Drinking water magnesium and cardiovascular mortality: A cohort study in Denmark, 2005-2016.

INTRODUCTION: Cardiovascular diseases are globally a major cause of death. Magnesium deficiency is associated with several diseases including cardiovascular diseases. OBJECTIVE: To examine if a low concentration of magnesium in drinking water is associated with increased cardiovascular mortality and mortality due to acute myocardial infarction and stroke. METHODS: A nationwide population-based cohort study using national health registries was used. A total of 4,274,132 individuals aged 30 years or more were included. Magnesium concentration in drinking water was estimated by linkage of residential addresses in the period 2005-2016 with the national drinking water quality monitoring database. The association between magnesium concentration in drinking water and cardiovascular mortality and mortality due to acute myocardial infarction and stroke was examined using a Poisson regression of number of deaths and logarithmic transformation of follow-up time as offset. The incidence rate ratio (IRR) was adjusted for differences in age, sex, calendar year, cohabitation, country of origin, and socioeconomic status. RESULTS: Median magnesium concentration in drinking water at inclusion was 12.4 mg/L (range: 1.37-54.2 mg/L). The adjusted IRR for cardiovascular mortality was 0.96 (95% CI: 0.94; 0.97) for the lowest magnesium quintile (<6.5 mg/L) as compared to the highest magnesium quintile (>21.9 mg/L). The adjusted IRR for mortality due to acute myocardial infarction and stroke was 1.22 (1.17; 1.27) and 0.96 (0.93; 0.99), respectively, for the lowest magnesium quintile as compared to the highest quintile A decreasing mortality due to acute myocardial infarction was seen with an increasing magnesium concentration in a dose-response manner. CONCLUSION: Low concentrations of magnesium in drinking water were associated with an increased mortality due to acute myocardial infarction. Low concentrations of magnesium in drinking water were associated with decreased cardiovascular mortality, and mortality due to stroke.

Return to work after COVID-19 infection - A Danish nationwide registry study.

OBJECTIVES: This study aimed to explore return to work after COVID-19 and how disease severity affects this. STUDY DESIGN: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. METHODS: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. RESULTS: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. CONCLUSION: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.

Temporal variation in out-of-hospital cardiac arrest occurrence in individuals with or without diabetes.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) occurrence has been shown to exhibit a circadian rhythm, following the circadian rhythm of acute myocardial infarction (AMI) occurrence. Diabetes mellitus (DM) is associated with changes in circadian rhythm. We aimed to compare the temporal variation of OHCA occurrence over the day and week between OHCA patients with DM and those without. METHODS: In two population-based OHCA registries (Amsterdam Resuscitation Studies [ARREST] 2010-2016, n = 4163, and Danish Cardiac Arrest Registry [DANCAR], 2010-2014, n = 12,734), adults (≥18y) with presumed cardiac cause of OHCA and available medical history were included. Single and double cosinor analysis was performed to model circadian variation of OHCA occurrence. Stratified analysis of circadian variation was performed in patients with AMI as immediate cause of OHCA. RESULTS: DM patients (22.8% in ARREST, 24.2% in DANCAR) were older and more frequently had cardiovascular risk factors or previous cardiovascular disease. Both cohorts showed 24 h-rhythmicity, with significant amplitudes in single and double cosinor functions (P-range < 0.001). In both registries, a morning peak (10:00-11:00) and an evening peak (20:00-21:00) was observed in both DM and non-DM patients. No septadian variation was observed in either DM or non-DM patients (P-range 0.13-84). CONCLUSIONS: In these two population-based OHCA registries, we observed a similar circadian rhythm of OHCA occurrence in DM and non-DM patients.

Increased long-term risk of heart failure and other adverse cardiac outcomes in dermatomyositis and polymyositis: Insights from a nationwide cohort.

