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 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.

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.

DNA Methylation Profiling in Inflammatory Bowel Disease Provides New Insights into Disease Pathogenesis.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBDs) are heterogeneous disorders with complex aetiology. Quantitative genetic studies suggest that only a small proportion of the disease variance observed in IBD is accounted for by genetic variation, indicating a potential role for differential epigenetic regulation in disease aetiology. The aim of this study was to assess genome-wide DNA methylation changes specifically associated with ulcerative colitis (UC), Crohn's disease (CD) and IBD activity. METHODS: DNA methylation was quantified in peripheral blood mononuclear cells (PBMCs) from 149 IBD cases (61 UC, 88 CD) and 39 controls using the Infinium HumanMethylation450 BeadChip. Technical and functional validation was performed using pyrosequencing and the real-time polymerase chain reaction. Cross-tissue replication of the top differentially methylated positions (DMPs) was tested in colonic mucosa tissue samples obtained from paediatric IBD cases and controls. RESULTS: A total of 3196 probes were differentially methylated between CD cases and controls, while 1481 probes were differentially methylated between UC cases and controls. There was considerable (45%) overlap between UC and CD DMPs. The top-ranked IBD-associated PBMC differentially methylated region (promoter region of TRIM39-RPP2) was also significantly hypomethylated in colonic mucosa from paediatric UC patients. In addition, we confirmed TRAF6 hypermethylation using pyrosequencing and found reduced TRAF6 gene expression in PBMCs of IBD patients. CONCLUSIONS: Our data provide new insights into differential epigenetic regulation of genes and molecular pathways, which may contribute to the pathogenesis and activity of IBD.

Heightened Expression of CD39 by Regulatory T Lymphocytes Is Associated with Therapeutic Remission in Inflammatory Bowel Disease.

BACKGROUND: To evaluate whether changes in expression of CD39 by regulatory T lymphocytes (Treg) impact treatment response in inflammatory bowel disease. To then define the biological role of expression of CD39 on Treg in an animal model of colitis. METHODS: A prospective study of consecutive patients commencing anti-tumor necrosis factor therapy with infliximab (IFX) or adalimumab (ADA), who were then followed for 12 months. Treatment responses were defined both symptomatically and by endoscopy showing mucosal healing. Peripheral blood Tregs were quantified by flow cytometry. Functional importance of CD39 expression by Treg was determined in an adoptive T-cell transfer model of colitis. RESULTS: Forty-seven patients (ulcerative colitis, n = 22; Crohn's disease, n = 25) were recruited; 16 patients were complete responders and 13 nonresponders to anti-tumor necrosis factor. CD39 expression by Treg was lower in active inflammatory bowel disease and increased significantly after treatment in responders (CD39Treg/total Treg; 8% at baseline to 22.5% at late time point, P < 0.001). Responders were more likely to have therapeutic drug levels and in multivariate analysis therapeutic drug levels were associated with higher expression of CD39 by FoxP3 Treg and lower frequencies of interleukin 17A expressing cells. Tregs with genetic deletion of CD39 exhibit decrements in potential to suppress intestinal inflammation in a murine (CD45RB) T-cell transfer model of colitis in vivo, when compared with wild-type Treg. CONCLUSIONS: Increased expression of CD39 by peripheral blood Treg is observed in the setting of clinical and endoscopic remission in inflammatory bowel disease. Deficiency of CD39 expression by Treg can be linked to inability to suppress experimental colitis.

Determinants of short- and long-term survival from colorectal cancer in very elderly patients.

PURPOSE: Over 5100 colorectal cancers (CRCs) are diagnosed in the United Kingdom in 85 years and older age group per year but little is known of cancer progression in this group. We assessed clinical, pathological and molecular features of CRC with early and late mortality in such patients. METHODS: Data were analysed in relation to early mortality and long-term survival in 90 consecutive patients with CRC aged 85 years or older in a single hospital. RESULTS: Patients not undergoing operation, those with an ASA score of III or greater and those with advanced tumour stage were more likely to die within 30 days. Regression analysis showed that 30 day mortality was independently related to failure to undergo resection (odds ratio (O.R.), 10.0; 95% confidence interval [C.I.], 1.7-58.2; p=0.01) and an ASA score of III or greater (O.R. 13.0; 95% C.I., 1.4-12.6; p=0.03). All cause three and five year survival were 47% and 23% respectively for patients who are alive 30 days after diagnosis. Three and five year relative survivals were 64% and 54%, respectively. Long-term outcome was independently related to tumour stage (relative risk [R.R.], 2; 95% C.I., 1.3-3.1; p=0.001), presence of co-morbid diseases (R.R., 2.8; 95% C.I., 1.3-6.0; p=0.007) and lipid peroxidation status (R.R., 2.9; 95% C.I., 1.1-7.5; p=0.025). CONCLUSIONS: An active multidisciplinary approach to the care of patients with CRC at the upper extreme of life is reasonable. It also seems sensible to individualise care based upon the extent of disease at diagnosis and the presence of co-morbid conditions. Further studies to examine the role of lipid peroxidation are warranted.

The body image scale: a simple and valid tool for assessing body image dissatisfaction in inflammatory bowel disease.

