Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population-based study.

BACKGROUND: It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs-gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community. METHODS: A population-based study was conducted by mailing a valid GI symptom questionnaire to an age- and gender-stratified random sample of residents of Olmsted County, MN. Rome III definitions were used to identify people with FGIDs, and GER was defined by weekly or more frequent heartburn or acid regurgitation. The prevalence of people meeting multiple symptom complexes was estimated. Moreover, potential risk factors for people with multiple disorders were evaluated. KEY RESULTS: A total of 3548 people provided data for each of the necessary symptom questions (mean age: 61±16 years, 54% female). Among these 3548 subjects, 2009 (57%) had no FGIDs-GER, 906 (26%) had a pure FGID-GER, 372 (10%) had 2 FGIDs-GER, and 261 (7%) had 3 or more FGIDs-GER. Somatization as assessed by a higher Somatic Symptom Checklist score (OR=3.3, 95% CI [2.7,4.1]) was associated with an increased odds for those with 3 or more FGIDs-GER compared to subjects with a pure FGID-GER adjusting for age and gender. CONCLUSIONS AND INFERENCES: Symptom complex overlap is common rather than rare in the community. GER is an integral symptom complex associated with both upper and lower FGIDs. Somatization is a strong risk factor for multiple FGIDs.

Serum alkylresorcinols as biomarkers of dietary gluten exposure in coeliac disease.

BACKGROUND: Therapy for coeliac disease (CD) mainly relies on following a gluten-free diet (GFD); however, a serum marker for gluten intake has yet to be established. AIM: To evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse. METHODS: Alkylresorcinol concentrations were compared among treated patients with coeliac disease (n = 34), untreated coeliac disease patients (n = 36) and controls (n = 33). Furthermore, seven additional coeliac disease patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of five mice fed a regular chow and 10 mice fed lifelong with a gluten-free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated. RESULTS: Total alkylresorcinol concentrations were significantly lower in treated with coeliac disease [median (IQR), 3 (2-8) nmol/L], compared to untreated patients [median (IQR), 32 (11-74) nmol/L; P < 0.0001] or healthy controls [median (IQR), 54 (23-112) nmol/L; P < 0.0001]. Moreover, alkylresorcinol concentrations in coeliac disease patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol/L after GFD, P = 0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten-free chow was 1.8 (1.6-2.3) nmol/L, which was further significantly increased to 16 (11-22) nmol/L after 8 days of feeding with the gluten-free chow that had gluten added to it. (P = 0.008). CONCLUSION: Serum alkylresorcinol concentrations could be a useful marker for dietary gluten in coeliac disease.

The incidence rate and characteristics of clinically diagnosed defecatory disorders in the community.

BACKGROUND: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community. METHODS: We reviewed the medical records of all patients older than 16 years in Olmsted County, MN, who had constipation and underwent anorectal manometry from 1999 through 2008. Criteria for diagnosing DD were constipation for 6 months or longer and one of the following: (i) abnormal rectal balloon expulsion test; (ii) reduced or increased perineal descent; or (iii) two or more abnormal features with defecography or surface electromyography. KEY RESULTS: Of 11 112 constipated patients, 516 had undergone anorectal tests; 245 of these (209 women, 36 men) had a DD. The mean (±SD) age at diagnosis was 44 years (±18) among women and 49 years (±19) among men. The overall age- and sex-adjusted incidence rate per 100 000 person-years was 19.3 (95% CI: 16.8-21.8). The age-adjusted incidence per 100 000 person-years was greater (p < 0.0001) in women (31.8, 95% CI: 27.4-36.1) than in men (6.6, 95% CI: 4.4-8.9). Prior to the diagnosis of DD, nearly 30% of patients had irritable bowel syndrome (IBS), 48% had a psychiatric diagnosis, 18% had a history of abuse, and 21% reported urinary and/or fecal incontinence. CONCLUSIONS & INFERENCES: Among constipated patients, DD are fourfold more common in women than men and often associated with IBS and psychiatric diagnoses.

Serologic microbial associated markers can predict Crohn's disease behaviour years before disease diagnosis.

