Esophagogastric junction outflow obstruction is often associated with coexistent abnormal esophageal body motility and abnormal bolus transit.

Currently, the diagnosis of esophageal motility disorders is in part based upon a hierarchical algorithm in which abnormalities of the esophagogastric junction (EGJ) is prioritized. An important metric in evaluating the EGJ is the integrated relaxation pressure (IRP). Patients who do not have achalasia but are found to have an elevated IRP are diagnosed with EGJ outflow obstruction. It has been our observation that a subset of these patients also has a second named motility disorder and may also have abnormal bolus transit. The aim of this study is to determine the frequency of abnormal body motility and or abnormal bolus movement in patients with EGJ outflow obstruction. Further, in an effort to evaluate the potential clinical value in measuring bolus transit as a complement to esophageal manometry, specifically in patients with EGJ outflow obstruction, we analyzed the presenting symptoms of these patients. A total of 807 patients with a mean age of 53 years completed esophageal function testing with impedance monitoring and high-resolution manometry between January 2012 and October 2016. There were 74 patients with achalasia who were excluded from the study. Of the remaining 733 patients, 138 (19%) had an elevated IRP and were given a diagnosis of EGJ outflow obstruction. Among these patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (ineffective esophageal motility = 28, distal esophageal spasm = 19, Jackhammer = 6), of which 44 (76%) had abnormal bolus transit to liquids, viscous, or both. In contrast, there were 82 patients with EGJ outflow obstruction and normal esophageal motility, of which 33 (40%) had abnormal bolus transit. Patients with preserved esophageal motility and EGJ outflow obstruction were then evaluated. Of the 733 patients, 299 (40%) had intact esophageal motility. Of the 299 patients with normal esophageal motility, 56 patients had an elevated IRP, of which 16 (28%) had abnormal bolus transit. There were 243 (33%) patients with intact esophageal motility and normal IRP. Of these, 56 (23%) patients had abnormal bolus transit. Among patients with abnormal bolus transit, the two most commonly presenting symptoms were dysphagia and heartburn. A substantial percentage of patients with EGJ outflow obstruction have abnormal esophageal body motility and or abnormal bolus transit. The clinical implications of EGJ outflow obstruction need to be further elucidated as current criteria do not allow for the description of other abnormalities in esophageal motility and bolus transit among patients who are given the diagnosis of EGJ outflow obstruction.

Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis.

AIM: To assess the relationship between the percentage of time intragastric pH >4.0 and healing of erosive oesophagitis. METHODS: In this proof-of-concept study, adults with endoscopically verified Los Angeles grade C or grade D erosive oesophagitis were randomly assigned to oral esomeprazole 10 or 40 mg once daily for 4 weeks. On day 5, patients underwent 24-h pH monitoring. At 4 weeks, erosive oesophagitis healing status was endoscopically assessed. Investigators scored gastro-oesophageal reflux disease symptoms on a 4-point scale [none to severe (0-3)] before and 4 weeks after treatment. The percentage of time intragastric pH was >4.0 and healing status were correlated and tested for significance using a Spearman rank correlation (r). RESULTS: 103 patients had evaluable data (mean age, 48.7 years; 65% men). Mean percentages of time with intragastric pH >4.0 on day 5 in patients with healed and unhealed erosive oesophagitis were 61% and 42%, respectively (P = 0.0002), indicating that erosive oesophagitis healing rates were positively related to the percentage of time intragastric pH was >4.0. Greater intragastric acid control correlated with lower final daytime and night-time heartburn and acid regurgitation symptom scores (r = -0.029, -0.029 and -0.021; P = 0.003, 0.003 and 0.032, respectively). CONCLUSION: A positive relationship between intragastric acid control and erosive oesophagitis healing was demonstrated.

Comparison of the effects of immediate-release omeprazole oral suspension, delayed-release lansoprazole capsules and delayed-release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night-time GERD symptoms.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) patients on proton pump inhibitors before breakfast or dinner have acid recovery at night. Bedtime immediate-release omeprazole (IR-OME) demonstrated better control of nocturnal pH than pantoprazole before dinner. AIM: To compare repeated once daily bedtime dosing of IR-OME, lansoprazole and esomeprazole on nocturnal gastric acidity. METHODS: Open-label, randomized, crossover study enrolling 54 patients with nocturnal GERD symptoms comparing IR-OME, lansoprazole and esomeprazole at steady state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH > 4 and median gastric pH. RESULTS: Onset of nocturnal acid control with IR-OME was rapid. During the first half of the night, percentage of time with gastric pH > 4 and median gastric pH were significantly higher after IR-OME compared to esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8-h night-time period, acid control with IR-OME was significantly better than lansoprazole (P < 0.001), and comparable to esomeprazole. IR-OME reduced NAB compared with esomeprazole and lansoprazole (61% vs. 92% and 92%; P < 0.001, both comparisons). CONCLUSIONS: Bedtime IR-OME provided more rapid control of night-time gastric pH and decreased NAB compared with esomeprazole and lansoprazole. Nocturnal acid control with IR-OME was superior to lansoprazole and comparable to esomeprazole. Bedtime dosing with IR-OME may be effective for patients with night-time heartburn.

