Reduction in Anxiety and Depression Scores Associated with Improvement in Quality of Life in Patients with Inflammatory Bowel Disease.

BACKGROUND: The aim of this study was to examine the associations among depression, anxiety and health-related quality of life and predictors of improvement of quality of life in patients with inflammatory bowel disease. METHODS: This was a prospective cohort study conducted in the gastroenterology clinic at McMaster University Medical Center in Hamilton, Ontario, Canada from May 2014 to March 2015. We included 60 adult patients above the age of 18 years old with a diagnosis of inflammatory bowel disease. We assessed anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and Health Related Quality of Life (HRQoL) using the Short Inflammatory Bowel Disease questionnaire (SIBDQ) at baseline and after 6 months. Linear regression was performed to estimate the associations among depression, anxiety and predictors of improvement in health-related quality of life. RESULTS: The anxiety scores decreased over the span of 6 months (median HADS-A baseline 9.00 [interquartile range {IQR} 6 to 12], and median HADS-A 6 months 7.00 [IQR 3.75 to 7.00]). There was a moderate negative correlation between anxiety (baseline r = -0.510, and 6-month r = -0.620; P < 0.001), depression (baseline r = -0.630, and 6-month r = -0.670; P < 0.001) and HRQoL scores. Using a multivariate linear regression model, elevated HADS score were associated with lower SIBDQ scores at baseline (Beta coefficient -0.696 [95% confidence interval {CI} -1.51 to -0.842]; P < 0.001). Lower SIBDQ score at baseline predicted decreased SIBDQ at 6 months (Beta coefficient 0.712 [95% CI 0.486 to 1.02]; P < 0.001). CONCLUSION: Anxiety and depression are frequently seen in inflammatory bowel disease patients and lead to poor HRQoL. Psychological comorbidities may contribute to maladaptive behaviours and difficult disease management.

Week 2 Adalimumab Levels Predict Short-term Clinical Remission in Patients With Inflammatory Bowel Disease.

BACKGROUND AND GOALS: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. MATERIALS AND METHODS: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. RESULTS: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P =0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P =0.11). CONCLUSIONS: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis: A Qualitative Assessment of Patient Perceptions and Experiences.

BACKGROUND: Fecal microbiota transplantation (FMT) is a promising experimental therapy for ulcerative colitis (UC), yet patient acceptance remains poorly understood. AIMS: The aim of this study was to explore perceptions and experiences of adult patients who received FMT for UC. METHODS: This study used a qualitative descriptive design with thematic content analysis. Patients who were approached for enrollment in a clinical trial (NCT02606032) were invited to participate in face-to-face semistructured interviews. Two groups were interviewed: those who chose to pursue FMT and those who declined FMT. Non-FMT patients were interviewed once; FMT patients were interviewed twice at pre- and post-treatment. RESULTS: Nine FMT patients (78% female, average age 46.7 years old) and eight non-FMT patients (50% female, average age 39.5 years old) were enrolled. Pretreatment themes included FMT as a natural therapy, external barriers to pursuing FMT, concerns with FMT and factors influencing the decision to pursue FMT. While both groups generally perceived FMT as a natural therapy, pre-FMT patients showed greater acceptance of alternative medicine. Both groups demonstrated poor understanding and similar initial concerns with product cleanliness. Pre-FMT patients were motivated to pursue FMT by feelings of last resort. Post-FMT themes included therapeutic impact of FMT and psychosocial impact of FMT. Post-FMT patients reported overall satisfaction and a unanimous preference for FMT over conventional medications. CONCLUSION: This is the first study to assess adult patient perceptions and real-life experiences with FMT for the treatment of UC. By improving patient education, we may achieve greater acceptance of FMT.

Patients' Experiences and Challenges in Living with Inflammatory Bowel Disease: A Qualitative Approach.

