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Background: The disease severity index (DSI) for inflammatory bowel disease (IBD) combines measures of disease phenotype, inflammatory activity, and patient-reported outcomes. We aimed to validate the DSI and assess its utility in predicting a complicated IBD course., Methods: A multicenter cohort of adults with IBD was recruited. Intraclass correlation coefficients (ICCs) and weighted Kappa assessed inter-rater reliability. Cronbach's alpha measured internal consistency of DSI items. Spearman's rank correlations compared the DSI with endoscopic indices, symptom indices, quality of life, and disability. A subgroup was followed for 24 months to assess for a complicated IBD course. Area under the receiver operating characteristics curve (AUROC) and multivariable logistic regression assessed the utility of the DSI in predicting disease progression., Results: Three hundred and sixty-nine participants were included (Crohn's disease [CD], n = 230; female, n = 194; mean age, 46 years [SD, 15]; median disease duration, 11 years [interquartile range, 5-21]), of which 171 (CD, n = 99; ulcerative colitis [UC], n = 72) were followed prospectively. The DSI showed inter-rater reliability for CD (ICC 0.93, n = 65) and UC (ICC 0.97, n = 33). The DSI items demonstrated inter-rater agreement (Kappa > 0.4) and internal consistency (CD, α > 0.59; UC, α > 0.75). The DSI was significantly associated with endoscopic activity (CDn=141, r = 0.65, P < .001; UCn=105, r = 0.80, P < .001), symptoms (CDn=159, r = 0.69, P < .001; UCn=132, r = 0.58, P < .001), quality of life (CDn=198, r = -0.59, P < .001; UCn=128, r = -0.68, P < .001), and disability (CDn=83, r = -0.67, P < .001; UCn=52, r = -0.74, P < .001). A DSI of 23 best predicted a complicated IBD course (AUROC = 0.82, P < .001) and was associated with this end point on multivariable analyses (aOR, 9.20; 95% confidence interval, 3.32-25.49)., Conclusions: The DSI reliably encapsulates factors contributing to disease severity and accurately prognosticates the longitudinal IBD course., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: Subcutaneous [SC] infliximab may provide multiple benefits over intravenous [IV] formulations. However, studies for efficacy and safety in inflammatory bowel disease [IBD] have been constrained by small sizes that limit the interpretation of outcomes, particularly for subgroups potentially at high risk of disease relapse., Methods: We conducted a systematic review and random-effects meta-analysis up to January 2023, to evaluate the change in clinical remission after transitioning from IV to SC infliximab in patients with IBD in clinical remission. The primary outcome was measured using the relative risk for meta-analysis., Results: We identified 15 studies of patients established ≥ 3 months on IV infliximab, consisting of 1371 patients and 840 patient-years of follow-up. There was no loss of clinical remission in the IBD cohort overall, Crohn's disease [CD], or perianal CD [p = 0.55 and p = 0.11 at 9-12 months, and p = 0.50 at 6 months, respectively]. Neither prior IV dose [≤ 10 mg/kg 6-weekly] [p = 0.48] nor IBD disease subtype was associated with an increased clinical relapse rate at 6 months (p = 0.48 and p = 0.45 [UC vs CD], respectively)., Conclusion: Changing patients established on IV infliximab to an SC formulation is associated with a high ongoing clinical remission and a low adverse event rate. Furthermore, there are no signals for adverse outcomes among different IBD disease subtypes, nor in those on escalated IV infliximab dosing schedules up to 10 mg/kg 6-weekly. These data should provide patients and clinicians alike with confidence in SC infliximab use in IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The management of pregnant women with inflammatory bowel disease (IBD) is complex. We aimed to assess health care professionals' (HCPs) theoretical and applied knowledge of pregnancy-related IBD issues., Methods: A cross-sectional international survey was distributed to HCPs providing IBD care between October 2020 and March 2021. Knowledge was assessed using the validated Crohn's and Colitis Pregnancy Knowledge Score (CCPKnow; range, 0-17). Decision-making was assessed by free text responses to 3 clinical scenarios scored against predetermined scoring criteria (maximum score 70)., Results: Among 81 participants, median CCPKnow score was 16 (range, 8-17), and median total scenario score was 29 (range, 9-51). Health care professionals who treat >10 IBD patients per week (CCPKnow P = .03; scenarios P = .003) and are more regularly involved in pregnancy care (CCPKnow P = .005; scenarios P = .005) had significantly better scores. Although CCPKnow scoring was consistently high (median score ≥15) across all groups, consultants scored better than trainees and IBD nurses (P = .008 and P = .031). Median scenario scores were higher for consultants (32) and IBD nurses (33) compared with trainees (24; P = .018 and P = .022). There was a significant positive correlation between caring for greater numbers of