Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea.

BACKGROUND: Many anti-nausea treatments are available for chronic gastrointestinal syndromes, but data on efficacy and comparative effectiveness are sparse. AIMS: To conduct a sectional survey study of patients with chronic nausea to assess comparative effectiveness of commonly used anti-nausea treatments. METHODS: Outpatients at a single center presenting for gastroenterology evaluation were asked to rate anti-nausea efficacy on a scale of 0 (no efficacy) to 5 (very effective) of 29 commonly used anti-nausea treatments and provide other information about their symptoms. Additional information was collected from the patients' chart. The primary outcome was to determine which treatments were better or worse than average using a t test. The secondary outcome was to assess differential response by individual patient characteristics using multiple linear regression. RESULTS: One hundred and fifty-three patients completed the survey. The mean efficacy score of all anti-nausea treatments evaluated was 1.73. After adjustment, three treatments had scores statically higher than the mean, including marijuana (2.75, p < 0.0001), ondansetron (2.64, p < 0.0001), and promethazine (2.46, p < 0.0001). Several treatments, including many neuromodulators, complementary and alternative treatments, erythromycin, and diphenhydramine had scores statistically below average. Patients with more severe nausea responded better to marijuana (p = 0.036) and diphenhydramine (p < 0.001) and less so to metoclopramide (p = 0.020). There was otherwise no significant differential response by age, gender, nausea localization, underlying gastrointestinal cause of nausea, and GCSI. CONCLUSIONS: When treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, and forgoing lower performing treatments. Further prospective research is needed, particularly with respect to highly effective treatments.

A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common Causality.

BACKGROUND: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship. AIMS: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes. METHODS: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) within a 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression. RESULTS: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p < 0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p = 0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES. CONCLUSIONS: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present.

Use of Esophageal pH Monitoring to Minimize Proton-Pump Inhibitor Utilization in Patients with Gastroesophageal Reflux Symptoms.

BACKGROUND: Due to concerns about long-term PPI use in patients with acid reflux, we aimed at minimizing PPI use, either by avoiding initiating therapy, downscaling to other therapies, or introducing endoscopic or surgical options. AIMS: To examine the role of esophageal ambulatory pHmetry in minimizing PPI use in patients with heartburn and acid regurgitation. METHODS: Retrospective cohort analysis of patients with reflux symptoms, who underwent endoscopy, manometry, and ambulatory pHmetry to define the need for PPI. Patients were classified as: (1) never users; (2) partial responders to PPI; (3) users with complete response to PPI. Patients were then managed as: (1) PPI non-users; (2) PPI-initiated, and (3) PPI-continued. RESULTS: Of 286 patients with heartburn and regurgitation, 103 (36%) were found to have normal and 183 (64%) abnormal esophageal acid exposure (AET). In the normal AET group, 44/103 had not been treated and were not initiated on PPI. Of the 59 who had previously received PPI, 52 stopped and 7 continued PPI. Hence, PPI were avoided in 96/103 patients (93%). In the abnormal AET group, 61/183 had not been treated and 38 were initiated on PPI and 23 on other therapies. In the 122 patients previously treated with PPI, 24 were not treated with PPI, but with H2RAs, prokinetics, endoscopic, or surgical therapy. Hence, PPI therapy was avoided in 47/183 patients (26%). CONCLUSIONS: In patients with GER symptoms, esophageal pHmetry may avert PPI use in 50%. In the era of caution regarding PPIs, early testing may provide assurance and justification.

Demographic factors affect willingness to register as an organ donor more than a personal relationship with a transplant candidate.