PURPOSE: Inflammatory bowel disease (IBD) significantly impacts patients' quality of life and imposes a considerable psychological, social, and financial burden. While the relationship between disease activity and quality of life is well established, the subjective challenges of living with IBD are more difficult to assess, and suggestions for improving patient experiences are lacking. The aim of this paper was to explore the various challenges patients encounter in living with IBD and to propose suggestions for overcoming them. PATIENTS AND METHODS: This study utilized a qualitative descriptive design with thematic content analysis. Patients were recruited from the Gastroenterology Clinic at McMaster University Medical Centre from December 2014 to April 2015. Data were collected over the course of 5 focus group interviews using a semi-structured interview guide. RESULTS: Seventeen patients aged 25 to 77 years old (mean age 43 years, SD 17 years) were interviewed. Fifteen patients were diagnosed with Crohn's disease and 2 patients were diagnosed with ulcerative colitis. Findings were categorized into 18 subthemes which were grouped into 4 broader themes: awareness factor, psychosocial impacts, financial burden, and quality of care. CONCLUSION: IBD is associated with complex personal challenges across various demographics. Identifying and meeting the unique needs of individual patients may be achieved through improving communication between patients and their healthcare providers. Family-based education approaches, individualized psychotherapy with therapists familiar with IBD, awareness initiatives addressed to important stakeholders, and patient involvement in community support groups may improve overall IBD care.

Fecal Calprotectin, CRP and Leucocytes in IBD Patients: Comparison of Biomarkers With Biopsy Results.

BACKGROUND: This study aimed to compare fecal calprotectin (FC) levels with other commonly used parameters as part of patient care during evaluation for inflammatory bowel disease (IBD). METHODS: We recruited adult IBD patients with ulcerative colitis (UC) and Crohn's disease (CD) and compared the results of the patient's biopsy results (i.e., inflamed versus noninflamed) for six sites (i.e., ileum, ascending colon, transverse colon, descending colon, sigmoid colon, rectum) with concentrations of C-reactive protein (CRP), total leucocytes and fecal calprotectin (FC). RESULTS: We found that FC was significantly elevated in a concentration-dependent manner that correlated with the number of active inflammation sites reported in biopsy. Although CRP and leucocyte measurements trended upwards in line with inflammation reported from biopsy, the results were highly variable and highlighted poor reliability of these biomarkers for indicating IBD inflammation. CONCLUSIONS: These results strongly suggest that FC correlates best with biopsy reports and is a superior marker than CRP and leucocytes.

Higher vedolizumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease.

Background: Although its mechanism of action may confer a safety benefit, vedolizumab has still been associated with adverse events (AE). We investigated whether inflammatory bowel disease (IBD) patients with higher trough vedolizumab serum levels experienced an increased risk of AEs.Methods: This was a retrospective study of 76 IBD patients with at least one measurement of serum vedolizumab available. Vedolizumab levels ranged from <3.5 mcg/mL to 87.2 mcg/mL (median = 15.8 mcg/mL). The primary outcome was the rate of overall AEs. Secondary outcomes included the rates of infections, dermatologic reactions, infusion reactions, and other AEs. Multivariate logistic regression analysis was performed to evaluate the relationship between serum vedolizumab levels and AEs.Results: 19 patients out of 76 reported AEs. In patients with higher vedolizumab levels, there were 10 AEs reported out of 38 patients, which was not significantly different from the 9 AEs reported in 38 patients with lower vedolizumab levels (26.3% vs. 23.7%, p = .79). After adjustment for potential covariates, IBD patients with higher vedolizumab levels did not have higher odds of an AE than patients with lower levels (OR 0.92, 95% CI 0.30-2.81). Longer duration of therapy had higher odds of AEs, (OR of 1.04 at 95% CI 1.00-1.09, p = .0494 per additional month). None of the other variables were associated with a greater risk of AEs.Conclusions: There does not appear to be an increased risk of adverse events in IBD patients with higher vedolizumab levels, but duration of therapy may increase the risk of AEs.

Characterization of Serotonin Signaling Components in Patients with Inflammatory Bowel Disease.

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.

Appropriateness of Biologics in the Management of Crohn's Disease Using RAND/UCLA Appropriateness Methodology.