pregnant IBD patients and higher CCPKnow (P = .001, r = .358) and scenario scores (P = .001, r = .377). There was a modest correlation between CCPKnow and scenario scores (r = .356; P < 0.001)., Conclusions: Despite "good" theoretical pregnancy-related IBD knowledge as assessed by CCPKnow, applied knowledge in the scenarios was less consistent. There is need for further HCP education and clinical experience to achieve optimal standardized care for IBD in pregnancy., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The UNIFI long-term extension [LTE] study reports the efficacy and safety of subcutaneous 90 mg ustekinumab through 3 years of maintenance therapy., Methods: Patients randomised to ustekinumab every 12 weeks [q12w] or every 8 weeks [q8w] at maintenance baseline [N = 348] and randomised ustekinumab-treated patients in the LTE [N = 284] were evaluated. Symptomatic remission [Mayo stool frequency = 0/1, rectal bleeding = 0] was assessed. Safety included all LTE patients [N = 188 placebo and N = 457 ustekinumab]., Results: Among patients randomised to the ustekinumab q12w and q8w groups at maintenance baseline, 54.1% and 56.3% achieved symptomatic remission at Week 152, respectively. Overall, 20% of patients discontinued ustekinumab, 10% of biologic-naïve and 30% of biologic-exposed patients. Among patients in symptomatic remission at Year 3, 94.6% and 98.0% of patients were also corticosteroid free, respectively. Corticosteroid-free symptomatic remission rates in the ustekinumab q12w and q8w groups were 51.2% and 55.1% at Week 152, respectively. Remission rates were higher for biologic-naïve patients than for those with a history of biologic failure. Biochemical evidence of response was demonstrated by stable, decreased C-reactive protein and faecal calprotectin measurements over 3 years. From Weeks 96 to 156, no deaths, major adverse cardiovascular events, or tuberculosis occurred. Nasopharyngitis, ulcerative colitis, and upper respiratory tract infection were most frequently reported. One ustekinumab-treated patient with a history of basal cell carcinoma [BCC] reported two BCCs. One patient in the q8w ustekinumab group, who was receiving concomitant 6-mercaptopurine, experienced serious adverse events of neutropenic sepsis and oral herpes., Conclusions: Efficacy of ustekinumab in patients with ulcerative colitis was confirmed through 3 years. No new safety signals were observed., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon. A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Poor knowledge of inflammatory bowel disease [IBD] in pregnancy underlies unwarranted voluntary childlessness [VC], and risks poorer obstetric outcomes and adverse fetal outcomes. IBD is increasing worldwide but education on IBD issues might be heterogeneous based on cultural differences and variations in models of care., Methods: Consecutive female IBD subjects aged 18-45 years were prospectively recruited from two dedicated IBD-pregnancy clinics, two multidisciplinary IBD clinics and nine general gastroenterology clinics. Subjects completed the validated CCPKnow [score 0-17] with questions on demographics, medical history and pregnancy knowledge. The primary outcome was knowledge per clinic-type and per geographical region., Results: Surveys were completed by 717 subjects from 13 hospitals across ten countries. Dedicated IBD-pregnancy clinics had the highest knowledge, followed by multidisciplinary IBD clinics then general IBD clinics (median CCPKnow 10.0 [IQR: 8.0-11.0], 8.0 [IQR: 5.0-10.5] and 4.0 [IQR:2.0-6.0]; p < 0.001). Median CCPKnow scores in Western, Asian and Middle Eastern clinics were 9.0, 5.0 and 3.0 respectively [p < 0.001]. Dedicated IBD-pregnancy clinics, IBD support organization membership, childbearing after IBD diagnosis and employment independently predicted greater knowledge. Patient perception of disease severity [r = -0.18, p < 0.01] and consideration of VC [r = -0.89, p = 0.031] negatively correlated with CCPKnow score. The overall VC rate was 15.0% [95% CI: 12.2-18.2]. VC subjects had significantly lower pregnancy-specific IBD knowledge than non-VC subjects (median CCPKnow 4.0 [IQR: 2.0-6.0] and 6.0 [IQR: 3.0-9.0] respectively; p < 0.001). Pregnancy-specific IBD knowledge and dedicated IBD-pregnancy clinic attendance were significant negative predictors of VC., Conclusions: In this large international study we identified predictors of pregnancy-specific IBD knowledge. Dedicated IBD-pregnancy clinics had the greatest IBD-related pregnancy knowledge and lowest VC rates, reflecting the benefits of pre-conception counselling., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: The use of immunomodulators (IMs) is often avoided in elderly patients with inflammatory bowel disease (IBD) due to concerns about complications. Our aim is to compare the use of IMs in elderly and younger patients with Crohn's disease (CD) or ulcerative colitis (UC) and identify markers that predict their use., Methods: In this retrospective cohort study, patients diagnosed with IBD from 1970 to 2009 were recruited from the "Sydney IBD Cohort." Patients diagnosed at age 60 years old or older and between 16 and old 40 years were classified as "elderly-onset" and "young-onset" respectively., Results: A total of 255 elderly-onset patients (115 CD, 140 UC) and 1244 young-onset patients (657 CD, 587 UC) were recruited. Most elderly-onset patients had colonic CD (61.4%), whereas young-onset patients had predominantly ileocolonic CD (42.8%, P < 0.0001). Left-sided UC was the most common disease localization for both elderly-onset (52.1%) and young-onset patients (42.2%, P = 0.013). The cumulative probability of IM exposure at 5 years post-diagnosis was significantly less in elderly-onset patients compared with young-onset patients for CD (20.0% vs 33.4%, P = 0.0002) and UC (7.8% vs 13.4%, P = 0.0007). Age at diagnosis was not associated with the time to IMs introduction. Charlson Comorbidity Index was shown to delay IM introduction in CD (hazard ratio [HR] 0.863; 95% CI, 0.787-0.946; P = 0.002) and UC (HR 0.807; 95% CI, 0.711-0.917; P = 0.001). Early IM use was associated with reduced need for abdominal and perianal surgery in CD (HR 0.177; 95% CI, 0.089-0.351; P < 0.0001)., Conclusions: Comorbidity and not age at diagnosis is associated with IM introduction. Early IM is associated with reduced surgery in both young- and elderly-onset CD but not UC., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adherence to maintenance medication for inflammatory bowel disease (IBD) is essential for disease control, albeit often poor. Adherence can be measured by drug metabolites, self-report tools, and prescription data. The aim of this study was to test implementation of self-report tools in IBD clinics by evaluating consistency and to validate them by correlation with drug metabolite levels and medication possession ratios (MPRs)., Methods: Ambulatory IBD patients on thiopurine maintenance therapy for >3 months were recruited. Patients self-reported adherence using a visual analog scale (VAS) and Medication Adherence Report Scale (MARS). Thiopurine metabolites levels were assessed using blood, and MPRs were calculated from patient records as the reference standard. Consistency was assessed by McNemar's test (primary outcome), and correlation analysis was performed using Pearson tests., Results: Of 96 patients (58 Crohn's disease, 33 ulcerative colitis, 5 IBD unclassified) 16.6% were classified as nonadherent based on thiopurine metabolites, 14.9% based on VAS, 13.2% based on MARS, and 22.9% based on MPR. VAS and MARS were consistent with thiopurine metabolites (McNemar test P = 0.79, P = 0.45). All 4 methods were consistent with each other when compared directly 1 to 1. Spearman's analysis demonstrated that all 4 methods significantly correlated with each other: (correlation between VAS and thiopurine metabolites: rho = 0.435; P < 0.001; and correlation between MARS and thiopurine metabolites: rho = 0.29; P = 0.005)., Conclusions: Self-report tools correlate significantly with thiopurine metabolites and medication possession ratios. The Medication Adherence Report Scale and VAS are validated adherence assessment tools for IBD and can be used as simple screening tools in clinical practice., (© 2018 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: While inflammatory bowel diseases (IBD) require long-term medication usage to maintain remission, nonadherence is common and adversely associated with poorer clinical outcomes. Personalized IBD Pharmacist Adherence Counselling, based on the Health Beliefs Model of medication perception, may increase medication adherence., Methods: This prospective multi-center longitudinal parallel study recruited consecutive IBD subjects that were classified as baseline medication non-adherers and adherers. Non-adherers received a single IBD Pharmacist Adherence Counselling intervention at baseline, while adherers served as controls. Medication Adherence Report Scale and Beliefs about Medicines Questionnaire were administered up to 24 months. Medication acceptance was defined as high perception of medication necessity with low concerns. The primary endpoint was medication adherence at 24 months., Results: Of 114 subjects approached, 100 completed follow-up, with 36 being baseline nonadherers (median Medication Adherence Report Scale = 15.0) and 64 baseline adherers (median Medication Adherence Report Scale = 19.0; P < 0.001). At 24 months, nonadherence in the IBD Pharmacist Adherence Counselling group decreased from 100% to 44.4% (P = 0.001), whereas nonadherence in controls remained unchanged (P = 0.38). Individually, Beliefs about Medicines Questionnaire Necessity and Concern scores showed no significant changes in both groups, but medication acceptance significantly improved in baseline nonadherers at 12 months (P = 0.031) with a trend toward durable improvement at 24 months (P = 0.063)., Conclusions: Medication nonadherence in IBD can be improved through a single personalized counseling session by an IBD pharmacist, and the benefit was durable for 2 years. This benefit was through improving the acceptance of medication.

