Objective
Parkinson's disease (PD) may be caused by an enteric neurotropic pathogen entering the brain through the vagal nerve, a process that may take over 20 years. We investigated the risk of PD ...in patients who underwent vagotomy and hypothesized that truncal vagotomy is associated with a protective effect, whereas superselective vagotomy has a minor effect.
Methods
We constructed cohorts of all patients in Denmark who underwent vagotomy during 1977–1995 and a matched general population cohort by linking Danish registries. We used Cox regression to compute hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders.
Results
Risk of PD was decreased in patients who underwent truncal (HR = 0.85; 95% CI = 0.56–1.27; follow‐up of >20 years: HR = 0.58; 95% CI: 0.28–1.20) compared to superselective vagotomy. Risk of PD was also decreased after truncal vagotomy when compared to the general population cohort (overall adjusted HR = 0.85; 95% CI: 0.63–1.14; follow‐up >20 years, adjusted HR = 0.53; 95% CI: 0.28–0.99). In patients who underwent superselective vagotomy, risk of PD was similar to the general population (HR = 1.09; 95% CI: 0.84–1.43; follow‐up of >20 years: HR = 1.16; 95% CI: 0.80–1.70). Statistical precision of risk estimates was limited. Results were consistent after external adjustment for unmeasured confounding by smoking.
Interpretation
Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD. Ann Neurol 2015;78:522–529
By mid March, 2021, vaccination against COVID-19 using the ChAdOx1 nCoV-19 (AZD1222) vaccine from Oxford–AstraZeneca1,2 was paused in a number of European countries due to reports of thromboembolic ...events in vaccinated individuals.3 According to the European Medicines Agency (EMA), 30 cases of thromboembolic events (predominantly venous) had been reported by March 10, 2021, among the approximately 5 million recipients of the Oxford–AstraZeneca COVID-19 vaccine in the European Economic Area.3 The EMA subsequently stated that “The number of thromboembolic events in vaccinated people is no higher than the number seen in the general population”.4 To inform the ongoing discussion on the safety of the Oxford–AstraZeneca COVID-19 vaccine, we analysed nationwide population-based data from Denmark to estimate the natural incidence of venous thromboembolism.5 Denmark has a tax-supported universal health-care system,6 in which all hospital contacts are registered in the Danish National Patient Registry.7 We first used the Danish Civil Registration System6 to identify all Danes who were at least 18 years old between Jan 1, 2010, and Nov 30, 2018. ...detailed clinical descriptions of the thromboembolic events reported in relation to Oxford–AstraZeneca COVID-19 vaccinations are still lacking.4 We are, however, aware that although a substantial fraction of the thromboembolisms seem to be venous, reports are emerging of rare types of multiple thrombosis, bleeding, and thrombocytopenia, apparently similar to disseminated intravascular coagulation, occurring in otherwise healthy individuals shortly after receiving the Oxford–AstraZeneca COVID-19 vaccine.13 These outcomes are not included in the present analysis. ...our estimated weekly and monthly venous thromboembolism case numbers in the population of 5 million individuals are based entirely on incidence rates from Denmark and might not be representative of the other countries where the Oxford–AstraZeneca COVID-19 vaccine has been used.
AbstractObjectiveTo examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and ...heart failure in patients with migraine and in a general population comparison cohort.DesignNationwide, population based cohort study.SettingAll Danish hospitals and hospital outpatient clinics from 1995 to 2013.Participants51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year.Main outcome measuresComorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis.ResultsHigher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 25 v 17 for myocardial infarction, 45 v 25 for ischaemic stroke, 11 v 6 for haemorrhagic stroke, 13 v 11 for peripheral artery disease, 27 v 18 for venous thromboembolism, 47 v 34 for atrial fibrillation or atrial flutter, and 19 v 18 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking.ConclusionsMigraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases.
Objective
To investigate the association between vaginal bleeding (VB) in pregnancy and women's mortality, using VB‐unaffected pregnancies, terminations and miscarriages as comparators.
Design
...Observational cohort study.
Setting
Nationwide registries of Denmark linked at an individual level.
Population or Sample
1 354 181 women and their 3 162 317 pregnancies (1979–2017), including 70 835 VB‐affected pregnancies and comparators: 2 236 359 VB‐unaffected pregnancies ending in childbirth; 589 697 terminations; and 265 426 miscarriages.
Methods
We followed pregnancies until the earliest date of woman's death, emigration or end of data.