Background: 3 classes of biologics are now available for the treatment of Crohn's disease. The availability of multiple treatment options has led to questions regarding the appropriateness of each agent for a given patient. We aimed to evaluate physician preferences for the use of specific biologic agents in a variety of Crohn's disease management scenarios using the RAND/UCLA Appropriateness Methodology. Methods: A panel consisting of members of the CINERGI group (Canadian IBD Network for Research and Growth in Quality Improvement) was assembled. A literature review was performed on factors identified as influential upon choice of biologic therapy. Clinical scenarios were developed, and panelists rated the appropriateness of biologic therapy classes in each scenario individually and again during a face-to-face meeting after moderated discussion. Results: Two hundred eighty-eight modifications of 3 clinical scenarios were rated. Factors that influenced biologic choice included perianal disease, antidrug antibody status, extraintestinal manifestations, consideration of potential pregnancy, and history of serious infection or malignancy. Anti-TNF therapy was considered appropriate in the postoperative patient. Ustekinumab and vedolizumab were considered appropriate in patients without perianal disease over the age of 65 with a history of malignancy or serious infection. The use of anti-TNF therapy was considered inappropriate in some scenarios whereby drug level was adequate and no antidrug antibody (ADA) was detectable. Conclusions: We evaluated the appropriateness of the 3 available classes of biologics in a number of scenarios for the treatment of Crohn's disease. History of serious infection and malignancy, particularly in individuals over 65 years, and consideration of future pregnancy were patient-specific variables that impacted treatment decisions. These findings can serve as a guide for providers considering biologic therapy in patients with Crohn's disease.10.1093/ibd/izy333_video1izy333.video15850922807001.

A Comparison of the Prevalence of Anxiety and Depression Between Uncomplicated and Complex IBD Patient Groups.

Our study aimed to assess the physical and mental health aspects and quality of life of patients with inflammatory bowel disease (IBD). We were interested in determining whether IBD patients with complex disease states had higher rates of anxiety and depression than those without complications. Complex and uncomplicated IBD patients were assessed using a demographic questionnaire, Short Form-12 (SF-12), and the Hospital Anxiety and Depression Scale (HADS). Complex IBD patients are defined as those specifically having active inflammation, nutritional, and/or surgical issues. All other IBD patients are defined as those with uncomplicated IBD. Analysis of SF-12 scores indicated that Physical Component Summary scores were below average in 71.9% and 56.0% of the complex and uncomplicated patients, respectively (p < .001), whereas Mental Component Summary scores were below average in 65.6% and 45.3% of the complex and uncomplicated patients, respectively (p < .001). HADS scores in the complex and uncomplicated IBD patients indicated that 29.2% and 18.5%, respectively, were anxiety cases (p < .1) and that 32.3% and 15.9%, respectively, were depression cases (p < .001). Efforts should be focused on the identification and management of anxiety and depression in complex IBD patients, as they may have higher likelihoods of anxiety and depression and lower quality of life.

Modified Delphi Process for the Development of Choosing Wisely for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The prevalence and incidence of inflammatory bowel disease (IBD) in North America is among the highest in the world and imparts substantial direct and indirect medical costs. The Choosing Wisely Campaign was launched in wide variety of medical specialties and disciplines to reduce unnecessary or harmful tests or treatment interventions. METHODS: The Choosing Wisely list for IBD was developed by the Canadian IBD Network for Research and Growth in Quality Improvement (CINERGI) in collaboration with Crohn's and Colitis Canada (CCC) and the Canadian Association of Gastroenterology (CAG). Using a modified Delphi process, 5 recommendations were selected from an initial list of 30 statements at a face-to-face consensus meeting. RESULTS: The 5 things physicians and patients should question: (1) Don't use steroids (e.g., prednisone) for maintenance therapy in IBD; (2) Don't use opioids long-term to manage abdominal pain in inflammatory bowel disease (IBD); (3) Don't unnecessarily prolong the course of intravenous corticosteroids in patients with acute severe ulcerative colitis (UC) in the absence of clinical response; (4) Don't initiate or escalate long-term medical therapies for the treatment of IBD based only on symptoms; and (5) Don't use abdominal computed tomography (CT) scan to assess IBD in the acute setting unless there is suspicion of a complication (obstruction, perforation, abscess) or a non-IBD etiology for abdominal symptoms. CONCLUSIONS: The Choosing Wisely recommendations will foster patient-physician discussions to optimize IBD therapy, reduce adverse effects from testing and treatment, and reduce medical expenditure.

Predictors of persistent gastrointestinal symptoms among new presenters to primary care.

