Talley, Nicholas J.

BackgroundChronic constipation (CC) is common in the community but surprisingly little is known about relevant gastro‐intestinal (GI) and non‐GI co‐morbidities.ObjectiveThe purpose of this study was to assess the epidemiology of CC and in particular provide new insights into the co‐morbidities linked to this condition.MethodsIn a prospective, population‐based nested case‐control study, a cohort of randomly selected community residents (n = 8006) were mailed a validated self‐report gastrointestinal symptom questionnaire. CC was defined according to Rome III criteria. Medical records of each case and control were abstracted to identify potential CC comorbidities.ResultsAltogether 3831 (48%) subjects returned questionnaires; 307 met criteria for CC. Age‐adjusted prevalence in females was 8.7 (95% confidence interval (CI) 7.1–10.3) and 5.1 (3.6–6.7) in males, per 100 persons. CC was not associated with most GI pathology, but the odds for constipation were increased in subjects with anal surgery relative to those without (odds ratio (OR) = 3.3, 95% CI 1.2–9.1). In those with constipation vs those without, neurological diseases including Parkinson’s disease (OR = 6.5, 95% CI 2.9–14.4) and multiple sclerosis (OR = 5.5, 95% CI 1.9–15.8) showed significantly increased odds for chronic constipation, adjusting for age and gender. In addition, modestly increased odds for chronic constipation in those with angina (OR = 1.4, 95% CI 1.1–1.9) and myocardial infarction (OR = 1.5, 95% CI 1.0–2.4) were observed.ConclusionsNeurological and cardiovascular diseases are linked to constipation but in the community constipation is unlikely to account for most lower GI pathology.

SummaryBackgroundEstimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy.AimsTo determine the sensitivity and specificity of oesophagogastroduodenoscopy (EGD) for oesophageal narrowing when compared to a structured oesophagram.MethodsWe conducted a retrospective chart review at Mayo Clinic, Rochester of adult patients with eosinophilic oesophageal infiltration of >15 eosinophils/hpf with symptomatic dysphagia, who underwent a structured barium oesophagram. The sensitivity and specificity of EGD were evaluated against the gold standard of oesophagram. Demographic and multiple clinical factors were evaluated as potential predictors of oesophageal narrowing.ResultsOf the 58 patients identified, 34 (58.6%) had a narrowed oesophageal diameter (<21 mm). EGD had poor sensitivity (14.7%, 95% CI 5.0–31.1%) for detection of a narrowed oesophagus and only modest specificity (79.2%, 95% CI 57.8–92.9%). Even at a cut‐off diameter of EDmax ≤ 15 mm, EGD had a sensitivity of only 25.0% (95% CI 5.5–57.2%) for narrowed oesophagus. A history of >5 food impaction episodes, endoscopic rings, and female sex were the best predictors of oesophageal narrowing. 86% (6/7) patients with persistent dysphagia despite remission of histological eosinophilia responded to oesophageal dilation all of whom had radiological oesophageal narrowing and 71% of whom had no perceived oesophageal narrowing at EGD.ConclusionsSymptomatic oesophageal narrowing identified by barium oesophagography is common and under‐recognised at endoscopy in patients with oesophageal eosinophilia.

AbstractBackgroundThere is symptom overlap between gastro‐esophageal reflux disease (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD cases are now more likely mislabeled as GERD.MethodsIn subjects from Olmsted County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates between 1985 and 2009. (ii) Assessment of survey‐based upper gastrointestinal symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD during a medical encounter. (iv) Assess the association between PPI use and GERD and/or FD symptoms and between actual diagnoses received.Key Results(i) Yearly GERD diagnosis rates rose between 1985 and 2009 (325–1866 per 100 000). FD diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100 000 in 2009. (ii) Reported GERD symptoms did not significantly change between three survey waves in the years 1988–2009 (p = 0.052), whereas FD symptoms slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms received a FD diagnosis. (iv) PPI use was associated with documented GERD diagnosis (p < 0.001), however there was no significant association between GERD symptoms and PPI use (p = 0.078).Conclusions & InferencesWe have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.

SummaryBackgroundThe population ≥65 years is rapidly increasing, but remarkably little is known about the natural history of abdominal pain with ageing.AimTo prospectively evaluate the natural history of abdominal pain (severity and frequency) in a US population, and evaluate potential risk factors (including somatisation) for the onset and disappearance of abdominal pain with increasing age.MethodsBetween 1988 and 2004, valid self‐report questionnaires that recorded gastrointestinal symptoms including severity and frequency of abdominal pain were mailed to randomly selected cohorts of community residents followed over time. This study identified all respondents who answered abdominal pain questions at an initial and follow‐up survey.ResultsOne thousand nine hundred and thirteen subjects were included (mean age in years at first survey: 48 ± 12 (SD), mean age at second survey: 59 ± 13 (SD); 53% female). The onset and disappearance rate of abdominal pain over the follow‐up were 18% (95% CI, 16, 20) and 47% (43, 50) respectively. The rates of increasing vs. decreasing abdominal pain score were 18% (16, 20) vs. 21% (20, 23) respectively. While younger age at initial survey was associated with the onset of abdominal pain {vs. subjects without abdominal pain, [OR 0.9 (0.7, 1.0)]}, older age at initial survey and times between surveys were associated with the disappearance of abdominal pain {vs. subjects with abdominal pain, [OR 1.2 (1.0, 1.5)]}. Female gender (OR 1.4 [1.0, 2.1]), higher somatisation scores (OR 5.3 [3.2, 8.7]) and larger changes in somatisation score (OR 2.1 [1.4, 3.2]) were positively associated with the onset of abdominal pain.ConclusionIncreasing age is associated with the disappearance of abdominal pain in the community.

SummaryBackgroundCurrent diagnostic guidelines recommend that eosinophilic oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of response to a trial of acid suppression. There is limited information available providing outcome data about the effectiveness of this approach.AimTo examine the impact of double‐dose proton pump inhibitor (PPI) therapy on symptoms, endoscopic and histological features in patients with documented oesophageal eosinophilia consistent with EoE (≥15 eosinophils/high‐power field).MethodsSixty consecutive symptomatic patients with documented oesophageal eosinophilia received open‐label omeprazole 20 mg orally twice daily before meals for 8 weeks. Clinical, endoscopic and histological (resolution: 0–5 eosinophils/HPF, partial improvement: 5–14 eosinophils/HPF), or no improvement: (≥15 eosinophils/HPF) evaluation was repeated at the end of this period. An expert GI pathologist, unaware of the study aims, reviewed all slides.ResultsClinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission.ConclusionsMore than 50% of patients with documented oesophageal eosinophilic infiltration in the EoE range improved when treated with a double‐dose PPI trial for 8 weeks. These findings support the published guidelines recommending a PPI trial prior to diagnosing EoE, and confirm the existence of an eosinophilic oesophageal infiltrationPPI‐responsive population.

AbstractBackgroundLow basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal.MethodsPatients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal.Key ResultsA total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%).Conclusions & InferencesIn GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1‐week treatment period.