Factors associated with nonadherence to thiopurines in adolescent and adult patients with inflammatory bowel disease.

OBJECTIVES: We hypothesised that nonadherence to thiopurines is more common in adolescents than in adults with inflammatory bowel disease. METHODS: We sought factors associated with thiopurine nonadherence defined by thiopurine metabolite levels. RESULTS: Multivariate logistic regression confirmed that adolescents (odds ratio [OR] 4.6 [95% confidence interval [CI] 1.9-11.5]; P < 0.01) compared with adults, patients with Crohn disease (OR 3.3 [CI 1.1-10.5] P = 0.04) compared with ulcerative colitis, and patients living in more socially deprived areas (OR 1.03 [CI 1.0-1.1] P = 0.02) were more likely to be nonadherent to thiopurines. CONCLUSIONS: Adolescents are more frequently nonadherent than adults: prospective studies are required to determine the reasons for nonadherence in adolescents.

Do children with IBD really respond better than adults to thiopurines?

BACKGROUND AND OBJECTIVES: Children and adolescents with inflammatory bowel disease (IBD) have more extensive and severe disease than adults. Despite a lack of comparative studies, thiopurines are frequently cited as being more efficacious in children. To test this assertion, we compared the efficacy of thiopurines in children with IBD with that in adults matched for disease phenotype. PATIENTS AND METHODS: Fifty paediatric and adult patients with IBD started on a thiopurine were matched for sex, disease type, and extent. Retrospective data were obtained by electronic case note review, and corticosteroid-free clinical remission and tolerance rates at 6 months as well as relapse rates during the subsequent year were recorded. RESULTS: Adverse effects caused discontinuation of thiopurines in 1 of 50 children and 16% (8/50) of adults (P < 0.05). At 6 months, steroid-free remission was achieved in 30% (15/50) of children and 38% (19/50) of adults (P = 0.53). No differences in remission rates were seen according to disease type. At the end of the following year, 73% (11/15) of children and 68% (13/19) of adults remained in remission (P = 1). CONCLUSIONS: Thiopurines are tolerated better by children. When phenotype is matched, there is no difference in the therapeutic response to thiopurines between children and adults with IBD.

Poster presentations at medical conferences: an effective way of disseminating research?

This study aimed to ascertain the value of posters at medical meetings to presenters and delegates. The usefulness of posters to presenters at national and international meetings was evaluated by assessing the numbers of delegates visiting them and the reasons why they visited. Memorability of selected posters was assessed and factors influencing their appeal to expert delegates identified. At both the national and international meetings, very few delegates (< 5%) visited posters. Only a minority read them and fewer asked useful questions. Recall of content was so poor that it prevented identification of factors improving their memorability. Factors increasing posters' visual appeal included their scientific content, pictures/graphs and limited use of words. Few delegates visit posters and those doing so recall little of their content. To engage their audience, researchers should design visually appealing posters by presenting high quality data in pictures or graphs without an excess of words.

Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study.

BACKGROUND: Primary care faecal calprotectin testing distinguishes inflammatory bowel disease (IBD) from functional gut disorder in young patients presenting with abdominal symptoms; however, previous evaluations have excluded patients with alarm symptoms. AIMS: We sought to evaluate the diagnostic accuracy of calprotectin to distinguish IBD from functional gut disorder in young adults in whom general practitioners (GPs) suspected IBD; including patients reporting gastrointestinal alarm symptoms. We hypothesised that calprotectin would reduce secondary care referrals and healthcare costs. METHODS: We undertook a prospective cohort study of 789 young adults (18-46 years old) presenting with gastrointestinal symptoms to 49 local general practices that had undergone calprotectin testing (1053 tests: between Jan 2014 and May 2016) because of suspected IBD. We considered calprotectin levels of ≥100 µg/g positive. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. RESULTS: Overall, 39% (308/789) patients reported gastrointestinal alarm symptoms and 6% (50/789) tested patients were diagnosed with IBD. The positive and negative predictive values of calprotectin testing for distinguishing IBD from functional gut disorder in patients with gastrointestinal alarm symptoms were 50% (95% CI 36%-64%) and 98% (96%-100%): and in patients without gastrointestinal alarm symptoms were 27% (16%-41%) and 99% (98%-100%), respectively. We estimate savings of 279 referrals and £160 per patient. CONCLUSIONS: Calprotectin testing of young adults with suspected IBD in primary care accurately distinguishes IBD from functional gut disorder, even in patients with gastrointestinal alarm symptoms and reduces secondary care referrals and diagnostic healthcare costs.

Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn's disease.