Background: Medication nonadherence is common in inflammatory bowel disease and is associated with poor outcomes. There has been no study on pediatric-to-adult transition as a risk factor for nonadherence in inflammatory bowel disease, which has been demonstrated in other diseases. We aimed to assess whether transitioned (TR) patients have higher nonadherence rates than young adults (YAs) diagnosed in adulthood., Methods: Consecutive ambulatory subjects were prospectively recruited and completed the validated Medication Adherence Reporting Scale (MARS), with the primary outcome being adherence differences between group age-matched TR and YA groups. Pediatric subjects were taken as the control group. Perceptions of medication-related necessity and concerns were assessed with the Beliefs about Medicines Questionnaire (BMQ). Nonadherers (defined as MARS ≤16) received the Inflammatory Bowel Diseases Pharmacist Adherence Counselling (IPAC) intervention and adherence change was reassessed after 6 months as a secondary outcome., Results: Adherence in TR patients (n = 38, mean age 20.4, 13.2% nonadherent) was noninferior to and numerically better than YAs diagnosed in adulthood (n = 41, mean age 21.2, 24.4%). Nonadherence in the pediatric control group (n = 50, mean age 14.7) was 8.0%. YAs had significantly higher medication-related concerns (14.6 versus 11.9, P = 0.02) than the pediatric group. The IPAC intervention reduced nonadherence rates by 60% (P = 0.004)., Conclusions: TR patients did not have worse adherence than YAs diagnosed in adulthood. Protective factors may include previous treatment in pediatric centers and the salient symptomatology of inflammatory bowel disease, whereas increasing concerns over medications contribute to nonadherence in YAs. Pharmacist-led counselling improves adherence in these patients.

Background and Aims: The inflammatory bowel disease [IBD] disability index [IBD-DI], which measures IBD-associated disability, has been validated on IBD patients but not those who have had restorative proctocolectomy with ileal pouch-anal anastomosis [RP with IPAA]. This study aimed to utilize the IBD-DI in RP with IPAA recipients and compare ulcerative colitis [UC]-indicated RP with IPAA patients to medically treated UC patients., Methods: This study was population based. Demographic, indication, complication and direct cost data were collected via medical records while disability, quality of life [QoL] and indirect costs were measured using questionnaires and structured interviews. De-identified raw data about medically treated UC patients were provided by a previous study for comparison., Results: In total there were 136 RP with IPAA patients [mean 11.5 years of follow up]. Eighty-four completed the IBD-DI and 80 completed the IBD questionnaire [IBDQ]. The IBDQ and IBD-DI were highly correlated [r = 0.84, p < 0.01]. Worse QoL and disability were found in those who had their position affected at work [both p < 0.01] and those who had more than 100 days off work in the last year [p < 0.01 for QoL and p = 0.012 for disability]. Lower QoL and disability scores were associated with higher indirect and total costs [p < 0.01]. UC patients treated with RP with IPAA had less disability than medically treated UC patients [p = 0.04]., Conclusions: Disability in RP with IPAA recipients can be measured using the IBD-DI. Perioperative complications and high costs of care are associated with higher levels of disability. Disability of RP with IPAA recipients was lower than that of medically managed UC patients., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Interferon-γ-inducible protein-10 [IP-10] mediates immune cell trafficking from the circulation to the inflamed colon and decreases gut epithelial cell survival. IP-10 expression is increased in patients with ulcerative colitis [UC]. We report efficacy and safety results from a dose-ranging induction study of eldelumab, a fully human monoclonal antibody to IP-10, in moderately to severely active UC., Methods: A total of 252 adults with UC [Mayo score ≥ 6 and endoscopic subscore ≥ 2] were randomised 1:1:1 to placebo or eldelumab 15 or 25 mg/kg administered intravenously on Days 1 and 8 and every other week thereafter. The primary endpoint was clinical remission [Mayo score ≤ 2; no individual subscale score > 1] at Week 11. Key secondary endpoints included Mayo score clinical response and mucosal healing at Week 11., Results: Neither eldelumab 15 or 25 mg/kg resulted in significant increases vs placebo in the proportion of patients achieving Week 11 clinical remission. Remission and response rates were 17.6% and 47.1% with eldelumab 25mg/kg, 13.1% and 44.0% with eldelumab 15mg/kg, and 9.6% and 31.3% with placebo. Clinical remission and response rates were higher in anti-tumour necrosis factor [TNF]-naïve patients treated with eldelumab compared with placebo. Eldelumab treatment was well tolerated and no immunogenicity was observed., Conclusions: The primary endpoint was not achieved with induction treatment with eldelumab 15 or 25 mg/kg in patients with UC. Trends towards clinical remission and response were observed in the overall population and were more pronounced in anti-TNF naïve patients. Eldelumab safety signals were consistent with those reported previously [ClinicalTrials.gov number, NCT01294410]., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Increasing demand for fecal microbiota transplantation (FMT) has created a need for stool banks sourced from long-term healthy donors. Here, we describe our experience in recruiting and screening fecal donors., Methods: Mailbox, newspaper, and online advertisements were used. Potential donors were required to satisfy a prescreen telephone conversation, pass blood and stool investigations, then undertake a screening interview including medical history, physical examination, and evaluation of donor selection criteria., Results: One hundred sixteen potential donors were prescreened of whom 74 failed-47 declined based on study donation requirements (primarily related to frequency and duration of donations), 13 had medical comorbidities, 6 variant Creutzfeldt-Jakob disease risk factors, 8 for other reasons. Thirty-eight completed stool and blood testing-1 failed blood testing (indeterminate hepatitis C serology), whereas 15 failed stool investigations (5 Dientamoeba fragilis, 5 Blastocystis hominis, 1 B. hominis and D. fragilis, 1 Giardia intestinalis plus D. fragilis, 1 Norovirus plus Clostridium difficile toxin positive, and 2 leucocytes or erythrocytes on stool microscopy). Of the 18 potential donors proceeding to screening interview, 6 were excluded (3 body mass index >30, 1 illicit drug use, 1 uncontrolled anxiety and concerns regarding compliance, 1 irregular bowel movements after new medication commencement). In total, only 12 of 116 (10%) potential donors were enrolled as study donors., Conclusions: Recruitment of fecal donors for FMT is challenging with only a small percentage ultimately serving as donors. Many were unable or unwilling to meet the donor commitment requirements. A surprisingly large proportion of healthy asymptomatic donors failed stool testing, primarily due to gastrointestinal parasites.

