Background Inflammatory bowel disease (IBD) causes serious morbidity and disability, and the incidence is increasing. The disease etiology is not well understood, though inflammatory reactions after antibiotic exposure may be associated with development of IBD. We investigated the association between IBD and prior antibiotic use. Methods We conducted this case–control study among individuals in the United Kingdom Clinical Practice Research Datalink GOLD (CPRD GOLD). Each case of IBD was matched to 4 controls on age, sex, general practice, and registration year in the CPRD GOLD. Antibiotic exposure was classified by ever or never use, number of prescriptions, and class of antibiotic before the index date. Odds ratios were calculated using conditional logistic regression. Results We identified 461 cases of ulcerative colitis (UC) and 683 cases of Crohn’s disease (CD). There was no association between ever use of any antibiotic and UC (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.72–1.44) or CD (OR, 1.01; 95% CI, 0.73–1.39) compared with never use. A slightly increased CD risk was observed among ever users of quinolones (OR, 1.76; 95% CI, 1.00–3.11) and metronidazole (OR, 1.43; 95% CI, 0.87–2.34) compared with never users. CD was associated with antibiotic exposure before age 5 (OR, 2.20; 95% CI, 0.75–6.43) in an analysis restricted to individuals followed from birth. Conclusions There was no association between UC or CD and overall prior use of antibiotics, though prior use of metronidazole and quinolones was associated with a slightly increased risk of CD. Antibiotic use in early childhood may increase the risk of CD.

Background and study aims: Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 50% of all colorectal cancers (CRCs) diagnosed in patients with inflammatory bowel disease (IBD). This may reflect a high colonoscopy frequency; however evidence remains limited. Patient and methods: We conducted a cohort study of IBD and non-IBD patients undergoing colonoscopy. We calculated 6-36 months CIPs of PCCRC after first-time and subsequent colonoscopies. We also computed crude and adjusted HRs of PCCRC, comparing IBD with non-IBD patients undergoing first-time and subsequent colonoscopies. Separate analyses were conducted for consecutive colonoscopies. We calculated PCCRC-3 year rates to estimate the proportion of IBD and non-IBD CRC patients experiencing PCCRC. Results: We observed 138 and 1,909 PCCRCs among 34,688 IBD and 358,217 non-IBD patients who underwent colonoscopy. The CIP of PCCRC after first-time colonoscopy was 0.21%, 95% confidence interval (CI): [0.17-0.27] for IBD patients and 0.37%, 95% CI: [0.35-0.39] for non-IBD patients. The adjusted HR of PCCRC after a first-time colonoscopy was 0.96, 95% CI: [0.75-1.22] and the adjusted HRs after subsequent colonoscopies had point estimates around 1.0. The PCCRC-3 year rate was 24.3%, 95% CI: [20.4-28.7] for IBD and 7.5%, 95% CI [7.2-7.8] for non-IBD patients. Conclusions: Although PCCRCs accounted for a substantial proportion of all IBD-related CRCs, IBD patients had a low CIP of PCCRC after colonoscopy. The elevated PCCRC-3 year rates may among other factors stem from increased colonoscopy frequency in IBD patients.

Summary Background Inflammatory bowel disease (IBD) may be associated with increased dementia risk, but the literature is conflicting. Aim To investigate dementia risk in patients with IBD. Methods We conducted a nationwide population‐based cohort study in Denmark (1977–2018) including all patients with incident IBD matched with up to 10 general population comparators without IBD by sex, year of birth and region of residence. We calculated cumulative incidence proportions (CIPs) of dementia treating death as a competing risk, and adjusted hazard ratios (HRs) comparing IBD patients with matched comparisons. In a nested case–control analysis, we investigated the impact of IBD severity, steroid use, colorectal and small bowel surgery, and healthcare system contacts on dementia risk. Results Of 88,985 patients with IBD (69.6% with ulcerative colitis [UC], 30.4% with Crohn's disease [CD]) and 884,108 comparisons, 2076 patients (78.1% with UC) and 23,011 comparisons (76.6% UC comparisons) developed dementia. The 40‐year CIP of all‐cause dementia was 7.2% for UC patients and 5.8% for CD patients. UC patients had a slightly increased HR of all‐cause dementia (HR = 1.07 [95% confidence interval (CI): 1.01;1.12]) and Alzheimer's disease (HR = 1.10 [95% CI: 1.01–1.19]). CD patients had an increased HR of all‐cause dementia (HR = 1.15 [95% CI: 1.05–1.27]) and frontotemporal dementia (HR = 2.70 [95% CI: 1.44–5.05]). Dementia in IBD patients was associated with frequent healthcare system contacts. Conclusions UC and CD are associated with slightly increased all‐cause dementia risk, particularly frontotemporal dementia in CD patients. Frequent healthcare system contacts by patients with IBD and detection bias may play a role in the association.