BACKGROUND: Patients with Crohn's disease (CD) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected before onset of symptoms. Their utility in pre-clinical disease or prediction of complicated disease course before diagnosis is unclear. AIM: To evaluate the pattern of serologic anti-microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis. METHODS: Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota-directed antibodies (ASCA-IgA, ASCA-IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2 and anti-FlaX). Associations between the presence and accumulation of Crohn's disease anti-microbial antibodies before diagnosis and with the later development of complications were evaluated. RESULTS: Overall, 65 patients were positive for at least one Crohn's disease associated anti-microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6-8.2). The number of positive anti-microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis. CONCLUSION: The presence and accumulation of circulating anti-microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.

Immunopathogenesis of olmesartan-associated enteropathy.

BACKGROUND: Olmesartan-associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue-like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil. AIM: To determine the mechanistic similarities of OAE with coeliac sprue. METHODS: Duodenal biopsies were extracted from OAE patients before (n = 11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven 'on/off' paired samples. Formalin-fixed biopsies were stained for CD8, CD4, FoxP3, IL-15R and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL-15, IL-15R and ZO-1. RESULTS: In the 'on olmesartan medoxomil' duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T-cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in olmesartan medoxomil-treated Caco-2 cells. CONCLUSIONS: Olmesartan-associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.

Prevalence and risk factors for dysphagia: a USA community study.

BACKGROUND: Dysphagia is considered an alarm symptom but detailed population-based data on dysphagia are lacking. We aimed to estimate in a representative USA Caucasian population, the prevalence of dysphagia and potential risk factors. METHODS: A modified version of the previously validated Bowel Disease Questionnaire was mailed to a population-based cohort (n = 7640) of Olmsted County, MN. Dysphagia was measured by one validated question 'In the last year, how often have you had difficulty swallowing (a feeling that food sticks in your throat or chest)?' The medical records were reviewed for organic causes of dysphagia. The associations of reported frequency of dysphagia with potential risk factors were assessed using logistic regression models. KEY RESULTS: The sex-specific, age-adjusted (US White 2000) prevalence for dysphagia experienced at least weekly was 3.0% (95% CI: 2.2, 3.7) in females and 3.0% (95% CI: 2.0, 4.0) in males. Those with frequent heartburn (OR = 5.9 [4.0, 8.6]) and acid regurgitation (OR = 10.6 [6.8, 16.6]) were significantly more likely to report frequent dysphagia. Proton pump inhibitor (PPI) use was significantly associated with frequent (3.1, 95% CI 2.2, 4.4) and infrequent dysphagia (1.5, 955 CI 1.3, 1.8). Gastro-esophageal reflux disease (GERD) was the most common diagnosis in those reporting dysphagia on the medical record; other organic explanations were rare and only found in the frequent dysphagia group. CONCLUSIONS & INFERENCES: Frequent dysphagia is not rare in the community (3%), occurs in both women and men across all adult age groups, and is most likely to indicate underlying GERD.

Overdiagnosis of gastro-esophageal reflux disease and underdiagnosis of functional dyspepsia in a USA community.

BACKGROUND: There 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. METHODS: In 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 & INFERENCES: We have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study.

BACKGROUND: Low 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. METHODS: Patients 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 RESULTS: A 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 & INFERENCES: In 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.

The effects of ageing on the onset and disappearance of unexplained abdominal pain: a population-based study.

BACKGROUND: The population ≥65 years is rapidly increasing, but remarkably little is known about the natural history of abdominal pain with ageing. AIM: To 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. METHODS: Between 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. RESULTS: One 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. CONCLUSION: Increasing age is associated with the disappearance of abdominal pain in the community.

Associations between medication use and functional gastrointestinal disorders: a population-based study.

BACKGROUND: Functional GI syndromes are known to be very prevalent, but this may be linked to unrecognized medications use. We aimed to estimate the prevalence of PPI, antidepressant, and narcotic use in the general population, and to evaluate the association between each medication and functional GI syndromes adjusting for potential confounders. METHODS: In 2008 and 2009, newly revised versions of a validated bowel disease questionnaire were mailed to a community-based cohort (total mailed = 8006) of Olmsted County, MN residents; 3831 returned the questionnaire (response rate = 48.0%). Medication usage, specifically PPIs, narcotics, and antidepressants in the last year, was elicited via three separate questions on the questionnaire. The association between each medication and GI symptom complexes was assessed using multiple variable logistic regression models. KEY RESULTS: A total of 3515 of the respondents (92%) had complete data (mean age: 61 ± 15; 54% female). The overall proportion reporting PPI use was 20% (95% CI: 19, 22), narcotic use 12% (95% CI: 11, 13), and antidepressant use 15% (95% CI: 14, 16). PPI use was significantly associated with IBS status (OR = 1.4, 95% CI 1.1, 1.7) as well as with GERD (OR = 3.5, 95% CI 2.7, 4.4) and dyspepsia (OR = 2.0, 95% CI 1.5, 2.7). The association of PPI use with IBS was not explained by coexistent GERD or dyspepsia. Antidepressant use was significantly associated only with bloating (OR = 1.6, 1.1, 2.2). CONCLUSIONS & INFERENCES: Some medications that may alter intestinal transit or bowel flora are commonly utilized by the general population, and PPI use appears to be linked to IBS.