Body mass index greater than 35 is associated with severe Clostridium difficile infection.

BACKGROUND: Obesity has been implicated in the acquisition of Clostridium difficile infections (CDI), however, no study has investigated whether there is a correlation between body mass index (BMI) and CDI severity. AIM: To determine whether obesity, as measured by BMI correlates with severe hospital-onset or community-onset CDI. METHODS: Patients admitted with CDI at a tertiary-care center from January 2013 to June 2015 were identified. The cohort was stratified by onset of disease using the National Healthcare Safety Network criteria, and by severity using the 2013 American College of Gastroenterology guidelines. Multivariate logistic regression was used to determine independent predictors of severe CDI. RESULTS: A total of 196 met the inclusion criteria, of which 57.1% (112) met criteria for severe disease. Overall, BMI >35 kg/m2 was 1.7-fold more likely to be associated with severe CDI compared to a BMI 20-35 kg/m2 (P < 0.005), and was an independent predictor of severe CDI (P = 0.038). In patients with community-onset-CDI and hospital-onset-CDI, a BMI >35 kg/m2 was associated with a 1.96-fold and 1.48 greater rate of severe CDI compared to a BMI 20-35 kg/m2 (P = 0.004 and 0.048), and was an independent predictor of severe CDI in these cohorts (P = 0.039 and 0.027) respectively. CONCLUSION: This study has identified an association between body mass index and Clostridium difficile infection severity. A BMI>35 kg/m2 is an independent risk factor for severe community-onset and hospital-onset Clostridium difficile infections.

Benchmarks for the interpretation of esophageal high-resolution manometry.

BACKGROUND: Competent interpretation of esophageal high-resolution manometry (HRM) is integral to a quality study. Currently, methods to assess physician competency for the interpretation of esophageal HRM do not exist. The aim of this study was to use formal techniques to (i) develop an HRM interpretation exam, and (ii) establish minimum competence benchmarks for HRM interpretation skills at the trainee, physician interpreter, and master level. METHODS: A total of 29 physicians from 8 academic centers participated in the study: 9 content experts separated into 2 study groups-expert test-takers (n=7) and judges (n=2), and 20 HRM inexperienced trainees ("trainee test-taker"; n=20). We designed the HRM interpretation exam based on expert consensus. Expert and trainee test-takers (n=27) completed the exam. According to the modified Angoff method, the judges reviewed the test-taker performance and established minimum competency cut scores for HRM interpretation skills. KEY RESULTS: The HRM interpretation exam consists of 22 HRM cases with 8 HRM interpretation skills per case: identification of pressure inversion point, hiatal hernia >3 cm, integrated relaxation pressure, distal contractile integral, distal latency, peristaltic integrity, pressurization pattern, and diagnosis. Based on the modified Angoff method, minimum cut scores for HRM interpretation skills at the trainee, physician interpreter, and master level ranged from 65-80%, 85-90% (with the exception of peristaltic integrity), and 90-95%, respectively. CONCLUSIONS & INFERENCES: Using a formal standard setting technique, we established minimum cut scores for eight HRM interpretation skills across interpreter levels. This examination and associated cut scores can be applied in clinical practice to judge competency.

Review article: intragastric and oesophageal pH monitoring in patients with gastro-oesophageal reflux disease.

Treatment of gastro-oesophageal reflux disease with acid suppressive therapy is based on the principle that effective control of intragastric pH (a marker of acid control) leads to healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease-associated symptoms. Most patients with gastro-oesophageal reflux disease can be managed successfully with current antisecretory therapy. In difficult-to-treat patients, oesophageal pH monitoring is a useful technique to assess pH control and to investigate the association of reflux with refractory symptoms. Intragastric pH monitoring allows direct assessment of acid suppression achieved with an agent, and is the most useful for head-to-head comparisons of antisecretory therapies, evaluating variability in individual gastric pH response, assessing dose timing and food effect, and determining alternate dosing strategies; as such, it is useful in the research laboratory, and may be useful clinically to guide clinicians in dose titration and in evaluating the effect of switching agents. This article reviews these and other uses of these tests in an effort to explore the question of how to optimally use oesophageal pH monitoring and gastric pH monitoring in patient management.

