Introduction
Treatment possibilities have changed in inflammatory bowel disease (IBD). We assessed changes in medical treatment and surgery over time and impact of medications on risk of surgery in a population-based cohort.
Methods
48 967 individuals were diagnosed with IBD (Crohn's disease (CD), 13 185; ulcerative colitis (UC), 35 782) during 1979–2011. Cumulative probability of receiving 5-aminosalicylic acids (5-ASA), topical, oral corticosteroids, thiopurines, and tumour necrosis factor-α (TNF-α) blockers, and of first minor or major surgery according to period of diagnosis, was estimated. Medication use and risk of surgery was examined by Cox regression.
Results
5-year cumulative probability of first major surgery decreased from 44.7% in cohort (1979–1986) to 19.6% in cohort (2003–2011) (p < 0.001) for CD, and from 11.7% in cohort (1979–1986) to 7.5% in cohort (2003–2011) (p < 0.001) for UC. Minor surgery risk decreased significantly in CD. From cohort (1995–2002) to cohort (2003–2011), a significant increase in use of thiopurines and TNF-α blockers was observed, paralleled by a significant decrease in use of 5-ASA and corticosteroids. Comparing use of azathioprine (or oral corticosteroids) to never-use, no convincing surgery-sparing effect was found. Comparing use in 3+ months of a given drug with use <3 months, only 3+ months use of oral corticosteroids reduced the risk of surgery in patients with disease duration of >1 year.
Conclusions
Parallel to an increasing use of thiopurines and TNF-α blockers in IBD over time, a persistent significant decrease in surgery rates was observed along with a significant decrease in use of 5-ASA and corticosteroids. However, no convincing surgery-sparing effect of newer medications was found.
Objectives To determine how soon after delivery the risk of post-pregnancy hypertension increases in women with hypertensive disorders of pregnancy and how the risk evolves over time.
Design Nationwide register based cohort study.
Setting Denmark.
Populations 482 972 primiparous women with a first live birth or stillbirth between 1995 and 2012 (cumulative incidence analyses), and 1 025 118 women with at least one live birth or stillbirth between 1978 and 2012 (Cox regression analyses).
Main outcome measures 10 year cumulative incidences of post-pregnancy hypertension requiring treatment with prescription drugs, and hazard ratios estimated using Cox regression.
Results Of women with a hypertensive disorder of pregnancy in a first pregnancy in their 20s, 14% developed hypertension in the first decade post partum, compared with 4% of women with normotensive first pregnancies in their 20s. The corresponding percentages for women with a first pregnancy in their 40s were 32% and 11%, respectively. In the year after delivery, women with a hypertensive disorder of pregnancy had 12-fold to 25-fold higher rates of hypertension than did women with a normotensive pregnancy. Rates in women with a hypertensive disorder of pregnancy were threefold to 10-fold higher 1-10 years post partum and remained twice as high even 20 or more years later.
Conclusions The risk of hypertension associated with hypertensive disorders of pregnancy is high immediately after an affected pregnancy and persists for more than 20 years. Up to one third of women with a hypertensive disorder of pregnancy may develop hypertension within a decade of an affected pregnancy, indicating that cardiovascular disease prevention in these women should include blood pressure monitoring initiated soon after pregnancy.
BMI was found to be associated with several Ads. This was most pronounced between obesity and risk of sarcoidosis and and risk of type 1 diabetes mellitus. These novel findings need confirmation and the possible role of adipose tissue-derived immunological changes in the development of autoimmune reactions needs consideration.
In this Danish nationwide study, exposure to TNF-α antagonists among patients with IBD was not associated with an increased risk of cancer over a median follow-up of 3.7 years among those exposed. An increased risk associated with longer-term accumulated doses and follow-up cannot be excluded.
The risk of IHD was highest in the first year after IBD diagnosis, possibly owing to ascertainment bias. The increased long-term risk of IHD in IBD may be related to chronic inflammation, and interventions reducing the inflammatory burden may attenuate this risk.
ObjectiveTo explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one live birth or stillbirth between 1978 and 2015.Main outcome measureHazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.ResultsThe cohort consisted of 1 178 005 women with 20 352 695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer’s disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83).ConclusionsPre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.
Background and ObjectiveVaricella zoster virus (VZV) is known to cause VZV vasculopathy, which may be associated with stroke. A recent study found an increased risk of stroke within one year of herpes zoster. We aimed to investigate the short and long-term effects of herpes zoster on the risk of stroke.MethodsUsing Danish national registers, we constructed a cohort consisting of all Danish adults ≥18 years old between 1995 and 2008 (n = 4.6 million; person-years of follow-up = 52.9 million). Individual-level information on prescriptions for herpes zoster antiviral treatment and diagnoses of stroke was obtained from national registers. We compared the risk of stroke in persons who had received the specific dosage of acyclovir for herpes zoster with persons who had never received antiviral treatment by Poisson regression.ResultsDuring follow-up, 2.5% received treatment for herpes zoster and 5.0% were diagnosed with stroke. Individuals who had received medication had a 127% (95% CI 83–182%) increased risk the first two weeks, 17% (CI 9–24%) between two weeks and one year, and 5% (2–9%) after the first year. The increased risk was greatest in the youngest age group (<40). To control for healthcare-seeking behaviour, we conducted parallel analyses investigating the risk of selected fractures after herpes zoster and found no similar increased risks.ConclusionsThis large nationwide cohort study found an increased risk of stroke after treatment for herpes zoster. Although the short-term risk was particularly high, we cannot rule out the possibility of a small but important long-term risk.
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