Prognostic biomarkers to identify patients destined to develop severe Crohn's disease who may benefit from early biological therapy: protocol for a systematic review, meta-analysis and external validation.

BACKGROUND: It is believed increasingly that patients with severe Crohn's disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. However, we cannot predict currently which new presentations of Crohn's disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Accordingly, via systematic review and meta-analysis we aim to identify if biomarkers of disease activity are able to predict development of severe disease. METHODS/DESIGN: We will search the primary literature and conference proceedings for studies of biomarkers of all types including clinical, endoscopic, radiological, faecal, urinary, serological, genetic, and histological. Precise definition of "severe" disease is elusive so we will include sensitivity analysis to account for different definitions. We will use the CHARMS checklist to frame our question and to extract data. We will extract the study design, setting, participant characteristics, biomarker(s) investigated, and study outcomes. Bias will be assessed via the PROBAST tool. We will present the results using narrative and graphical methods. We will present the summary by meta-analysis where there are sufficient studies with reasonable homogeneity, using methods appropriate to the type of data extracted. Heterogeneity will be presented via Forest and ROC plots. DISCUSSION: If this systematic review and meta-analysis identifies biomarkers that appear sufficiently predictive for subsequent severe disease course, we aim to combine them in a predictive model, followed by external validation using individual patient data. A predictive model able to identify new presentations of Crohn's disease destined to develop severe disease subsequently would have considerable clinical utility for patient management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016029363 .

Non- or full-laxative CT colonography vs. endoscopic tests for colorectal cancer screening: a randomised survey comparing public perceptions and intentions to undergo testing.

OBJECTIVES: Compare public perceptions and intentions to undergo colorectal cancer screening tests following detailed information regarding CT colonography (CTC; after non-laxative preparation or full-laxative preparation), optical colonoscopy (OC) or flexible sigmoidoscopy (FS). METHODS: A total of 3,100 invitees approaching screening age (45-54 years) were randomly allocated to receive detailed information on a single test and asked to return a questionnaire. Outcomes included perceptions of preparation and test tolerability, health benefits, sensitivity and specificity, and intention to undergo the test. RESULTS: Six hundred three invitees responded with valid questionnaire data. Non-laxative preparation was rated more positively than enema or full-laxative preparations [effect size (r) = 0.13 to 0.54; p < 0.0005 to 0.036]; both forms of CTC and FS were rated more positively than OC in terms of test experience (r = 0.26 to 0.28; all p-values < 0.0005). Perceptions of health benefits, sensitivity and specificity (p = 0.250 to 0.901), and intention to undergo the test (p = 0.213) did not differ between tests (n = 144-155 for each test). CONCLUSIONS: Despite non-laxative CTC being rated more favourably, this study did not find evidence that offering it would lead to substantially higher uptake than full-laxative CTC or other methods. However, this study was limited by a lower than anticipated response rate. KEY POINTS: • Improving uptake of colorectal cancer screening tests could improve health benefits • Potential invitees rate CTC and flexible sigmoidoscopy more positively than colonoscopy • Non-laxative bowel preparation is rated better than enema or full-laxative preparations • These positive perceptions alone may not be sufficient to improve uptake • Health benefits and accuracy are rated similarly for preventative screening tests.