Background and aims: Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G2207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci. Methods: A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN22207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA. Results: OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p = 0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D9 0.79 and 0.88, and r 2 = 0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale. Conclusions: The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD.
Objective: Fatigue is frequently reported by patients with inflammatory bowel disease (IBD), irrespective of disease activity; however, evidence regarding fatigue management is limited. This study tested the effect of individualised advice to increase physical activity and/or omega-3 fatty acids supplementation on fatigue in inactive IBD. Methods:Patients in remission were recruited to a pilot study utilising a randomised Results: From n=656 screened patients, n=74 who met the eligibility criteria (designed to remove confounding factors) were randomised, n=60 commenced, and n=52 completed the study. The primary outcome, fatigue measured with FACIT-F score, was worse with omega-3 supplementation (95%CI:-8.6-(-0.7);p=0.02), and unchanged with exercise advice (p=0.38). Fatigue, measured by IBD-F score, was reduced with exercise 2 advice (95%CI:-3.8-(-0.2);p=0.03). One treatment-related adverse event (musculoskeletal pain) was reported with exercise. Conclusions:Advice to increase physical activity and omega-3 supplementation, singly or in combination, were shown to be well-tolerated in IBD patients in remission. There was no evidence of exercise-related adverse effects on gut symptoms. Fatigue (IBD-F score) was reduced with exercise advice, but fatigue (FACIT-F score) was unchanged.Increasing fatigue with omega-3 supplementation is unexplained. Regular exercise may be a self-management option in IBD-related fatigue.
CyA can be administered orally with good tolerability. We use it as a bridging therapy to Azathioprine. In our population, 84% of those who responded to CyA have not required surgery.
Introduction Corticosteroids are important treatments for acute exacerbations of infl ammatory bowel disease (IBD). In severe fl ares, or when oral steroid has proven unsuccessful, high dose intravenous steroid can be given in a hospital setting. Two intravenous corticosteroids are in common usage: hydrocortisone (HC) and methylprednisolone (MP). As well as the therapeutic glucocorticoid effect, both agents have mineralocorticoid effect. The mineralocorticoid effect of HC is greater than MP at the doses commonly used. It has been noted that high dose HC can cause life threatening hypokalaemia. To the authors' knowledge, the effects of MP and HC on serum potassium levels have not been assessed for a group of patients being treated for fl ares of IBD. Methods The case notes of patients with IBD were studied and details of admissions requiring intravenous steroid were noted. Blood potassium (K) levels on admission and throughout the inpatient stay were recorded. Disease extent and severity on admission was noted. Length of admission, length of steroid course, and whether the patient had surgical intervention or started ciclosporin or biologic therapy was also noted.
Background Patients with Inflammatory Bowel Disease (IBD) often experience the problematic and burdensome symptom of fatigue, both during periods of relapse and remission. The optimal management of fatigue in IBD is uncertain, however there is evidence suggesting that physical activity is likely to be a beneficial way of managing the symptom. The aim of this study is to explore the relationship between fatigue and objective measurements of both physical activity metrics and varying intensities of physical activity for individuals with IBD. Methods A multi-centred, European, cross-sectional, correlational study was employed. A consecutive sample of 187 patients with Crohn’s disease (59%) or ulcerative colitis (41%) were recruited from six IBD centres in the Republic of Ireland (42%), United Kingdom (40%) and Denmark (18%). Fatigue was measured using the IBD-Fatigue (IBD-F) scale, including both the level of fatigue (IBD-F, Section 1) and impact of fatigue (IBD-F, Section 2). Physical activity was objectively measured using scientifically validated triaxial accelerometers (ActiGraph wGT3X-BT) during seven consecutive days. Results A moderate level of fatigue (IBD-F Section 1 Md (IQR) = 10 (6 – 13)), predominantly intermittent in nature (72%) was reported by participants (57.4% female; 59% Crohn’s disease; 43% active disease). Participants self-reported sleeping an average of 8.7 hours over the seven nights. During the week, the intensity of activity was predominantly sedentary (Md 5 days, 22 hours, 20 minutes) or light (Md 19 hours, 35 minutes). The median moderate-to-vigorous intensity of physical activity per day was 32.2 minutes and step count over the week was 47052 steps. There was no evidence of a unique linear or non-linear relationship between each of the objective measurements of physical activity with IBD-related fatigue. This lack of evidence extended separately to patients in remission and to patients with active disease. These findings are in the context of a statistically significant moderately-strong relationship between disease activity (measured using both HBI and SCCAI) and level of fatigue for both patients of Crohn’s disease (rs = .327, p = .001, n = 96) and ulcerative colitis (rs = .353, p = .003, n = 71). Conclusion This large multi-centred study shows no association between objective measurements of physical activity and IBD-fatigue. These findings suggest that engaging or not engaging in physical activity has no differential impact on self-assessment of fatigue.
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