Psychological illness is commonly associated with functional gastrointestinal disorders and is important to consider during patient consultation: a population-based study

BACKGROUND: Some individuals with functional gastrointestinal disorders (FGID) suffer long-lasting symptoms without ever consulting their doctors. Our aim was to study co-morbidity and lifestyle differences among consulters and non-consulters with persistent FGID and controls in a defined adult population. METHODS: A random sample of the general adult Swedish population was obtained by a postal questionnaire. The Abdominal Symptom Questionnaire (ASQ) was used to measure GI symptomatology and grade of GI symptom severity and the Complaint Score Questionnaire (CSQ) was used to measure general symptoms. Subjects were then grouped for study by their symptomatic profiles. Subjects with long-standing FGID (n = 141) and subjects strictly free from gastrointestinal (GI) symptoms (n = 97) were invited to attend their local health centers for further assessment. RESULTS: Subjects with FGID have a higher risk of psychological illness [OR 8.4, CI(95)(4.0–17.5)] than somatic illness [OR 2.8, CI(95)(1.3–5.7)] or ache and fatigue symptoms [OR 4.3, CI(95)(2.1–8.7)]. Subjects with psychological illness have a higher risk of severe GI symptoms than controls; moreover they have a greater chance of being consulters. Patients with FGID have more severe GI symptoms than non-patients. CONCLUSION: There is a strong relation between extra-intestinal, mental and somatic complaints and FGID in both patients and non-patients. Psychological illness increases the chance of concomitantly having more severe GI symptoms, which also enhance consultation behaviour

Abuse in Women and Men with and without Functional Gastrointestinal Disorders

We aimed to investigate the history of abuse in childhood and adulthood and health-related quality of life (HRQL) in women and men with FGID in the general adult population. A cross-sectional study in a random population sample (n = 1,537, 20–87 years) living in Östhammar municipality, Sweden, in 1995 was performed. Persons with FGID (n = 141) and a group of abdominal symptom-free controls (SSF, n = 97) were selected by means of a validated questionnaire assessing gastrointestinal symptoms (the ASQ). Abuse, anxiety and depression (the HADS) and HRQL (the PGWB) were measured. Women with FGID had a higher risk of having a history of some kind of abuse, as compared with the SSF controls (45% vs.16%, OR = 2.0, 95% CI: 1.01–3.9; SSF = 1), in contrast to men (29% vs. 24% n.s.). Women with a history of abuse and FGID had reduced HRQL 91 (95% CI 85–97) as compared with women without abuse history 100 (95% CI 96–104, P = 0.01, “healthy” = 102–105 on PGWB). Childhood emotional abuse was a predictor for consulting with OR = 4.20 (95% CI: 1.12–15.7.7). Thus, previous abuse is common in women with FGID and must be considered by the physician for diagnosis and treatment of the disorder

Collagen type III alpha I is a gastro-oesophageal reflux disease susceptibility gene and a male risk factor for hiatus hernia

Published Online First 26 April 2009Background and objectives: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal disorder with a genetic component. Our aim was to identify genetic factors associated with GORD. Patients and methods: Four separate patient cohorts were analysed using a step-wise approach. (1) Whole genome linkage analysis was performed in 36 families. (2) Candidate genes were tested for GORD association in a trio cohort. (3) Genetic association was replicated in a case–control cohort. We also investigated genetic association to hiatus hernia (HH). (4) Protein expression was analysed in oesophageal biopsies. Results: A region on chromosome 2, containing collagen type III alpha 1 (COL3A1), was identified (LOD = 3.3) in families with dominant transmission of GORD, stratified for hiatus hernia (HH). COL3A1 showed significant association with GORD in an independent paediatric trio cohort (pcorr = 0.003). The association was male specific (pcorr = 0.018). The COL3A1 association was replicated in an independent adult case control cohort (pcorr = 0.022). Moreover, male specific association to HH (pcorr = 0.019) was found for a SNP not associated to GORD. Collagen type III protein was more abundant in oesophageal biopsies from male patients with GORD (p = 0.03). Conclusion: COL3A1 is a disease-associated gene in both paediatric and adult GORD. Furthermore, we show that COL3A1 is genetically associated with HH in adult males. The GORD- and HH-associated alleles are different, indicating two separate mechanisms leading to disease. Our data provides new insight into GORD aetiology, identifying a connective tissue component and indicating a tissue remodelling mechanism in GORD. Our results implicate gender differences in the genetic risk for both for GORD and HH.B Åsling, J Jirholt, P Hammond, M Knutsson, A Walentinsson, G Davidson, L Agreus, A Lehmann, M Lagerström-Ferme

