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Background: Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting., Methods: We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024., Results: The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients., Conclusions: Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future., (© 2024 John Wiley & Sons Ltd.)

Background: Predicting adverse disease outcomes and high-volume users of healthcare amongst patients with inflammatory bowel disease (IBD) is difficult., Aims: The aim of this study is to use latent class analysis to create novel clusters of patients and to assess whether these predict outcomes during 6.5 years of longitudinal follow-up., Methods: Baseline demographic features, disease activity indices, anxiety, depression, and somatoform symptom-reporting scores were recorded for 692 adults. Faecal calprotectin (FC) was analysed at baseline in 348 (50.3%) patients (<250 mcg/g defined biochemical remission). Using baseline gastrointestinal and psychological symptoms, latent class analysis identified specific patient clusters. Rates of glucocorticosteroid prescription or flare, escalation, hospitalisation, or intestinal resection were compared between clusters using multivariate Cox regression., Results: A three-cluster model was the optimum solution; 132 (19.1%) patients had below-average gastrointestinal and psychological symptoms (cluster 1), 352 (50.9%) had average levels of gastrointestinal and psychological symptoms (cluster 2), and 208 (30.1%) had the highest levels of both gastrointestinal and psychological symptoms (cluster 3). Compared with cluster 1, cluster 3 had significantly increased risk of flare or glucocorticosteroid prescription (hazard ratio (HR): 2.13; 95% confidence interval (CI): 1.46-3.10), escalation (HR: 1.92; 95% CI: 1.34-2.76), a composite of escalation, hospitalisation, or intestinal resection (HR: 2.05; 95% CI: 1.45-2.88), or any of the endpoints of interest (HR: 2.06; 95% CI: 1.45-2.93). Healthcare utilisation was highest in cluster 3., Conclusions: Novel model-based clusters identify patients with IBD at higher risk of adverse disease outcomes who are high-volume users of healthcare., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: The long-term natural history and impact of irritable bowel syndrome (IBS)-type symptoms on outcomes in inflammatory bowel disease (IBD) are uncertain., Aim: To assess this in a longitudinal follow-up study of patients in secondary care METHODS: We assessed the natural history of IBS-type symptoms in IBD via Rome III criteria applied at baseline, and 2 and 6 years. We defined longitudinal disease activity as the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. To assess healthcare utilisation, we recorded the number of outpatient clinic attendances and investigations. We also collected anxiety, depression and somatoform symptom scores and quality of life scores during follow-up., Results: Among 125 individuals with Rome III data at all three time points, only 41 (32.8%) never reported IBS-type symptoms. Fifteen patients (12.0%) had IBS-type symptoms at baseline that resolved, 19 (15.2%) had fluctuating symptoms, 35 (28.0%) had new-onset symptoms, and 15 (12.0%) had persistent symptoms. Among more than 300 patients with IBD activity data, IBS-type symptoms were not associated with an increased likelihood of the need for glucocorticosteroids or flare, escalation, hospitalisation or intestinal resection. However, the mean numbers of outpatient appointments and endoscopic investigations were significantly higher among those with IBS-type symptoms. Anxiety, depression and somatoform symptom scores were significantly higher, and quality of life scores were significantly lower, in those reporting IBS-type symptoms at least once during the study., Conclusions: IBS-type symptoms affected more than two-thirds of patients with IBD during >6 years of follow-up and were associated with increased healthcare utilisation, and worse anxiety, depression, somatoform symptom and quality of life scores, but not adverse disease activity outcomes., (© 2022 John Wiley & Sons Ltd.)