Main outcome measures
All‐cause and cause‐specific mortality rates per 10 000 person‐years (PY) and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted using Cox proportional hazards regression for age, calendar year, pre‐existing chronic conditions and socio‐economic factors.
Results
There were 2320 deaths from any cause among women following VB‐affected pregnancy (mortality rate 15.2, 95% CI 14.6–15.9 per 10 000 PY); 55 030 deaths following VB‐unaffected pregnancy (mortality rate 12.7, 95% CI 12.6–12.8); 27 500 deaths following a termination (mortality rate 21.9, 95% CI 21.6–22.1), and 10 865 deaths following a miscarriage (mortality rate 19.2, 95% CI 18.8–19.6). For comparison of VB‐affected versus VB‐unaffected pregnancies, associations with all‐cause (HR 1.14, 95% CI 1.09–1.19), natural causes (HR 1.15, 95% CI 1.09–1.22) and non‐natural causes (HR 1.27, 95% CI 1.08–1.48) mortality were attenuated in a sensitivity analysis of pregnancies recorded in 1994–2017 (HR 1.00, 95% CI 0.90–1.12, HR 0.98, 95% CI 0.85–1.14 and HR 1.04, 95% CI 0.72–1.51, respectively). Contrasts with remaining comparators did not suggest increased risks of all‐cause, natural or non‐natural mortality causes.
Conclusion
We found no evidence of an increased risk of women's mortality following VB‐affected versus VB‐unaffected pregnancy, termination or miscarriage.
Background
Vaginal bleeding (VB) before 20 gestational weeks of a viable pregnancy is a manifestation of a threatened miscarriage. VB is associated with increased levels of pro‐inflammatory cytokines ...such as interferon‐gamma, tumour necrosis factor‐alpha and interleukin‐6. Increased levels of these cytokines and oxidative stress are risk factors for cancer. The risk of cancer following a VB‐affected pregnancy that ended in childbirth is unknown.
Objectives
To investigate the associations between VB in pregnancy that resulted in delivery and risk of incident cancer.
Methods
We conducted a cohort study (1995–2018) in Denmark using administrative and healthcare registries. We included 37,082 VB‐affected deliveries, 1,363,614 VB‐unaffected deliveries, 324,328 pregnancies ending in terminations, and 137,104 miscarriages. We computed the absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidities, and socio‐economic factors using Cox proportional hazards regression. Multiple pregnancies to the same woman were accounted for in the analysis.
Results
The median (25th–75th percentile) follow‐up in the study was 12.6 (6.9, 18.2) years. The prevalence of VB in the present study was 3%. At the end of the follow‐up, there were 1320 cancer cases among the VB‐affected delivery cohort, 40,420 among the VB‐unaffected delivery cohort, 10,300 among the termination cohort and 4790 among the miscarriage cohort. HRs for any cancer among VB‐affected deliveries were 1.03 (95% CI 0.97, 1.08) compared with VB‐unaffected deliveries, 1.03 (95% CI 0.97, 1.09) compared with terminations and 0.90 (95% CI 0.84, 0.95) compared with miscarriages. There were no increased risks of premenopausal breast cancer, cervical cancer, ovary and fallopian tube cancer or uterine cancer following VB‐affected deliveries vs. comparison cohorts.
Conclusions
We found no evidence of an association between vaginal bleeding in pregnancy and an increased risk of cancer.
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.
Risk of dementia in patients with inflammatory bowel disease
Intensive follow-up of patients after curative surgery for colorectal cancer is common in clinical practice, but evidence of a survival benefit is limited.
To examine overall mortality, colorectal ...cancer-specific mortality, and colorectal cancer-specific recurrence rates among patients with stage II or III colorectal cancer who were randomized after curative surgery to 2 alternative schedules for follow-up testing with computed tomography and carcinoembryonic antigen.
Unblinded randomized trial including 2509 patients with stage II or III colorectal cancer treated at 24 centers in Sweden, Denmark, and Uruguay from January 2006 through December 2010 and followed up for 5 years; follow-up ended on December 31, 2015.
Patients were randomized either to follow-up testing with computed tomography of the thorax and abdomen and serum carcinoembryonic antigen at 6, 12, 18, 24, and 36 months after surgery (high-frequency group; n = 1253 patients) or at 12 and 36 months after surgery (low-frequency group; n = 1256 patients).
The primary outcomes were 5-year overall mortality and colorectal cancer-specific mortality rates. The secondary outcome was the colorectal cancer-specific recurrence rate. Both intention-to-treat and per-protocol analyses were performed.