BACKGROUND: Mounting evidence suggests that dermatomyositis/polymyositis (DM/PM) are associated with increased risk of atherosclerotic events and venous thromboembolism. However, data on the association between DM/PM and other cardiac outcomes, especially heart failure (HF), are scarce. OBJECTIVES: To examine the long-term risk and prognosis associated with adverse cardiac outcomes in patients with DM/PM. METHODS: Using Danish administrative registries, we included all patients ≥18 years with newly diagnosed DM/PM (1996-2018). Risks of incident outcomes were compared with non-DM/PM controls from the background population (matched 1:4 by age, sex, and comorbidity). In a secondary analysis, we compared mortality following HF diagnosis between DM/PM patients with HF and non-DM/PM patients with HF (matched 1:4 by age and sex). RESULTS: The study population included 936 DM/PM patients (median age 58.5 years, 59.0% women) and 3744 matched non-DM/PM controls. The median follow-up was 6.9 years. Absolute 10-year risks of incident outcomes for DM/PM patients vs matched controls were as follows: HF, 6.98% (CI, 5.16-9.16%) vs 4.58% (3.79-5.47%) (P = 0.002); atrial fibrillation, 10.17% (7.94-12.71%) vs 7.07% (6.09-8.15%) (P = 0.005); the composite of ICD implantation/ventricular arrhythmias/cardiac arrest, 1.99% (1.12-3.27%) vs 0.64% (0.40-0.98%) (P = 0.02); and all-cause mortality, 35.42% (31.64-39.21%) vs 16.57% (15.10-18.10%) (P < 0.0001). DM/PM with subsequent HF was associated with higher mortality compared with HF without DM/PM (adjusted hazard ratio 1.58 [CI, 1.01-2.47]). CONCLUSION: Patients with DM/PM had a higher associated risk of HF and other adverse cardiac outcomes compared with matched controls. Among patients developing HF, a history of DM/PM was associated with higher mortality.

Increased vulnerability to COVID-19 in chronic kidney disease.

BACKGROUND: The significance of chronic kidney disease on susceptibility to COVID-19 and subsequent outcomes remains unaddressed. OBJECTIVE: To investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID-19 and subsequent adverse outcomes. METHODS: Rates of hospital-diagnosed COVID-19 were compared across strata of eGFR based on conditional logistic regression using a nested case-control framework with 1:4 matching of patients diagnosed with COVID-19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID-19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G-computation of results to determine 60-day risk standardized to the distribution of risk factors in the sample. RESULTS: Estimated glomerular filtration rate was inversely associated with rate of hospital-diagnosed COVID-19: eGFR 61-90 mL/min/1.73m2 HR 1.13 (95% CI 1.03-1.25), P = 0.011; eGFR 46-60 mL/min/1.73m2   HR 1.26 (95% CI 1.06-1.50), P = 0.008; eGFR 31-45 mL/min/1.73m2 HR 1.68 (95% CI 1.34-2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50-4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60-day risk of death or severe COVID-19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7-15.0); eGFR 90-61 mL/min/1.73m2 16.1% (95% CI 14.5-17.7); eGFR 46-60 mL/min/1.73m2 17.8% (95% CI 14.7-21.2); eGFR 31-45 mL/min/1.73m2 22.6% (95% CI 18.2-26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1-29.1). CONCLUSIONS: Renal insufficiency was associated with progressive increase in both rate of hospital-diagnosed COVID-19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID-19.

Incidence of acute myocardial infarction-related cardiogenic shock during corona virus disease 19 (COVID-19) pandemic.

AIMS: The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). METHODS: On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015-2019 and in 2020. RESULTS: We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015-2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015-2019 was 9.2 (95% CI: 8.3-10.2) and after 8.9 (95% CI: 8.0-9.9). In 2020, the IR was 7.5 (95% CI: 5.8-9.7) before March 11 and 7.7 (95% CI: 6.0-9.9) after. The IRRs comparing the 2020-period with the 2015-2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59-1.12) and 0.87 (95% CI: 0.57-1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74-1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. CONCLUSION: We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.

Long-term outcomes after in-hospital cardiac arrest: 30-day survival and 1-year follow-up of mortality, anoxic brain damage, nursing home admission and in-home care.