Background: Psychological co-morbidity is more common in patients with inflammatory bowel disease (IBD), compared with the general population, but little is known about the cumulative effect of increasing psychological burden on disease behaviour., Aims: To examine the effect of psychological co-morbidity on inflammatory bowel disease in a longitudinal follow-up study., Methods: We collected complete demographic, symptom and psychological co-morbidity data (anxiety, depression and somatisation scores) at baseline from adults with IBD in biochemical remission (faecal calprotectin <250 µg/g). Objective markers of disease activity, including glucocorticosteroid prescription or flare of disease activity, escalation of therapy, hospitalisation or intestinal resection, were reviewed ≥2 years of follow-up. We performed multivariate Cox regression, controlling for patient characteristics and follow-up duration, to examine cumulative effect of psychological co-morbidities on subsequent IBD behaviour., Results: Among 218 participants, 48 (22.0%) had one, 13 (6.0%) two and nine (4.1%) three psychological co-morbidities at baseline. Following multivariate Cox regression analysis, glucocorticosteroid prescription or flare, and escalation of medical therapy were significantly higher among those with two (hazard ratio [HR] = 3.18; 95% confidence interval [CI] 1.44-7.02, and HR = 2.48; 95% CI 1.03-5.93, respectively) or three (HR = 3.53; 95% CI 1.26-9.92, and HR = 8.19; 95% CI 2.88-23.23, respectively) psychological co-morbidities. Occurrence of at least one endpoint of interest was significantly higher with increasing psychological co-morbidity (HR = 1.74; 95% CI 1.07-2.82 for one, HR = 2.47; 95% CI 1.12-5.46 for two and HR = 4.93; 95% CI 1.84-13.17 for three psychological co-morbidities)., Conclusions: Individuals with IBD in biochemical remission experienced a worse disease course with increasing psychological co-morbidity at baseline., (© 2021 John Wiley & Sons Ltd.)

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis., Aim: To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD., Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs)., Results: The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission., Conclusions: VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known., (© 2017 John Wiley & Sons Ltd.)

Background: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest., Aims: To derive and validate a new test that utilises latent class analysis., Methods: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models., Results: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15., Conclusions: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin., (© 2017 John Wiley & Sons Ltd.)

Background: Patient education forms a cornerstone of management of inflammatory bowel disease (IBD). The Internet has opened new avenues for information gathering., Aim: To determine the relationship between different information sources and patient knowledge and anxiety in patients with IBD., Methods: The use of information sources in patients with IBD was examined via questionnaire. Anxiety was assessed with the hospital anxiety and depression scale and disease-related patient knowledge with the Crohn's and colitis knowledge score questionnaires. Associations between these outcomes and demographics, disease-related factors, and use of different information sources were analysed using linear regression analysis., Results: Of 307 patients (165 Crohn's disease, 142 ulcerative colitis) 60.6% were female. Participants used the hospital IBD team (82.3%), official leaflets (59.5%), and official websites (53.5%) most frequently in contrast to alternative health websites (9%). University education (P < 0.001), use of immunosuppressants (P = 0.025), Crohn's and Colitis UK membership (P = 0.001), frequent use of the hospital IBD team (P = 0.032), and frequent use of official information websites (P = 0.005) were associated with higher disease-related patient knowledge. Female sex (P = 0.004), clinically active disease (P < 0.001), frequent use of general practitioners (P = 0.014), alternative health websites (homoeopathy, nutritionists, etc.) (P = 0.004) and random links (P = 0.016) were independently associated with higher anxiety., Conclusions: Different patient information sources are associated with better knowledge or worse anxiety levels. Face-to-face education and written information materials remain the first line of patient education. Patients should be guided towards official information websites and warned about the association between the use of alternative health websites or random links and anxiety., (© 2016 John Wiley & Sons Ltd.)

