Jamshid S. Kalantar

The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study

Objective Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain–gut mechanism in FGIDs. Design Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. Results Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. Conclusions The central nervous system and gut interact bidirectionally in FGIDs.

Familial aggregation of irritable bowel syndrome: a prospective study

Background: Patients with irritable bowel syndrome (IBS) often report family members with similar symptoms, but family studies are lacking. We hypothesised that if there is familial aggregation, there would be an increased frequency of IBS in first degree relatives of IBS patients compared with relatives of controls (the patient’s spouse). Methods: A valid self report bowel disease questionnaire (BDQ) that recorded symptoms, the somatic symptom checklist (a measure of somatisation), and a family information form (FIF) to collect the names and addresses of all first degree relatives were mailed to two groups of patients and their spouses (patients attending an IBS educational programme and residents of Olmsted County, Minnesota, who had been coded as IBS on a database). A BDQ was then mailed to all first degree relatives of subjects identified from the FIF. IBS diagnosis in the relatives was based on the Manning criteria. Results: The BDQ was sent to a total of 355 eligible relatives; 71% responded (73% relatives of patients, 67% relatives of spouses). Relatives were comparable in mean age, sex distribution, and somatisation score. IBS prevalence was 17% in patients’ relatives versus 7% in spouses’ relatives (odds ratio adjusted for age and sex 2.7 (95% confidence interval (CI) 1.2, 6.3)). When also adjusted for somatisation score, the odds ratio was reduced to 2.5 (95% CI 0.9, 6.7). Conclusions: Familial aggregation of IBS occurs, supporting a genetic or intrafamilial environment component, but this may be explained in part by familial aggregation of somatisation.

The Effects of Lottery Incentive and Length of Questionnaire on Health Survey Response Rates: A Randomized Study

Maximizing the response rate of self-administered questionnaires is key in survey research. We aimed to evaluate the effects of lottery incentive and length of questionnaire on health survey response rates when used in isolation or combined. A random sample of 440 residents in Western Sydney, Australia was randomly allocated to four equal groups to receive or not receive an instant lottery ticket and a long (seven page) or short (one page) questionnaire. The overall response rate was 71.8%. The final response rates were higher among those receiving the short, rather than the long, questionnaire (75.6% versus 68.2%) (P = 0.08); and among those receiving the lottery incentive compared with those not receiving the incentive (75% versus 68.2%) (P = 0.09). By logistic regression analysis, the success of obtaining a completed questionnaire without any follow-up reminders was significantly associated with the lottery incentive but not the questionnaire length (P = 0.03 and P = 0.54, respectively). The difference between lottery and no lottery groups decreased gradually during the follow-up. A lottery incentive is associated with an increased response after the first mailing. A small up-front cost for a lottery ticket may be worthwhile, since it can save further costs by obviating the need for repeated follow-ups.

Antral-type mucosa in the gastric incisura, body, and fundus (antralization): a link between Helicobacter pylori infection and intestinal metaplasia?

OBJECTIVES:Helicobacter pylori is a carcinogen; gastric carcinoma involves a multistep process from chronic gastritis to atrophy, intestinal metaplasia, and dysplasia. The aims of this study were to determine the types of mucosa at different gastric sites in H. pylori-infected and uninfected patients, and whether the presence of antral-type mucosa in the incisura, body, and fundus is associated with gastric atrophy and intestinal metaplasia.METHODS:Two hundred and sixty-eight patients with dyspepsia were enrolled. Eight biopsies (i.e., antrum ×3, body ×2, fundus ×2, and incisura ×1) were obtained. One antral biopsy was used for the CLO-test. Three (each from the antrum, body, and fundus) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with hematoxylin and eosin and Giemsa. A validated serological test was also applied.RESULTS:Overall, 113 (42%) patients were infected with H. pylori. At the incisura, antral-type mucosa was more prevalent in infected than in uninfected patients (84% vs 18%; odds ratio [OR] = 23.9, 95% confidence interval [CI] 12.5–45.8; p < 0.001). Atrophic gastritis and intestinal metaplasia at the incisura was present in 19.5% and 13.3%, respectively, of infected, and 4.5% and 3.2%, respectively, of uninfected patients (both p < 0.01). Moreover, atrophic gastritis at the incisura was associated with the presence of antral-type mucosa at the site (termed antralization); the prevalence of atrophic gastritis was 19.5% (24/123) in the presence of antralization, whereas the rate was 2.1% (3/145) without antralization (OR = 11.4, 95% CI 3.4–39.2; p < 0.001). Similarly, at the incisura, 16.3% (20/123) of “antralized” cases and 1.4% (2/145) of “unantralized” cases had intestinal metaplasia (OR = 13.8, 95% CI, 3.2–60.7; p < 0.001). The association between antralization at gastric body and fundus also appeared to be associated with atrophic gastritis and intestinal metaplasia at these sites.CONCLUSIONS:Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.