Introduction: Patients with Crohn's disease have poorer health-related quality of life [HRQoL] than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised., Methods: In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein [CRP], Crohn's Disease Activity Index [CDAI], and faecal calprotectin [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time points., Results: A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly [p < 0.001] at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on HRQoL., Conclusion: Intestinal resection of all macroscopic Crohn's disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Defects in the interleukin 10 (IL-10) signalling pathway have been shown to cause very early onset inflammatory bowel disease (IBD). We report a patient with severe infantile-onset IBD with a compound heterozygous IL-10 receptor alpha subunit (IL-10RA) mutation, one of which was paternally-inherited and the other occurring de novo., Methods: Deep sequencing of IL-10, IL-10RA and IL-10 receptor beta subunit (IL-10RB) were performed. Peripheral blood mononuclear cell (PBMC) surface expression of IL-10RA was analysed by flow cytometry. IL-10 signalling pathway was examined by measuring phosphorylated STAT3 in PBMC cultured in the presence of IL-6 or IL-10., Result: We identified a missense mutation in exon 4 of IL-10RA (c.583T>C) in one allele and a nonsense mutation in exon 7 of IL-10RA (c.1368G>T) in the other allele. Neither mutation has been reported previously. The patient has functional IL-10RA deficiency despite normal IL-10RA expression., Conclusion: This represents the first case report of a de novo mutation of IL-10RA that is associated with very early onset severe IBD. Therefore, IL-10 pathway defect should be considered in patients with infantile-onset IBD even if the parents are non-consanguineous., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Inflammatory bowel diseases (IBD) may result in disability. We aim to validate a novel scoring system for the IBD disability index (IBD-DI), and identify predictors of disability and its correlation with work absenteeism., Methods: This prospective IBD ambulatory clinic cohort study measured IBD-DI, Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) or partial Mayo score (pMayo) for ulcerative colitis (UC), IBDQ quality-of-life, and Work Productivity and Activity Impairment. Negative IBD-DI represented greater disability. Validation tests were performed and predictors and extent of work absenteeism were determined., Results: 166 consecutive subjects were recruited (75 CD, 41 UC, 50 controls). IBD-DI correlated with CDAI (r=-0.77, P<0.001), pMayo (r=-0.82, P<0.001) and IBDQ (r=0.86, P<0.001). IBD-DI differentiated CD, and UC from controls (medians -7, -4, +10; P<0.001) with a score of >3.5 identifying controls with 94% sensitivity and 83% specificity (area-under-curve 0.92). Stable patients had unchanged IBD-DI (P=ns) but not in those who relapsed (P<0.001). Intraclass correlation was 0.89 and Cronbach's alpha of internal consistency was 0.94. Diagnosis age, sex, phenotype, perianal disease, prior surgery, steroid-use and disease duration did not influence the IBD-DI but active use of biological agents significantly reduced disability (P=0.03). 21.6% of IBD patients had moderate-severe disability equating to missing >25% of work hours in the previous week. Multivariate analysis identified that only IBD-DI to be predictive of unemployment status (OR: 0.94; 95% CI: 0.89-0.99)., Conclusions: The IBD-DI is a valid tool measuring disability in both CD and UC and correlates with workforce participation. It is a potential useful tool in the assessment of participation restriction and activity limitation., Trial Registration: ACTRN12613000903785., (Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Earlier introduction of immunomodulators (IM) thiopurine or methotrexate is advocated to improve Crohn's disease (CD) outcomes, but whether abdominal surgery can be prevented remains controversial., Methods: A specialist-referred cohort of CD was recruited from 1970 to 2009. Early IM use was defined as commencement of azathioprine or methotrexate within 3 years of CD diagnosis and adherence of at least 6 months. Propensity score matching was conducted to correct for confounders influencing early IM introduction. Outcomes of interest were rates of initial and recurrent major abdominal surgery for CD and their predictive factors., Results: A total of 1035 consecutive patients with CD (13,061 patient-years) were recruited. The risk of first and recurrent major abdominal surgery at 1, 5, and 10 years were 17.5%, 28.4%, and 39.5% and 5.9%, 19.0%, and 33.3%, respectively. Early IM use increased over time from 1.3% to 55.3% (P < 0.0001) and was a significant independent predictor of lower rates of initial abdominal surgery (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.35-0.69), recurrent abdominal surgery (HR, 0.44; 95% CI, 0.25-0.79) and perianal surgery (HR, 0.30; 95% CI, 0.16-0.56). Using propensity score matching, early IM significantly reduced surgical rates (HR, 0.54; 95% CI, 0.37-0.79). Number needed to treat to prevent a surgical event at 5 years from diagnosis and after initial surgery was 6.99 (95% CI, 5.34-11.95) and 8.59 (95% CI, 6.26-23.93), respectively., Conclusions: Early IM use with thiopurines or methotrexate was significantly associated with the reduced need for abdominal and perianal surgery in CD.