BACKGROUND AND AIMS: To quantify the relative contribution of environmental, clinical, infection and psychosocial factors in the persistence of gastrointestinal (GI) symptoms among new patients presenting to primary care. METHODS: We conducted a population-based prospective cohort study of 4986 adults aged 25-65 years. The study team obtained permission from the participants to monitor their general practice records for consultation with GI symptoms and to contact them at that time. Group 1 (n = 177) patients completed a postal questionnaire, whereas those in group 2 (n = 191) completed an identical questionnaire and provided a blood and stool sample. The participants were followed up for 1 and 6 months postconsultation. RESULTS: Of 610 (12.2%) participants who consulted, 368 (60.3%) agreed to participate. Two hundred and eighty participants (76.1%) completed 1 and 6-month follow-up questionnaires and 106 (37.9%) had persistent (present 1 and 6 months postconsultation) GI symptoms. After adjusting for age, sex, area of residence and duration of symptoms before consultation, symptom persistence was independently predicted by high levels of psychological distress [odds ratio (OR): 2.5, 95% confidence interval (CI): (1.1-5.3)], symptom episode duration of more than 2 h [OR: 3.1, 95% CI: (1.3-7.1)] and symptom interference with daily activities [OR: 2.3, 95% CI: (1.1-4.8)]. Changing diet [OR: 0.2, 95% CI: (0.1-0.9)] and recent gastroenteritis or food poisoning [OR: 0.2, 95% CI: (0.1-0.98)] were associated with protective effects. Infection was not associated. Exposure to three or more of these factors identified 87.3% (n = 92) of the participants with persistent symptoms. CONCLUSION: The factors measured at the time of consultation with GI symptoms can accurately predict those patients at increased risk of persistent symptoms up to 6 months later.

Impact of functional gastrointestinal disorders on survival in the community.

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. METHODS: Between 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). RESULTS: 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% CI: 0.92-1.30)), or dyspepsia (HR=1.08 (95% CI: 0.58-2.02)). Reporting symptoms of chronic constipation was associated with poorer survival (HR=1.23 (95% CI: 1.07-1.42)). This association remained significant after adjusting for the CCI (HR=1.19 (95% CI: 1.03-1.37)). CONCLUSIONS: In this large population-based cohort study with over 30,000 person-years of follow-up, no significant association was observed between survival and IBS, chronic diarrhea, dyspepsia, or abdominal pain. Furthermore, no association was found between increasing burden of FGIDs and survival. However, in contrast to these other FGIDs, subjects with symptoms of chronic constipation were found to be at increased risk of poorer survival. Further investigation is required to determine the cause of this observed association.

The future of molecular approaches to inflammatory bowel disease.

Technological advances in genomics and transcriptomics have resulted in the introduction of molecular tests into the clinical arena. Despite established uses of such tests in the oncology field, their integration into the management of complex diseases has not been widely evaluated. Progress in the field of inflammatory bowel disease (IBD) genetics has been rapid in recent years, and these advances have provided more urgent impetus to investigating the role of molecular tests in IBD. This article summarizes the current state of molecular testing available for IBD, and the potential utility of such tests as research in the area widens.

Functional Dyspepsia: A New Rome III Paradigm.

Functional dyspepsia (FD) is a condition commonly seen in gastroenterological practice. With the introduction of Rome III criteria in 2006, a new approach for categorizing patients has been recommended. The diagnostic criteria suggest that meal-related and pain-predominant symptom groupings that presumably have distinct pathophysiologic mechanisms and potentially different therapeutic targets exist. The new classification is in the early stages of testing; in the meantime, the umbrella term of FD should continue to be utilized in clinical practice. Treatment of FD remains a major challenge. Unfortunately, most of the agents used in practice have limited or no evidence of efficacy, and the results typically are short-lived once therapy is ceased. Appropriate therapy currently is based on a consideration of putative pathophysiologic mechanisms. Testing for and eradicating Helicobacter pylori is a first-line strategy irrespective of the symptom pattern. In patients who have epigastric pain, antisecretory agents are recommended. Antacids, bismuth, and sucralfate seem to be no better than placebo. For meal-related symptoms such as postprandial fullness or early satiety, prokinetics may confer some benefit. However, few choices are available, and the efficacy for those drugs on the market is limited at best. Antidepressants are of uncertain efficacy but are widely used. Psychological therapies seem promising and may confer benefits on both pain and meal-related symptoms. Efficacy of complementary medicines has been suggested in controlled trials, but more data are needed. Emerging treatments include gastric fundus relaxors and visceral analgesics, although their application in FD is still in the preliminary stages.

Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study.

