Acceptance and Commitment Therapy Reduces Psychological Stress in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). METHODS: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair. RESULTS: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group × time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar between groups over the study period (all P values >.05). Hair cortisol concentrations correlated with stress (rs = 0.205, P = .050) and anxiety (rs = 0.208, P = .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P = .831). CONCLUSION: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920.

Impact of a higher fecal immunochemistry test cut-off on pathology detected in subsequent rounds of a colorectal screening program.

BACKGROUND AND AIMS: Fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening is superior to the traditional binary fecal occult blood test. Its quantitative nature allows the investigator to choose a positivity threshold to match cost and endoscope capacity. The optimal threshold is still debated. BowelScreen, the Irish national colorectal cancer screening program, has a cut-off of 45 µg Hb/g feces, and in this study we investigated the impact of this threshold on pathology detected in round 2 in individuals who had a negative result for round 1 FIT (FIT1). METHODS: All individuals with a negative FIT1 result who completed a round 2 FIT (FIT2) 2 years later were included. Pathology outcomes for individuals who had positive FIT2 results were correlated with FIT1 levels. RESULTS: A total of 37,877 individuals had negative FIT1 results and completed FIT2. One thousand two hundred thirty (3.2%) had positive FIT2 results (702 men [57%], median age 69, age range 60-70 years). Quantitative analysis showed that at an FIT1 level <5 µg Hb/g feces, 2.3% had positive FIT2 results. At a higher cut-off of 40.1 to 45 µg Hb/g feces, 15.6% of individuals had positive FIT2 results. One thousand two (81.5%) underwent colonoscopy, with clinical outcomes in all cases. Three hundred fifty-one (35%) had normal colonoscopy results. The proportion of individuals with normal colonoscopy results decreased as FIT1 levels rose. Conversely, advanced pathology (CRC + high-risk adenomas) rates rose from 7% to 50% when FIT1 was <5 compared with 40.1 to 45 µg Hb/g feces, respectively. There were 51 screen-detected cancers in round 2 among individuals with negative FIT1 results (22 stage I, 12 stage II, 14 stage III, 3 stage IV). All 3 stage IV individuals had FIT1 results <20 µg Hb/g feces. CONCLUSIONS: Varying rates of pathology are observed in round 2 of a screening program based on the quantitative level of a negative round 1 FIT result when the positivity threshold is relatively high. A CRC rate of 5.1% within this group appears acceptable. Although patients with incurable cancer were observed, the positivity threshold to capture these cases within round 1 would have been so sensitive that it would create an unsustainable endoscopy referral burden.

CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis.

INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Covered self-expanding metal stents for the management of common bile duct stones.

BACKGROUND AND AIMS: Little medical literature exists for the use of fully covered self-expanding metal stents (CSEMSs) in the management of retained common bile duct (CBD) stones. Our aim was to assess the safety and efficacy of CSEMSs for the indication of retained "difficult" CBD stones. METHODS: This retrospective cases series included 44 patients (30 women; median age, 69 years [range, 24-88]) who underwent CSEMS insertion for the indication of retained "difficult" CBD stones in 2 tertiary referral centers. Patients underwent temporary placement of CSEMSs after incomplete stone clearance at ERCP. Follow-up ERCP was arranged for stent removal and subsequent attempt at duct clearance. Procedure-related adverse events were also recorded. RESULTS: Successful biliary drainage was achieved in all cases after CSEMS placement. Forty-two stents were removed with successful duct clearance achieved in 36 cases (82%) after a median in-stent duration of 8 weeks. There were 10 cases (22.7%) of stent migration, all noted incidentally during follow-up. One patient died of nonbiliary causes before attempted removal. CONCLUSION: This is the largest published retrospective case series for use of CSEMSs for management of retained CBD stone disease to date. We have shown high success rates for this indication. A well-designed, multicenter, randomized controlled trial might address the uncertainty of cost-to-benefit ratio and appropriate duration for CSEMSs to be left in situ. Specific stent modification for this indication, including wider distal flare and retrieval purse string loop, may also be useful.