Doubtful outcome of the validation of the Rome II questionnaire: validation of a symptom based diagnostic tool

<p>Abstract</p> <p>Background</p> <p>Questionnaires are used in research and clinical practice. For gastrointestinal complaints the Rome II questionnaire is internationally known but not validated. The aim of this study was to validate a printed and a computerized version of Rome II, translated into Swedish. Results from various analyses are reported.</p> <p>Methods</p> <p>Volunteers from a population based colonoscopy study were included (n = 1011), together with patients seeking general practice (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67). The questionnaire consists of 38 questions concerning gastrointestinal symptoms and complaints. Diagnoses are made after a special code. Our validation included analyses of the translation, feasibility, predictability, reproducibility and reliability. Kappa values and overall agreement were measured. The factor structures were confirmed using a principal component analysis and Cronbach's alpha was used to test the internal consistency.</p> <p>Results and Discussion</p> <p>Translation and back translation showed good agreement. The questionnaire was easy to understand and use. The reproducibility test showed kappa values of 0.60 for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for the predictability when the diagnoses by the questionnaire were compared to the diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and 0.49 and 86% for IBS. Corresponding figures for the agreement between the printed and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76 and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS 0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly validated before even if diagnoses made by the Rome criteria have been compared to diagnoses made in clinical practice.</p> <p>Conclusion</p> <p>The accuracy of the Swedish version of the Rome II is of doubtful value for clinical practice and research. The results for reproducibility and reliability were acceptable but the outcome of the predictability test was poor with IBS as an exception. The agreement between the digital and the paper questionnaire was good.</p

Future research demands of the United European Gastroenterology (UEG) and its member societies

AIMS: The purpose of this study was to initiate and stimulate collaborative research efforts to support United European Gastroenterology Federation (UEG) member societies facilitating digestive health research in European on the one hand and, on the other hand, to increase EU-funded digestive health research by providing evidence and advice to funding bodies on priority areas. The UEG Research Committee initiated a survey of the current and future research interests of each individual UEG ordinary member society (specialist societies). METHODS: A questionnaire was sent by mail to 17 UEG ordinary member societies asking them to specify research demands related to the most urgent medical need including basic science research, translational research, clinical research, patient management research and research on disease prevention, in an open fashion but with limited word count. RESULTS: The responses from 13 societies were analysed in a semi-quantitative and in a qualitative way, and were clustered into five domains with two aspects each that were consented and shared between three and seven of the responding 13 societies. These clusters resemble topics such as ‘Hot topics’ (e.g. life-style, nutrition, microbial-host interaction), Biomarkers (genetic profiling, gut-brain interaction), Advanced technology (artificial intelligence, personalised medicine), Global research tools (bio-banking, EU trials), and Medical training (education, prevention). CONCLUSION: The generated topic list allows both collaboration between individual specialist societies as well as initiating and fostering future research calls at the EU level and beyond when approaching stakeholders

Exploring the genetics of irritable bowel syndrome: A GWA study in the general population and replication in multinational case-control cohorts

OBJECTIVE: IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. DESIGN: We conducted a GWA study (GWAS) of IBS in a general population sample of 11\u2005326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. RESULTS: One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31 710(-6) in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. CONCLUSIONS: Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