Background: Tobacco smoking is associated with a reduced risk of developing ulcerative colitis (UC). A high proportion of UC patients perceive a benefit in disease outcomes secondary to smoking. However, the effects of smoking on the natural history of UC are uncertain., Aim: To conduct a systematic review and meta-analysis of the effects of tobacco smoking on the natural history of UC., Methods: A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to December 2015) to identify observational studies reporting data on smoking and rates of colectomy, flare of disease activity, proximal disease extension, and development of pouchitis following panproctocolectomy and ileal pouch-anal anastomosis in patients with UC. Dichotomous data were pooled to obtain odds ratios (ORs), with 95% confidence intervals (CIs)., Results: The search identified 16 eligible studies: five (2615 patients) studying colectomy; four (620 patients) reporting on flare of disease activity; four (687 patients) examining proximal disease extension and three (355 patients) assessing development of pouchitis. Compared with nonsmokers, the odds of colectomy (OR = 0.89; 95% CI 0.62-1.26), flare of disease activity (OR = 1.26; 95% CI 0.65-2.44), proximal extension of disease (OR = 0.57; 95% CI 0.20-1.66) or the development of pouchitis (OR = 0.57; 95% CI 0.21-1.53) were not significantly lower in smokers., Conclusions: Smoking may not improve the natural history of ulcerative colitis. Given the health benefits of smoking cessation and the lack of clear benefit in ulcerative colitis, smoking cessation advice should be incorporated into guidance on the management of ulcerative colitis., (© 2016 John Wiley & Sons Ltd.)

Background: Tobacco smoking is a well-established risk factor for the development of Crohn's disease, and this may lead to a more complicated disease course. However, recent evidence suggests that many patients with Crohn's disease are unaware of this fact., Aim: To perform a systematic review and meta-analysis of the effects of smoking on disease course in Crohn's disease., Methods: A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to July 2015) to identify observational studies reporting data on smoking and rates of surgery or flares of disease activity in patients with Crohn's disease. Dichotomous data were pooled to obtain odds ratios (ORs) for flares of disease activity or need for surgery, with 95% confidence intervals (CIs)., Results: The search identified 33 eligible studies. Compared with nonsmokers, smokers had increased odds of flare of disease activity (OR, 1.56; 95% CI, 1.21-2.01), flare after surgery (OR, 1.97; 95% CI, 1.36-2.85), need for first surgery (OR, 1.68; 95% CI, 1.33-2.12) and need for second surgery (OR, 2.17; 95% CI, 1.63-2.89). The odds of these outcomes among ex-smokers diminished upon smoking cessation, with ORs comparable to those among nonsmokers and, in the case of flare or second surgery, significantly lower than smokers., Conclusions: Smokers with Crohn's disease have a more complicated disease course than nonsmokers, and quitting smoking may ameliorate this. Patients should be reminded of the detrimental effects of smoking on the course of their disease, and smoking cessation advice should be provided to reduce disease burden and costs in these patients., (© 2016 John Wiley & Sons Ltd.)

Background: Irritable bowel syndrome (IBS) is a complex, heterogeneous disease which can be challenging to diagnose. No study has identified and assessed the accuracy of all available methods of diagnosing IBS., Aim: To conduct a systematic review of the literature to identify and assess accuracy of symptom-based diagnostic criteria, biomarkers, psychological markers or combinations thereof., Methods: MEDLINE, EMBASE and EMBASE Classic were searched (until April 2015) to identify studies reporting accuracy of available methods to diagnose IBS in adult populations. Eligible studies assessed accuracy of these diagnostic tests against an accepted reference standard. Data were extracted to calculate positive and negative likelihood ratios, with 95% confidence intervals (CIs), of the diagnostic test utilised. Where more than one study used the same test, data were pooled in a meta-analysis., Results: Twenty-two studies (7106 patients) were eligible. Positive and negative likelihood ratios of the current gold standard, the Rome III criteria, were 3.35 (95% CI: 2.97-3.79) and 0.39 (95% CI: 0.34-0.46), similar to other symptom-based criteria. Eleven biomarkers performed no better than symptom-based criteria. Psychological markers performed well in one study. Five different combinations were assessed. The best in terms of positive likelihood ratio was faecal calprotectin, intestinal permeability and Rome I criteria (26.4; 95% CI: 11.4-61.9), and in terms of negative likelihood ratio serum-based biomarkers and psychological markers (0.18; 95% CI: 0.12-0.25)., Conclusions: Symptom-based diagnostic criteria, biomarkers and psychological markers performed modestly in predicting IBS. Combining symptoms with markers appears more effective, and may represent the way forward in the diagnosis of IBS., (© 2015 John Wiley & Sons Ltd.)