Review article: acid-related disease--what are the unmet clinical needs?

Proton pump inhibitors have dramatically improved the management options available for patients with acid-related disorders. In patients with gastro-oesophageal reflux disease, currently available proton pump inhibitors provide an excellent outcome for the majority; however, they do not provide optimal pH control in many. Proton pump inhibitors co-therapy reduces, but does not eliminate, the risk of gastrointestinal ulcers and complications in patients taking non-steroidal anti-inflammatory drugs, while in patients with upper gastrointestinal bleeding, it may be difficult to reach and maintain the current therapeutic target of intragastric pH of 6-7. This article reviews the effectiveness of current antisecretory therapy in these three acid-related diseases and areas of unmet clinical need. The potential role of a proton pump inhibitor with an extended duration of action and enhanced acid control from a single daily dose, particularly improved control at night, is discussed. Finally, therapy that could be administered without regard to time of day and/or food intake would offer dosing flexibility and thus have a positive effect on patients' compliance.

Functional disorders of swallowing.

Swallowing involves complex coordination of the neuromuscular anatomy and physiology of the oropharynx and esophagus, controlled by the enteric and central nervous systems. Dysphagia is classified as either oropharyngeal or esophageal and results from mechanical or structural disturbances. Videofluoroscopy, fiberoptic endoscopic evaluation of swallowing, barium swallow, manometry, and endoscopy are common modalities utilized in diagnosis, but none is as important as a patient's history. Functional dysphagia is a diagnosis of exclusion and is based on Rome criteria. Its mechanism is unknown but potentially related to visceral hypersensitivity, inappropriate pain perception, or unidentified contraction abnormalities. Its management is mainly supportive; however, there is literature to suggest, but not confirm, benefit with the use of antidepressants. Continued understanding of functional dysphagia and other functional esophageal disorders, including globus sensation, will require further investigation into diagnostic algorithms and finding treatment methods.

Review article: putting immediate-release proton-pump inhibitors into clinical practice--improving nocturnal acid control and avoiding the possible complications of excessive acid exposure.

Nocturnal gastro-oesphageal reflux is an under-appreciated clinical challenge. This condition may cause symptoms such as nocturnal heartburn, or it may be asymptomatic. In addition, patients may experience sleep disturbances that can potentially lead to complications such as erosive oesophagitis and Barrett's oesophagus, and may be a risk factor for development of oesophageal adenocarcinoma. Delayed-release proton-pump inhibitors (PPIs) have traditionally been effective in treating both daytime and night-time reflux symptoms, but are limited in control of nocturnal acidity by their pharmacodynamic characteristics. This narrative review addresses the prevalence, impact and pharmacologic approaches used to control nocturnal acidity. Methods to optimize nocturnal acid control include careful attention to dosing schedule, using higher doses of PPIs, adding an histamine H2-receptor antagonist at bedtime to once or twice daily delayed-release PPI, or using immediate-release omeprazole (Zegerid powder for oral suspension; Santarus, Inc., San Diego, CA, USA). This new formulation appears to provide sustained control of intragastric pH at steady state, and when dosed at bedtime, and may be effective in improving control of nocturnal pH and treating night-time GERD.

Venous thrombosis as a cause of superior vena cava syndrome. Rapid response to streptokinase.

Venous thrombosis, resulting in superior vena cava syndrome, developed in a patient with two permanent transvenous pacemaker wires. Therapy with streptokinase resulted in prompt relief of the obstruction, with no complications. In properly selected patients, streptokinase may be the treatment of choice for this potentially life-threatening problem.

Medical therapy of supraesophageal gastroesophageal reflux disease.

Medical therapy of supraesophageal gastroesophageal reflux disease (GERD) is based on the principals for treating patients with heartburn and erosive esophagitis, observations from the few available clinical trials, and clinical experience. In general, patients with supraesophageal GERD require higher doses of antireflux therapy, principally with proton pump inhibitors, for longer periods of time to effectively relieve symptoms compared with patients with heartburn and/or erosive esophagitis. This article reviews the current literature and discusses a suggested approach to medical management of these often complex patients.

