Murray, Joseph A.

INTRODUCTION: Patients with eosinophilic gastritis and/or gastroenteritis (EG/EGE) experience significantly reduced health-related quality of life related to the symptoms and signs of their disease. There is a need to develop a PRO questionnaire for clinical research in EG/EGE. The objectives of this study were to develop a symptom questionnaire (drafted using literature and clinician input to determine preliminary measurement concepts) and then (1) identify, describe, and substantiate signs, symptoms, and impacts of EG/EGE from the perspective of adults with the condition via concept elicitation methods; and (2) evaluate the properties of the questionnaire and make modifications via cognitive debriefing methods. METHODS: Interviews were conducted, transcribed, coded, and analyzed. Eligible adults with EG/EGE first participated in a concept elicitation segment where they described their experiences with EG/EGE, continuing until saturation was achieved, adding symptoms to the draft symptom questionnaire as needed. This was followed by a cognitive debrief to assess the appropriateness of the draft symptom questionnaire, where patients assessed readability, comprehensibility, relevance, and comprehensiveness. The questionnaire was modified based on patient feedback, then re-evaluated to confirm its appropriateness. RESULTS: In total, 16 interviews were conducted and 24 signs and symptoms were reported during concept elicitation. The most frequently reported (Figure 1) were abdominal pain, nausea, diarrhea, vomiting, and abdominal cramping; while abdominal pain, nausea, and diarrhea were the most bothersome to patients. Saturation was achieved after 12 interviews. In the cognitive debriefing, revisions included the addition of a vomiting frequency item and revision of the early satiety item for clarity. Response options were modified to instruct the participants to assess each symptom “at its worst”. For the final version of the EG/EGE-SQ©, participants were able to read, comprehend, and provide appropriate responses, and reported that the resulting questionnaire was comprehensive for their condition. CONCLUSION: The results of this research support the content validity, including comprehensiveness and interpretability, of the EG/EGE-SQ© which offers the potential for use in clinical research to assess symptoms in patients with EG/EGE. Future research is needed to assess its psychometric properties including reliability and validity, responsiveness, and potential for use in pediatric populations.

INTRODUCTION: Eosinophilic gastrointestinal diseases (EGIDs) are a set of inflammatory diseases subclassified according to the site(s) of abnormal accumulation of eosinophils (eos) in the gastrointestinal (GI) tract such as eosinophilic esophagitis (EoE), gastroenteritis (EGE), and colitis. These conditions often decrease quality of life due to debilitating symptoms. While the pathogenesis of EGIDs is primarily thought to be driven by eos, there is increasing evidence for the involvement of mast cells (MCs). AIM: To characterize symptomatic patients (pts) with suspected EG/EGE who did not meet histopathologic entry criteria for mucosal eosinophilia for a Phase 2 randomized, double-blind, placebo-controlled study of AK002, an anti-Siglec-8 antibody. METHODS: To undergo screening endoscopy for this study, pts were required to report an average symptom score ≥3 (0 to 10 scale) for abdominal pain, nausea, and/or diarrhea on a daily patient-reported outcome questionnaire for ≥2 weeks and have no other known cause for GI symptoms. During the screening endoscopy, biopsies were systematically obtained from the stomach and duodenum, and read by a single pathologist. Eos counts (eos/hpf; hpf area = 0.237 mm 2 ) were assessed on H&E slides. To quantify MCs, immunohistochemistry for tryptase was performed. We quantified eos and MCs in the stomach and duodenum. Histopathologic entry criteria for the randomized study was ≥30 eos/hpf in 5 hpfs in the stomach (EG) and/or ≥30 eos/hpf in 3 hpfs in the duodenum (EGE). A literature review was conducted to determine normal MC counts in the GI tract. RESULTS: Eighty-eight pts underwent screening endoscopy based upon suspected EG/EGE and active symptoms, and 72 pts met histopathologic eos criteria. All pts whose eos did not meet entry criteria (n = 16) were found to have elevated MC counts (Figure 1; reported normal range = 12-19 MCs/hpf). In these pts, the mean gastric eos count was 6 eos/hpf in 5 hpfs and mean duodenal eos count was 15 eos/hpf in 3 hpfs. In contrast, these pts exhibited a mean gastric MC count of 47 MC/hpf in 5 hpfs and a mean duodenal MC count of 49 MC/hpf in 3 hpfs. Almost all symptomatic pts screened (87/88; 99%) had elevated MC counts. CONCLUSION: Data from this large randomized EG/EGE study showed that symptomatic pts with suspected EG/EGE had increased mucosal MCs with or without mucosal eosinophilia. These data suggest that MCs may play a role in pts with suspected EG/EGE and raise the possibility of a unique clinical presentation driven by MCs.

Abstract Background Capsule endoscopy (CE) is frequently hindered by intra-luminal debris. Our aim was to determine whether a combination bowel preparation would improve small-bowel visualization, diagnostic yield, and the completion rate of CE. Methods Single-blind, prospective randomized–controlled study of outpatients scheduled for CE. Bowel-preparation subjects ingested 2 L of polyethylene glycol solution the night prior to CE, 5 mL simethicone and 5 mg metoclopramide 20 minutes prior to CE and laid in the right lateral position 30 minutes after swallowing CE. Controls had no solid food after 7 p.m. the night prior to CE and no liquids 4 hours prior to CE. Participants completed a satisfaction survey. Capsule readers completed a small-bowel-visualization assessment. Results Fifty patients were prospectively enrolled (56% female) with a median age of 54.4 years and 44 completed the study (23 patients in the control group and 21 in the preparation group). There was no significant difference between groups on quartile-based small-bowel visualization (all P > 0.05). There was no significant difference between groups in diagnostic yield (P = 0.69), mean gastric (P = 0.10) or small-bowel transit time (P = 0.89). The small-bowel completion rate was significantly higher in the preparation group (100% vs 78%; P = 0.02). Bowel-preparation subjects reported significantly more discomfort than controls (62% vs 17%; P = 0.01). Conclusions Combined bowel preparation did not improve small-bowel visualization but did significantly increase patient discomfort. The CE completion rate improved in the preparation group but the diagnostic yield was unaffected. Based on our findings, a bowel preparation prior to CE does not appear to improve CE performance and results in decreased patient satisfaction (ClinicalTrials.gov, No. NCT01243736).

ABSTRACTBackground:Patients with autoimmune disorders (ADs) are at increased risk for celiac disease (CD), but data are conflicting on the risk of ADs in treated patients with CD. We aimed to assess the incidence of ADs in treated patients with CD.Methods:Using the Rochester Epidemiology Project, we retrospectively searched for the medical records at Mayo Clinic and Olmsted Medical Center from January 1997 to December 2015 for patients with CD who met accepted diagnostic criteria. For each patient with CD, we identified 2 age and sex‐matched controls during the same study period. The incidence rate of AD diagnosis 5 years after index date was calculated using Kaplan‐Meier analysis for the CD cases and controls and compared using the log‐rank test.Results:We identified 249 treated patients with CD during the study period and 498 matched controls, with mean (standard deviation) ages of 32 (22) years and 33 (22) years, respectively. One third of patients (n = 85) and controls (n = 170) were boys. Five years after the index date, 5.0% of patients with CD and 1.3% of controls had a de novo AD diagnosis (P = 0.006). In the presence of a prior AD, the cumulative risk of a de novo or additional AD was significantly higher in the CD group compared with controls (P < 0.001). Children had a significantly higher risk of AD development compared with adults (P = 0.010).Conclusions:Treated patients with CD are at higher risk for the development of ADs. The risk of a new AD is higher in children, especially when >1 AD diagnosis exists.