Validation of the IBD-Control Questionnaire across different sociodemographic and clinical subgroups: secondary analysis of a nationwide electronic survey.

BACKGROUND: The IBD-Control Questionnaire is a simple, generic measure of patient-perceived disease control used increasingly in clinical practice and research. We aimed to address knowledge gaps in its psychometric performance, to ensure that it can be used with confidence in a variety of contexts. METHODS: We analysed 7341 responses to the IBD Registry COVID-19 survey, sent to 40 911 patients who completed an online self-assessment tool during the pandemic. Questions covered demographics, comorbidities, inflammatory bowel disease [IBD] sub-type, and IBD-Control Questionnaire and symptom scores [CD-PRO2 or UC-PRO2]. Psychometric properties of IBD-Control-8 were tested overall and within subgroups (Crohn's disease [CD], ulcerative colitis [UC] and IBD unclassified; male and female; ≤65 and >65 years; number of co-morbidities; deprivation status). RESULTS: Internal consistency was very strong overall [α: 0.84, ω: 0.89] and for each subgroup [α range: 0.81-0.85; ω: 0.86-0.90]. Construct validity was demonstrated by moderate correlation of each item with global rating [VAS] [rs range: 0.47-0.65], strong correlation between IBD-Control-8 score and VAS [rs = 0.74], moderate-to-strong with PRO2 scores [CD: rs = -0.718; UC: rs = -0.602] and significantly higher IBD-Control-8 scores for PRO2-remission vs PRO2-active, consistent across subgroups. Exploratory and confirmatory factor analyses demonstrated a two-factor model (items loading onto 'Health-related Quality of Life' [HRQoL] or 'Treatment' domains). Extensive tests for factorial invariance confirmed consistency. CONCLUSIONS: IBD-Control-8 is a psychometrically robust scale which can be used across a range of populations. It offers a quick, reliable, and valid method of assessing patient-perceived control. The construct of 'control' includes traditional HRQoL and a novel domain relating to treatment perception.

Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia.

Background: Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. Objectives: We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. Design: Retrospective cohort study. Methods: Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. Results: In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). Conclusion: Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia.

Establishing key performance indicators for inflammatory bowel disease in the UK.

Background and aims: Healthcare quality improvement (QI) is the systematic process to continuously improve the quality of care and outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means to measure the variation in care, highlighting the need to define the standards of excellence in IBD care. Through a consensus approach, we aimed to establish key performance indicators (KPIs), providing reliable benchmarks for IBD care delivery in UK. Methods: KPIs that measure critical aspects of a patient journey within an IBD service were identified though stakeholder meetings. A two-stage Delphi consensus was then conducted. The first involved a multidisciplinary team of IBD clinicians and patients to refine definitions and methodology. The second stage assessed feasibility and utility of the proposed QI process by surveying gastroenterology services across UK. Results: First, the four proposed KPIs were refined and included time from primary care referral to diagnosis in secondary care, time to treatment recommendation following a diagnosis, appropriate use of steroids and advanced therapies prescreening and assessment. Second, the Delphi consensus reported >85% agreement on the feasibility of local adoption of the QI process and >75% agreement on the utility of benchmarking of the KPIs. Conclusions: Through a structured approach, we propose quantifiable KPIs for benchmarking to improve and reduce the individual variation in IBD care across the UK.

METRIC-EF: magnetic resonance enterography to predict disabling disease in newly diagnosed Crohn's disease-protocol for a multicentre, non-randomised, single-arm, prospective study.

INTRODUCTION: Crohn's disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis. METHODS AND ANALYSIS: We describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis. ETHICS AND DISSEMINATION: This study protocol achieved National Health Service Research Ethics Committee (NHS REC), London-Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN76899103.

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab.

Background: Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4ß7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting. Methods: Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period. Results: Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001). Conclusion: Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Use of contraceptives and risk of inflammatory bowel disease: a nested case-control study.

BACKGROUND: How contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described. AIM: To examine associations between types of hormonal contraception and development of IBD. METHODS: This was a nested case-control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated. RESULTS: 4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively). CONCLUSIONS: We observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.

Constipation in ulcerative colitis: pathophysiology and practical management.

