Jeff Chang

Prospective validation study of the International Classification of Functioning, Disability and Health score in Crohn's disease and ulcerative colitis

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, Crohns Disease Activity Index (CDAI) for Crohns 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 Cronbachs 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.

Clinical utility and diagnostic accuracy of faecal calprotectin for IBD at first presentation to gastroenterology services in adults aged 16–50 years

Background: Distinguishing inflammatory bowel disease (IBD) from functional gastrointestinal (GI) disease remains an important issue for gastroenterologists and primary care physicians, and may be difficult on the basis of symptoms alone. Faecal calprotectin (FC) is a surrogate marker for intestinal inflammation but not cancer. Aim: This large retrospective study aimed to determine the most effective use of FC in patients aged 16–50 presenting with GI symptoms. Methods: FC results were obtained for patients presenting to the GI clinics in Edinburgh between 2005 and 2009 from the Edinburgh Faecal Calprotectin Registry containing FCs from >16,000 patients. Case notes were interrogated to identify demographics, subsequent investigations and diagnoses. Results: 895 patients were included in the main analysis, 65% female and with a median age of 33 years. 10.2% were diagnosed with IBD, 7.3% with another GI condition associated with an abnormal GI tract and 63.2% had functional GI disease. Median FC in these three groups were 1251, 50 and 20 μg/g (p < 0.0001). On ROC analysis, the AUC for FC as a predictor of IBD vs. functional disease was 0.97. Using a threshold of ≥ 50 μg/g for IBD vs. functional disease yielded a sensitivity of 0.97, specificity of 0.74, positive predictive value of 0.37 and negative predictive value of 0.99. Combined with alarm symptoms, the sensitivity was 1.00. Conclusions: Implementation of FC in the initial diagnostic workup of young patients with GI symptoms, particularly those without alarm symptoms, is highly accurate in the exclusion of IBD, and can provide reassurance to patients and physicians.

564 Elevated Faecal Calprotectin Predicts Disease Progression in Crohn's Disease

Introduction Historical cohort studies have clearly demonstrated that over time the majority of patients with Crohn’s disease (CD) will progress from inflammatory (B1) to stricturing (B2) or fistulating (B3) disease. Emerging data suggest that more intensive treatment targeted towards mucosal healing will help to prevent disease progression. Faecal calprotectin (FC) is an established surrogate biomarker for endoscopic mucosal healing. It has yet to be established whether tailoring therapy to FC levels prevents disease progression. In the present study we aimed to determine whether FC levels in patients with established CD were predictive of disease progression. Methods The Edinburgh Faecal Calprotectin Registry (EFCR) comprises data on 22,130 FC assays in 16,278 patients from 2005–2012. Detailed phenotypic information was obtained on patients with CD by retrospective casenote review. Data collected included demographics, disease location, disease behaviour over time, CD-related surgery, investigations, hospitalisations and drug therapy. Patients were included in the main analysis if they had at least 12 months’ follow-up since first FC. The a priori primary endpoint was a composite of progression in Montreal luminal behaviour, hospitalisation for flare and resectional surgery. Results There were 881 CD patients identified with at least one FC, of which 723 had at least one year’s follow-up, with median follow-up time 40 months (IQR 25–60). The median age was 28y (IQR 20–42) at diagnosis and 40y (28–53) at time of first FC. 239 patients (33%) reached the primary endpoint, of whom 68 had had progression of their Montreal behaviour from B1 to B2 or B3, or from B2 to B3. The median of the earliest FC was significantly higher in the group that reached the primary endpoint at 586 µg/g (IQR 210–1235) vs. 289 (75–1001) in those that did not (p Conclusion This large single-centre study presents compelling evidence that measurement of FC can be used to predict disease course, which creates the opportunity for physicians to intervene earlier and perhaps alter the disease course. Disclosure of Interest None Declared

Occupational health and safety of anti-tumour necrosis factor alpha monoclonal antibodies with casual exposure

Introduction: As the incidence of chronic inflammatory diseases continues to rise, so has cumulative use of biological therapy particularly anti-tumour necrosis factor (TNF) alpha agents. As longer term data emerges about the safety of these drugs, there is increasing attention drawn to safety of those with casual exposure. At present, there is little in the published literature to give guidance for healthcare workers regarding their health and safety in handling of anti-TNF agents, nor the appropriate precautions required. Areas covered: The aim of this review is to summarize the currently known adverse effects, risk assessment tools for classifying and handling hazardous substances, and present evidence for systemic absorption through occupational exposure in handling anti-TNF antibodies at the level of reconstitution. Expert opinion: There is no evidence for systemic absorption of these drugs in context of handling or accidental spillage and no reports of subsequent biological adverse effects. Given the need of this class of medication to be used for long-term maintenance therapy and their increasing indications, improved efficiency and cost-containing measures are recommended. As such, simple universal precautions of protective clothing of glove, gown, facemask and eye goggles are appropriate measures for reconstitution of anti-TNF antibodies.