Comparison of potential cytoprotective action of sucralfate and cimetidine. Studies with experimental feline esophagitis.

The potential mucosal protective effects of a liquid sucralfate preparation and the histamine (H2)-antagonist cimetidine on acid-induced esophagitis were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N hydrochloric acid at 1 ml/minute for 20 minutes. Mucosal lesions were evaluated by blinded investigators using both fiber-optic endoscopy and light microscopy. Histology was scored for basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions, demonstrated by quantitative histologic scoring. Although cimetidine did not show the same degree of protection as sucralfate, the results did show a trend towards a cytoprotective effect.

Review article: the role of non-acid reflux in gastro-oesophageal reflux disease.

The role of acid in the pathogenesis of gastro-oesophageal reflux disease (GERD) has been extensively studied and is well accepted. The role, if any, of non-acid reflux, in particular duodenogastro-oesophageal reflux, is much debated. The availability of new technology to detect non-acid reflux has heightened interest in this question. This article reviews the following: How do we define non-acid reflux? Does duodenogastro-oesophageal reflux (alone or in combination) cause oesophageal injury, symptoms or both? What is its role in complicated GERD? What methods are available to assess non-acid reflux? Does non-acid reflux need treatment and if so what modalities are available?

Control of intragastric pH with omeprazole 20 mg, omeprazole 40 mg and lansoprazole 30 mg.

BACKGROUND: Single daily doses of proton pump inhibitors, omeprazole and lansoprazole provide effective acid suppression and equal healing and symptom relief in patients with GERD. Despite this, controversy exists as to the efficacy of available proton pump inhibitors in the control of gastric acidity. AIM: To assess the efficacy of omeprazole 20 mg vs. lansoprazole 30 mg and omeprazole 40 mg vs. lansoprazole 30 mg in intragastric pH control. METHODS: Study I: 12 Helicobacter pylori-negative volunteers (mean age 33 years) were treated with omeprazole 20 mg and lansoprazole 30 mg in random order before breakfast for 7 days. Study II: 24 subjects (mean age 36 years) were similarly treated with omeprazole 40 mg and lansoprazole 30 mg for 7 days after a baseline pH study. One week washout was allowed between studies. Subjects had the same meal on each study day. On day seven, a 24-h intragastric pH study was performed. The percentage time for which gastric pH > 4 was analysed (Gastrosoft, Synectics Medical Inc.) and expressed as mean +/- s.d. RESULTS: (1) Omeprazole 20 mg and lansoprazole 30 mg showed no significant difference in the percentage time for which gastric pH > 4 in the daytime and night-time periods. (2) The percentage time for which pH > 4 with omeprazole 40 mg was significantly greater than lansoprazole 30 mg in both daytime (61 +/- 19% vs. 48 +/- 14%, P < 0.001), and night-time periods (34 +/- 21% vs. 26 +/- 14%, P < 0.05). (3) A large inter-subject variation existed in both studies. (4) In 10 subjects who participated in both studies, omeprazole 40 mg showed a significantly higher percentage time for which pH > 4 in the daytime (69 +/- 18% vs. 51 +/- 15%, P=0.015) than omeprazole 20 mg. CONCLUSION: These pH data support the therapeutic equivalency of FDA approved doses of omeprazole and lansoprazole.

Esomeprazole resolves chronic heartburn in patients without erosive oesophagitis.

BACKGROUND: Patients with chronic heartburn but with no endoscopic evidence of erosive oesophagitis require gastric acid suppression to relieve symptoms. AIM: To assess the efficacy and safety of esomeprazole in patients with frequent heartburn for >or = 6 months and no evidence of erosive oesophagitis on endoscopy. METHODS: Two randomized, double-blind, 4-week, multi-centre trials with identical methodology compared once-daily esomeprazole, 40 mg (n = 241) or 20 mg (n = 234), with placebo (n = 242) for the rigorous end-point of complete resolution of heartburn. Secondary end-points included the percentage of heartburn-free days and the time to first and sustained resolution of heartburn. RESULTS: Patients treated with either dose of esomeprazole were two to three times more likely to achieve complete resolution of heartburn than patients treated with placebo (P < 0.001). The percentage of heartburn-free days was significantly higher with esomeprazole 40 mg (63%, 66%) or 20 mg (63%, 68%) than with placebo (46%, 36%; P < or = 0.001) in each of the two studies. Esomeprazole was associated with a significantly shorter mean time to first (6-7 days) and sustained (12-17 days) resolution of heartburn compared with placebo (first, 10-12 days; sustained, 21-22 days; P < or = 0.008). The spectrum and frequency of adverse events with esomeprazole were similar to those with placebo. CONCLUSIONS: Esomeprazole, at daily doses of 40 mg or 20 mg, is effective and safe for the treatment of chronic heartburn in patients without erosive oesophagitis.

