Antibiotic use is common in childhood and its potential as an environmental risk factor for IBD warrants scrutiny. This is the first prospective study to show a strong association between antibiotic use and CD in childhood. However, as with any observational study, causality cannot be inferred from our results and confounding by indication--in particular, prescribing of antibiotics to children with intestinal symptoms of as yet undiagnosed CD--should also be considered as a possible explanation.

ObjectiveTo assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern.DesignRegister based cohort study.SettingSweden and Denmark from July 2013 to December 2016.ParticipantsA propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists.Main outcome measuresThe primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models.ResultsUse of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 v 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 v 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 v 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 v 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 v 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 v 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 v 1.2, 1.16, 0.64 to 2.12).ConclusionsIn this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.

ObjectiveTo investigate whether oral fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection.DesignNationwide historical cohort study using linked register data on patient characteristics, filled prescriptions, and cases of aortic aneurysm or dissection.SettingSweden, July 2006 to December 2013.Participants360 088 treatment episodes of fluoroquinolone use (78%ciprofloxacin) and propensity score matched comparator episodes of amoxicillin use (n=360 088).Main outcome measuresCox regression was used to estimate hazard ratios for a first diagnosis of aortic aneurysm or dissection, defined as admission to hospital or emergency department for, or death due to, aortic aneurysm or dissection, within 60 days from start of treatment.ResultsWithin the 60 day risk period, the rate of aortic aneurysm or dissection was 1.2 cases per 1000 person years among fluoroquinolone users and 0.7 cases per 1000 person years among amoxicillin users. Fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection (hazard ratio 1.66 (95% confidence interval 1.12 to 2.46)), with an estimated absolute difference of 82 (95% confidence interval 15 to 181) cases of aortic aneurysm or dissection by 60 days per 1 million treatment episodes. In a secondary analysis, the hazard ratio for the association with fluoroquinolone use was 1.90 (1.22 to 2.96) for aortic aneurysm and 0.93 (0.38 to 2.29) for aortic dissection.ConclusionsIn a propensity score matched cohort, fluoroquinolone use was associated with an increased risk of aortic aneurysm or dissection. This association appeared to be largely driven by aortic aneurysm.

Azithromycin use was not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults. (Funded by the Danish Medical Research Council.).