Over a 1-year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S-protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non-cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 mumol l-1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin-deficient subjects, and below this level in 10 of the 11 non-deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non-cobalamin deficiency (efficiency = 0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.

Background It is unclear whether nonvitamin K antagonist oral anticoagulants ( NOAC s) can mitigate dementia development in atrial fibrillation. We compared dementia development among users of NOACs or warfarin in patients with atrial fibrillation with no prior neurological diagnoses. Methods and Results We conducted a Danish nationwide cohort study including 33 617 new oral anticoagulant users with nonvalvular atrial fibrillation, of which 11 052 were aged 60 to 69 years, 13 237 were aged 70 to 79 years, and 9238 were aged 80 years and older. To exclude prevalent non ‐oral anticoagulants– associated dementia, we considered the at‐risk population of patients alive and free of dementia at 180 days following inclusion. We compared rates of new‐onset dementia by age and treatment regimen using inverse probability of treatment weighting to account for confounding. Approximately 60% of patients were NOAC users and 40% were warfarin users. Mean follow‐up was 3.4 years. Dementia occurred in 41 patients aged 60 to 69 years, 276 patients aged 70 to 79 years, and 441 patients aged 80 years and older. Relative to warfarin users, dementia rates were nonsignificantly lower among NOAC users aged 60 to 69 years (0.11 events/100 person‐years versus 0.12 events/100 person‐years; weighted hazard ratio, 0.92 [95% CI, 0.48–1.72]) and NOAC users aged 70 to 79 years (0.64 events/100 person‐years versus 0.78 events/100 person‐years; weighted hazard ratio , 0.86 [95% CI, 0.68–1.09]), whereas NOAC s were associated with significantly higher dementia rates (2.16 events/100 person‐years versus 1.70 events/100 person‐years; weighted hazard ratio , 1.31 [95% CI, 1.07–1.59]) in patients 80 years and older. Conclusions This nationwide cohort of patients with atrial fibrillation revealed no clinically meaningful difference in dementia development between users of NOACs or warfarin apart from a higher risk in NOAC users 80 years and older, which may relate to residual confounding from selective prescribing and unobserved comorbidities.

Aim Patient-reported outcome measures (PROMs) may predict poor clinical outcome in patients with heart failure (HF). It remains unclear whether PROMs are associated with subsequent adherence to HF medication. We aimed to determine whether health-related quality of life, anxiety and depression were associated with long-term medication adherence in these patients. Methods and results A national cohort study of Danish patients with HF with three-year follow-up (n = 1,464). PROMs included the EuroQol five-dimensional, five-level questionnaire (EQ-5D-5L), the HeartQoL and the Hospital Anxiety and Depression Scale (HADS). Patient-reported outcomes (PRO) data were linked to demographic and clinical data at baseline, and data on all redeemed prescriptions for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor neprilysin inhibitors (ACEI/ARB/ARNI), β-blockers and mineralocorticoid receptor antagonists (MRAs) during follow-up. Medication non-adherence was defined as < 80% of proportion of days covered (PDC). In adjusted regression analyses, lower health-related quality of life (EQ-5D and HeartQoL) and symptoms of depression (HADS-D) at discharge were associated with non-adherence. After three years of follow-up, lower health-related quality of life (EQ-5D) was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 2.78, 95% CI:1.19-6.49), β-blockers (adjusted OR 2.35, 95% CI:1.04-5.29), whereas HADS-D was associated with non-adherence for ACEI/ARB/ARNI (adjusted OR 1.07, 95% CI:1.03-1.11) and β-blockers (adjusted OR 1.06, 95% CI:1.02-1.10). Conclusion Lower health-related quality of life and symptoms of depression were associated with non-adherence across HF medications at one- and three years of follow-up. Person-centred care using PROMs may carry a potential for identifying patients at increased risk of future medication non-adherence.

Stressful life events have been associated with high risk of suicidal behavior. The aim of this study was to examine whether persons who died by suicide in Denmark had more frequently been exposed to stressful life events, specifically divorce, death of a close relative, exposure to violence, and imprisonment, when compared to gender and age-matched controls. Data from Danish national registers were obtained for the period of 2000-2010 and a nested case-control design was applied. The association between exposure to stressful life events and suicide was examined using logistic regression analysis. In all, 7,115 suicides were identified during the 11 years of follow-up. For each of these, 20 age- and gender-matched controls were randomly selected (n = 142,300). Cases who died by suicide had an odds ratio of 9.3 (CI-95%: 7.8-11.0) of having been exposed to imprisonment five or more times when compared to controls. People who died by suicide had 1.5-fold (CI-95%: 1.3-1.6) higher risk of having experienced a divorce. Stressful life events, such as divorce and imprisonment, were more frequent in temporal proximity to the date of death among the suicide cases than for end of exposure for controls (p < .001 and p < .001, respectively). Our findings confirm that, using nationwide data, stressful life events are positively associated to subsequent suicide. Causal pathways linking the two may, however, be indirect.