An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis.

BACKGROUND & AIMS: Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. METHODS: We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. RESULTS: There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03). CONCLUSIONS: In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

Inflammatory Bowel Disease Disability Index is a valid and reliable measure of disability in an English-speaking hospital practice and predicts long-term requirement for treatment escalation.

Objective: The Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to WHO standards and has been validated in population-based cohorts. However, there are limited data on its relationship to various psychosocial and economic variables or its relevance to hospital clinical practice. The study aims were to determine the validity and reliability of the IBD-DI in an English-speaking hospital out-patient population and to evaluate its association with short and long-term disease activity. Design/Methods: 329 subjects were enrolled in a cross-sectional and longitudinal study assessing the IBD-DI and a range of quality of life, work impairment, depression, anxiety, body image, interpersonal, self-esteem, disease activity, symptom scoring scales in addition to long-term outcome. Results: The IBD-DI had adequate structure, was internally consistent and demonstrated convergent and predictive validity and was reliable in test-retest study. Disability was related to female sex (p=0.002), antidepressant use (p<0.001), steroid use (p<0.001) and disease activity (p<0.001). Higher IBD-DI scores were associated with long-term disease activity and need for treatment escalation in univariate (p<0.001) and multivariate (p=0.002) analyses. Conclusion: The IBD-DI is a valid and reliable measure of disability in English-speaking hospital populations and predicts long-term requirement for treatment escalation.

A comparative study of short- and medium-term outcomes comparing emergent surgery and stenting as a bridge to surgery in patients with acute malignant colonic obstruction.

BACKGROUND: The use of self-expanding metal stents as a bridge to surgery in the setting of malignant colorectal obstruction has been advocated as an acceptable alternative to emergency surgery. However, concerns about the safety of stenting have been raised following recent randomized studies. OBJECTIVES: The aim of the current study was to compare outcomes. DESIGN: This was an observational, comparative study. SETTINGS: This study was conducted at a tertiary referral center and university teaching hospital. PATIENTS AND INTERVENTIONS: Patients with malignant colonic obstruction (n = 49) treated by either emergency surgery (n = 26) or with stent placement (n = 23) as a bridge to surgery were identified and followed. MAIN OUTCOME MEASURES: Short-term outcomes including stoma rates and postoperative morbidity and medium-term oncological outcomes were compared based on an "intention-to-treat" analysis. RESULTS: Patients in both groups were well matched on clinicopathological parameters. Technical and clinical successful stent deployment was achieved in 91% and 83%. This did not adversely impact cancer-specific and overall survival (log rank = nonsignificant). No difference was observed in stoma rates, primary anastomosis rates, perioperative mortality rates, or reoperation rates between the 2 groups. Significantly fewer patients underwent total colectomy in the stent group in comparison with the emergency surgery group (1/23 vs 6/26: p = 0.027). There was no difference in postoperative morbidity (59% vs 66%: p = 0.09). There was a significant reduction in readmission rates in the stent group (5/26 vs 0/23: p = 0.038). LIMITATIONS: The small sample size of this study could lead to type II error. In addition, the study was nonrandomized and demonstrated a limited length of follow-up. CONCLUSION: Despite a high rate of technical and clinical success in selected patients with colonic obstruction, stenting has no impact on stoma rates. Despite concerns about the rate of stent-associated perforation, stenting does not adversely impact disease progression or survival. Future comparative trials are essential to better define the role of stenting in this setting and to ensure that we are not using costly technology to create an elective operative situation without concomitant patient benefits.

Development, validation and clinical assessment of a short questionnaire to assess disease-related knowledge in inflammatory bowel disease patients.