AIMS: Long-term functional outcomes after in-hospital cardiac arrest (IHCA) are scarcely studied. However, survivors are at risk of neurological impairment from anoxic brain damage which could affect quality of life and lead to need of care at home or in a nursing home. METHODS: We linked data on ICHAs in Denmark with nationwide registries to report 30-day survival as well as factors associated with survival. Furthermore, among 30-day survivors we reported the one-year cumulative risk of anoxic brain damage or nursing home admission with mortality as the competing risk. RESULTS: In total, 517 patients (27.3%) survived to day 30 out of 1892 eligible patients; 338 (65.9%) were men and median age was 68 (interquartile range 58-76). Lower age, witnessed arrest by health care personnel, monitored arrest and presumed cardiac cause of arrest were associated with 30-day survival. Among 454 30-day survivors without prior anoxic brain damage or nursing home admission, the risk of anoxic brain damage or nursing home admission within the first-year post-arrest was 4.6% (n = 21; 95% CI 2.7-6.6%) with a competing risk of death of 15.6% (n = 71; 95% CI 12.3-19.0%), leaving 79.7% (n = 362) alive without anoxic brain damage or nursing home admission. When adding the risk of need of in-home care among 343 30-day survivors without prior home care needs, 68.8% (n = 236) were alive without any of the composite events one-year post-arrest. CONCLUSION: The majority of 30-day survivors of IHCA are alive at one-year follow-up without anoxic brain damage, nursing home admission or need of in-home care.

Time trends and patient selection in the use of continuous electrocardiography for detecting atrial fibrillation after stroke: a nationwide cohort study.

BACKGROUND AND PURPOSE: Clinical use of continuous electrocardiography (cECG) for detecting atrial fibrillation (AF) after stroke is unclear. In a Danish nationwide cohort, we described post-stroke time trends in outpatient cECG usage and AF incidence and characterized factors associated with cECG use. METHODS: Patients without AF discharged after their first ischaemic stroke between 2010 and 2016 were identified from Danish nationwide registries. cECG included Holter or event recording within 120 days from discharge. Cumulative incidence analysis and multivariable adjusted logistic regression were used to assess time trends and factors associated with cECG usage and AF. RESULTS: The study population comprised 39 641 patients. Cumulative use of cECG increased threefold from 3.3% [95% confidence intervals (CI), 2.8-3.8] in 2010 to 10.5% (95% CI, 9.7-11.3) in 2016. Correspondingly, cumulative incidence of post-stroke AF increased from 1.9% (95% CI, 1.5-2.3) to 2.8% (95% CI, 2.4-3.2). Of all cECG-evaluated patients, 6.3% received an AF diagnosis versus 2.2% of the unevaluated. Receiving cECG was associated with increased odds of AF (odds ratio, 3.4; 95% CI, 2.8-4.0). Lower age, milder strokes and less comorbidity were associated with increased odds of receiving cECG. In contrast, risk factors for AF were increasing age and more comorbidity. CONCLUSIONS: Post-stroke outpatient cECG use and AF incidence have increased over time, but screening rates were low. cECG use was associated with tripled odds of detecting AF. There was a disparity between factors associated with cECG use and risk factors of AF. This raise questions as to the appropriateness of the current clinical approach to post-stoke AF detection.

Preheart failure comorbidities and impact on prognosis in heart failure patients: a nationwide study.

BACKGROUND: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. OBJECTIVES: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. METHODS: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51-74 and >74 years). RESULTS: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64-11.3), 51-74 years (23.3; 22.9-23.7), >74 years (58.5; 57.9-59.0); hazard ratios 245.18 (141.45-424.76), 45.85 (42.77-49.15) and 24.5 (23.64-25.68) for those ≤50, 51-74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). CONCLUSIONS: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.

Bystander cardiopulmonary resuscitation and survival in patients with out-of-hospital cardiac arrest of non-cardiac origin.

BACKGROUND: Knowledge about the effect of bystander cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OHCA) of non-cardiac origin is lacking. We aimed to investigate the association between bystander CPR and survival in OHCA of presumed non-cardiac origin. METHODS: From the Danish Cardiac Arrest Registry and through linkage with national Danish healthcare registries we identified all patients with OHCA of presumed non-cardiac origin in Denmark (2001-2014). These were categorized further into OHCA of medical and non-medical cause. We analyzed temporal trends in bystander CPR and 30-day survival during the study period. Multiple logistic regression was used to examine the association between bystander CPR and 30-day survival and reported as standardized 30-day survival chances with versus without bystander CPR standardized to the prehospital OHCA-factors and patient characteristics of all patients in the study population. RESULTS: We identified 10,761 OHCAs of presumed non-cardiac origin. Bystander CPR was associated with a significantly higher 30-day survival chance of 3.4% (95% confidence interval [CI]: 2.9-3.9) versus 1.8% (95% CI: 1.4-2.2) without bystander CPR. A similar association was found in subgroups of both medical and non-medical OHCA. During the study period, the overall bystander CPR rates increased from 13.6% (95% CI: 11.2-16.5) to 62.7% (95% CI: 60.2-65.2). 30-day survival increased overall from 1.3% (95% CI: 0.7-2.6) to 4.0% (95% CI: 3.1-5.2). CONCLUSION: Bystander CPR was associated with a higher chance of 30-day survival among OHCA of presumed non-cardiac origin regardless of the underlying cause (medical/non-medical). Rates of bystander CPR and 30-day survival improved during the study period.

