor (PPI) treatment. Resolution of dysphagia was associated with a mean healing rate of 90% across all treatments. Seventeen percent of patients reported persistent dysphagia, and in these patients the healing rates were decreased significantly (mean 72%; P < 0.0001). Conclusions: Dysphagia is common in patients with erosive esophagitis but is not a reliable clinical predictor of severe erosive esophagitis. Dysphagia resolved with PPI therapy in most cases, but persistent dysphagia may indicate failed healing.

Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough

Adding histamine 2 receptor antagonists (H2RAs) to proton pump inhibitor (PPI) therapy is a common practice to block nocturnal acid breakthrough (NAB). Controversy exists over its efficacy because of H2RA intolerance. No prospective study has addressed this issue. Twenty-three healthy volunteers and 20 gastroesophageal reflux disease (GERD) patients were studied. Ambulatory pH monitoring was performed with one electrode in the gastric fundus and the other 5 cm above the lower esophageal sphincter. Baseline pH testing was performed and repeated after 2 weeks on PPI twice daily before meals (omeprazole 20 mg). All subjects then received 28 days of PPI plus H2RA Qhs (ranitidine 300 mg) with repeat pH testing on days 1, 7, and 28. Eighteen controls and 16 GERD patients completed all 5 studies. Compared with baseline, all 4 medication regimens decreased supine % time pH < 4 (P = 0.001). The administration of PPI + 1 day of H2RA was the only therapy that significantly decreased % time gastric pH < 4 for the supine period compared with PPI twice daily alone (P < 0.001). There was no difference in % time supine gastric pH < 4 between 2 weeks of PPI twice daily alone and either 1 week or 1 month of PPI + bedtime H2RA. The combination of H2RA and PPI therapy reduced NAB only with the introduction of therapy. Because of H2RA tolerance, there is no difference in acid suppression between PPI twice daily and PPI twice daily + H2RA after 1 week of combination therapy.