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

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.

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.

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

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.

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

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.

Despite the notable increase on the prescription of antidepressants and anxiolytics during pregnancy, recommendation on maintaining the treatment during prenatal period is still controversial. We aimed to separately assess the role of effects of the antidepressants and anxiolytic and the underlying illness, controlled by potential confounding associated with miscarriage onset.

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.

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.

ATP-sensitive K⁺ channels (KATP channels), NO, prostaglandins, 20-HETE and L-type Ca²⁺ channels have all been suggested to be involved in oxygen sensing in skeletal muscle arterioles, but the role of the individual mechanisms remain controversial. We aimed to establish the importance of these mechanisms for oxygen sensing in arterioles in an in vivo model of metabolically active skeletal muscle. For this purpose we utilized the exteriorized cremaster muscle of anesthetized mice, in which the cremaster muscle was exposed to controlled perturbation of tissue PO₂.

Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension.

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.

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.

The case-crossover (CXO) and self-controlled case series (SCCS) designs are increasingly used in pharmacoepidemiology. In both, relative risk estimates are obtained within persons, implicitly controlling for time-fixed confounding variables.

Midregional proadrenomedullin (MR-proADM) has demonstrated prognostic potential after myocardial infarction (MI). Yet, the prognostic value of MR-proADM at admission has not been examined in patients with ST-segment-elevation MI (STEMI).

Safety regarding switching from vitamin K antagonist (VKA) to dabigatran therapy in post-ablation patients has never been investigated and safety data for this is urgently needed. The objective of this study was to examine if switch from VKA to dabigatran increased the risk of stroke, bleeding, and death in patients after ablation for atrial fibrillation.

The public-private ADVANCE collaboration developed and tested a system to generate evidence on vaccine benefits and risks using European electronic healthcare databases. In the safety of vaccines, background incidence rates are key to allow proper monitoring and assessment. The goals of this study were to compute age-, sex-, and calendar-year stratified incidence rates of nine autoimmune diseases in seven European healthcare databases from four countries and to assess validity by comparing with published data.

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from 'real-world' and 'clinical trial' cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHA2DS2-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3-2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6-3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598-0.758) and 0.712 [95% CI, 0.618-0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHA2DS2-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up.

While clinical trials have suggested that a high ventricular rate is associated with increased risk of heart failure (HF) and mortality, all-comers studies are warranted.