Association between parental autoimmune disease and atopic dermatitis in their offspring: a matched case-control study.

BACKGROUND: Atopic dermatitis (AD) is associated with many autoimmune diseases, in part due to overlapping genetic risk loci. While parental atopic disease is an important risk for AD in the offspring, little is known on the putative associations between parental autoimmune disease and AD in their children. MATERIALS AND METHODS: All children born between 1996 and 2011 who received a diagnosis of AD in the hospital system before their fifth birthday were matched 1 : 10 with children from the general population. Maternal and paternal autoimmune diseases were assessed using registry-based data. Conditional logistic regression was performed on the relationships between parental autoimmune diseases and AD in their children. RESULTS: A total of 8589 children with AD were matched with controls. One or more autoimmune disease was identified in 5.89% (506/8589) of mothers to AD children and 3.67% (315/8589) of fathers to AD children compared to 4.85% (4163/85 890) and 3.28% (2816/85 890) in parents of control children. Maternal autoimmune disease but not paternal autoimmune disease was associated with AD in the offspring (odds ratio [OR] 1.20 [95% confidence interval (CI) 1.20-1.32] and OR 1.08 [0.96-1.22], respectively), Two or more maternal autoimmune diseases, maternal dermatologic autoimmune disease and maternal digestive autoimmune disease were all also associated with AD development in her children (1.96 [95% CI 1.36-2.84], OR 1.60 [95% CI 1.24-2.07] and OR 1.24 [95% CI 1.06-1.45], respectively). CONCLUSIONS: The risk of AD is influenced by many factors including atopy status and filaggrin gene mutations. In this matched case-control study, maternal autoimmune disease was associated with AD diagnosis in the offspring. Maternal dermatologic and digestive autoimmune diseases were most closely associated with subsequent AD diagnosis in the offspring.

Pregnancy complications, treatment characteristics and birth outcomes in women with atopic dermatitis in Denmark.

BACKGROUND: The risk of prenatal, obstetric and birth complications in mothers with atopic dermatitis (AD), along with treatment use during pregnancy, is unknown. OBJECTIVES: To examine the associations between prenatal, obstetric and birth complications in mothers with AD and describe the dermatologic care received during pregnancy. METHODS: Mother-child pairs, in which the mother had a history of AD, were identified through the Danish Medical Birth Registry and matched 1 : 10 with non-AD pairs. Data on dermatologic treatment and prenatal, obstetric and birth complications were obtained through linkage via nationwide registers. Multiple logistic regression was performed. RESULTS: We identified 10 668 births from 1997 through 2014 to women with AD. Women with a hospital/ambulatory contact for AD during pregnancy had increased topical corticosteroid and ultraviolet therapy use during pregnancy compared to prior. However, overall, women with AD received decreased dermatologic therapy during pregnancy compared to prior. In adjusted analysis, maternal AD was inversely associated with gestational diabetes [OR 0.79, 95% CI (0.68-0.92)], but positively associated with premature rupture of membranes [1.15 (1.05-1.27)] and staphylococcal neonatal septicemia [2.45 (1.33-4.49)]-albeit the latter was rare. These associations did not meet statistical significance in sub-analysis where body mass index data were available. No associations were found with preeclampsia, prematurity or non-staphylococcal neonatal septicaemia. CONCLUSIONS: Women with AD during pregnancy mainly used topical corticosteroids and ultraviolet therapy to control their disease. While premature rupture of membranes and staphylococcal neonatal septicaemia were over-represented in maternal AD, no associations were found with any other significant prenatal, obstetric or birth outcome.

Exploring the association between parental psychiatric disease and childhood atopic dermatitis: a matched case-control study.