Clinical experience suggests that there is a cohort of patients with refractory colitis who do have faecal stasis that contributes to symptoms. The underlying physiology is poorly understood, partly because until recently the technology to examine segmental colonic motility has not existed. Patients are given little information on how proximal faecal stasis can complicate colitis. Treatment guidelines are scanty and many patients are offered little apart from laxatives and advice on increasing fibre intake, which often makes symptoms worse. This article aims to review the history, pathology and management, and create impetus for future research on this underappreciated condition.

Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review.

BACKGROUND: Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. OBJECTIVE: To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. DESIGN: This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). DATA SOURCES: PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. REVIEW METHODS: Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. RESULTS: In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). LIMITATIONS: Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. CONCLUSIONS: Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. FUTURE WORK: We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016029363. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.

Crohn's disease causes inflammation of the intestines. Traditional treatment uses drugs, such as steroids, at a gradually increasing dose as symptoms worsen. Newer 'biological' drugs may stop disease, but are not used as an early treatment because they are expensive and have serious side effects. Using biologicals early means knowing which patients will develop severe disease in the future. A 'prognostic biomarker' is a measurement made on a patient that predicts a future outcome. A lot of research has attempted to identify biomarkers that predict severe Crohn's disease, but research is haphazard and of variable quality. We therefore carried out a 'systematic review', which identifies research in a comprehensive and unbiased fashion. We found nearly 30,000 research papers, 71 of which were acceptable quality and described 56 groups of Crohn's disease patients. We then used a statistical method called 'meta-analysis' to combine results from multiple studies. This allowed us to identify the most promising biomarkers to predict future severe disease. We found five clinical biomarkers (e.g. age and smoking), two blood biomarkers and one genetic biomarker that seemed reasonably able to predict future severe Crohn's disease. However, we also found that most research was poorly performed and frequently confused diagnosis (current disease) with prognosis (future disease). Some commonly used biomarkers were not sufficiently investigated. We were surprised to identify so few prognostic biomarkers in the face of a seemingly vast amount of research. Future research should be better conducted and not confuse diagnosis with prognosis. We will use statistical methods to combine the promising biomarkers that we identified into a 'prognostic model', which is a mathematical formula that provides the likelihood of developing severe disease in the future. We will then test how well this works by using patient data from existing Crohn's disease databases.

Incidence and prevalence of inflammatory bowel disease in UK primary care: a population-based cohort study.

OBJECTIVES: We describe temporal trends in the recorded incidence of inflammatory bowel disease (IBD) in UK primary care patients between 2000 and 2018. DESIGN: A cohort study. SETTING: The IQVIA Medical Research data (IMRD) primary care database. PARTICIPANTS: All individuals registered with general practices contributing to IMRD during the period 01 January 2000-31 December 2018. MAIN OUTCOME MEASURES: The primary outcome was the recorded diagnosis of IBD. RESULTS: 11 325 025 individuals were included and 65 700 IBD cases were identified, of which 22 560 were incident diagnoses made during the study period. Overall, there were 8077 incident cases of Crohn's disease (CD) and 12 369 incident cases of ulcerative colitis (UC). Crude incidence estimates of 'IBD overall', CD and UC were 28.6 (28.2 to 28.9), 10.2 (10.0 to 10.5) and 15.7 (15.4 to 15.9)/100 000 person years, respectively. No change in IBD incidence was observed for adults aged 17-40 years and children aged 0-9 years. However, for adults aged over 40 years, incidence fell from 37.8 (34.5 to 41.4) to 23.6 (21.3 to 26.0)/100 000 person years (average decrease 2.3% (1.9 to 2.7)/year (p<0.0001)). In adolescents aged 10-16 years, incidence rose from 13.1 (8.4 to 19.5) to 25.4 (19.5 to 32.4)/100 000 person years (average increase 3.0% (1.7 to 4.3)/year (p<0.0001)). Point prevalence estimates on 31 December 2018 for IBD overall, CD and UC were 725, 276 and 397 per 100 000 people, respectively. CONCLUSIONS: This is one of the largest studies ever undertaken to investigate trends in IBD epidemiology. Although we observed stable or falling incidence of IBD in adults, our results are consistent with some of the highest reported global incidence and prevalence rates for IBD, with a 94% rise in incidence in adolescents. Further investigation is required to understand the aetiological drivers.

