This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin.

Psychiatric patients have excess mortality compared to the general population, and several potential mechanisms may explain this increased risk. This study examined the relationship between serum potassium levels and risk of all-cause mortality in patients co-treated with antipsychotic and diuretic drugs. Using a register-based cohort design, we identified patients between 1995 and 2012 who received a combination of an antipsychotic and a diuretic drug and who further had a serum potassium measurement within 90 days. During the study period, we included the most frequently redeemed antipsychotic drugs with regard to the propensity of corrected QT (QTc) prolongation: zuclopenthixol (unknown/mild), flupentixol (mild), levomepromazine (moderate), and quetiapine (moderate/severe). Patients co-treated with antidepressant drugs, lithium, and other antipsychotic drugs were excluded. Outcome was 6-month all-cause mortality, estimated with multivariable Cox regression. Patients were divided into seven serum potassium levels using restricted cubic splines (reference: 4.2-4.4 mmol/L) and stratified according to the included antipsychotic drugs. Of 6729 patients (median age: 74.0 years; women: 65.3%), 10.8% had hypokalemia and 4.9% had hyperkalemia. Hyperkalemia (>5.0 mmol/L, HR 2.82 [95% CI 2.25-3.54]), hypokalemia (<3.5 mmol/L, HR 1.59 [95% CI 1.29-1.95]), and high normal potassium levels (4.5-4.7 mmol/L, HR 1.44 [95% CI 1.19-1.75]; 4.8-5.0 mmol/L, HR 1.60 [95% CI 1.26-2.04]) were associated with an increased risk of 6-month all-cause mortality. This risk was independent of antipsychotic drugs (interaction: P = 0.06). Our findings imply that excess mortality in patients co-treated with antipsychotic and diuretic drugs is related to serum potassium levels and independent of antipsychotic drugs.

Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes.

High prices of pharmaceutical products are an increasing challenge in high- and low-income countries. Governments in many countries have implemented pricing policies to ensure affordability of medicines to patients and healthcare systems. The World Health Organization published in 2015 the Guideline on Country Pharmaceutical Pricing Policies, which was based on a series of evidence reviews in the preceding years.As part of the ongoing update of this guideline, we present a protocol for 10 systematic literature reviews on pharmaceutical pricing policies to be covered by the updated guideline.

Many low- and middle-income countries (LMIC) are moving towards enforcing prescription-only access to antibiotics. This systematic literature review aims to assess the interventions used to enforce existing legislation prohibiting over-the-counter (OTC) sales of antibiotics in LMICs, their impact and examine the methods chosen for impact measurement including their strengths and weaknesses.

Rare cases of genetically inherited atrioventricular block (AVB) have been reported; however, the heredity of AVB remains unknown. We aimed to assess the heredity of AVB.

Background Little is known about how COVID-19 influenced engagement of citizen responders dispatched to out-of-hospital cardiac arrest (OHCA) by a smartphone application. The objective was to describe and analyze the Danish Citizen Responder Program and bystander interventions (both citizen responders and nondispatched bystanders) during the first COVID-19 lockdown in 2020. Methods and Results All OHCAs from January 1, 2020, to June 30, 2020, with citizen responder activation in 2 regions of Denmark were included. We compared citizen responder engagement for OHCA in the nonlockdown period (January 1, 2020, to March 10, 2020, and April 21, 2020, to June 30, 2020) with the lockdown period (March 11, 2020, to April 20, 2020). Data are displayed in the order lockdown versus nonlockdown period. Bystander cardiopulmonary resuscitation rates did not differ in the 2 periods (99% versus 92%; P=0.07). Bystander defibrillation (9% versus 14%; P=0.4) or return-of-spontaneous circulation (23% versus 23%; P=1.0) also did not differ. A similar amount of citizen responders accepted alarms during the lockdown (6 per alarm; interquartile range, 6) compared with the nonlockdown period (5 per alarm; interquartile range, 5) (P=0.05). More citizen responders reported performing chest-compression-only cardiopulmonary resuscitation during lockdown compared with nonlockdown (79% versus 59%; P=0.0029), whereas fewer performed standardized cardiopulmonary resuscitation, including ventilations (19% versus 38%; P=0.0061). Finally, during lockdown, more citizen responders reported being not psychologically affected by attending an OHCA compared with nonlockdown period (68% versus 56%; P<0.0001). Likewise, fewer reported being mildly affected during lockdown (26%) compared with nonlockdown (35%) (P=0.003). Conclusions The COVID-19 lockdown in Denmark was not associated with decreased bystander-initiated resuscitation in OHCAs attended by citizen responders.