BACKGROUND: Few studies have reported the systematic use of exclusive enteral nutrition in the perioperative setting. AIM: To test the hypothesis that exclusive enteral nutrition provides a safe and effective bridge to surgery and reduces post-operative complications, in adult patients with Crohn's disease requiring urgent surgery for stricturing or penetrating complications. METHODS: Patients treated with exclusive enteral nutrition prior to surgery were each matched with two control patients for disease behaviour, type of surgery, age at diagnosis and disease duration. Data on disease phenotype, nutritional status, operative course and post-operative complications were obtained. RESULTS: Twenty-five per cent [13/51] patients treated with exclusive enteral nutrition avoided surgery. Exclusive enteral nutrition had no effect on pre-operative weight, but it significantly reduced serum CRP [median at baseline 36 (interquartile range, IQR: 13-91] vs. pre-operation 8 (4-31) mg/L, P = 0.02]. The median (IQR) length of surgery was shorter in patients pre-optimised with exclusive enteral nutrition than controls [3.0 (2.5-3.5) vs. 3.5 (3.0-4.0) hours respectively, P < 0.001]. Multivariable logistic regression analysis confirmed that going straight-to-surgery compared exclusive enteral nutrition pre-optimisation was associated with a ninefold increase in the incidence of post-operative abscess and/or anastomotic leak [OR 9.1; 95% CI (1.2-71.2), P = 0.04]. CONCLUSIONS: Exclusive enteral nutrition frequently down-stages the need for surgery in patients presenting with stricturing or penetrating complications of Crohn's disease; it is associated with a reduction in systemic inflammation, operative times and the incidence of post-operative abscess or anastomotic leak. Further trials are needed to elucidate how exclusive enteral nutrition may improve operative outcomes.

Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study.

BACKGROUND: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the effects of psychoactive drugs on disease course are unclear. METHODS: Using retrospective electronic case note review, after exclusion of five patients on low-dose tricyclic antidepressants we compared the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohn's disease), during the years before (year 1) and after (year 2) they were started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and relapse rate in year 1. RESULTS: Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0-4] (median [range]) vs. 0 [0-4], P = 0.002; 1 [0-3] vs. 0 [0-4], P < 0.001, respectively); the controls showed no changes between years 1 and 2 in relapses (1 [0-4] vs. 1 [0-3], respectively) or courses of steroids (1 [0-2] vs. 0 [0-3]). Although there were no differences in the use of other relapse-related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in year 2 compared with year 1 (P < 0.01). No such changes were seen in the controls. CONCLUSIONS: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endoscopies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease course in patients with IBD.

Mood disorders in inflammatory bowel disease: relation to diagnosis, disease activity, perceived stress, and other factors.

BACKGROUND: Anxiety and depression are common in patients with inflammatory bowel disease (IBD); however, the factors associated with mood disorders in patients with ulcerative colitis (UC) and Crohn's disease (CD) are poorly defined. METHODS: In all, 103 patients with UC, 101 with CD, and 124 healthy controls completed the Hospital Anxiety and Depression Scale (HADS). Disease activity was defined both from symptom scores and in UC endoscopically, and in CD by fecal calprotectin and/or serum C-reactive protein. Multivariate regression analyses were used to identify factors associated with anxiety and depression. RESULTS: In both UC and CD, anxiety (HADS-A) and depression (HADS-D) scores were higher than in controls (HADS-A: 8.5 ± 4.1 [mean ± SD], 8.6 ± 3.9, 3.2 ± 1.8, P < 0.001; and HADS-D: 4.1 ± 3.3, 4.7 ± 3.3, 1.7 ± 1.4, P < 0.001, respectively). There were no differences in the prevalence of mild, moderate, and severe anxiety and depression in UC and CD. In UC, anxiety scores were associated with perceived stress and a new diagnosis of IBD; depression was associated with stress, inpatient status, and active disease. In CD, anxiety was associated with perceived stress, abdominal pain, and lower socioeconomic status, and depression with perceived stress and increasing age. CONCLUSIONS: Anxiety and depression are common in IBD. Perceived stress is associated with mood disturbances in both UC and CD, but the other associated factors differ in the two diseases. Gastroenterologists should look for mood disorders in IBD and consider stress management and psychotherapy in affected patients.

The phenotype and course of inflammatory bowel disease in UK patients of Bangladeshi descent.