Expert-led didactic versus self-directed audiovisual training of confocal laser endomicroscopy in evaluation of mucosal barrier defects

Background and study aims  Confocal laser endomicroscopy (CLE) allows mucosal barrier defects along the intestinal epithelium to be visualized in vivo during endoscopy. Training in CLE interpretation can be achieved didactically or through self-directed learning. This study aimed to compare the effectiveness of expert-led didactic with self-directed audiovisual teaching for training inexperienced analysts on how to recognize mucosal barrier defects on endoscope-based CLE (eCLE). Materials and methods  This randomized controlled study involved trainee analysts who were taught how to recognize mucosal barrier defects on eCLE either didactically or through an audiovisual clip. After being trained, they evaluated 6 sets of 30 images. Image evaluation required the trainees to determine whether specific features of barrier dysfunction were present or not. Trainees in the didactic group engaged in peer discussion and received feedback after each set while this did not happen in the self-directed group. Accuracy, sensitivity, and specificity of both groups were compared. Results  Trainees in the didactic group achieved a higher overall accuracy (87.5 % vs 85.0 %, P  = 0.002) and sensitivity (84.5 % vs 80.4 %, P  = 0.002) compared to trainees in the self-directed group. Interobserver agreement was higher in the didactic group (k = 0.686, 95 % CI 0.680 – 0.691, P  < 0.001) than in the self-directed group (k = 0.566, 95 % CI 0.559 – 0.573, P  < 0.001). Confidence (OR 6.48, 95 % CI 5.35 – 7.84, P  < 0.001) and good image quality (OR 2.58, 95 % CI 2.17 – 2.82, P  < 0.001) were positive predictors of accuracy. Conclusion  Expert-led didactic training is more effective than self-directed audiovisual training for teaching inexperienced analysts how to recognize mucosal barrier defects on eCLE.

306 Impaired Mucosal Permeability Underlies Ongoing Irritable Bowel Syndrome-Like Symptoms, in Patients With Inflammatory Bowel Disease Who Have Achieved Mucosal Healing

Rationale: Idiopathic pulmonary fibrosis (IPF) identifies patients with pulmonary fibrosis in a usual interstitial pattern, with no identifiable associations. Esophageal motility disorders and gastroesophageal reflux (GER) are common in patients with end-stage lung disease including IPF. GER-induced aspiration has been proposed as a risk factor for development of IPF and may contribute to further lung injury. Recognition of subtle manifestations of GER in this population is therefore imperative. We intend to characterize esophageal motility disturbances and GER in IPF and explore their relationship to clinical symptoms and lung function. Methods: We performed a retrospective data review of patients with idiopathic pulmonary fibrosis (IPF) referred for combined 24-hour pH-impedance off PPI and high resolution esophageal manometry studies between January 2009 and October 2013 from an interstitial lung disease clinic and a pre-lung transplant clinic. Results: Twenty-eight patients qualified for our study, 71% male, mean age 64±1.4 years, with a mean total lung capacity (TLC) of 62.8±2.9% predicted. Sixty-eight percent of patients had abnormal high resolution manometry: 22% of all patients had ineffective esophageal motility (IEM), 18% had weak upper esophageal sphincters, 14% had weak lower esophageal sphincters (LES), 11% had elevated LES resting pressures, and 28% had a hiatus hernia. Fifteen patients had symptomatic heartburn at the time of investigations, of whom three had a DeMeester score >14.7. Four of the 28 patients (14.3%) reported esophageal symptoms (dysphagia or regurgitation) at the time of the investigations, which was associated with a sensitivity of 16%, and a specificity of 89% for a manometric abnormality. There was no association between abnormal esophageal motility, increased esophageal acid exposure and forced vital capacity (FVC), diffusion capacity of carbon monoxide adjusted for alveolar volume, or 6MWT. Conclusions: Esophageal motility is frequently abnormal in patients with IPF. Despite symptoms of heartburn, GERD is infrequent in patients with IPF. The presence or absence of GERD and/or esophageal dysmotility is not associated with the severity of lung function in IPF patients.