Consensus standards of healthcare for adults and children with inflammatory bowel disease in the UK.

OBJECTIVE: Symptoms and clinical course during inflammatory bowel disease (IBD) vary among individuals. Personalised care is therefore essential to effective management, delivered by a strong patient-centred multidisciplinary team, working within a well-designed service. This study aimed to fully rewrite the UK Standards for the healthcare of adults and children with IBD, and to develop an IBD Service Benchmarking Tool to support current and future personalised care models. DESIGN: Led by IBD UK, a national multidisciplinary alliance of patients and nominated representatives from all major stakeholders in IBD care, Standards requirements were defined by survey data collated from 689 patients and 151 healthcare professionals. Standards were drafted and refined over three rounds of modified electronic-Delphi. RESULTS: Consensus was achieved for 59 Standards covering seven clinical domains; (1) design and delivery of the multidisciplinary IBD service; (2) prediagnostic referral pathways, protocols and timeframes; (3) holistic care of the newly diagnosed patient; (4) flare management to support patient empowerment, self-management and access to specialists where required; (5) surgery including appropriate expertise, preoperative information, psychological support and postoperative care; (6) inpatient medical care delivery (7) and ongoing long-term care in the outpatient department and primary care setting including shared care. Using these patient-centred Standards and informed by the IBD Quality Improvement Project (IBDQIP), this paper presents a national benchmarking framework. CONCLUSIONS: The Standards and Benchmarking Tool provide a framework for healthcare providers and patients to rate the quality of their service. This will recognise excellent care, and promote quality improvement, audit and service development in IBD.

British Society of Gastroenterology guidance for management of inflammatory bowel disease during the COVID-19 pandemic.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government's advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.

Magnetic resonance enterography compared with ultrasonography in newly diagnosed and relapsing Crohn's disease patients: the METRIC diagnostic accuracy study.

BACKGROUND: Magnetic resonance enterography and enteric ultrasonography are used to image Crohn's disease patients. Their diagnostic accuracy for presence, extent and activity of enteric Crohn's disease was compared. OBJECTIVE: To compare diagnostic accuracy, observer variability, acceptability, diagnostic impact and cost-effectiveness of magnetic resonance enterography and ultrasonography in newly diagnosed or relapsing Crohn's disease. DESIGN: Prospective multicentre cohort study. SETTING: Eight NHS hospitals. PARTICIPANTS: Consecutive participants aged ≥ 16 years, newly diagnosed with Crohn's disease or with established Crohn's disease and suspected relapse. INTERVENTIONS: Magnetic resonance enterography and ultrasonography. MAIN OUTCOME MEASURES: The primary outcome was per-participant sensitivity difference between magnetic resonance enterography and ultrasonography for small bowel Crohn's disease extent. Secondary outcomes included sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease extent, and sensitivity and specificity for small bowel Crohn's disease and colonic Crohn's disease presence; identification of active disease; interobserver variation; participant acceptability; diagnostic impact; and cost-effectiveness. RESULTS: Out of the 518 participants assessed, 335 entered the trial, with 51 excluded, giving a final cohort of 284 (133 and 151 in new diagnosis and suspected relapse cohorts, respectively). Across the whole cohort, for small bowel Crohn's disease extent, magnetic resonance enterography sensitivity [80%, 95% confidence interval (CI) 72% to 86%] was significantly greater than ultrasonography sensitivity (70%, 95% CI 62% to 78%), with a 10% difference (95% CI 1% to 18%; p = 0.027). For small bowel Crohn's disease extent, magnetic resonance enterography specificity (95%, 95% CI 85% to 98%) was significantly greater than ultrasonography specificity (81%, 95% CI 64% to 91%), with a 14% difference (95% CI 1% to 27%). For small bowel Crohn's disease presence, magnetic resonance enterography sensitivity (97%, 95% CI 91% to 99%) was significantly greater than ultrasonography sensitivity (92%, 95% CI 84% to 96%), with a 5% difference (95% CI 1% to 9%). For small bowel Crohn's disease presence, magnetic resonance enterography specificity was 96% (95% CI 86% to 99%) and ultrasonography specificity was 84% (95% CI 65% to 94%), with a 12% difference (95% CI 0% to 25%). Test sensitivities for small bowel Crohn's disease presence and extent were similar in the two cohorts. For colonic Crohn's disease presence in newly diagnosed participants, ultrasonography sensitivity (67%, 95% CI 49% to 81%) was significantly greater than magnetic resonance enterography sensitivity (47%, 95% CI 31% to 64%), with a 20% difference (95% CI 1% to 39%). For active small bowel Crohn's disease, magnetic resonance enterography sensitivity (96%, 95% CI 92% to 99%) was significantly greater than ultrasonography sensitivity (90%, 95% CI 82% to 95%), with a 6% difference (95% CI 2% to 11%). There was some disagreement between readers for both tests. A total of 88% of participants rated magnetic resonance enterography as very or fairly acceptable, which is significantly lower than the percentage (99%) of participants who did so for ultrasonography. Therapeutic decisions based on magnetic resonance enterography alone and ultrasonography alone agreed with the final decision in 122 out of 158 (77%) cases and 124 out of 158 (78%) cases, respectively. There were no differences in costs or quality-adjusted life-years between tests. LIMITATIONS: Magnetic resonance enterography and ultrasonography scans were interpreted by practitioners blinded to clinical data (but not participant cohort), which does not reflect use in clinical practice. CONCLUSIONS: Magnetic resonance enterography has higher accuracy for detecting the presence, extent and activity of small bowel Crohn's disease than ultrasonography does. Both tests have variable interobserver agreement and are broadly acceptable to participants, although ultrasonography produces less participant burden. Diagnostic impact and cost-effectiveness are similar. Recommendations for future work include investigation of the comparative utility of magnetic resonance enterography and ultrasonography for treatment response assessment and investigation of non-specific abdominal symptoms to confirm or refute Crohn's disease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03982913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 42. See the NIHR Journals Library website for further project information.