Gastric acidity and acid breakthrough with twice-daily omeprazole or lansoprazole.

BACKGROUND: In patients with severe gastro-oesophageal reflux disease (GERD), proton pump inhibitors are being used increasingly in twice-daily regimens to improve control of gastric acidity. Few data exist to compare the ability of the most-often used proton pump inhibitors, omeprazole and lansoprazole, to control gastric acid at twice-daily dosage regimens. Nocturnal acid breakthrough, defined as gastric pH < 4.0 continuously for > 60 min, may compromise treatment goals in patients with GERD. AIM: To compare the effects of omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. on gastric acidity and the relative ability of each dosage regimen to prevent acid breakthrough. METHODS: In a crossover pharmacodynamic study, 20 healthy volunteers (10 male, 10 female, mean age 38 years) were given omeprazole 20 mg b.d. or lansoprazole 30 mg b.d. for 7 days each, in a randomized manner. Each dosage regimen was separated by a minimum 7-day period where no medication was administered. On day 7 of each regimen, 24-h intragastric pH-metry was performed. The percentage of time for which gastric pH was below 4.0 and 3.0, the occurrence of daytime and nocturnal acid breakthrough, and the duration of action of each regimen were compared. Non-parametric statistics for paired data were used. RESULTS: The percentage time for which gastric pH was below 4.0 was significantly lower with omeprazole 20 mg b.d. (median 14.8%) than with lansoprazole 30 mg b. d. (median 24.2; P=0.0372). Fourteen subjects showed more effective acid control when taking omeprazole; these were significantly more often H. pylori-negative patients compared with those for whom acid control was better on lansoprazole (P < 0.001). Nocturnal acid breakthrough occurred in seven patients (35%) on omeprazole and in 10 (50%) on lansoprazole (N.S.). CONCLUSION: In healthy volunteers, twice-daily dosing of omeprazole 20 mg b.d. appears to be significantly more effective than lansoprazole 30 mg b.d. in controlling gastric acidity. The clinical importance of such a difference remains to be defined in GERD patients.

Oesophageal motility defects associated with nocturnal gastro-oesophageal reflux on proton pump inhibitors.

BACKGROUND: Recent studies from our laboratory reveal that 70% of patients with gastro-oesophageal reflux disease (GERD) on proton pump inhibitors twice daily (b.d.) have nocturnal gastric acid breakthrough (gastric pH < 4 > 1 h) which is often accompanied by oesophageal acid exposure. The pathogenesis of GER during gastric acid breakthrough is not clear. AIM: To determine the prevalence of oesophageal motility abnormalities in patients with nocturnal GER associated with nocturnal acid breakthrough on proton pump inhibitor b.d. METHODS: We reviewed the pH-metry and manometric studies of 100 consecutive patients with GERD who were on proton pump inhibitor b.d. pH tracings were analysed for the nocturnal period (10.00 hours until 06.00 hours). Nocturnal GER was defined as> 0.5% time distal oesophageal pH < 4. Manometric tracings were reviewed for lower oesophageal sphincter (LES) pressure and oesophageal body motility. Chi-squared and Fischer's test were used for statistical analysis. RESULTS: Of the 100 patients, 74 (74%) had nocturnal gastric acid breakthrough. Thirty-one (42%) had concurrent abnormal nocturnal GER (refluxers) and 43 out of 74 (58%) had no GER (non-refluxers). The prevalence of ineffective oesophageal motility, and low LES pressure was significantly higher in refluxers than in non-refluxers (P < 0. 05, P < 0.001, respectively). Ineffective-oesophageal motility has a high specificity (91%), but low sensitivity (45%) as a diagnostic predictor for patients who are more likely to develop nocturnal GER on proton pump inhibitor b.d. CONCLUSION: Ineffective oesophageal motility is a risk factor for proton pump inhibitor refractory GER.

Bedtime ranitidine does not eliminate the need for a second daily dose of omeprazole to suppress nocturnal gastric pH.