Cyclic vomiting syndrome and functional vomiting in adults: association with cannabinoid use in males.

BACKGROUND: Cyclic vomiting syndrome (CVS) is characterized by stereotypical episodes of vomiting separated by symptom-free intervals. However, the difficulty encountered in the management of patients with CVS may be a reflection of a deficiency in our understanding of the disorder. We aimed to evaluate whether clinical or gastric emptying (GE) data discriminate patients labeled as having CVS from functional vomiting (FV) or irritable bowel syndrome (IBS). METHODS: The medical records of patients diagnosed with any vomiting (including CVS, FV) over a 13-year period (1993-2006) at our institution were carefully reviewed. Disease controls were age and gender matched subjects with IBS. Gastric emptying was performed by scintigraphy (99mTc-egg meal). The associations of clinical factors and GE data with patient status (CVS vs FV or IBS) were analyzed. KEY RESULTS: A total of 82 patients with CVS and 62 FV patients were identified. Younger age [per 10 years, OR = 0.7 (0.5, 0.9)], male gender [OR = 0.4 (0.2, 0.9)], and cannabinoid use [OR = 2.9 (1.2, 7.2)] were significantly associated with CVS compared with FV. However, there were no significant associations between patient status (CVS vs FV) and age, BMI, smoking, alcohol use, gastrointestinal symptoms, or GE. The proportion of cannabinoid users was significantly higher in patients with CVS compared with patients with IBS, whereas proportions for headaches and psychiatric disease were higher in subjects with IBS. CONCLUSIONS & INFERENCES: Cyclic vomiting syndrome (vs FV) was not associated with clinical factors, but was associated with younger age, male gender and cannabinoid use. A larger proportion of CVS (vs IBS) patients had used cannabinoids.

Overlap of dyspepsia and gastroesophageal reflux in the general population: one disease or distinct entities?

BACKGROUND: The overlap of dyspepsia and gastroesophageal reflux (GER) is known to be frequent, but whether the overlap group is a distinct entity or not remains unclear. The aims of the study was to evaluate whether the overlap of dyspepsia and GER (dyspepsia-GER overlap) occurs more than expected due to chance alone, and evaluate the risk factors for dyspepsia-GER overlap. METHODS: In 2008 and 2009, a validated Bowel Disease Questionnaire was mailed to a total of 8006 community sample from Olmsted County, MN. Overall, 3831 of the 8006 subjects returned surveys (response rate 48%). Dyspepsia was defined by symptom criteria of Rome III; GER was defined by weekly or more frequent heartburn and/or acid regurgitation. KEY RESULTS: Dyspepsia and GER occurred together more commonly than expected by chance. The somatic symptom checklist score was significantly associated with dyspepsia-GER overlap vs GER alone or dyspepsia alone [OR = 1.9 (1.4, 2.5), and 1.6 (1.2, 2.1), respectively]. Insomnia was also significantly associated with dyspepsia-GER overlap vs. GER alone or dyspepsia alone [OR = 1.4 (1.1, 1.7), OR = 1.3 (1.1, 1.6), respectively]. Moreover, proton pump inhibitor use was significantly associated with dyspepsia-GER overlap vs dyspepsia alone [OR = 2.4 (1.5, 3.8)]. CONCLUSIONS & INFERENCES: Dyspepsia-GER overlap is common in the population and is greater than expected by chance.

Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture.

BACKGROUND: There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited. AIM: Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO. METHODS: A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression. RESULTS: A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO. CONCLUSION: Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation.

Longitudinal direct medical costs associated with constipation in women.

