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.

Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study.

OBJECTIVE: To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application. DESIGN: A retrospective review of BS colonoscopies performed in 2015-2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis' (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed. RESULTS: Total number of index BS colonoscopies performed in 2015-2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the 'potentially deferred' procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort. CONCLUSION: BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies.

Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

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.

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.

Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19. METHODS: Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated. RESULTS: Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [ß coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [ß coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001]. CONCLUSIONS: Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.

A case-control study examining the association of smad7 and TLR single nucleotide polymorphisms on the risk of colorectal cancer in ulcerative colitis.

AIM: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation and an increased risk of colorectal cancer. smad7, TLR2 and TLR4 modulate intestinal inflammation and their polymorphisms affect the risk of development of sporadic colorectal cancer. The aim of the current study was to examine the association between single nucleotide polymorphisms (SNPs) in smad7, TLR2 and TLR4 and the development of colorectal cancer in patients with UC. METHOD: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 90 patients with UC who had undergone panproctocolectomy between 1985 and 2013 (30 with UC-associated colorectal cancer and 60 control UC patients). Control cases were matched 2:1 for age at diagnosis of colitis, duration of disease and gender. Genotyping was performed for the smad7 rs4464148, rs11874392, rs12953717 and rs4939827 SNPs, the TLR2 rs5743704 and rs5743708 SNPs and the TLR4 rs4986790 and rs4986791 SNPs. RESULTS: Sixty three of the 90 patients (70%) were men and the mean age at diagnosis of UC was 38.6 ± 1.6 years. The mean time to the diagnosis of UC-associated colorectal cancer was 13.5 ± 1.9 years. The 5-year recurrence-free and cancer-specific survival rates were 76% and 88%, respectively. All eight SNPs were in Hardy-Weinberg equilibrium. None of the eight SNPs assessed in smad7, TLR2 or TLR4 were associated with the development of UC-associated colorectal cancer at an allelic or genotypic level. CONCLUSIONS: These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.

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.

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

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.

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.

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.

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.

Severe Symptomatic Primary CMV Infection in Inflammatory Bowel Disease Patients with Low Population Seroprevalence.

BACKGROUND: Cytomegalovirus disease in patients with inflammatory bowel disease is frequently the result of viral reactivation. Conversely, primary CMV infection is believed to be uncommon in immunocompetent adults due to high population seroprevalence. OBJECTIVES: The aim of this study was to examine the frequency and severity of primary cytomegalovirus infection in an adult cohort of IBD patients. STUDY DESIGN: A retrospective review of a prospectively maintained database of 3200 IBD patients attending a single academic centre was performed. Patients with primary CMV infection 2010-13 were identified; clinical, serologic, and virologic parameters were studied in detail. The seroprevalence of CMV in the patient population was also evaluated. RESULTS: Eight patients with IBD (UC = 3, IBD-U = 1, CD = 4) presented with primary CMV infection. Patients presented with both gastrointestinal and extraintestinal symptoms. Mean age was 33 years, and median duration of disease was 72 months. All eight patients were receiving a thiopurine immunomodulator. Median duration of IM use was 144 weeks (range 7-720 weeks). All 8 patients required hospitalisation, with 1 ICU admission; the median length of hospital stay was 11 days (range 6-27). Infection resolved in all cases with withdrawal of immunomodulator and/or antiviral therapy. Seroprevalence of IgG to CMV, indicating prior exposure, in a subgroup of IBD patients (n = 80) was 30.5% and increased with age. CONCLUSION: Primary cytomegalovirus infection can cause a severe illness in IBD patients, particularly those receiving immunosuppression. In areas where adult CMV seroprevalence is low, evidence of CMV should be sought in IBD patients presenting with any febrile systemic illness.

Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis.

BACKGROUND AND AIMS: Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. PATIENTS AND METHODS: Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. RESULTS: Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting. CONCLUSION: These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment.

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC.

Patient Education in Inflammatory Bowel Disease: A Patient-Centred, Mixed Methodology Study.

BACKGROUND: Consensus guidelines from the European Crohns and Colitis Organisation conclude that optimizing quality of care in inflammatory bowel disease [IBD] involves information and education. However, there is no standardized patient education programme in IBD and education varies from centre to centre. AIM: To assess patients' education needs in IBD to facilitate design of a patient education programme. METHODS: We created focus groups of 12 patients with IBD and used qualitative analysis to generate hypotheses. We then developed a quantitative questionnaire which was disseminated to 327 IBD patients attending three different centres. Five patients declined to participate and thus 322 patients (159 [49%] male, 180 [58%] Crohn's disease, median age 38 years and disease duration 7 years) were included. RESULTS: Patients were most keen to receive education on medications, 'what to expect in future', living with IBD and diet. They wanted to receive this information from specialist doctors or nurses and believed it could improve their quality of life. Though the internet was the preferred source of general information [i.e. planning holidays], it was the least preferred source of IBD education. While there was a trend for females to prefer peer education, family history of IBD was the only statistically significant factor associated with information preferences. CONCLUSION: This is a patient-centred, mixed methodology study on patient education in IBD. Patients' preferences for education include components such as what to expect and diet and patients seem to distrust the internet as an IBD information source. International validation would be valuable to create a consensus education programme.