BACKGROUND: Body image refers to a persons' sense of their own physical appearance. This can be negatively influenced by a number of factors including disease states and treatments. Inflammatory bowel disease (IBD) carries a distinct psychosocial and a physical burden, but body image has not been formally assessed in patients with IBD, nor is there a validated body image questionnaire. Our aim was to assess and validate a body image questionnaire for patients with IBD. METHODS: Three hundred thirty-eight ambulatory patients (median age, 36; 174 male) completed a questionnaire that included the Hopwood body image scale adapted from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Study Group. Data from another scale, the Cash Body Image Disturbance Questionnaire, were also collected in addition to demographic and clinical data. RESULTS: Factor analysis resulted in a single factor solution explaining 65% of the variance. Internal consistency of the body image scale was demonstrated with a Cronbach alpha of 0.93. Convergent validity was established with a correlation coefficient of 0.64 (P < 0.001) with the Cash Body Image Disturbance Questionnaire. Females (P < 0.001) and those who had undergone either stoma or nonstoma forming surgery experienced more body image dissatisfaction (P = 0.002), indicating predictive validity. Reliability was confirmed with a test-retest correlation of 0.82 (P < 0.001). CONCLUSIONS: The modified body image scale is a valid tool for assessing body image in patients with IBD.

Sources of information and factual knowledge in Europeans with inflammatory bowel diseases: a cross-cultural comparison between German and Irish patients.

BACKGROUND: Disease related knowledge may be associated with quality of life, coping skills and medication adherence. However, little is known of cross-cultural variations regarding inflammatory bowel disease knowledge or sources of information and no study has assessed knowledge in diverse European IBD populations. AIM: To assess sources of information and patient knowledge in Irish and German inflammatory bowel disease patients. METHODS: Three hundred and three disease, gender, age and education matched German and Irish patients completed a previously validated knowledge questionnaire. Additional data were collected on age, gender, education, disease type and duration, family history, smoking habits, medication use, previous surgery and quality of life. RESULTS: German patients obtained knowledge from a wider range of sources than Irish patients (p<0.001), most notably from the internet (p<0.001), newspapers and magazines (p=0.002). Both cohorts answered a similar number of questions correctly (Irish, mean 4.4 questions (Standard deviation (S.D.) 2.4); German, mean 4.3 (S.D. 2.2); p=0.67). In addition, both nationalities answered "don't know" to a similar number of questions (Irish, mean 3.3 (S.D. 3.1); German, mean 2.7 (S.D. 2.8); p=0.12) while Irish patients answered slightly fewer questions wrongly (Irish, mean 2.4 (S.D. 1.8); German, mean 3.1 (S.D. 1.9); p=0.002). A multivariate analysis included only Crohn's disease, female gender, young age and higher educational status as being significantly and independently associated with knowledge. CONCLUSIONS: Our data suggest few differences between German and Irish IBD patients, despite cultural and linguistic differences, with regard to disease related knowledge of IBD.

Efficacy of Adalimumab as a long term maintenance therapy in ulcerative colitis.

INTRODUCTION: Adalimumab is a recombinant human IgG1 monoclonal antibody to TNF-alpha. There are limited data with regard to its efficacy in ulcerative colitis. We report experience of adalimumab in ulcerative colitis in a single centre with a focus on the ability of this agent to maintain response and avoid colectomy in the medium to long-term. METHODS: Twenty-three ulcerative colitis patients (mean age 32 years; 7 female) who received adalimumab were identified from a prospectively maintained database of over 2700 IBD patients. The primary study endpoint was treatment failure defined as discontinuation of adalimumab due to lack of efficacy, as defined by requiring an alternative maintenance therapy or colectomy, or intolerance. Colectomy rate was recorded as a secondary endpoint. RESULTS: Most patients (96%) had received immunosuppressants prior to adalimumab therapy (infliximab 20/23 87%). Sixteen of 23 patients (70%) discontinued adalimumab. Six primary failures, 8 secondary loss of response, one had unacceptable side effects and one discontinued treatment after 6 months but remains in remission. Overall estimated cumulative treatment failure rates at 6, 12 and 24 months were 50%, 65% and 72% respectively. Median follow-up in patients continuing adalimumab is 23 months (IQR 17-31 months). Treatment failure was unrelated to patient age, gender, disease extent, smoking status or CRP. Colectomy free survival was 59% at 2 years. No patient experienced a major adverse event. CONCLUSION: Adalimumab shows some efficacy as a maintenance strategy in Ulcerative Colitis, but only a limited proportion of patients remain well on continued treatment at 2 years.

The Short Health Scale: a valid and reliable measure of health related quality of life in English speaking inflammatory bowel disease patients.

BACKGROUND: Health related quality of life in inflammatory bowel disease is influenced both by disease activity as well as by the psychosocial characteristics of the individual patient. The Short Health Scale (SHS) is a four-part visual analogue scale questionnaire using open-ended questions that are designed to assess the impact of inflammatory bowel disease on a health related quality of life. The four dimensions include bowel symptoms, activities of daily life, worry and general wellbeing. It has previously been validated in Swedish and Norwegian speaking patients. AIM: To evaluate the SHS in an English speaking inflammatory bowel disease population. METHODS: Four hundred and ninety Crohn's disease and ulcerative colitis patients completed the SHS. Individual SHS items were correlated with Inflammatory Bowel Disease Questionnaire (IBDQ) dimensions and with disease activity to assess validity. Test-retest reliability was assessed in 38 patients who completed the Short Health Scale two weeks apart. RESULTS: All four items correlated with corresponding IBDQ dimensions with correlation coefficients ranging from -0.66 to -0.74 (all p values<0.001). In addition, total SHS scores correlated with total IBDQ scores in both Crohn's disease (-0.836) and ulcerative colitis (0.797). There was a stepwise increase in Short Health Scale scores with increasing disease activity (all p values<0.001). Reliability was confirmed with test-retest correlations ranging from 0.70 to 0.89 (all p values<0.005). CONCLUSIONS: The Short Health Scale is a valid and reliable measure of health related quality of life in English speaking inflammatory bowel disease patients.