BACKGROUND: Transplant candidate caregivers (TCCs) are an under-utilized but potentially devoted pool of advocates who themselves may be recruited to register for deceased organ donation. AIM: The purpose of this study was to assess and compare recruitment barriers to deceased donor registration efforts in TCCs and health fair attendees (HFAs). METHODS: A 42-item questionnaire assessing willingness to register as an organ donor and perceptions and knowledge about organ donation was administered to 452 participants (174 in Denver, 278 in San Francisco). Logistic regression, stratified by study site, was used to assess associations between explanatory variables and willingness to register as an organ donor. RESULTS: In Denver, 83 % of TCCs versus 68 % of HFAs indicated a willingness to register (p = 0.03). Controlling for study group (TCC vs HFA), predictors of willingness to register were female gender [odds ratio (OR) 2.4], Caucasian race (OR 2.3), college graduate (OR 11.1), married (OR 2.4) and higher positive perception of organ donation (OR 1.2), each p < 0.05. In San Francisco, 58 % of TCCs versus 70 % of HFAs indicated a willingness to register (p = 0.03). Controlling for study group (TCC vs HFA), predictors of willingness to register were Caucasian race (OR 3.5), college graduate (OR 2.2), married (OR 1.9), higher knowledge (OR 1.6) and higher positive perception of organ donation (OR 1.2), each p < 0.05. In both locales, Caucasians were more likely to have positive perceptions about organ donation and were more willing to register. CONCLUSIONS: Demographic characteristics, not personal connection to a transplant candidate, explain willingness to register as an organ donor.

The integrated relaxation pressure may not be an appropriate gold standard for deglutitive relaxation due to reliance on a single intragastric reference sensor.

BACKGROUND: Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis. METHODS: We identified high-resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as "stable" (no change in diagnosis) or "variable" (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into "variable normal/dysmotility" (≥1 normal IRP measurement and ≥1 CCv3 diagnosis), or "variable dysmotility" (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland-Altman plots were used to compare IRP measurements within HRM studies. KEY RESULTS: The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7 mmHg for variable normal/dysmotility and 5.9 mmHg for variable dysmotility. The average difference between the proximal-most and distal-most sensors was -1.52 mmHg (lower limit of agreement -10.03 mmHg, upper limit of agreement 7.00 mmHg). CONCLUSIONS & INFERENCES: IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered.

Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) refers to 2 chronic inflammatory diseases of the intestine, ie, ulcerative colitis and Crohn's disease. IBD results from environmental factors (eg, bacterial antigens) triggering a dysregulated immune response in genetically predisposed hosts. Although the basis of IBD is incompletely understood, a number of recent studies have implicated defective innate immune responses in the pathogenesis of IBD. In this regard, there is much interest in therapies that activate innate immunity (eg, recombinant granulocyte-macrophage colony-stimulating factor). METHODS: In this study, we screened expression and function of circulating leukocyte granulocyte-macrophage colony-stimulating factor receptor (CD116) messenger RNA and surface protein in 52 IBD patients and 52 healthy controls. RESULTS: Our results show that both granulocyte and monocyte CD116 levels, but not CD114 or interleukin-3Rα, were significantly decreased in IBD compared to control (P<.001) and disease controls (irritable bowel syndrome; P<.001; rheumatoid arthritis; P<.025). IBD-associated CD116 repression was more prominent in patients with ulcerative colitis compared to Crohn's disease (P<.05), was independent of disease activity (P>.05), and was not influenced by current medications (P>.05). Receiver operating characteristic curve analysis revealed that leukocyte CD116 expression is a sensitive (85%) and specific (92%) biomarker for IBD. Moreover, granulocyte CD116-mediated function (phosphorylation of signal transducers and activators of transcription 3) paralleled decreased expression of CD116 in IBD granulocytes compared to control (P<.001). CONCLUSIONS: These studies identify defective expression and function of CD116 as a distinguishing feature of IBD and implicate an associated defect in innate immune responses toward granulocyte-macrophage colony-stimulating factor.

Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease.

BACKGROUND: Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms. METHODS: In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients. RESULTS: 70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= -0.5 to -0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms. CONCLUSIONS: Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

Baclofen and gastroesophageal reflux disease: seeing the forest through the trees.

Baclofen has been shown to decrease reflux events and increase lower esophageal sphincter pressure, yet has never established a clear role in the treatment of gastroesophageal reflux disease (GERD). Lei and colleagues have shown in a recent elegant study that baclofen reduces the frequency and initiation of secondary peristalsis and heightens esophageal sensitivity to capsaicin-mediated stimulation. These findings may help explain both the benefit of baclofen in conditions such as rumination and supragastric belching, as well as the apparent lack of benefit of baclofen and other GABAB agonists in long-term treatment of GERD.