To evaluate the association between regulatory drug safety advisories and changes in drug utilisation.

The aim of this study was to provide information about immunity against COVID-19 along with risk factors and behavior among employees in day care facilities and preschools (DCS) in Denmark. In collaboration with the Danish Union of Pedagogues, during February and March 2021, 47,810 members were offered a point-of-care rapid SARS-CoV-2 antibody test (POCT) at work and were invited to fill in an electronic questionnaire covering COVID-19 exposure. Seroprevalence data from Danish blood donors (total Ig enzyme-linked immunosorbent assay [ELISA]) were used as a proxy for the Danish population. A total of 21,018 (45%) DCS employees completed the questionnaire and reported their POCT result {median age, 44.3 years (interquartile range [IQR], [32.7 to 53.6]); females, 84.1%}, of which 20,267 (96.4%) were unvaccinated and included in analysis. A total of 1,857 (9.2%) participants tested seropositive, significantly higher than a seroprevalence at 7.6% (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.14 to 1.27) among 40,541 healthy blood donors (median age, 42 years [IQR, 28 to 53]; males, 51.3%). Exposure at work (RR, 2.9; 95% CI, 2.3 to 3.6) was less of a risk factor than exposure within the household (RR, 12.7; 95% CI, 10.2 to 15.8). Less than 25% of participants reported wearing face protection at work. Most of the participants expressed some degree of fear of contracting COVID-19 both at work and outside work. SARS-CoV-2 seroprevalence was slightly higher in DCS staff than in blood donors, but possible exposure at home was associated with a higher risk than at work. DCS staff expressed fear of contracting COVID-19, though there was limited use of face protection at work. IMPORTANCE Identifying at-risk groups and evaluating preventive interventions in at-risk groups is imperative for the ongoing pandemic as well as for the control of future epidemics. Although DCS staff have a much higher risk of being infected within their own household than at their workplace, most are fearful of being infected with COVID-19 or bringing COVID-19 to work. This represents an interesting dilemma and an important issue which should be addressed by public health authorities for risk communication and pandemic planning. This study design can be used in a strategy for ongoing surveillance of COVID-19 immunity or other infections in the population. The findings of this study can be used to assess the need for future preventive interventions in DCS, such as the use of personal protective equipment.

Background Citizen responder programs are implemented worldwide to dispatch volunteer citizens to participate in out-of-hospital cardiac arrest resuscitation. However, the risk of injuries in relation to activation is largely unknown. We aimed to assess the risk of physical injury for dispatched citizen responders. Methods and Results Since September 2017, citizen responders have been activated through a smartphone application when located close to a suspected cardiac arrest in the Capital Region of Denmark. A survey was sent to all activated citizen responders, including a specific question about risk of acquiring an injury during activation. We included all surveys from September 1, 2017, to May 15, 2020. From May 15, 2019, to May 15, 2020, we followed up on all survey nonresponders by phone call, e-mail, or text messages to examine if nonresponders were at higher risk of severe or fatal injuries. In 1665 suspected out-of-hospital cardiac arrests, 9574 citizen responders were dispatched and 76.6% (7334) answered the question regarding physical injury. No injury was reported by 99.3% (7281) of the responders. Being at risk of physical injury was reported by 0.3% (24), whereas 0.4% (26) reported an injury (25 minor injuries and 1 severe injury [ankle fracture]). When following up on nonresponders (2472), we reached 99.1% (2449). No one reported acquired injuries, and only 1 reported being at risk of injury. Conclusions We found low risk of physical injury reported by volunteer citizen responders dispatched to out-of-hospital cardiac arrest. Risk of injury should be considered and monitored as a safety measure in citizen responder programs.

