Mortality in people with coeliac disease: Long-term follow-up from a Scottish cohort

Background: Few studies have determined the very long-term mortality risks in adult and childhood-diagnosed coeliac disease. Objective: We quantified mortality risks in coeliac disease and determined whether age at diagnosis, or time following diagnosis, modified these risks. Methods: Standardised mortality ratios were determined using data from a cohort of 602 coeliac patients assembled between 1979�1983 from Lothian, Scotland, and followed up from 1970�2016. Results: All-cause mortality was 43 higher than in the general population. Excess deaths were primarily from haematological malignancies (standardised mortality ratio, 4.77) and external causes (standardised mortality ratio, 2.62) in adult and childhood-diagnosed cases respectively. Mortality risks declined steadily with time in adult-diagnosed cases (standardised mortality ratio, 4.85 in first year compared to 0.97, 25 years post-diagnosis). Beyond 15 years, this group had a significantly reduced risk of any malignancy (standardised mortality ratio, 0.57 (95 confidence interval: 0.33�0.92)). In contrast, for childhood-diagnosed cases an increased risk existed beyond 25 years (standardised mortality ratio, 2.24). Conclusions: Adult-diagnosed coeliac patients have a temporarily increased mortality risk mainly from malignant lymphomas and a decreased risk of any malignancy beyond 15 years post-diagnosis. In contrast, childhood-diagnosed cases are at an increased risk of mortality mainly from external causes, and have long-term mortality risks that requires further investigation. © Author(s) 2018

A randomised controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma (or polyp) prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme: The seAFOod (Systematic Evaluation of Aspirin and Fish Oil) Polyp Prevention Trial

YesThe naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients.Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnershi