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SUMMARYBackground: The health-related quality of life is impaired in patients with functional gastrointestinal disorders seen in referral centres. Aim: To determine whether the health-related quality of life is impaired in subjects with functional disorders in the community and whether any differences can be explained by psychological co-morbidity. Methods: In a population-based, nested, case-control study, subjects reporting symptoms of either dyspepsia or irritable bowel syndrome and healthy controls were interviewed and completed a battery of psychological measures plus a validated, generic, health-related quality of life measure (Medical Outcomes Study 36-item short form health survey, SF-36). The association between irritable bowel syndrome and dyspepsia and the physical and mental composite scores of SF-36 were assessed with and without adjustment for psychological state. Results: One hundred and twelve cases (30 dyspepsia, 39 irritable bowel syndrome, 32 dyspepsia and irritable

OBJECTIVES-Functional gastrointestinal disorders (FGIDs) comprise a constellation of symptoms that have no identifiable structural or biochemical abnormality. In view of the lack of data from large-scale population-based studies evaluating the effects of these disorders on survival, we aimed to examine whether FGIDs are associated with impaired survival. 1988 and 1993, valid self-report questionnaires that recorded gastrointestinal symptoms required for the diagnosis of irritable bowel syndrome (IBS), chronic constipation, chronic diarrhea, dyspepsia, and abdominal pain were mailed to randomly selected cohorts of Olmsted County, Minnesota residents. Minnesota administrative death records were used to identify which of the survey respondents had died over the follow-up period (through April 2008). The association between survival and each FGID was assessed using proportional hazards regression models with univariate and adjusted hazard ratios (HRs, 95% confidence intervals (CIs)), adjusting for age at time of survey, gender, smoking, alcohol, marital status, and Charlson Comorbidity Index (CCI). METHODS-BetweenRESULTS-Of the 5,262 randomly selected eligible subjects who received a questionnaire, a total of 4,176 responded to the surveys (overall response rate 79%). From these respondents, 243 subjects were excluded because of lack of research authorization (or were registered solely at a different medical institution in Olmsted County, MN), resulting in 3,933 eligible subjects for analysis (eligible response rate 75%); 10% reported symptoms of IBS; 16% chronic constipation; 18% chronic diarrhea; 2% dyspepsia; and 15% abdominal pain. At baseline, the mean (s.d.) age was 54 (18) years, and 52% were female. No association with overall survival was detected for IBS (HR = 1.06 (95% CI: 0.86-1.32)), chronic diarrhea (HR = 1.03 (95% CI: 0.90-1.19)), abdominal pain (HR = 1.09 (95%

SUMMARY BackgroundGastro-oesophageal reflux disease (GERD) and irritable bowel syndrome may occur more often than expected by chance, but little community data exists and risk factors are unknown.

Irritable bowel syndrome (IBS) affects up to 22% of the general population. Its aetiology remains unclear. Previously reported cross-sectional associations with psychological distress and depression are not fully understood. We hypothesised that psychosocial factors, particularly those associated with somatisation, would act as risk markers for the onset of IBS. We conducted a community-based prospective study of subjects, aged 25–65 years, randomly selected from the registers of three primary care practices. Responses to a detailed questionnaire allowed subjects’ IBS status to be classified using a modified version of the Rome II criteria. The questionnaire also included validated psychosocial instruments. Subjects free of IBS at baseline and eligible for follow-up 15 months later formed the cohort for this analysis (n = 3732). An adjusted participation rate of 71% (n = 2456) was achieved at follow-up. 3.5% (n = 86) of subjects developed IBS. After adjustment for age, gender and baseline abdominal pain status, high levels of illness behaviour (odds ratio (OR) = 5.2; 95% confidence interval (95% CI) 2.5–11.0), anxiety (OR = 2.0; 95% CI 0.98–4.1), sleep problems (OR = 1.6; 95% CI 0.8–3.2), and somatic symptoms (OR = 1.6; 95% CI 0.8–2.9) were found to be independent predictors of IBS onset. This study has demonstrated that psychosocial factors indicative of the process of somatisation are independent risk markers for the development of IBS in a group of subjects previously free of IBS. Similar relationships are observed in other “functional” disorders, further supporting the hypothesis that they have similar aetiologies.

In a randomized controlled trial, an intensive promotional campaign failed to increase the uptake of vaccination against influenza among health care workers. The uptake of vaccination was low.

Background Gastrointestinal infections are risk factors for irritable bowel syndrome (IBS) and functional dyspepsia (FD). We investigated whether non-enteric infections and antibiotic exposure are also associated with the development of functional gastrointestinal disorders (FGIDs). Methods In a nested case-control study, random samples of Olmsted County, MN, were mailed valid self-report questionnaires from 1988 through 1994, and then follow-up questionnaires from 1995 through 2003. Survey responders who did not report any FGID symptoms at baseline, but then reported such symptoms in at least 1 subsequent survey, were classified as new-onset cases. Age-matched controls were individuals that did not have symptoms at either the initial or subsequent surveys. Key Results The overall response rate was 78% to the initial survey and 52% to the follow-up survey. Based on the responses, 316 participants had a new onset of an FGID (43 IBS constipation, 95 IBS diarrhea, 25 IBS mixed, and 153 other FGIDs, including FD) and 250 did not (controls). 76% (241/316) of cases reported a non-enteric infection vs 66% (166/250) of the controls. The frequency of enteric infections was similar between the two groups. Of the new FGID cases, 83% had a non-enteric infection that was treated with antibiotic. In a logistic regression model, treatment with antibiotics for a non-gastrointestinal infection was associated with development of an FGID (odds ratio=1.90; 95% CI, 1.21–2.98; P=.005), after adjusting for age and sex. Conclusions & Inference Based on a case-control study, treatment of a non-gastrointestinal infection with antibiotics appears to be a risk factor for development of an FGID.

Background Tryptophan hydroxylase (TPH)1 catalyzes the biosynthesis of serotonin (5-hydroxytrptamine; 5-HT) in enterochromaffin (EC) cells, the predominant source of gut 5-HT. Secreted 5-HT regulates various gut functions through diverse 5-HT receptor (5-HTR) families, and 5-HT transporter (5-HTT) sequesters its activity via uptake into surrounding cells. In inflammatory bowel disease (IBD) mucosal 5-HT signaling is altered, including upregulated EC cell numbers and 5-HT levels. We examined key mucosal 5-HT signaling components and blood 5-HT levels and, as part of a pilot study, investigated the association between 5-HTT gene-linked polymorphic region (5HTTLPR) and Crohn’s disease (CD). Methods In the context of inflammation, colonic expressions of TPH1, 5-HTT and 5-HTRs were studied in CD patients (n=15) and healthy controls (HC; n=10) using quantitative polymerase chain reaction (qPCR). We also investigated 5HTTLPR in 40 CD patients and HC utilizing PCR and measured platelet-poor plasma (PPP) and plasma 5-HT concentrations. Results Compared with HC, inflammation in CD patients was associated with elevated TPH1, 5-HTR3, 5-HTR4, 5-HTR7 and downregulated 5-HTT expressions. In our second cohort of participants, significantly higher PPP and plasma 5-HT levels and higher S-genotype (L/S+S/S) than L/L genotype were observed in CD patients compared with HC. Conclusion Our results suggest that augmented mucosal 5-HT signaling and specific 5-HTTLPR genotype–associated decreased efficiency in 5-HT reuptake, the latter through increased 5-HT availability, may contribute to inflammation in CD patients. These findings revealed important information on various components of 5-HT signaling in intestinal inflammation which may ultimately lead to effective strategies targeting this pathway in IBD.