The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19.

To evaluate the association between common biomarkers, death and intensive care unit (ICU) admission in patients with COVID-19.

Objective: To determine the frequency and extent of cardiac involvement in female carriers of pathogenic variants in DMD, 53 women were examined through an observational, cross-sectional study. Methods: Genetically verified female carriers of pathogenic DMD variants were examined by cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement, echocardiography, 24-h Holter monitoring, ECG, and blood concentrations of skeletal and cardiac muscle biomarkers. Results: Fifty-three female carriers of pathogenic DMD variants (mean age 49.6 years, 33 associated with DMD, and 20 with BMD) were included in the study. Sixty-two percent had cardiac dysfunction on echocardiography. On CMR, 49% had myocardial fibrosis, 35% had dilated left ventricles, and 10% had left ventricular hypertrophy. ECGs were abnormal in 72%, and abnormal Holter monitoring was found in 43%. Age did not correlate with myocardial fibrosis or cardiac dysfunction. Myocardial fibrosis was more frequent in carriers of pathogenic variants associated with DMD vs. BMD (61 vs. 28%, p = 0.02). Conclusion: This study shows that cardiac involvement, affecting both structure and function of the heart, is found in over 2/3 of women with a pathogenic DMD variant. The study supports early cardiac screening, including ECG, Holter, and cardiac imaging, in this group of carriers, so that symptoms related to pathogenic variants in DMD can be recognized, and relevant treatment can be initiated. Longitudinal studies are needed to assess morbidity and mortality related to single, pathogenic DMD variants in women.

In Denmark, multiple national initiatives have been associated with improved bystander defibrillation and survival following out-of-hospital cardiac arrest (OHCA) in public places. However, OHCAs in residential neighbourhoods continue to have poor outcomes. The Cardiac Arrest in Residential Areas with MoBile volunteer responder Activation trial aims to improve bystander defibrillation and survival following OHCA in residential neighbourhoods with a high risk of OHCA. The intervention consists of: (1) strategically deployed automated external defibrillators accessible at all hours, (2) cardiopulmonary resuscitation (CPR) training of residents and (3) recruitment of residents for a volunteer responder programme.

The prediction of the durability of immunity against COVID-19 is relevant, and longitudinal studies are essential for unraveling the details regarding protective SARS-CoV-2 antibody responses. It has become challenging to discriminate between COVID-19 vaccine- and infection-induced immune responses since all approved vaccines in Europe and the USA are based on the viral spike (S) protein, which is also the most commonly used antigen in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a nucleocapsid (N) protein-based sandwich ELISA for detecting pan anti-SARS-CoV-2 Ig with a sensitivity and specificity of 97%. Generalized mixed models were used to determine the degree of long-term humoral immunity against the N protein and the receptor-binding domain (RBD) of the S protein in a cohort of infected individuals to distinguish between COVID-19 vaccine- and infection-induced immunity. N-specific waning could be observed in individuals who did not experience reinfection, while individuals who experienced reinfection had a new significant increase in N-specific Ig levels. In individuals that seroconverted without a reinfection, 70.1% remained anti-N seropositive after 550 days. The anti-RBD Ig dynamics were unaffected by reinfection but exhibited a clear increase in RBD-specific Ig when vaccination was initiated. In conclusion, a clear difference in the dynamics of the antibody response against N protein and RBD was observed over time. Anti-N protein-specific Igs can be detected up to 18 months after SARS-CoV-2 infection allowing long-term discrimination of infectious and vaccine antibody responses.IMPORTANCELongitudinal studies are essential to unravel details regarding the protective antibody responses after COVID-19 infection and vaccination. It has become challenging to distinguish long-term immune responses to SARS-CoV-2 infection and vaccination since most approved vaccines are based on the viral spike (S) protein, which is also mostly used in immunoassays measuring immunoglobulins (Igs) against SARS-CoV-2. We have developed a novel nucleocapsid (N) protein-based sandwich ELISA for detecting pan-anti-SARS-CoV-2 Ig, exhibiting high sensitivity and specificity. Generalized mixed models were used to determine long-term humoral immunity in a cohort of infected individuals from the Faroe Islands, distinguishing between COVID-19 vaccine- and infection-induced immunity. A clear difference in the dynamics of the antibody response against N protein and S protein was observed over time, and the anti-N protein-specific Igs could be detected up to 18 months after SARS-CoV-2 infection. This enables long-term discrimination between natural infection and vaccine-dependent antibody responses.