BACKGROUND: Although direct medical costs for constipation-related medical visits are thought to be high, to date, there have been no studies examining longitudinal resource utilisation in adults with constipation. AIM: To estimate the incremental direct medical costs associated with constipation in women. METHODS: This is a nested case-control study. The study population consisted of all mothers of 5718 children in the population-based birth cohort born during 1976-1982 in a community. The cases presented to the medical facilities with constipation. The controls were randomly selected and matched to cases in a 2:1 ratio. Direct medical costs for constipated women and controls were collected for the years 1987-2002. RESULTS: We identified 168 women with a diagnosis of constipation. The total direct medical costs over the 15-year period for constipated subjects were more than double those of controls [$63 591 (95% CI: 49 786-81 396) vs. $24 529 (95% CI: 20 667-29 260)]. The overall out-patient costs for constipated women were $38 897 (95% CI: 31 381-48 253) compared to $15 110 (95% CI: 12 904-17 781) for controls. The median of annual out-patient visits for constipated women was 0.16 compared to 0.11 for controls. CONCLUSION: Women with constipation have significantly higher medical care utilisation and expenditures compared with women without constipation.

Measurement of abdominal symptoms by validated questionnaire: a 3-month recall timeframe as recommended by Rome III is not superior to a 1-year recall timeframe.

BACKGROUND: Rome III incorporates changes in the definition of functional gastrointestinal disorder that involve a 3-month recall time for symptoms, rather than 1-year. AIM: To validate a new version of the Talley-Bowel Disease Questionnaire (Talley-BDQ) and assess the impact of recall time period on the prevalence of symptoms. METHODS: A sample of community residents were randomly mailed a survey using 1-year (n = 396) or 3-month recall period (n = 374). We evaluated the reliability and the concurrent validity of the two versions of the questionnaire. The proportions of subjects reporting symptoms in the two versions were compared. RESULTS: The median (IQR) kappa on symptom-related questions was 0.70 (0.57-0.76) from the 1-year version and 0.66 (0.56-0.77) from the 3-month version. A median kappa of 0.39 (0.19-0.70) and 0.58 (0.39-0.73) was observed for concurrent validation of the 1-year and 3-month versions respectively. Except for gastro-oesophageal reflux symptoms, no differences were observed on the prevalence of clinically relevant symptoms. CONCLUSION: The revised Talley-BDQ is reliable, with excellent reproducibility and validity. There were few differences in reported symptom rates between the 3-month and 1-year recall time versions of the questionnaire. A 1-year recall time may more efficiently capture infrequent or subtle symptoms.

Prevalence and risk factors for abdominal bloating and visible distention: a population-based study.

BACKGROUND: Abdominal bloating and visible distention are common yet poorly understood symptoms. Epidemiological data distinguishing visible distention from bloating are not available. We aimed to evaluate the prevalence and potential risk factors for abdominal bloating and visible distention separately in a representative US population, and their association with other functional gastrointestinal disorders (FGIDs). METHODS: The validated Talley Bowel Disease Questionnaire was mailed to a cohort selected at random from the population of Olmsted County, Minnesota. The complete medical records of responders were abstracted; 2259 subjects (53% females; mean age 62 years) provided bloating and distention data. RESULTS: The age and sex-adjusted (US White 2000) overall prevalence per 100 for bloating was 19.0 [95% confidence interval (CI), 16.9 to 21.2] vs 8.9 (95% CI, 7.2 to 10.6) for visible distention. Significantly increased odds for bloating alone and separately for distention (vs neither) were detected in females, and in those with higher overall Somatic Symptom Checklist (SSC) scores and higher scores of each individual SSC item. Further, females [odds ratio (OR), 1.5; 95% CI, 1.0 to 2.1], higher SSC score (OR, 1.4; 95% CI, 1.1 to 1.8), constipation-predominant irritable bowel syndrome (OR, 2.3; 95% CI, 1.3 to 4.1), dyspepsia (OR, 1.9; 95% CI, 1.1 to 3.2), and gastro-intestinal symptom complex overlap (OR, 1.7; 95% CI, 1.1 to 2.7) significantly increased odds for distention over bloating alone. CONCLUSIONS: Bloating and distention are common and have similar risk factors; somatisation probably plays a role.

Asimadoline, a kappa-opioid agonist, and satiation in functional dyspepsia.