OBJECTIVES: Only two inflammatory bowel disease (IBD) knowledge scales are available, both primarily aimed at evaluating the effectiveness of clinical education programs. The aim of this study was to develop and validate a short knowledge questionnaire for clinical and academic research purposes. MATERIAL AND METHODS: Following initial development, the questionnaire was tested on junior doctors, nurses and administrative staff to assess validity. The questionnaire was then assessed and compared with a previous questionnaire in 31 IBD patients. Three hundred and three further patients completed the questionnaire to establish reliability and determine factors independently associated with disease-related knowledge. RESULTS: Doctors answered more questions correctly than nurses who scored better than administrative staff (p < 0.001). There was a fair correlation in scores between the short knowledge questionnaire and a previously validated long survey (r = 0.488; p = 0.005). The short knowledge questionnaire was quicker to complete (p < 0.001), was rated as less difficult to understand (p = 0.004) and induce less anxiety (p = 0.004). Both questionnaires were rated similarly with regard to relevance (p = 0.71). Internal consistency was demonstrated with a Cronbach's alpha of 0.73. In clinical testing on 301 patients, the final multivariate model identified young age, Crohn's disease, higher educational status and the presence of a first-degree family member with IBD as being independently and significantly associated with disease-related knowledge. CONCLUSIONS: The short knowledge questionnaire is a simple, valid, reliable and easy to understand research instrument for rapidly assessing knowledge in IBD patients.

Satisfaction with telemedicine-delivered inflammatory bowel disease care depends on disease activity, personality and economic factors.

Objective: Patients with inflammatory bowel disease (IBD) traditionally receive follow-up care at face-to-face outpatient clinics. During the COVID-19 pandemic, gastroenterology societies recommended IBD clinics to be carried out remotely where possible using telephone or telemedicine-delivered virtual clinics. Previous studies have demonstrated patient satisfaction with virtual clinics but few studies have examined factors that impact satisfaction or assessed patient's personal perception of the virtual clinic experience. Design/method: Patients who had their IBD clinic appointment changed from face-to-face to telephone virtual clinic completed a questionnaire relating to their clinical experience and preference for future care. Qualitative data were also collected and evaluated using content analysis to identify major themes associated with the patient experience. Results: 141 patients were included for analysis. The virtual clinic satisfaction questionnaire was found to be valid while patients expressed high-satisfaction levels with virtual clinics (median satisfaction score 18, range 0-20). Multivariate analysis identified open personality type (p=0.004), short disease duration (p=0.047) and higher cost to attend clinic (p=0.047) as predictors of high-satisfaction levels, with active disease (p=0.035) and an agreeable personality type (p=0.042) associated with low satisfaction levels. Content analysis of the qualitative data identified three major themes connected to virtual clinic convenience, lack of physical interaction and disease activity. Conclusion: Patients expressed high levels of satisfaction with telemedicine-delivered IBD clinics, with most wishing to continue their use. Personality type should be recognised as an important variable affecting clinical satisfaction, in addition to socioeconomic and disease-related factors.

Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding.

AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.

Brief and Telehealth Acceptance and Commitment Therapy (ACT) Interventions for Stress in Inflammatory Bowel Disease (IBD): A Series of Single Case Experimental Design (SCED) Studies.

Psychological intervention targeting distress is now considered an integral component of inflammatory bowel disease (IBD) management. However, significant barriers to access exist which necessitate the development of effective, economic, and accessible brief and remote interventions. Acceptance and commitment therapy (ACT) is a therapy with demonstrated acceptability and a growing evidence base for the treatment of distress in IBD populations. The present paper trialled two brief ACT interventions via randomized multiple baseline designs. Study 1 trialled a single-session ACT intervention (delivered face-to-face and lasting approximately two hours) targeting stress and experiential avoidance, respectively. Participants were seven people with an IBD diagnosis who presented with moderate to extremely severe stress (five females, two males; M age = 39.57, SD = 5.74). The findings of study 1 indicate that a single-session ACT intervention represented an insufficient dosage to reduce stress and experiential avoidance. Study 2 investigated a brief telehealth ACT intervention (delivered via a video conferencing platform and lasting approximately four hours) targeting stress and increased psychological flexibility. Participants (N = 12 people with an IBD diagnosis and mild to extremely severe stress) completed baselines lasting from 21 to 66 days before receiving a two-session ACT telehealth intervention supplemented by a workbook and phone consultation. Approximately half of participants experienced reduced stress, increased engagement in valued action, and increased functioning. Despite shortcomings such as missing data and the context of COVID-19, the present findings suggest that brief ACT interventions in this population may be effective and economic, though further research and replications are necessary.