Background & Aims: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population., Methods: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires., Results: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment., Conclusions: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities., (Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Poor adherence frequently impaired the efficacy of therapy to maintain remission from inflammatory bowel diseases (IBD). There is a lack of practical and effective interventions to improve adherence. This study aimed to identify modifiable risk factors, which may yield targets for new interventions., Methods: Participants with IBD were recruited from hospital outpatient clinics and office-based gastroenterologists. Demographic and disease-related data were recorded by means of self-administered questionnaires. Modifiable risk factors were assessed with the validated Belief about Medicine Questionnaire, Hospital Anxiety and Depression Score, and short inflammatory bowel disease questionnaire. Adherence was assessed separately for 5-aminosalicylates, thiopurines, and biological agents using the validated Medicine Adherence Report Scale (good adherence defined as >16)., Results: Nonadherence occurred in 102 of 356 participants (28.7%). Adherence increased significantly with more aggressive therapies (median Medicine Adherence Report Scale: 5-aminosalicylates 18, thiopurines 19, biological 20; P < 0.0001). Nonadherence was not associated with anxiety and depression or disease-related patient knowledge. Adherent patients had significantly higher belief of necessity for medication (P < 0.0001) and a trend toward lower concerns about medication (P = 0.08). Membership of an IBD patient organization was associated with better adherence (P < 0.0001). Concerns about medication rose significantly with more aggressive therapies (P = 0.009), but belief of necessity was similar for all medications., Conclusions: Nonadherence occurs most frequently with 5-aminosalicylates. Belief of necessity may prove the key target for future interventions, although general IBD education is unlikely to yield an adherence benefit. Patient organization membership should be encouraged.

Background and Aim: Adherence to medication that maintains remission by patients with ulcerative colitis (UC) is poor but little is known regarding patients' perception of medication benefit that may enhance adherence rates. The aims were to study patients' understanding and preference on methods of conveying statistical information and to study indicated thresholds for adherence to medication for UC., Methods: Four methods of displaying information on benefits of maintenance therapy were explained to patients with UC in remission: relative risk reduction [RR], absolute risk reduction [AR], number needed to treat [NNT] and optical representation via Cates plot [CP]. Patients' understanding and preference for each method were evaluated. Participants were asked to state minimum thresholds relating to relapse prevention and colorectal cancer risk reduction that they would require in order for them to adhere to medication for UC., Results: Of 50 participants, 48% preferred data presentation by RR over CP (28%), AR (20%) and NNT (4%). 94% found RR easy to understand, better than AR (88%), CP (74%), or NNT (48%). For bowel cancer prevention, 94% indicated adherence for benefit levels of 61% RR but only 57% for the corresponding CP (P<0.001). For relapse prevention, 78% of patients indicated adherence for benefit levels of 40% RR but only 43% for the corresponding CP (P<0.001)., Conclusion: Patients with UC prefer data presented by RR, and apply significantly higher thresholds for adherence when presented with CP compared to RR. Reduction of cancer risk may be a stronger motivator than maintenance of remission., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohn's disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia., Methods: A prevalence cohort (1977-1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women., Results: Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971-1979) or later (1980-1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047)., Conclusions: In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.