Background Guideline recommendations on the use of non–vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with aortic stenosis are based on studies including a low number of patients with aortic stenosis. The aim of this study was to estimate the effects of NOAC versus warfarin on thromboembolism and major bleeding among AF patients with aortic stenosis. Methods and Results We emulated a target trial using observational data from Danish nationwide registries between 2013 and 2018. Thromboembolism was defined as a hospital diagnosis of ischemic stroke and/or systemic embolism, and major bleeding was defined as a hospital diagnosis of intracranial bleeding, gastrointestinal bleeding, or major or clinically relevant bleeding in other anatomic sites. Treatment effect estimates were based on an intention‐to‐treat and per‐protocol approach. A total of 3726 patients with AF and aortic stenosis claimed a prescription for either a NOAC (2357 patients) or warfarin (1369 patients) and met the eligibility criteria for the trial. During 3 years of follow‐up, the adjusted hazard ratios for thromboembolism and major bleeding were 1.62 (95% CI, 1.08–2.45) and 0.73 (0.59–0.91) for NOAC compared with warfarin in the intention‐to‐treat analyses. Similar results were observed in the per‐protocol analyses. Conclusions In this observational study, we observed a higher risk of thromboembolism but a lower risk of major bleeding for treatment with NOACs compared with warfarin in patients with AF and aortic stenosis. This observation needs confirmation in large randomized trials in these commonly encountered patients.

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Introduction Uncertainty remains about the most appropriate timing of induction of labor in late‐term pregnancies. To address this issue, this study aimed to compare the risk of neonatal morbidity and pregnancy‐ and birth‐related complications between gestational age (GA) 41+4–42+0 and GA 41+0–41+3 weeks. Material and methods This nationwide registry‐based cohort study included singleton births without major congenital malformations, with registered GA, and with intended vaginal delivery at GA 41+0– 42+0 weeks between 2009 and 2018 in Denmark. Logistic regression models were used to estimate the crude risk ratio and adjusted risk ratio (RRA) of neonatal and obstetric adverse outcomes in births at GA 41+4– 42+0 weeks compared with GA 41+0– 41+3 weeks. The results were adjusted for relevant confounders, including induction of labor. Results A higher incidence of neonatal morbidity and birth complications was observed in births at GA 41+4–42+0 weeks than in births at GA 41+0–41+3 weeks. Neonatal morbidities included an increased risk of low Apgar score (Apgar 0–6 after 5 min; RRA 1.17, 95% confidence interval [CI] 1.01–1.34), meconium aspiration (RRA 1.25, 95% CI 1.06–1.48), need for respiratory support (continuous positive airway pressure; RRA 1.09, 95% CI 1.03–1.15), and a composite outcome of need for comprehensive treatment at a neonatal department or neonatal death (RRA 1.65, 95% CI 1.29–2.11). Birth complications included emergency cesarean section (RRA 1.17, 95% CI 1.14–1.21), severe lacerations (RRA 1.11, 95% Cl 1.04–1.17), and increased blood loss after birth (RRA 1.13, 95% CI 1.06–1.21). Conclusions Births at GA 41+4–42+0 weeks were associated with an increased risk of neonatal morbidity and birth complications compared with births at GA 41+0–41+3 weeks. The results of this study may aid clinicians in deciding when to recommend induction of labor in late‐term pregnancies.

Aims To describe the risks of thromboembolism and major bleeding complications in anticoagulated patients with atrial fibrillation (AF) and native aortic or mitral valvular heart disease using data reflecting clinical practice. Methods and results Descriptive cohort study of anticoagulated patients with incident AF and native aortic or mitral valvular heart disease, identified in nationwide Danish registries from 2000 to 2018. A total of 10 043 patients were included, of which 5190 (51.7%) patients had aortic stenosis, 1788 (17.8%) patients had aortic regurgitation, 327 (3.3%) patients had mitral stenosis, and 2738 (27.3%) patients had mitral regurgitation. At 1 year after AF diagnosis, the risk of thromboembolism was 4.6% in patients with mitral stenosis taking a vitamin K antagonist (VKA), and 2.6% in patients with aortic stenosis taking a VKA or non-vitamin K antagonist oral anticoagulant (NOAC). For patients with aortic or mitral regurgitation, the risks of thromboembolism ranged between 1.5%-1.8% in both treatment groups. For the endpoint of major bleeding, the risk was ∼5.5% in patients with aortic stenosis or mitral stenosis treated with a VKA, and 3.3–4.0% in patients with aortic or mitral regurgitation. For patients treated with a NOAC, the risk of major bleeding was 3.7% in patients with aortic stenosis and ∼2.5% in patients with aortic or mitral regurgitation. Conclusion When using data reflecting contemporary clinical practice, our observations suggested that 1 year after a diagnosis of AF, anticoagulated patients with aortic or mitral valvular heart disease had dissimilar risk of thromboembolism and major bleeding complications. Specifically, patients with aortic stenosis or mitral stenosis were high-risk subgroups. This observation may guide clinicians regarding intensity of clinical follow-up.