BACKGROUND: We have previously shown that 70% of patients experience nocturnal gastric acid breakthrough (defined as pH<4 for more than 60 min between 22.00 and 06.00 hours) on twice a day (b.d.) proton pump inhibitor. Adding 150 or 300 mg of ranitidine at bedtime is more effective than additional omeprazole at bedtime in control of night-time acid breakthrough. AIM: To assess whether omeprazole 20 mg AM plus ranitidine 150 mg HS would be as effective as omeprazole 20 mg before breakfast and dinner (b.d. AC) in intragastric pH control, particularly during the overnight period. METHODS: Twenty healthy volunteers (11 males, 9 females, mean age 32.7 years) were treated with omeprazole (OME) 20 mg b.d. AC and placebo HS or omeprazole 20 mg AM and placebo before dinner plus ranitidine (RAN) 150 mg HS for 7 days, in a randomized, double-blind, crossover design, with a 1 week washout between study periods. On day 8 subjects were monitored for 24 h with a single channel pH probe placed in the stomach 10 cm below the proximal border of the LES. Percentage time pH<4 for total, upright and recumbent positions were compared between the two regimens using Wilcoxon matched pairs testing. RESULTS: Expressed in median values of percentage time pH<4: upright time intragastric pH<4 on OME 20 mg b.d. AC was 18.9 compared to 29.7 on OME AM + RAN HS (P = 0.003). Recumbent time pH<4 on OME 20 mg b.d. AC was 23.45 compared to 44.75 on OME AM + RAN HS (P = 0.02). CONCLUSION: Bedtime ranitidine does not eliminate the need for an evening dose of omeprazole to control intragastric pH in patients requiring more than a single daily dose of omeprazole.

Dose-dependent control of intragastric pH by pantoprazole, 10, 20 or 40 mg, in healthy volunteers.

BACKGROUND: Proton pump inhibitors have emerged as the most effective class of drugs for the treatment of gastro-oesophageal reflux. Pantoprazole is a proton pump inhibitor that has demonstrated high clinical efficacy. AIM: To evaluate the effect of once-daily doses of pantoprazole, 10, 20 and 40 mg, on gastric acidity in healthy volunteers. METHODS: Thirty-six subjects received pantoprazole in a three-way crossover design study. Ambulatory 24-h intragastric pH and distal oesophageal pH were monitored at baseline and on the last day of each treatment period. The measured endpoints were the median intragastric and oesophageal pH, the percentage of time the intragastric pH < 4 and oesophageal pH < 4 and the area under the curve for gastric acidity over 24 h. Safety was evaluated by incidence and severity of adverse events. RESULTS: Pantoprazole demonstrated a linear dose- dependent suppression of gastric acidity over the dose range 10-40 mg. The dose of 40 mg demonstrated a significantly greater response than the lower doses, particularly at night. All pantoprazole doses were well tolerated. CONCLUSIONS: Pantoprazole demonstrates a dose-related effect in the range 10-40 mg once daily. The once-daily dose of 40 mg provides the highest and most consistent control of gastric pH, especially at night.

Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH.

BACKGROUND: Omeprazole controls acid but not non-acid reflux. The GABA B agonist baclofen decreases acid reflux through the inhibition of transient lower oesophageal sphincter relaxations (TLESRs) and should similarly decrease non-acid reflux. Using combined multichannel intraluminal impedance and pH (MII/pH), we compared acid and non-acid reflux after placebo and baclofen. METHODS: Nine healthy volunteers and nine heartburn patients underwent two 2-h studies of combined MII/pH in right lateral decubitus after a refluxogenic meal in random order: on placebo and after baclofen 40 mg p.o. Tracings were analysed for acid and non-acid reflux episodes, re-reflux and symptoms in the heartburn patients. RESULTS: In normal subjects baclofen significantly reduced the median number of episodes of acid (7 vs. 1, P = 0.02), non-acid (2 vs. 0, P = 0.005), and all reflux combined (10 vs. 2, P = 0.006); re-reflux was not reduced (0 vs. 0, P = N.S.). In heartburn patients, baclofen significantly decreased the median number of episodes of acid (15 vs. 6, P = 0.004), non-acid (4 vs. 2, P = 0.003), re-reflux (2 vs. 0, P = 0.02), and all reflux combined (23 vs. 8, P = 0.004); it also reduced the median number of acid-related (9 vs. 1, P = 0.008) and non-acid-related (1 vs. 0, P = 0.04) symptoms. CONCLUSIONS: Baclofen reduces post-prandial acid and non-acid reflux and their associated symptoms. GABA B agonists may have a role in treating GERD.