Background: Inflammatory bowel disease (IBD)-related knowledge not only empowers patients, but may also engender anxiety. The study aimed to identify predictors of anxiety in IBD and examine the interplay between anxiety and disease-related patient knowledge. The effect of anxiety on quality of life was also explored., Methods: Ambulatory IBD patients provided data on demographics, their IBD and Crohn's Colitis Association (CCA) membership status. Disease-related knowledge was assessed using the validated Crohn's and Colitis Knowledge score (CCKnow) and disease related QOL using the short IBD questionnaire (SIBDQ). Anxiety and depression were assessed with the Hospital Anxiety and Depression Scores., Results: Of the 258 patients 19.4% had a potential anxiety and a further 22.4% had a probable anxiety disorder. Females (P=0.003), tertiary care patients (P=0.014) and non-Caucasian patients (P=0.037) had significantly higher anxiety levels. CCA members had marginally higher levels of anxiety (P=0.07). Anxiety was associated with significantly better patient knowledge (P=0.016) and increased depression (P<0.001). Disease related quality of life was significantly lower in patients with anxiety (P<0.001)., Conclusions: This is the first study to demonstrate that better patient knowledge is associated with higher anxiety levels. The reason for this is unclear: educating patients about their disease might trigger anxiety, but, equally, anxious patients might seek out information and hence have better knowledge. It is thus noteworthy that an educational intervention may not necessarily reduce anxiety. Further work is needed to evaluate the association between anxiety and knowledge and to develop targeted interventions that will improve knowledge and simultaneously reduce anxiety., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Background: Enabling women with inflammatory bowel diseases (IBD) to have successful pregnancies requires complex decisions. The study aimed to assess patients' views on IBD and pregnancy and to evaluate any association with subject knowledge., Methods: General attitudes of females with IBD were assessed on fertility, medication use, delivery mode and pregnancy outcomes. Attitudes regarding personal situation were assessed in participants nulliparous since IBD diagnosis. Knowledge of pregnancy-related issues in IBD was assessed by the Crohn's and Colitis Pregnancy Knowledge Score 'CCPKnow'., Results: Of 145 participants 68% of participants agreed with need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms. 36% believed that all IBD medication is harmful to unborn children. Of 96 women nulliparous after IBD diagnosis, 46% were worried about infertility, 75% expressed concern about passing IBD to offspring and 30% considered not having children. Nearly all participants worried about the effects of IBD on pregnancy and the effects of pregnancy on IBD. General attitudes that 'medication should be stopped prior to conception' (P<0.001), 'pregnant women should avoid all IBD drugs' (P<0.001), and 'put up with symptoms' (P<0.001) were associated with significantly lower CCPKnow scores., Conclusion: Over a third of patients considered IBD medication harmful to unborn children. Fear of infertility and concerns about inheritance may explain high rates of voluntary childlessness. Attitudes contrary to medical evidence were associated with significantly lower knowledge. Young women with IBD, particularly those with poor knowledge, should be offered education and counselling about pregnancy-related issues., (Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.)

Ulcerative colitis (UC) and Crohn's disease (CD) may directly result in morbidity and rarely mortality from complications such as colorectal cancer or sepsis. Mortality rates compared with the matched general population, measured by standardized mortality ratio, may therefore be increased. This review examines the evidence derived from cohort- and population-based mortality studies. In CD the majority of studies and two meta-analyses demonstrated increased standardized mortality ratios of ≈ 1.5-fold, especially for those diagnosed at younger ages and requiring extensive or multiple resection surgery. In UC mortality rates are similar to those of the general population in most studies and a meta-analysis. Proctocolectomy removes the inflammatory burden of UC and can manage colorectal dysplasia but may result in perioperative complications. There is no clear temporal trend of improvement in survival for either CD or UC. Few data are available from countries outside Europe and North America, so geographical influences remain largely unknown., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Background: Crohn's disease (CD) exhibits significant clinical heterogeneity. Classification systems attempt to describe this; however, their utility and reliability depends on inter-observer agreement (IOA). We therefore sought to evaluate IOA using the Montreal Classification (MC)., Methods: De-identified clinical records of 35 CD patients from 6 Australian IBD centres were presented to 13 expert practitioners from 8 Australia and New Zealand Inflammatory Bowel Disease Consortium (ANZIBDC) centres. Practitioners classified the cases using MC and forwarded data for central blinded analysis. IOA on smoking and medications was also tested. Kappa statistics, with pre-specified outcomes of κ>0.8 excellent; 0.61-0.8 good; 0.41-0.6 moderate and ≤0.4 poor, were used., Results: 97% of study cases had colonoscopy reports, however, only 31% had undergone a complete set of diagnostic investigations (colonoscopy, histology, SB imaging). At diagnosis, IOA was excellent for age, κ=0.84; good for disease location, κ=0.73; only moderate for upper GI disease (κ=0.57) and disease behaviour, κ=0.54; and good for the presence of perianal disease, κ=0.6. At last follow-up, IOA was good for location, κ=0.68; only moderate for upper GI disease (κ=0.43) and disease