The heterogeneity of the SARS-CoV-2 immune responses has become considerably more complex over time and diverse immune imprinting is observed in vaccinated individuals. Despite vaccination, following the emergence of the Omicron variant, some individuals appear more susceptible to primary infections and reinfections than others, underscoring the need to elucidate how immune responses are influenced by previous infections and vaccination. IgG, IgA, neutralizing antibodies and T-cell immune responses in 1,325 individuals (955 of which were infection-naive) were investigated before and after three doses of the BNT162b2 vaccine, examining their relation to breakthrough infections and immune imprinting in the context of Omicron. Our study shows that both humoral and cellular responses following vaccination were generally higher after SARS-CoV-2 infection compared to infection-naive. Notably, viral exposure before vaccination was crucial to achieving a robust IgA response. Individuals with lower IgG, IgA, and neutralizing antibody responses postvaccination had a significantly higher risk of reinfection and future Omicron infections. This was not observed for T-cell responses. A primary infection before Omicron and subsequent reinfection with Omicron dampened the humoral and cellular responses compared to a primary Omicron infection, consistent with immune imprinting. These results underscore the significant impact of hybrid immunity for immune responses in general, particularly for IgA responses even after revaccination, and the importance of robust humoral responses in preventing future infections.

Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.

To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by mutations in genes coding for proteins involved in sarcomere function. The disease is associated with mitochondrial dysfunction. Evolutionarily developed variation in mitochondrial DNA (mtDNA), defining mtDNA haplogroups and haplogroup clusters, is associated with functional differences in mitochondrial function and susceptibility to various diseases, including ischemic cardiomyopathy. We hypothesized that mtDNA haplogroups, in particular H, J and K, might modify disease susceptibility to HCM. Mitochondrial DNA, isolated from blood, was sequenced and haplogroups identified in 91 probands with HCM. The association with HCM was ascertained using two Danish control populations. Haplogroup H was more prevalent in HCM patients, 60% versus 46% (p = 0.006) and 41% (p = 0.003), in the two control populations. Haplogroup J was less prevalent, 3% vs. 12.4% (p = 0.017) and 9.1%, (p = 0.06). Likewise, the UK haplogroup cluster was less prevalent in HCM, 11% vs. 22.1% (p = 0.02) and 22.8% (p = 0.04). These results indicate that haplogroup H constitutes a susceptibility factor and that haplogroup J and haplogroup cluster UK are protective factors in the development of HCM. Thus, constitutive differences in mitochondrial function may influence the occurrence and clinical presentation of HCM. This could explain some of the phenotypic variability in HCM. The fact that haplogroup H and J are also modifying factors in ischemic cardiomyopathy suggests that mtDNA haplotypes may be of significance in determining whether a physiological hypertrophy develops into myopathy. mtDNA haplotypes may have the potential of becoming significant biomarkers in cardiomyopathy.

Renal function is an important predictor of mortality in patients with myocardial infarction (MI), but changes in the impact over time have not been well described.We examined the importance of renal function by estimated GFR (eGFR) and se-creatinine as an independent long-term prognostic factor.