Crohn's disease is a waxing and waning lifelong inflammatory condition that affects the colon (large bowel) and small bowel. Treatment relies on accurately determining disease extent and underlying inflammation. Colonoscopy is very good for examining the colon, but it is invasive and, at best, can only visualise a few centimetres of the small bowel, so radiological imaging is very important. Magnetic resonance enterography (a type of magnetic resonance imaging scan) and ultrasonography are both radiological tests commonly performed in the NHS, and it is unclear which method is better. We performed a study to compare the accuracy of magnetic resonance enterography and ultrasonography for determining the extent of Crohn's disease in the bowel of participants newly diagnosed and in those participants with established Crohn's disease but with suspected deterioration. We also investigated how often radiologists agree with each other during test interpretation, the participant experience of undergoing the tests and their cost-effectiveness. We compared the tests in 284 participants (133 newly diagnosed and 151 with suspected deterioration). We found that both tests were accurate for detecting the presence (97% for magnetic resonance enterography and 92% for ultrasonography) and location (80% for magnetic resonance enterography and 70% for ultrasonography) of disease in the small bowel, but magnetic resonance enterography was better than ultrasonography for both (correctly classifying disease extent in 107 more participants for every 1000 participants with Crohn's disease). Magnetic resonance enterography was similarly better than ultrasonography at determining if the bowel was inflamed. The results were similar in newly diagnosed participants and those participants with suspected deterioration. Agreement between radiologists interpreting the same images was, at best, moderate for both tests. A total of 88% of participants tolerated magnetic resonance enterography well or fairly well, which was less than the percentage (99%) of participants who tolerated ultrasonography well or fairly well. Both tests had a similar effect on the treatment decisions made by doctors. Both tests were also similar in their value for money for the NHS.

Nationwide improvement in outcomes of emergency admission for ulcerative colitis in England, 2005-2013.