BACKGROUND: We have tested the hypotheses that compared with local white Caucasians, UK-resident patients of Bangladeshi descent develop inflammatory bowel disease (IBD) at a younger age; more often have Crohn's disease than ulcerative colitis (UC); and have a more aggressive disease course. AIM: To test the hypotheses that compared to white Caucasian patients of English, Scottish or Welsh descent, patients of Bangladeshi descent develop IBD at a younger age; more often have Crohn's disease; and have a more aggressive disease course by screening case-records of these patients. METHODS: We screened the case-records of 132 Bangladeshi and 623 white Caucasian consecutive out-patients. We then matched each Bangladeshi to a patient of white Caucasian descent for age at diagnosis and disease duration. Data on migration status, phenotype, disease course, treatments and extra-intestinal manifestations and complications were obtained. RESULTS: No differences were seen in the adjusted age at diagnosis of IBD between Bangladeshi and white Caucasian patients. More Bangladeshis than white Caucasian patients (P < 0.01) were diagnosed with Crohn's disease than UC. Crohn's phenotype at diagnosis was similar in both groups. However, multivariate Cox logistic regression analyses showed that Bangladeshis developed perianal complications (HR [95% confidence interval CI] 8.6 [1.4, 53.1], P = 0.02), and received anti-TNFs (HR [95% CI] 3.0 [1.2, 7.7], P = 0.02) earlier and underwent surgery later (HR [95% CI] 0.4 [0.2, 0.9], P = 0.03) than white Caucasians. More Bangladeshis with UC had extensive disease (24/40 [60%]) than white Caucasians (16/49 [33%], P = 0.02). Overall, more Bangladeshis were anaemic and vitamin D deficient. CONCLUSIONS: Bangladeshi patients with IBD more frequently have Crohn's than UC. Bangladeshis with Crohn's more frequently develop perianal disease, have earlier medication escalation and undergo surgery later than white Caucasians. Bangladeshis have more extensive UC than white Caucasians. The relative contributions of genotype and environmental factors, including vitamin D, to these phenotypic differences require additional study.

Systematic review: Clostridium difficile and inflammatory bowel disease.

BACKGROUND: There is increasing concern about the apparently rising incidence and worsening outcome of Clostridium difficile infection (CDI) associated with inflammatory bowel disease (IBD). We have systematically reviewed the literature to evaluate the incidence, risk factors, endoscopic features, treatment and outcome of CDI complicating IBD. AIM: To systematically review: clostridium difficile & inflammatory bowel disease. METHODS: Structured searches of Pubmed up to September 2010 for original, cross-sectional, cohort and case-controlled studies were undertaken. RESULTS: Of 407 studies, 42 met the inclusion criteria: their heterogeneity precluded formal meta-analysis. CDI is commoner in active IBD, particularly ulcerative colitis, than in controls. Certainty about a temporal trend to its increasing incidence in IBD is compromised by possible detection bias and miscoding. Risk factors include immunosuppressants and antibiotics, the latter less commonly than in controls. Endoscopy rarely shows pseudomembranes and is unhelpful for diagnosing CDI in IBD. There are no controlled therapeutic trials of CDI in IBD. In large studies, outcome of CDI in hospitalised IBD patients appears worse than in controls. CONCLUSIONS: The complication of IBD by Clostridium difficile infection has received increasing attention in the past decade, but whether its incidence is really increasing or its outcome worsening remains unproven. Therapeutic trials of Clostridium difficile infection in IBD are lacking and are needed urgently.

Application of the WHO fracture risk assessment tool (FRAX) to predict need for DEXA scanning and treatment in patients with inflammatory bowel disease at risk of osteoporosis.

BACKGROUND: Although patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis, low bone mineral density (BMD) alone confers only a modest increase in risk of fracture. The FRAX score, developed by the WHO, is a free web-based clinical scale assessing the 10-year fracture risk and need for lifestyle advice/reassurance, dual X-ray absorptiometry (DEXA) scanning or preventive treatment. AIM: To assess the accuracy of pre-BMD FRAX scores in identifying at risk IBD patients needing BMD measurement (intermediate risk) and/or therapy (high risk). METHODS: We calculated FRAX scores retrospectively in 116 consecutive IBD out-patients (81 Crohn's disease, 35 ulcerative colitis), who were having DEXA scans in 2005-2009 because they were considered at risk of osteoporosis. RESULTS: On DEXA scans, 47% (38/81) and 12% (10/81) patients with Crohn's disease were osteopaenic and osteoporotic, respectively; equivalent figures for patients with UC were 34% (12/35) and 14% (5/35). The clinical FRAX score alone, when compared with the FRAX score including the BMD result, had a sensitivity of 100% (95% CI: 70-100%), specificity of 40% (95% CI: 31-50%), positive predictive value of 16% (95% CI: 9-27%) and negative predictive value of 100% (95% CI: 90-100%) in identifying those patients needing BMD measurement (intermediate risk) or preventive therapy (high risk). CONCLUSIONS: In patients with IBD perceived to be at risk of osteoporosis and/or osteopaenia, the clinical FRAX score alone can predict accurately the risk of osteoporotic fracture, and thereby reduce the need for DEXA scans and unnecessary anti-osteoporosis treatment.