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.

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.

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.

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.

Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate-to-severe erosive oesophagitis - the results of two double-blind studies.

BACKGROUND: Current PPIs may not achieve desired outcomes in some GERD patients due to limited duration of acid inhibition. AIM: To evaluate a novel rabeprazole extended release (ER), which provides longer duration of drug exposure and acid suppression, in healing and symptomatic resolution of moderate-severe erosive oesophagitis. METHODS: Patients with LA grade C or D oesophagitis were randomised to rabeprazole-ER 50 mg or esomeprazole 40 mg once daily in two identical 8-week double-blind trials (N = 2130). Two primary endpoints were tested sequentially: (1) healing by 8 weeks [hypothesis: rabeprazole-ER non-inferior to esomeprazole (non-inferiority margin = 8%)], (2) healing by 4 weeks [hypothesis: rabeprazole-ER superior to esomeprazole (P < 0.05)]. The secondary endpoint was sustained heartburn resolution at 4 weeks. RESULTS: Rabeprazole-ER was non-inferior to esomeprazole in week-8 healing (80.0% vs. 75.0%; 77.5% vs. 78.4%). Week-4 healing (54.8% vs. 50.3%; 50.9% vs. 50.7%) and sustained heartburn resolution (48.3% vs. 48.2%; 53.2% vs. 52.5%) were not significantly different. Post hoc combined results for grade D revealed rabeprazole-ER vs. esomeprazole differences in week-8 healing = 10.4% (95% CI: -1.4%, 22.2%) and week-4 healing = 12.0% (P = 0.048). CONCLUSIONS: Rabeprazole-ER is as effective as esomeprazole in healing moderate-severe oesophagitis and achieves similar rates of heartburn resolution. Subgroup analysis suggests the possibility of benefit in severe oesophagitis, but this requires further evaluation (ClinicalTrials.gov: NCT00658528 and NCT00658775).

Prevalence, knowledge and care patterns for gastro-oesophageal reflux disease in United States minority populations.

BACKGROUND: While there is evidence of ethnic variation in the prevalence of gastro-oesophageal reflux disease (GERD) symptoms, few population-based studies examine GERD symptom prevalence amongst the growing Hispanic minority in the US as well as Asians in the West. AIM: To examine the prevalence, awareness and care patterns for GERD across different ethnic groups. METHODS: A population-based, cross-sectional survey was fielded in English, Chinese and Spanish that assessed self-reported GERD prevalence, awareness and care patterns in four ethnic groups (Caucasian, African American, Asian, Hispanic). RESULTS: A total of 1172 subjects were included for analysis: 34.6% experienced GERD symptoms at least monthly, 26.2% at least weekly and 8.2% at least daily. Statistically significant differences in raw prevalence rates between racial groups were found: 50% of Hispanics experienced heartburn at least monthly, compared with 37% of Caucasians, 31% of African Americans and 20% of Asians (P > 0.0001). Significant differences in knowledge and care-seeking patterns by ethnicity were also observed. CONCLUSIONS: This study confirms the high prevalence of GERD symptoms in the US and introduces Hispanics as the ethnicity with the highest prevalence rate. Asians in the US have higher rates of symptoms than in the Far East. These data demonstrate a need for culturally appropriate education about GERD symptoms and treatment.

Clinical trial: gastric acid suppression in Hispanic adults with symptomatic gastro-oesophageal reflux disease - comparator study of esomeprazole, lansoprazole and pantoprazole.

BACKGROUND: Hispanic-Americans are a rapidly growing population in the United States, yet gastro-oesophageal reflux disease (GERD) is not well studied in this population. AIM: To compare the efficacy of esomeprazole, lansoprazole and pantoprazole in suppressing gastric acid, including the area of the 'acid pocket,' in Hispanics with GERD. METHODS: In this open-label, 3-way crossover study, 83 Hispanics with symptomatic GERD were randomized to 1 of 6 possible treatment sequences of three 5-7-day dosing periods with esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg daily separated by 10-17-day washout periods. Intragastric pH was measured for 24 h using dual probes with a distal and proximal (area of the 'acid pocket') electrode. RESULTS: Esomeprazole suppressed intragastric acid (pH >4.0) significantly longer over 24 h (primary end point) compared with lansoprazole and pantoprazole (P < 0.0001), and proximal gastric acid (pH >4.0) significantly longer over 24 h compared with lansoprazole (P < 0.05) and pantoprazole (P < 0.0001). CONCLUSIONS: Esomeprazole was more effective than lansoprazole and pantoprazole in suppressing gastric acidity at both intragastric distal and proximal (area of the acid pocket) sites in Hispanics with GERD. Future studies are warranted to understand better the role of the acid pocket in GERD (Clinical trial numbers: D9612L00106; ClinicalTrials.gov: NCT00410592).

A model of healing of Los Angeles grades C and D reflux oesophagitis: is there an optimal time of acid suppression for maximal healing?

BACKGROUND: In patients with Los Angeles (LA) grade C or D oesophagitis, a positive relationship has been established between the duration of intragastric acid suppression and healing. AIM: To determine whether there is an apparent optimal time of intragastric acid suppression for maximal healing of reflux oesophagitis. METHODS: Post hoc analysis of data from a proof-of-concept, double-blind, randomized study of 134 adult patients treated with esomeprazole (10 or 40 mg od for 4 weeks) for LA grade C or D oesophagitis. A curve was fitted to pooled 24-h intragastric pH (day 5) and endoscopically assessed healing (4 weeks) data using piecewise quadratic logistic regression. RESULTS: Maximal reflux oesophagitis healing rates were achieved when intragastric pH >4 was achieved for approximately 50-70% (12-17 h) of the 24-h period. Acid suppression above this threshold did not yield further increases in healing rates. CONCLUSION: After 4 weeks' acid-suppressive therapy for LA grade C or D oesophagitis, successful healing appears to reach a threshold above which improvements are unlikely to be achieved despite an increase in number of hours with intragastric pH >4.

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.

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.

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: 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.