Surgery, Crohn's disease, and the biological era: has there been an impact?

INTRODUCTION: The management of Crohn's disease (CD) has changed considerably over the last 20 years. Immunomodulators and biological therapies now play a role in treating patients with CD, but little is known of their influence on surgical rates. AIM: To review the surgery rates for CD in an Irish university hospital over a 20-year period and to determine whether newer therapies had an impact on surgical rates. METHOD: Seven hundred twenty-two patients attending St Vincent's University Hospital, Dublin, with CD over a 20-year period (January 1986 to December 2005) were identified. The patients were divided into quartiles. Resection rates were determined in all the quartiles, at both 1 and 3 years from diagnosis. RESULTS: A decline in surgery, 3 years from diagnosis, was noted between the first quartile (72 patients, 40%) and the second quartile (58 patients, 32%; P=0.03). No significant change in surgical rates at 3 years occurred between the other 3 quartiles (32%, 30%, and 35%, respectively; P=NS). The patients who required a resection within 3 years were diagnosed at a younger age in later years. There was a similar predominance of 60% of female patients requiring surgery in all groups. The patients requiring surgery were twice as likely to be ex-smokers or current smokers in all groups. Use of infliximab, within 3 years from diagnosis, increased from 0, 0, and 16 patients (8.8%) to 40 patients (22.1%) in the last quartile. The majority of patients were treated with infliximab on an "on demand" basis. Use of infliximab earlier within the course of the disease was seen in later quartiles (ie, within 1 y of diagnosis): 0, 0, 6, and 21 patients. CONCLUSION: Despite the introduction of infliximab over the past 10 years, no demonstrable difference has been seen in the rates of patients requiring resection surgery within 3 years of diagnosis. The reasons for this are unclear, but may relate to episodic treatment, rather than regular maintenance treatment. Female patients and smokers seem to be particularly at risk of resection surgery.

Correlation of Fecal Immunochemical Testing Levels With Pathology Results in a National Colorectal Cancer Screening Program.

INTRODUCTION: Fecal immunochemical testing (FIT) positivity is determined by a threshold decided by individual screening programs. Data are limited on correlation between FIT levels and pathology identified at colonoscopy. Our aim was to examine the correlation between FIT levels and pathology identified in a national colorectal cancer screening program. METHODS: FIT levels (n = 9,271) were analyzed and correlated with patient demographics and pathology identified, including adenomas, sessile serrated lesions, number/size of adenomas, and presence of dysplasia. Levels were divided into 2 categories: FIT levels were defined as "high" or "low" based on whether they were above or below the median (479 ngHb/mL). Multivariate analysis was performed. RESULTS: A total of 8,084 patients (87%) underwent colonoscopy. Those younger than 65 years (odds ratio [OR] 1.267, 95% confidence interval [CI] 1.107-1.45, P = 0.001), those with an adenoma >10 mm (OR 1.736, 95% CI 01.512-1.991, P < 0.001), and those with left-sided adenomas (OR 1.484, 95% CI 1.266-1.74, P < 0.001) had higher FIT levels. Cancers (OR 2.8, 95% CI 2.09-3.75, P < 0.001) and high-grade dysplasia (OR 1.356, 95% CI 1.08-1.7, P = 0.008) had higher FIT levels, but varied greatly. The number of adenomas was not significant. DISCUSSION: In this study, FIT levels were high for left-sided and large adenomas, suggesting that FIT has poor sensitivity for detection of diminutive and right-sided neoplasia. FIT levels had no association with gender and declined with age. Adenoma burden did not correlate with FIT levels; this is a novel finding. FIT levels vary greatly even in those with advanced neoplasia; therefore, FIT is unlikely to be useful as a risk stratification tool.