behaviour, κ=0.46; but excellent for the presence/absence of perianal disease, κ=0.88. IOA for immunosuppressant use ever and presence of stricture were both good (κ=0.79 and 0.64 respectively)., Conclusion: IOA using MC is generally good; however some areas are less consistent than others. Omissions and inaccuracies reduce the value of clinical data when comparing cohorts across different centres, and may impair the ability to translate genetic discoveries into clinical practice., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Background: According to the Montreal Classification, upper gastrointestinal tract phenotype L4 is uncommon in Caucasian patients with Crohn's disease (CD) but carries excess risk of recurrence. We studied the clinical course of CD in Chinese patients presenting with the L4 phenotype and factors predicting its occurrence upon longitudinal follow-up., Methods: This prospective cohort study included 132 Chinese CD patients (median age at diagnosis, 30.0 years, range: 14.0-77.0 years) who were followed for 770 person-years. Demographic data including disease behavior and location, details of surgery, and hospitalization were collected. The Kaplan-Meier method was used to estimate the probabilities of further hospitalization and major surgery followed by Cox proportional hazards regression to determine if clinical variables independently predicted the endpoints., Results: The L4 phenotype was found in 30 (22.7%) patients at presentation. There were significantly more stricturing (46.7% versus 18.6%) and penetrating (30.0% versus 3.9%) phenotypes in the L4 group than in the non-L4 group (P < 0.0001). The 3-year cumulative probability of further hospitalization was 86.9% (95% confidence interval [CI]: 73.8%-100.0%) in the L4 group as compared with 49.3% (95% CI: 39.3%-59.3%) in the non-L4 group (log-rank test, P < 0.0001). The L4 phenotype independently predicted further hospitalization (adjusted hazards ratio [HR]: 2.1; 95% CI: 1.3-3.5). The cumulative probability of major surgery was significantly higher in the L4 than in the non-L4 group (P < 0.0001). Eighteen (17.6%) patients developed the L4 phenotype on follow-up and the stricturing phenotype predicted its occurrence (adjusted HR: 5.5; 95% CI: 2.2-14.0)., Conclusions: Chinese CD patients more often had the L4 phenotype, which predicted the need of subsequent hospitalization.

Background: Phenotypic evolution of Crohn's disease occurs in whites but has never been described in other populations. The Montreal classification may describe phenotypes more precisely. The aim of this study was to validate the Montreal classification through a longitudinal sensitivity analysis in detecting phenotypic variation compared to the Vienna classification., Methods: This was a retrospective longitudinal study of consecutive Chinese Crohn's disease patients. All cases were classified by the Montreal classification and the Vienna classification for behavior and location. The evolution of these characteristics and the need for surgery were evaluated., Results: A total of 109 patients were recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease behavior changed 3 years after diagnosis (P = 0.025), with an increase in stricturing and penetrating phenotypes, as determined by the Montreal classification, but was only detected by the Vienna classification after 5 years (P = 0.015). Disease location remained stable on follow-up in both classifications. Thirty-four patients (31%) underwent major surgery during the follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI: 1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes according to the Montreal classification associated with the need for major surgery. In contrast, colonic disease was protective against a major operation (P = 0.02; HR: 0.3; 95% CI: 0.08-0.8)., Conclusions: This is the first study demonstrating phenotypic evolution of Crohn's disease in a nonwhite population. The Montreal classification is more sensitive to behavior phenotypic changes than is the Vienna classification after excluding perianal disease from the penetrating disease category and was useful in predicting course and the need for surgery.

Background: Inflammatory bowel disease is uncommon in Southeast Asia but is increasing in incidence. The epidemiology and phenotype of Crohn disease (CD) in the Chinese population is not well-known. The purpose of this study was to determine the incidence, temporal trend, clinical features, risk factors, extraintestinal manifestations, and the treatment of CD in the Chinese population of Hong Kong., Methods: We performed a single-center study of consecutive definite CD cases based on internationally accepted criteria, with strict exclusion of infective enterocolitis., Results: Eighty Chinese CD patients were recruited, characterized by male gender predominance (male:female ratio 2.5:1), no association with ever smoking (OR 1.02, 95% CI: 0.54-1.92), absence of familial clustering (0%), high proportion of upper gastrointestinal tract disease proximal to the terminal ileum (19%), and a low proportion of isolated terminal ileal disease (4%). The mean age at diagnosis was 33 years. Forty-five percent of patients had penetrating disease, 18% stricturing disease, and 37% had nonstricturing, nonpenetrating disease. Twenty-five percent of patients had at least 1 extraintestinal manifestation, and there was a high rate of ankylosing spondylitis (9%). The incidence of CD was 1.0 per 100,000 and has increased by 3 fold during the past decade. The age-adjusted incidence was 3.0 per 100,000 (95% CI: 2.3-3.7 per 100,000)., Conclusions: The incidence of CD in the Chinese is increasing. There are some notable epidemiological and phenotypic differences between Chinese CD with Caucasian CD including the lack of familial clustering, male predominance, and higher proportion of upper GIT involvement and lower frequency of isolated terminal ileal disease., (Copyright 2004 Lippincott Williams & Wilkins)