A self administered reliable questionnaire to assess lower bowel symptoms

<p>Abstract</p> <p>Background</p> <p>Bowel symptoms are considered indicators of the presence of colorectal cancer and other bowel diseases. Self administered questionnaires that elicit information about lower bowel symptoms have not been assessed for reliability, although this has been done for upper bowel symptoms. Our aim was to develop a self administered questionnaire for eliciting the presence, nature and severity of lower bowel symptoms potentially related to colorectal cancer, and assess its reliability.</p> <p>Methods</p> <p>Immediately before consulting a gastroenterologist or colorectal surgeon, 263 patients likely to have a colonoscopy completed the questionnaire. Reliability was assessed in two ways: by assessing agreement between patient responses and (a) responses given by the doctor at the consultation; and (b) responses given by patients two weeks later.</p> <p>Results</p> <p>There was more than 75% agreement for 78% of the questions for the patient-doctor comparison and for 92% of the questions for the patient-patient comparison. Agreement for the length of time a symptom was present, its severity, duration, frequency of occurrence and whether or not medical consultation had been sought, all had agreement of greater than 70%. Over all questions, the chance corrected agreement for the patient-doctor comparison had a median kappa of 65% (which represents substantial agreement), interquartile range 57–72%. The patient-patient comparison also showed substantial agreement with a median kappa of 75%, interquartile range 68–81%.</p> <p>Conclusion</p> <p>This self administered questionnaire about lower bowel symptoms is a useful way of eliciting details of bowel symptoms. It is a reliable instrument that is acceptable to patients and easily completed. Its use could guide the clinical consultation, allowing a more efficient, comprehensive and useful interaction, ensuring that all symptoms are assessed. It will also be a useful tool in research studies on bowel symptoms and their predictive value for colorectal cancer and other diseases. Studies assessing whether bowel symptoms predict the presence of colorectal cancer should provide estimates of the reliability of the symptom elicitation.</p

The risk of oesophago-gastric cancer in symptomatic patients in primary care: A large case-control study using electronic records

BACKGROUND: Over 15 000 new oesophago-gastric cancers are diagnosed annually in the United Kingdom, with most being advanced disease. We identified and quantified features of this cancer in primary care. METHODS: Case-control study using electronic primary-care records of the UK patients aged ≥40 years was performed. Cases with primary oesophago-gastric cancer were matched to controls on age, sex and practice. Putative features of cancer were identified in the year before diagnosis. Odds ratios (ORs) were calculated for these features using conditional logistic regression, and positive predictive values (PPVs) were calculated. RESULTS: A total of 7471 cases and 32 877 controls were studied. Sixteen features were independently associated with oesophago-gastric cancer (all P5% in patients ≥55 years was for dysphagia. In patients <55 years, all PPVs were <1%. CONCLUSION: Symptoms of oesophago-gastric cancer reported in secondary care were also important in primary care. The results should inform guidance and commissioning policy for upper GI endoscopy

Evaluation of the Birmingham IBS symptom questionnaire

Abstract Background Irritable Bowel Syndrome (IBS) is a chronic/common condition that causes a significant effect on the individual (reduced quality of life), society (time lost off work) and health services. Comparison of studies evaluating the management of IBS has been hindered by the lack of a widely adopted validated symptom score. The aim of this study was to develop and validate a disease specific score to measure the symptoms of patients with IBS. Methods A self-administered 14-item symptom questionnaire (based on Rome II criteria) was mailed to 533 persons included in a prevalence study of IBS. The reliability of each underlying dimension identified was measured by Cronbach's α. Validity was assessed by comparing symptom scores with concurrent IBS specific quality of life (QoL) scores. Reproducibility was measured by the test-retest method and responsiveness measured by effect size. Results 379 (71%) questionnaires were returned. The underlying dimensions identified were pain, diarrhoea and constipation. Cronbach's α was 0.74 for pain, 0.90 for diarrhoea and 0.79 for constipation. Pain and diarrhoea dimensions had good external validity (r = -0.3 to -0.6), constipation dimension had moderate external validity (r = -0.2 to -0.3). All dimensions were reproducible (ICCs 0.75 to 0.81). Effect sizes of 0.27 to 0.53 were calculated for those with a reported improvement in symptoms. Conclusion The Birmingham IBS Symptom Questionnaire has been developed and tested. It has been shown to be suitable for self-completion and acceptable to patients. The questionnaire has 3 internal dimensions which have good reliability, external validity and are responsive to a change in health status.</p

Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome

<p>Abstract</p> <p>Background</p> <p>Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen <it>Chlamydia </it>could be involved in the pathogenesis of IBS.</p> <p>Methods</p> <p>We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to <it>Chlamydia </it>lipopolysaccharide (LPS) and species-specific monoclonal antibodies to <it>C. trachomatis </it>and <it>C. pneumoniae</it>. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively.</p> <p>Results</p> <p><it>Chlamydia </it>LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for <it>C. trachomatis </it>major outer membrane protein (MOMP). Staining for <it>C. pneumoniae </it>was negative in both patients and controls. <it>Chlamydia </it>LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of <it>Chlamydia </it>LPS up to 11 years. The odds ratio for the association of <it>Chlamydia </it>LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS.</p> <p>Conclusions</p> <p>We found <it>C. trachomatis </it>antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.</p