BACKGROUND: Maternal prenatal psychiatric disease has been identified as a possible risk factor for atopic dermatitis development in her children. We quantified the associations between maternal and paternal psychiatric disease and the development of atopic dermatitis in their offspring using nationwide registries. METHODS: All children in Denmark born between 1 January 1996 and 31 December 2011 who developed atopic dermatitis prior to their fifth birthday were identified and individually matched 1:10 with controls from the general population and with children receiving care in a similar ambulatory/hospital setting. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals. RESULTS: A total of 8602 children with atopic dermatitis were matched with controls. Rates of parental psychiatric care were similar in the atopic dermatitis and control groups. When compared to the general population, weak associations were found between childhood atopic dermatitis and maternal history of depression [OR 1.18 (95% confidence interval: 1.12-1.26)], alcohol abuse [OR 1.37 (1.17-1.60)] and illicit drug use [OR 1.34 (1.14-1.60)]. However, associations became insignificant when the paediatric ambulatory/hospital control group was used [OR 1.05 (0.99-1.13)], [OR 1.14 (0.98-1.34)] and [OR 1.03 (0.88-1.22)], respectively. No paternal psychiatric disease or prenatal maternal psychiatric disease associated with the AD development in the offspring. CONCLUSIONS: While we found no consistent associations between maternal or paternal psychiatric disease and the subsequent development of atopic dermatitis in their offspring, children of parents with substance abuse issues may be more likely to receive an atopic dermatitis diagnosis.

Increased risk of depression in patients with cutaneous lupus erythematosus and systemic lupus erythematosus: a Danish nationwide cohort study.

BACKGROUND: There is a wide range in the reported prevalences of depression in patients with systemic lupus erythematosus (SLE), while the prevalence of depression in patients with cutaneous lupus erythematosus (CLE) remains severely understudied. OBJECTIVES: To examine whether patients with SLE or CLE have an increased risk of depression. METHODS: In this nationwide observational cohort study, we included patients aged ≥ 18 years with a first-time diagnosis of SLE or CLE between 2000 and 2015 identified in the Danish National Patient Register, which were matched with the general population in a ratio of 1 : 10. After linkage to national Danish health registers of primary and secondary care, analyses of risk for depression and antidepressant use were performed using Cox regression models adjusted for age, sex, socioeconomic status, smoking, alcohol abuse, prior depression and prior antidepressant use. RESULTS: A total of 3489 patients with lupus erythematosus were followed for 23 373 person-years. Compared with the general population, the adjusted hazard ratios (HRs) of depression were 2·07 [95% confidence interval (CI) 1·55-2·75] and 2·22 (95% CI 1·77-2·77) for patients with CLE and SLE, respectively; for hospitalization owing to depression at a department of psychiatry HRs were 2·63 (95% CI 0·80-8·67) and 3·52 (95% CI 1·53-8·11) for patients with CLE and SLE, respectively. The adjusted HRs for antidepressant use were 1·47 (95% CI 1·34-1·63) and 1·70 (95% CI 1·58-1·83) for patients with CLE and SLE, respectively. CONCLUSIONS: The risk of depression was significantly increased in patients with SLE and CLE. Awareness of an increased risk of depression in patients with SLE and CLE might be warranted.

Importance of beta-blocker dose in prevention of ventricular tachyarrhythmias, heart failure hospitalizations, and death in primary prevention implantable cardioverter-defibrillator recipients: a Danish nationwide cohort study.