BACKGROUND: The UK IBD Audit Programme reported improved inpatient care processes for ulcerative colitis (UC) between 2005 and 2013. There are no independent data describing national or institutional trends in patient outcomes over this period. AIM: To assess the association between the outcome of emergency admission for UC and year of treatment. METHODS: Retrospective analysis of hospital administrative data, focused on all emergency admissions to English public hospitals with a discharge diagnosis of UC. We extracted case mix factors (age, sex, co-morbidity, emergency bed days in last year, deprivation status), outcomes of index admission (death and first surgery), 30-day emergency readmissions (all-cause, and selected causes) and outcome of readmission. RESULTS: There were 765 deaths and 3837 unplanned first operations in 44 882 emergency admissions, with 5311 emergency readmissions (with a further 171 deaths and 517 first operations). Case mix adjusted odds of death for any given year were 9% lower (OR 0.91, 95% CI: 0.89-0.94), and that for emergency surgery 3% lower (OR 0.97, 95% CI: 0.95-0.98) than the preceding year. Results were robust to sensitivity analysis (admissions lasting ≥4 days). There was no reduction in odds for all-cause readmission, but rates for venous thromboembolism declined significantly. Analysis of institutional-level metrics across 136 providers showed a stepwise reduction in outliers for mortality and unplanned surgery. CONCLUSIONS: Risk of death and unplanned surgery for UC patients admitted as emergencies declined consistently, as did unexplained variation between hospitals. Risk of readmission was unchanged (over 1 in 10). Multiple factors are likely to explain these nationwide trends.

Current Practices in Ileal Pouch Surveillance for Patients With Ulcerative Colitis: A Multinational, Retrospective Cohort Study.

BACKGROUND AND AIMS: There are no universally accepted guidelines regarding surveillance of ulcerative colitis [UC] patients after restorative proctocolectomy and ileal pouch-anal anastomosis [IPAA]. There also exists a lack of validated quality assurance standards for performing pouchoscopy. To better understand IPAA surveillance practices in the face of this clinical equipoise, we carried out a retrospective cohort study at five inflammatory bowel disease [IBD] referral centres. METHODS: Records of patients who underwent IPAA for UC or IBD unclassified [IBDU] were reviewed, and patients with <1-year follow-up after restoration of intestinal continuity were excluded. Criteria for determining the risk of pouch dysplasia formation were collected as well as the use of pouchoscopy, biopsies, and completeness of reports. RESULTS: We included 272 patients. Median duration of pouch follow-up was 10.5 [3.3-23.6] years; 95/272 [35%] had never undergone pouchoscopy for any indication; 191/272 [70%] had never undergone pouchoscopy with surveillance as the specific indication; and 3/26 [12%] high-risk patients had never undergone pouchoscopy. Two cases of adenocarcinoma were identified, occurring in the rectal cuff of low-risk patients. Patients under the care of surgeons appeared more likely to undergo surveillance, but rates of incomplete reporting were higher among surgeons [78%] than gastroenterologists [54%, p = 0.002]. CONCLUSIONS: We observed wide variation in surveillance of UC/IBDU-IPAA patients. In addition, the rate of neoplasia formation among 'low-risk' patients was higher than may have been expected. We therefore concur with previous recommendations that pouchoscopy be performed at 1 year postoperatively, to refine risk-stratification based on clinical factors alone. Reports should document findings in all regions of the pouch and biopsies should be taken.

A New Look at Familial Risk of Inflammatory Bowel Disease in the Ashkenazi Jewish Population.

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBD) are particularly common among the Ashkenazi Jewish (AJ) population. Population-specific estimates of familial risk are important for counseling; however, relatively small cohorts of AJ IBD patients have been analyzed for familial risk to date. This study aimed to recruit a new cohort of AJ IBD patients, mainly from the UK, to determine the familial occurrence of disease. METHODS: A total of 864 AJ IBD patients were recruited through advertisements, hospital clinics, and primary care. Participants were interviewed about their Jewish ancestry, disease phenotype, age of diagnosis, and family history of disease. Case notes were reviewed. RESULTS: The 864 probands comprised 506 sporadic and 358 familial cases, the latter with a total of 625 affected relatives. Of the UK cases, 40% had a positive family history with 25% having at least one affected first-degree relative. These percentages were lower among those recruited through hospital clinics and primary care (33% for all relatives and 22% among first-degree relatives). Examining all probands, the relative risk of IBD for offspring, siblings, and parents was 10.5, 7.4, and 4, respectively. Age of diagnosis was significantly lower in familial versus sporadic patients with Crohn's disease. CONCLUSIONS: This study reports familial risk estimates for a significant proportion of the AJ IBD population in the UK. The high rate of a positive family history in this cohort may reflect the greater genetic burden for IBD among AJs. These data are of value in predicting the likelihood of future recurrence of IBD in AJ families.

Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103).

Purpose Bevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2-negative disease. Patients and Methods Patients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease-free survival (IDFS). Results Four thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade ≥ 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C. Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation.

Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial.

BACKGROUND: Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue. METHODS: We recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed. FINDINGS: 284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72-86]) and presence (97% [91-99]) were significantly greater than that of ultrasound (70% [62-78] for disease extent, 92% [84-96] for disease presence); a 10% (95% CI 1-18; p=0·027) difference for extent, and 5% (1-9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85-98]) was significantly greater than that of ultrasound (81% [64-91]); a difference of 14% (1-27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86-99) with MRE and 84% (65-94) with ultrasound (difference 12% [0-25]; p=0·054). There were no serious adverse events. INTERPRETATION: Both MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly. FUNDING: National Institute of Health and Research Health Technology Assessment.

Reliability among central readers in the evaluation of endoscopic disease activity in pouchitis.

BACKGROUND AND AIMS: Pouchitis is a common adverse event after proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis. Evaluation of pouchitis disease activity and response to treatment requires use of validated indices. We assessed the reliability of items evaluating endoscopic pouchitis disease activity. METHODS: Twelve panelists used a modified RAND appropriateness methodology to rate the appropriateness of items evaluating endoscopic pouchitis disease activity derived from a systematic review and also identified additional potential endoscopic items based on expert opinion. Four central readers then evaluated 50 pouchoscopy videos in triplicate, in random order. Intra- and inter-rater reliability for each item was assessed by calculating and comparing intraclass correlation coefficients (ICCs). A Delphi process identified common sources of disagreement among the readers. RESULTS: Ten existing endoscopic items were identified from the systematic review and an additional 7 exploratory items from the panelists. ICCs for inter-rater reliability were highest for the existing item of pouch ulceration (.72; 95% confidence interval [CI], .60-.82) and for the exploratory item of ulcerated surface in the pouch body (.67; 95% CI, .53-.75). Inter-rater reliability for all other existing and exploratory items was "moderate" (ICC < .60). The item "ulcerated surface in the pouch body" demonstrated the best correlation with a global evaluation of lesion severity (r = .80; 95% CI, .73-.85). CONCLUSION: Substantial reliability was observed only for the endoscopic items of ulceration and ulcerated surface in the pouch body. Future studies should assess responsiveness to treatment in the next stage toward development of an endoscopic pouchitis disease activity index.

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Pilot Study of Cannabidiol-rich Botanical Extract in the Symptomatic Treatment of Ulcerative Colitis.

Background: Cannabidiol (CBD) exhibits anti-inflammatory properties that could improve disease activity in inflammatory bowel disease. This proof-of-concept study assessed efficacy, safety and tolerability of CBD-rich botanical extract in ulcerative colitis (UC) patients. Methods: Patients aged 18 years or older, with left-sided or extensive UC, Mayo scores of 4-10 (endoscopy scores ≥1), and on stable 5-aminosalicylic acid dosing, were randomized to 10-weeks' CBD-rich botanical extract or placebo capsules. The primary endpoint was the percentage of patients in remission after treatment. Statistical testing was 2-sided, using a 10% significance level. Results: Patients were less tolerant of CBD-rich botanical extract compared with placebo, taking on average one-third fewer capsules, and having more compliance-related protocol deviations (principally insufficient exposure), prompting identification of a per protocol (PP) analysis set. The primary endpoint was negative; end of treatment remission rates were similar for CBD-rich botanical extract (28%) and placebo (26%). However, PP analysis of total and partial Mayo scores favoured CBD-rich botanical extract (P = 0.068 and P = 0.038, respectively). Additionally, PP analyses of the more subjective physician's global assessment of illness severity, subject global impression of change, and patient-reported quality-of-life outcomes were improved for patients taking CBD-rich botanical extract (P = 0.069, P = 0.003, and P = 0.065, respectively). Adverse events (AEs) were predominantly mild/moderate with many in the CBD-rich botanical extract group potentially attributable to the ∆9-tetrahydrocannabinol content. A greater proportion of gastrointestinal-related AEs, indicative of UC worsening, was seen on placebo. Conclusion: Although the primary endpoint was not reached, several signals suggest CBD-rich botanical extract may be beneficial for symptomatic treatment of UC.