Among 2555 patients who were randomized, 2509 were included in the intention-to-treat analysis (mean age, 63.5 years; 1128 women 45%) and 2365 (94.3%) completed the trial. The 5-year overall patient mortality rate in the high-frequency group was 13.0% (161/1253) compared with 14.1% (174/1256) in the low-frequency group (risk difference, 1.1% 95% CI, -1.6% to 3.8%; P = .43). The 5-year colorectal cancer-specific mortality rate in the high-frequency group was 10.6% (128/1248) compared with 11.4% (137/1250) in the low-frequency group (risk difference, 0.8% 95% CI, -1.7% to 3.3%; P = .52). The colorectal cancer-specific recurrence rate was 21.6% (265/1248) in the high-frequency group compared with 19.4% (238/1250) in the low-frequency group (risk difference, 2.2% 95% CI, -1.0% to 5.4%; P = .15).
Among patients with stage II or III colorectal cancer, follow-up testing with computed tomography and carcinoembryonic antigen more frequently compared with less frequently did not result in a significant rate reduction in 5-year overall mortality or colorectal cancer-specific mortality.
clinicaltrials.gov Identifier: NCT00225641.
Abstract
Background
Women’s reproductive health is associated with cardiovascular morbidity. However, an association of vaginal bleeding (VB) in pregnancy with diabetes and cardiovascular outcomes ...has scarcely been investigated.
Methods
We conducted a population-based cohort study in Denmark (1994–2018). Using nationwide registries, among 903 327 women we identified 1 901 725 pregnancies: 39 265 ended in childbirth and were affected by VB; 1 389 285 ended in childbirth and were unaffected by VB; 333 785 ended in a termination, and 139 390 ended in a miscarriage. The outcomes were diabetes types 1 and 2, hypertension, ischaemic heart disease including myocardial infarction, atrial fibrillation or flutter, heart failure and ischaemic and haemorrhagic stroke. We computed incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, calendar year of pregnancy end, morbidities and reproductive and socioeconomic factors, using inverse probability of treatment-weighted Cox proportional hazards regression.
Results
In analyses of VB-affected vs VB-unaffected pregnancies, aHRs were 1.15 (1.03–1.28) for diabetes type 1, 1.19 (1.13–1.26) for diabetes type 2, 1.19 (1.14–1.25) for hypertension, 1.26 (1.16–1.37) for ischaemic heart disease, 1.21 (1.03–1.42) for myocardial infarction, 1.32 (1.14–1.51) for atrial fibrillation or flutter and 1.23 (0.99–1.52) for heart failure. aHRs were 1.41 (1.26–1.57) and 1.46 (1.23–1.72) for ischaemic and haemorrhagic stroke, respectively. When contrasting VB-affected pregnancies with terminations, aHRs were up to 1.3-fold increased for diabetes and hypertension; however, when contrasting VB-affected pregnancies with miscarriages, estimates were below or close to the null value.
Conclusions
Women’s risks of diabetes and cardiovascular outcomes later in life were increased following VB-affected vs VB-unaffected pregnancy or termination, but not following VB-affected pregnancy vs miscarriage.
Aims
The association between heart failure and dementia remains unclear. We assessed the risk of dementia among patients with heart failure and members of a general population comparison cohort.
...Methods and results
Individual‐level data from Danish medical registries were linked in this nationwide population‐based cohort study comparing patients with a first‐time hospitalization for heart failure between 1980 and 2012 and a year of birth‐, sex‐, and calendar year‐matched comparison cohort from the general population. Stratified Cox regression analysis was used to compute 1–35‐year hazard ratios (HRs) for the risk of all‐cause dementia and, secondarily, Alzheimer's disease, vascular dementia, and other dementias. Analyses included 324 418 heart failure patients and 1 622 079 individuals from the general population (median age 77 years, 52% male). Compared with the general population cohort, risk of all‐cause dementia was increased among heart failure patients adjusted HR 1.21, 95% confidence interval (CI) 1.18–1.24. The associations were stronger in men and in heart failure patients under age 70. Heart failure patients had higher risks of vascular dementia (adjusted HR 1.49, 95% CI 1.40–1.59) and other dementias (adjusted HR 1.30, 95% CI 1.26–1.34) than members of the general population cohort. Heart failure was not associated with Alzheimer's disease (adjusted HR 1.00, 95% CI 0.96–1.04).
Conclusion
Heart failure was associated with an increased risk of all‐cause dementia. Heart failure may represent a risk factor for dementia, but not necessarily for Alzheimer's disease.
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