Aims: There is a paucity of studies investigating a dose-dependent association between beta-blocker therapy and risk of outcome. In a nationwide cohort of primary prevention implantable cardioverter-defibrillator (ICD) patients, we aimed to investigate the dose-dependent association between beta-blocker therapy and risk of ventricular tachyarrhythmias (VT/VF), heart failure (HF) hospitalizations, and death. Methods and results: Information on ICD implantation, endpoints, comorbidities, beta-blocker usage, type, and dose were obtained through Danish nationwide registers. The two major beta-blockers carvedilol and metoprolol were examined in three dose levels; low (metoprolol ≤ 25 mg; carvedilol ≤ 12.5 mg), intermediate (metoprolol 26-199 mg; carvedilol 12.6-49.9 mg), and high (metoprolol ≥ 200 mg; carvedilol ≥ 50 mg). Time to events was investigated utilizing multivariate Cox models with beta-blocker as a time-dependent variable. From 2007 to 2012, 2935 first-time ICD devices were implanted. During follow-up, 399 patients experienced VT/VF, 728 HF hospitalizations and 361 died. As compared with patients not on beta-blockers, low, intermediate, and high dose had significantly reduced risk of HF hospitalizations {hazard ratio (HR) = 0.68 [0.54-0.87], P = 0.002; HR = 0.53 [0.42-0.66], P < 0.001; HR = 0.43 [0.34-0.54], P < 0.001} and death (HR = 0.47 [0.35-0.64], P < 0.001; HR = 0.29 [0.22-0.39], P = 0.001; HR = 0.24 [0.18-0.33], P < 0.001). For the endpoint of VT/VF, only intermediate and high dose beta-blocker was associated with significantly reduced risk (HR = 0.58 [0.43-0.79], P < 0.001; HR = 0.53 [0.39-0.72], P < 0.001). No significant difference was found between comparable doses of carvedilol and metoprolol on any endpoint (P = 0.06-0.94). Conclusion: In primary prevention ICD patients, beta-blocker therapy was associated with significantly reduced risk of all endpoints, as compared with patients not on beta-blocker, with the suggestion of a dose-dependent effect. No detectable difference was found between comparable doses of carvedilol and metoprolol.

Risk of uncommon cancers in patients with psoriasis: a Danish nationwide cohort study.

BACKGROUND: Cancer-associated mortality is increased in psoriasis. However, little is known about the risk of less common cancers. OBJECTIVE: We aimed to evaluate the risk of less common cancers in patients with psoriasis compared to persons without psoriasis using a nationwide cohort study. METHODS: Between 1 January 2008 and 31 December 2012, we identified all Danish patients with a first-time hospital diagnosis of a less common cancer defined as <100 new cases/year/100.000 persons in Denmark. The primary endpoint was the occurrence of a diagnosis of cancer. RESULTS: We included 4 361 869 individuals. Of these, 58 138 were classified as having psoriasis. After adjusting for age, sex, socio-economic status and healthcare consumption, we found significantly elevated hazard ratios for cancers of bone and cartilage (HR 4.97 [2.32-10.62], P < 0.0001) in patients with psoriasis on systemic treatment. CONCLUSION: We provide further evidence of an increased cancer of bone and cartilage risk in patients with psoriasis.

Standard and reduced doses of dabigatran, rivaroxaban and apixaban for stroke prevention in atrial fibrillation: a nationwide cohort study.

BACKGROUND: Comparative data of non-vitamin K antagonist oral anticoagulants (NOAC) are lacking in patients with atrial fibrillation (AF). OBJECTIVE: We compared effectiveness and safety of standard and reduced dose NOAC in AF patients. METHODS: Using Danish nationwide registries, we included all oral anticoagulant-naïve AF patients who initiated NOAC treatment (2012-2016). Outcome-specific and mortality-specific multiple Cox regressions were combined to compute average treatment effects as 1-year standardized differences in stroke and bleeding risks (g-formula). RESULTS: Amongst 31 522 AF patients, the distribution of NOAC/dose was as follows: dabigatran standard dose (22.4%), dabigatran-reduced dose (14.0%), rivaroxaban standard dose (21.8%), rivaroxaban reduced dose (6.7%), apixaban standard dose (22.9%), and apixaban reduced dose (12.2%). The 1-year standardized absolute risks of stroke/thromboembolism were 1.73-1.98% and 2.51-2.78% with standard and reduced NOAC dose, respectively, without statistically significant differences between NOACs for given dose level. Comparing standard doses, the 1-year standardized absolute risk (95% CI) for major bleeding was for rivaroxaban 2.78% (2.42-3.17%); corresponding absolute risk differences (95% CI) were for dabigatran -0.93% (-1.45% to -0.38%) and apixaban, -0.54% (-0.99% to -0.05%). The results for major bleeding were similar for reduced NOAC dose. The 1-year standardized absolute risk (95% CI) for intracranial bleeding was for standard dose dabigatran 0.19% (0.22-0.50%); corresponding absolute risk differences (95% CI) were for rivaroxaban 0.23% (0.06-0.41%) and apixaban, 0.18% (0.01-0.34%). CONCLUSIONS: Standard and reduced dose NOACs, respectively, showed no significant risk difference for associated stroke/thromboembolism. Rivaroxaban was associated with higher bleeding risk compared with dabigatran and apixaban and dabigatran was associated with lower intracranial bleeding risk compared with rivaroxaban and apixaban.