BACKGROUND: Asimadoline, a kappa-opioid agonist, reduces visceral sensitivity in experimental animal models and may decrease satiation and postprandial fullness in healthy individuals. However, its effect on satiation in functional dyspepsia is unclear, and any symptom benefit has not been explored. AIM: To evaluate the effects of asimadoline on satiation volume and postchallenge symptoms in functional dyspepsia. METHODS: A randomized, double-blind trial evaluated gastric satiation and symptoms before and after 8 weeks of asimadoline 0.5 mg (n = 13) or 1.0 mg (n = 13) or placebo (n = 14) b.d. in patients with functional dyspepsia (Rome II). Gastrointestinal Symptom Rating Scale and Nepean Dyspepsia Index were used to assess symptoms during the 8-week treatment. RESULTS: Over 8 weeks of treatment, asimadoline had no significant effect on maximum-tolerated volume or aggregate symptom score with nutrient drink challenge, and on the mean of the total daily symptom severity score compared to placebo. In a post hoc analysis, asimadoline 0.5 mg significantly increased the maximum-tolerated volume (1217 mL +/- 90.2) compared to placebo (807 mL +/- 111.8) in patients with higher postprandial fullness scores (P = 0.01). CONCLUSION: Asimadoline overall did not significantly alter maximum-tolerated volume, symptoms postnutrient challenge or symptoms over 8 weeks in functional dyspepsia.

A novel partial 5HT3 agonist DDP733 after a standard refluxogenic meal reduces reflux events: a randomized, double-blind, placebo-controlled pharmacodynamic study.

BACKGROUND: DDP733, a selective partial 5HT(3) receptor agonist, increases lower oesophageal sphincter pressure in experimental animal models. However, its effect on gastro-oesophageal reflux or lower oesophageal sphincter pressure in humans remains unknown. AIM: To evaluate the effect of DDP733 on reflux episodes in healthy volunteers receiving a refluxogenic meal. METHODS: A randomized, double-blind, placebo-controlled cross-over study evaluated the pharmacodynamic effects of DDP733 (0.5, 0.8 and 1.4 mg). Healthy subjects underwent oesophageal manometry and intra-oesophageal multichannel intraluminal impedance and pH after a refluxogenic meal. RESULTS: DDP733 0.5 mg significantly (P = 0.013) reduced the rate of reflux episodes after a refluxogenic meal from 10 (+/-2.2) on placebo to 6 (+/-1.2) on drug over a 2-h period. DDP733 0.8 and 1.4 mg had no significant effect on reducing the number of reflux episodes. Significant differences in resting lower oesophageal sphincter pressure and the proportion of time pH was <4 (placebo minus drug) after a refluxogenic meal were not observed. No serious adverse events were reported. CONCLUSION: In healthy subjects, the partial 5HT(3) agonist DDP733 at a dose of 0.5 mg significantly reduces the rate of reflux events, but did not result in a significant change in lower oesophageal sphincter pressure at 1 h postdosing.

The effect of short-term, low-dose tricyclic and tetracyclic antidepressant treatment on satiation, postnutrient load gastrointestinal symptoms and gastric emptying: a double-blind, randomized, placebo-controlled trial.

Antidepressants are commonly prescribed for patients with functional dyspepsia. However, the effect of tricyclic antidepressants on satiation and gastric emptying remains unclear, and there are no data for tetracyclic compounds. To compare the effects of nortriptyline (maximum dose: 50 mg daily) and mirtazapine (30 mg daily) vs placebo on gastric emptying, gastric satiation and postprandial symptoms after a nutrient load in healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 14 days of nortriptyline (n = 13), mirtazapine (n = 13), or placebo (n = 14) in healthy volunteers. Validated methods were used to study gastric emptying ((13)C-octanoate) and satiation postnutrient drink test. The three arms were comparable with regard to age, gender, body mass index and hospital anxiety/depression scale. There were no statistically significant effects of mirtazapine or nortriptyline on gastric emptying compared to placebo (P = 0.34). Maximum tolerated volume was similar on drug and placebo (P = 0.56). Aggregate symptom score 30 min postmaximum tolerated volume after nutrient drink challenge on placebo was 132 (+/-21), vs 165 (+/-21) on mirtazapine, and 126 (+/-21) on nortriptyline 50 mg respectively (P = 0.28). Tricyclic and tetracyclic antidepressant agents do not appear to have significant effects on gastric motor or satiation postnutrient challenge in healthy individuals at the doses tested.