Characteristics and attitudes of first round invitees in the Irish National Colorectal Cancer Screening Programme.

Background/objective: Colorectal cancer (CRC) screening is proven to reduce CRC-related mortality. Faecal immunochemical testing (FIT)-positive clients in the Irish National CRC Screening Programme underwent colonoscopy. Round 1 uptake was 40.2%. We sought to identify barriers to participation by assessing knowledge of CRC screening and examining attitudes towards FIT test and colonoscopy. Methods: Questionnaires based on a modified Champion's Health Belief Model were mailed to 3500 invitees: 1000 FIT-positive, 1000 FIT-negative and 1500 non-participants. 44% responded: 550 (46%) FIT-positive, 577 (48%) FIT-negative and 69 (6%) non-responders (NR). Results: 25% of respondents (n=286) did not perceive a personal risk of cancer, did not perceive CRC to be a serious disease and did not perceive benefits to screening. These opinions were more likely to be expressed by men (p=0.035). One-fifth (n=251) found screening stressful. Fear of cancer diagnosis and test results were associated with stress. FIT-positive clients, women and those with social medical insurance were more likely to experience stress. Conclusions: The CRC screening process causes stress to one-fifth of participants. Greater use of media and involvement of healthcare professionals in disseminating information on the benefits of screening may lead to higher uptake in round 2.

Comparison of medium to long-term outcomes of acute severe ulcerative colitis patients receiving accelerated and standard infliximab induction.

INTRODUCTION: Accelerated dose infliximab (IFX) induction is associated with reduced short-term colectomy rate in acute severe ulcerative colitis (ASUC). Data on medium/long-term outcomes of this strategy are limited. AIMS: Evaluate medium/long-term outcomes in patients receiving IFX induction for ASUC, comparing accelerated dose (AD) and standard dose (SD) induction. METHODS: Retrospective study of consecutive patients admitted with corticosteroid-refractory ASUC in four tertiary referral centres within INITIative IBD research network (www.initiativeibd.ie). IFX rescue was given either as SD (weeks 0, 2, 6) or AD (<28 days) from January 2010 to September 2017. AD induction has been utilised in participating centres since 2014. Consequently SD patients were subdivided based on time period of IFX rescue: historical SD group (SD1) (2010-2013) and current SD group (SD2) (2014-2017). Primary endpoint was time to colectomy; secondary endpoint was time to IFX discontinuation if induction was complete. RESULTS: 145 patients received rescue IFX (AD=58, SD1=32, SD2=55). Disease severity at induction was comparable between AD and SD1 groups; however, SD2 group had less severe disease: median C-reactive protein (CRP) 39, 44 and 20 mg/L for AD, SD1 and SD2 groups, respectively (p=0.026, Kruskal-Wallis); median CRP: albumin ratio was 1.4, 1.8 and 0.6 (p=0.016). Median follow-up for AD, SD1 and SD2 groups was 1.6 (IQR 1.1-3.1), 4.9 (IQR 2.6-5.5) and 1.5 (IQR 0.9-2.3) years. Time to colectomy was shorter in SD1 (log rank p=0.0013); no significant difference in time to colectomy was observed comparing AD and SD2 groups (log rank p=0.32). 123 patients (84%) completed IFX induction and received maintenance therapy. Time to IFX discontinuation was shorter in SD1 (log rank p=0.009). CONCLUSION: Time to colectomy is significantly prolonged with use of AD IFX in selected ASUC patients with more severe disease. Historical use of standard IFX induction for all ASUC patients is associated with inferior long-term outcomes.

A 5-year prospective observational study of the outcomes of international treatment guidelines for Crohn's disease.