Background Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. Objectives To examine the cancer risk in patients with kidney disease following a VTE. Methods We conducted a nationwide population-based cohort study in Denmark (1996–2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. Results We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6–5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3–5.8), with a SIR of 2.9 (95% CI: 2.5–3.4) when compared with the general population, and 2.0 (95% CI: 1.8–2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3–1.6) when compared with the general population, and 1.1 (95% CI: 0.9–1.2) compared with VTE patients without kidney disease. Conclusions Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

ObjectivePrevalent type 2 diabetes (T2D) is associated with an increased risk of colorectal cancer and could impair the quality of bowel preparation for colonoscopy. This may in turn increase the risk of overlooked precancerous polyps and subsequent risk of post-colonoscopy colorectal cancer (PCCRC). We investigated whether patients with T2D are at increased risk of PCCRC compared with patients without T2D.DesignWe conducted a population-based cohort study of patients with T2D and without T2D undergoing colonoscopy in Denmark (1995–2015). We investigated the risk of PCCRC by calculating >6 to 36 months cumulative incidence proportions (CIPs) treating death and colectomy as competing risks. Using Cox proportional-hazards regression analyses, we also computed HRs of PCCRC, comparing patients with T2D and non-T2D. According to the World Endoscopy Organization guidelines, we calculated PCCRC 3-year rates to estimate the proportions of T2D and non-T2D CRC patients experiencing PCCRC.ResultsWe identified 29 031 patients with T2D and 333 232 patients without T2D undergoing colonoscopy. We observed 250 PCCRCs among patients with T2D and 1658 PCCRCs among patients without T2D. The >6 to 36 months CIP after a first-time colonoscopy was 0.64% (95% CI 0.55% to 0.74%) for T2D and 0.36% (95% CI 0.34% to 0.38%) for patients without T2D. The HRs of PCCRC were 1.43 (95% CI 1.21 to 1.72) after a first-time colonoscopy and 1.18 (95% CI 0.75 to 1.85) after a second-time colonoscopy. The PCCRC 3-year rate was 7.9% for patients with T2D and 7.4% for patients without T2D.ConclusionT2D may be associated with an increased HR of PCCRC.

ObjectiveAspirin may increase the risk of lower gastrointestinal bleeding (LGIB) from precursors of colorectal cancer (CRC). We investigated whether use of low-dose aspirin, through initiation of LGIB, may lead patients to undergo colonoscopy and polypectomy before manifest CRC.DesignWe conducted a historical cohort study (2005–2013) of all Danish residents who initiated low-dose aspirin treatment (n=412 202) in a setting without screening for CRC. Each new aspirin user was matched with three non-users (n=1 236 560) by age, sex and region of residence on the date of their matched new user’s first-time aspirin prescription (index date). We computed absolute risks (ARs), risk differences and relative risks (RRs) of LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC, comparing aspirin users with non-users.ResultsThe ARs were higher for new users than non-users for LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC within 3 months after index. Comparing new users with non-users, the RRs were 2.79 (95% CI 2.40 to 3.24) for LGIB, 1.73 (95% CI 1.63 to 1.84) for lower gastrointestinal endoscopy, 1.56 (95% CI 1.42 to 1.72) for colorectal polyps and 1.73 (95% CI 1.51 to 1.98) for CRC. The RRs remained elevated for more than 12 months after the index date, with the exception of CRC where the RRs were slightly decreased during the 3–5 years (RR 0.90, 95% CI 0.83 to 0.98) and more than 5 years (RR 0.91, 95% CI 0.82 to 1.00) following the index date.ConclusionThese findings indicate that aspirin may contribute to reduce CRC risk by causing premalignant polyps to bleed, thereby expediting colonoscopy and polypectomy before CRC development.

AimA laparoscopic approach to total colectomy (TC) for inflammatory bowel disease (IBD) is being increasingly used, but data on its comparative benefits over open TC are conflicting. The aim of this study was to examine 90‐day outcomes following laparoscopic and open TC for IBD in a nationwide cohort after the introduction of laparoscopy.MethodIBD patients undergoing TC in Denmark from 2005 to 2017 were identified from the Danish National Patient Registry. We used Kaplan–Meier methodology to estimate mortality and Cox regression analysis to estimate adjusted mortality rate ratios (aMRRs) and adjusted hazard ratios (aHRs) of reoperation, readmission and intensive care unit (ICU) transfer, comparing patients undergoing laparoscopic versus open TC.ResultsWe identified 1095 patients undergoing laparoscopic TC and 1523 patients undergoing open TC. Following emergency TC, 90‐day mortality was 2.8% (1.6%–4.9%) after laparoscopic TC and 9.1% (7.0%–11.8%) after open TC. Ninety‐day mortality was 0.9% (0.3%–2.5%) after laparoscopic TC and 2.6% (1.5%–4.3%) after open elective TC. The aMRRs associated with laparoscopic TC were 0.45 (95% CI 0.25–0.80) in emergency cases and 0.29 (95% CI 0.10–0.86) in elective cases. Risks of readmission were comparable following laparoscopic versus open TC, both in emergency [aHR = 0.93 (95% CI 0.76–1.15)] and elective [aHR = 0.83 (95% CI 0.68–1.02)] cases, while risks of ICU transfer and reoperation were lower following laparoscopic TC, both in emergency cases [aHR = 0.53 (95% CI 0.35–0.82) and aHR = 0.26 (95% CI 0.15–0.47)] and elective [aHR = 0.58 (95% CI 0.35–0.95) and aHR = 0.37 (95% CI 0.21–0.66)] cases.ConclusionThe introduction of laparoscopic TC for IBD in Denmark was not associated with increased mortality or morbidity. In fact, laparoscopic TC for IBD may be associated with lower short‐term mortality and morbidity compared with open TC.

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