P318 The prevalence of anaemia in inflammatory bowel disease in relation to disease activity, as stratified by faecal calprotectin

Background: The prevalence of anaemia in IBD varies significantly between published studies, ranging from 6 74%. However, underlying disease activity, a potential explanation for this variability, has not been accurately correlated with the frequency of anaemia to date. Faecal calprotectin (FC) is a surrogate marker of underlying mucosal inflammation. The objective of this study was to investigate the prevalence of anaemia and its correlation with disease activity in IBD, in a large cohort of patients with matched full blood count (FBC) and FC data. Methods: Patients with confirmed IBD from the Edinburgh faecal calprotectin registry (EFCR) were identified. Where multiple FCs were available, the most recent result was taken as reference. Blood test results were obtained from the electronic record covering a period one month either side of the FC. The WHO criteria, as adopted by ECCO, was used to define anaemia (Hb <130 g/L in men, <120 g/L in women). A FC value of 200mg/g was used to indicate active disease. The cohort was subdivided into 4 groups: active and inactive CD, active and inactive UC. Results: 1226 patients (771 CD, F = 65%, 455 UC, F = 35%) with matched FC and FBC data were analysed. The median age was 44y (IQR 31 57), median disease duration 102 months (IQR 31 207). Overall, 314/1226 patients (25.6%) were anaemic, 185/314 (58.9%) of which were female. Anaemia was observed more frequently in patients with active as opposed to inactive CD (110/328 [33.5%] vs 65/443 [14.7%], p < 0.0001). This pattern was also seen in patients with UC (129/293 [44%] vs 23/162 [14.2%], p < 0.0001). The prevalence of anaemia in active UC was greater than in active CD (p = 0.014); however, this could be explained by the higher median FC in the UC cohort (900 vs. 618, p < 0.0001). There was no statistically significant difference in age or Montreal location (L1+L3 vs L2, p = 0.16) between the groups. ROC analysis of FC as a predictor of anaemia showed an AUC of 0.69 with a sensitivity and specificity of 0.73 and 0.57 respectively at a cut off of 200mg/g. Conclusions: In this cohort over 25% of patients with IBD were anaemic. There is a clear correlation between disease activity and anaemia in both CD and UC but this is unrelated to disease distribution in CD. Anaemia in asymptomatic patients should alert clinicians to the possibility of subclinical active mucosal inflammation. These data and the ROC analysis provide further support for optimising disease treatment in IBD targeting a FC level of <200mg/g.

Mo1260 The Prevalence of Anaemia in Inflammatory Bowel Disease in Relation to Disease Activity, As Stratified by Faecal Calprotectin

Introduction The prevalence of anaemia in IBD varies significantly between published studies, ranging from 6–74%. However, underlying disease activity, a potential explanation for this variability, has not been accurately correlated with the frequency of anaemia to date. Faecal calprotectin (FC) is a surrogate marker of underlying mucosal inflammation. The objective of this study was to investigate the prevalence of anaemia and its correlation with disease activity in IBD, in a large cohort of patients with matched full blood count (FBC) and FC data. Methods Patients with confirmed IBD from the Edinburgh faecal calprotectin registry (EFCR) were identified. Where multiple FCs were available, the most recent result was taken as reference. Blood test results were obtained from the electronic record covering a period one month either side of the FC. The WHO criteria was used to define anaemia (Hb Results 1226 patients (771 CD, F = 65%, 455 UC, F = 35%) with matched FC and FBC data were analysed. The median age was 44y (IQR 31–57), median disease duration 102 months (IQR 31–207). Overall, 314/1226 patients (25.6%) were anaemic, 185/314 (58.9%) of which were female. Anaemia was observed more frequently in patients with active as opposed to inactive CD (110/328 [33.5%] vs 65/443 [14.7%], p Conclusion In this cohort over 25% of patients with IBD were anaemic. There is a clear correlation between disease activity and anaemia in both CD and UC, but this is unrelated to disease distribution in CD. Anaemia in asymptomatic patients should alert clinicians to the possibility of subclinical active mucosal inflammation. These data and the ROC analysis provide further support for optimising disease treatment in IBD, targeting a FC level of Disclosure of Interest None Declared.