BACKGROUND & AIMS: Therapeutic strategies for patients with Crohn's disease are based on American and European guidelines. High rates of corticosteroid dependency and low remission rates are identified as weaknesses of this therapy and as justification for early introduction of biologic agents (top-down treatment) in moderate/severe Crohn's disease. We reviewed outcomes and corticosteroid-dependency rates of patients with moderate-to-severe disease who were treated according to the international guidelines. METHODS: Consecutive patients (102) newly diagnosed with Crohn's disease in 2000-2002 were identified from a prospectively maintained database. Severity of disease was scored using the Harvey-Bradshaw Index (HBI). Disease was classified by Montreal classification. Five-year follow-up data were recorded. RESULTS: Seventy-two patients had moderate/severe disease at diagnosis (HBI >8). Fifty-four (75%) had nonstricturing, nonpenetrating disease (B1). Sixty-four (89%) received corticosteroids, and 44 (61%) received immunomodulators. Twenty-one patients (29%) received infliximab. Thirty-nine patients (54%) required resection surgery. At a median of 5 years, 66 of 72 (92%) patients with moderate/severe disease were in remission (median HBI, 1). Twenty-five patients (35%) required neither surgery nor biologic therapy. CONCLUSIONS: When international treatment guidelines are strictly followed, Crohn's disease patients can achieve high rates of remission and low rates of morbidity at 5 years. Indiscriminate use of biologic agents therefore is not appropriate for all patients with moderate-to-severe disease.

DUBLIN [Degree of Ulcerative colitis Burden of Luminal Inflammation] Score, a Simple Method to Quantify Inflammatory Burden in Ulcerative Colitis.

BACKGROUND AND AIMS: Endoscopic scores of local severity do not reflect disease extent, or disease burden. The DUBLIN score is a simple bedside clinical score that estimates inflammatory burden using both disease severity and extent. As the need to personalize therapy for ulcerative colitis [UC] patients increases, a score accurately assessing disease burden will be of great relevance. The aim of this study was to assess the clinical utility of the DUBLIN score by comparing its performance with objective biomarkers. METHODS: The DUBLIN score was calculated as a product of the Mayo Endoscopic Score [0-3] and disease extent [E1-E3]. Correlation with objective biomarkers was performed in a retrospective 'discovery cohort'. A 'validation cohort was recruited from a single centre, where clinical outcomes, colectomy rate, and biochemical data were collected prospectively. RESULTS: The discovery cohort included 70 patients with UC. The DUBLIN score correlated significantly with faecal calprotectin [FCP] levels [r = 0.394; p < 0.01]. Receiver operating characteristic [ROC] analysis using FCP>50µg/g showed a higher area under the ROC curve [AUC] with the DUBLIN score [AUC = 0.76] than with the Mayo Score [AUC = 0.73]. The validation cohort included 41 patients. Patients with a high inflammatory burden [DUBLIN >3] had higher C-reactive protein and FCP, and lower albumin than patients with a low inflammatory burden. A high DUBLIN score was associated with an increased risk of treatment failure. [hazard ratio 2.98 95%, confidence interval 1.002-8.87; p = 0.049]. CONCLUSION: The DUBLIN score is a simple measure of inflammatory burden, which correlates with objective inflammatory markers and is associated with clinical outcomes, such as treatment failure. The DUBLIN score has the potential to assist in personalizing therapy for patients with UC.

A prospective study of faecal immunochemical testing following polypectomy in a colorectal cancer screening population.

INTRODUCTION: 52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT. AIMS: Determine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up. METHODS: A single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4-6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention. RESULTS: 112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3-11.9, P=0.04)). CONCLUSION: FIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.

Ustekinumab Drug Levels in Maternal and Cord Blood in a Woman With Crohn's Disease Treated Until 33 Weeks of Gestation.

A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was delivered by caesarean section at 37 weeks. Maternal trough USK levels remained stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than contemporaneous maternal serum levels. To our knowledge, this is the first report of maternal and cord USK levels in a patient with Crohn's disease.