Duodenal eosinophilia and early satiety in functional dyspepsia: Confirmation of a positive association in an Australian cohort

Functional dyspepsia (FD), defined by unexplained pain or discomfort centered in the upper abdomen, is common. Diagnosis and treatment of FD based on the symptom‐based Rome criteria remains challenging. Recently, eosinophilia in the duodenum has been implicated in the pathophysiology of FD in adults, specifically increased eosinophils in early satiety and postprandial distress, but the association remains controversial. The aim of this study was to characterize upper gastrointestinal (GI) tract pathology, specifically duodenal eosinophilia, in an Australian cohort of patients with FD.

The impact of laxative use upon symptoms in patients with proven slow transit constipation

BackgroundConstipation severity is often defined by symptoms including feelings of complete evacuation, straining, stool frequency and consistency. These descriptors are mostly obtained in the absence of laxative use. For many constipated patients laxative usage is ubiquitous and long standing. Our aim was to determine the impact of laxative use upon the stereotypic constipation descriptors.MethodsPatients with confirmed slow transit constipation completed 3-week stool diaries, detailing stool frequency and form, straining, laxative use and pain and bloating scores. Each diary day was classified as being under laxative affect (laxative affected days) or not (laxative unaffected days). Unconditional logistic regression was used to assess the affects of laxatives on constipation symptoms.ResultsNinety four patients with scintigraphically confirmed slow transit constipation were enrolled in the study. These patients reported a stool frequency of 5.6 ± 4.3 bowel motions/week, only 21 patients reported <3 bowel motions/week. Similarly, 21 patients reported a predominant hard stool at defecation. The majority (90%) of patients reported regular straining. A regular feeling of complete evacuation was reported in just 7 patients. Daily pain and/or bloating were reported by 92% of patients. When compared with laxative unaffected days, on the laxative affected days patients had a higher stool frequency (OR 2.23; P <0.001) and were more likely to report loose stools (OR 1.64; P <0.009). Laxatives did not increase the number of bowel actions associated with a feeling of complete evacuation. Laxative use had no affect upon straining, pain or bloating scoresConclusionsThe reporting of frequent and loose stools with abdominal pain and/or bloating is common in patients with slow transit constipation. While laxative use is a significant contributor to altering stool frequency and form, laxatives have no apparent affect on pain or bloating or upon a patients feeling of complete evacuation. These factors need to be taken into account when using constipation symptoms to define this population.

Metronidazole- and clarithromycin-resistant Helicobacter pylori in dyspeptic patients in western Sydney as determined by testing multiple isolates from different gastric sites.

It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility. We aimed to determine: (i) the prevalence of metronidazole‐ and clarithromycin‐resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites. Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro‐aerophilic conditions for 5–7 days. Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests. Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin‐resistant strains. The prevalence of metronidazole resistance was not significantly different between men and women (65%vs 60%) or across different age groups. In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others. Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients. It is concluded that metronidazole‐resistant strains of H. pylori are common while clarithromycin‐resistant strains are rare. Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.

Identification of early environmental risk factors for irritable bowel syndrome and dyspepsia

The role of childhood environment including exposure to infection via siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively unknown. We assessed proxy measures of microbial exposure in early childhood to assess if these are associated with IBS and functional dyspepsia in later life.

Rectal bleeding: epidemiology, associated risk factors, and health care seeking behaviour: a population-based study

Purpose  Rectal bleeding is considered an important sign of colonic disease, particularly colorectal cancer. The epidemiology of rectal bleeding in the community is poorly understood. Moreover, there is little information as to whether individuals seek health care for this problem. This study aimed to determine the prevalence of rectal bleeding and levels of healthcare seeking amongst an Australian population.

Is irritable bowel syndrome more likely to be persistent in those with relatives who suffer from gastrointestinal symptoms? A population‐based study at three time points

Background: We tested the hypothesis that subjects with relatives who suffered from abdominal pain or bowel dysfunction would be at an increased risk of more persistent irritable bowel syndrome.