BACKGROUND & AIMS: Functional gastrointestinal disorders (FGID) are common in the community. The natural history of FGID is unknown because of a lack of prospective population-based studies and the indistinct nature of the phenotype. We sought to report the natural history of FGID in a US population. METHODS: This prospective cohort study used data from multiple validated surveys of random samples of Olmsted County, MN, residents over a mean of a 12-year period between 1988 and 2003 (n = 1365). The surveys measured gastrointestinal symptoms experienced during the past year. Each subject received a minimum of 2 surveys. Point prevalence, onset, and disappearance rates and transition probabilities were calculated for individual FGIDs. RESULTS: Between the initial and final surveys, the point prevalences (per 100 residents) were stable for irritable bowel syndrome (8.3% and 11.4%, respectively) and functional dyspepsia (1.9% and 3.3%, respectively). The onset of each of the disorders studied was greater than the disappearance rate, but the transition probabilities varied across the different subgroups. Among people with symptoms at baseline, approximately 20% had the same symptoms, 40% had no symptoms, and 40% had different symptoms at follow-up. CONCLUSIONS: Although the prevalence of the FGID was stable over time, the turnover in symptom status was high. Many episodes of symptom disappearance were due to subjects changing symptoms rather than total symptom resolution. This transition between different FGIDs suggests a common etiopathogenesis.

Treatment of functional dyspepsia.

Functional dyspepsia (FD) is a common reason a patient presents with upper gastrointestinal symptoms for medical care. Although treatment of FD remains expensive, the agents are rarely used in a systematic manner; the majority of treatments are empirical and the results short lived once therapy is ceased. This is partly due to the lack of consistent pathophysiologic markers in FD, so therapy is symptom driven. This review appraises the best evidence on available interventions. A structured scheme for deciding on appropriate therapies is to consider the possible putative pathophysiologic mechanisms. Eradicating Helicobacter pylori, if present, is a first-line strategy. In patients who have symptoms suggesting excessive gastric acid secretion, particularly epigastric pain, antisecretory agents are recommended. Prokinetics may confer benefits on symptoms suggestive of upper gastrointestinal dysmotility, like fullness or early satiety. However, their use is limited due to availability issues. The expanding field of psychologic therapies provides a promising avenue of treatment. Complementary medicines are now widely use and their benefits have been suggested in recent controlled trials. Emerging treatments include cholecystokinin 1 blockers, opioid receptor agonists, and serotonergic agents, although their application in FD is in the preliminary stages.

Psychosocial risk factors for the onset of abdominal pain. Results from a large prospective population-based study.

OBJECTIVE: To determine the psychosocial risk factors for the development of abdominal pain and to determine whether, in those people who consulted, symptoms had been attributed to an organic cause. DESIGN: Prospective population-based postal survey with follow-up survey at 12 months. SETTING: A mixed sociodemographic suburban area of Manchester, UK. PARTICIPANTS: Subjects aged 18-65 years were randomly selected from a population-based primary care register who had responded to a detailed pain questionnaire, which included a pain manikin drawing. They also completed the following psychosocial instruments: General Health Questionnaire, Somatic Symptom Checklist, Fatigue Questionnaire and the Illness Attitude Scales (including the 'health anxiety' and 'illness behaviour' sub-scales). MAIN OUTCOME MEASURES: The onset of new abdominal pain. RESULTS: Of the 1953 participants at baseline, 1763 were free of abdominal pain: 1551 were followed up at 12 months (adjusted follow-up rate of 92%) of which 69 subjects reported new abdominal pain (new onset rate 4.6%). New abdominal pain was similar in females (4.9%) and males (4.2%), and did not vary by age group. Baseline factors which predicted onset were high levels of fatigue (odds ratio [OR] = 3.3, 95% CI: 1.9-5.8), psychological distress (OR = 3.4, 95% CI: 1.9-6.0), high scores on the illness behaviour scale (OR = 3.3, 95% CI: 1.7-6.7) and high levels of health anxiety (OR = 2.1, 95% CI: 1.1-3.9). Reporting low back pain at baseline was also associated with an increased risk of reporting abdominal pain (OR = 2.0, 95% CI: 1.2-3.3). On multivariate analysis, high levels of psychological distress and aspects of prior illness behaviour were the major independent predictors of outcome. Of those who sought health care, only one consultation led to a definite diagnosis. CONCLUSION: In subjects free of abdominal pain, psychological distress, fatigue, health anxiety and illness behaviour are predictors of future onset rather than merely a consequence of symptoms. These results suggest that abdominal pain shares some common features of onset with pain at other sites thought not to be primarily organic in origin.