Search

Aims Cancer and heart failure (HF) share risk factors, pathophysiological mechanisms, and possibly genetics. Improved HF survival may increase the risk of cancer due to a competing risk. Whether the incidence of cancer has increased over time in patients with HF as survival has improved is unclear. Therefore, temporal trends of new onset cancer in HF patients between 1997 and 2016 were investigated. Methods and results Using Danish nationwide registers, 103 711 individuals alive, free of cancer, and aged 30–80 years 1 year after HF diagnosis (index date) were included between 1 January 1997 and 31 December 2016. A five-year incidence rate of cancer for each year after index date was calculated. The median age and proportion of women at the index date decreased with advancing calendar time [1997–2001: 70.3 interquartile range (Q1–Q3 62.5–75.7), 60.9% men; 2012–16: 67.6 (59.2–73.8), 67.5% men]. The five-year incidence rate of cancer was 20.9 and 20.2 per 1,000 person-years in 1997 and 2016, respectively. In a multivariable Cox regression model, the hazard rates between index years 1997 (reference) and 2016 were not significantly different [hazard ratio 1.09 (0.97–1.23)]. The five-year absolute risk of cancer did not change with advancing calendar year, going from 9.0% (1997–2001) to 9.0% (2012–16). Five-year cumulative incidence of survival for HF patients increased with advancing calendar year, going from 55.9% (1997–2001) to 74.3% (2012–2016). Conclusion Although cancer rates during 1997–2016 have remained stable within 1–6 years after the HF diagnosis, long-term survival following a HF diagnosis has increased significantly.

Background. Pacemakers are used to treat syncope in patients with bradyarrhythmia; however, the risk of recurrent syncope has only been investigated in few and smaller studies. Objective. The aim of this study was to investigate the risk of recurrent syncope after pacemaker implantation in patients with bradyarrhythmia and prior syncope. Methods. This retrospective, population-based cohort study included patients with a prior syncope and implantation of a pacemaker using data from the Danish nationwide registers from 1996 to 2017. Cumulative incidence and cox regression was used to estimate the 5-year incidence and the risk of recurrent syncope, respectively. Results. In total, 11,126 patients (median age: 78 years, interquartile range: 69–85, 56% male) were included and the 5-year cumulative incidence of recurrent syncope was 19.6% (95% confidence interval (CI): 18.8–20.3%). Sinus node dysfunction (hazard ratio [HR]: 1.29, 95%CI: 1.17–1.42) and unspecified type of bradyarrhythmia (HR: 1.32, 95%CI: 1.15–1.52) were associated with an increased risk of syncope compared to advanced atrioventricular (AV) block. Male sex (HR: 1.22, 95%CI: 1.22–1.34), cerebrovascular disease (HR: 1.17, 95%CI: 1.05–1.30), and prior number of syncopes were significantly associated with a higher HR of recurrent syncope. Conclusion. Almost one-in-five patients with bradyarrhythmia and prior syncope who had a pacemaker implanted had a recurrent syncope within five years. A higher risk of syncope was observed among patients with sinus node dysfunction and unspecified type of bradyarrhythmia compared to AV block. Male sex, cerebrovascular disease, and prior number of syncopes were associated risk factors of recurrent syncope.

BACKGROUND: Data concerning the long-term risk of heart failure (HF) in patients with takotsubo syndrome (TTS) are sparse. We compared the rates of death and hospitalization due to HF with matched individuals from the background population and patients with ST-segment elevation myocardial infarction (STEMI).METHODS: In this nationwide observational cohort study, all patients with first-time TTS (2011-2018) who were alive at discharge were identified by using data from Danish nationwide registries. These were matched for age and sex with individuals from the background population (1:4 matching) and with patients with STEMI who were alive at discharge (1:3 matching).RESULTS: A total of 881 patients with TTS who were alive at discharge were identified (median age 70 years; 89.4% men). During a mean follow-up of 2.9 years, the incidence rates of death, HF hospitalization, and TTS recurrence in survivors of TTS were 6.9, 0.9 and 1.1 events per 100 person-years. The corresponding absolute 3-year risks were 9.3%, 1.8% and 2.5%, respectively. Survivors of TTS had higher associated rates of death compared with the background population (hazard ratio [HR] 2.05 [95% CI, 1.62-2.60]) and survivors of STEMI (HR 1.69 [1.34-2.13]). Similarly, survivors of TTS had higher associated rates of hospitalization due to HF compared with the background population (HR 4.24 [1.88-9.53]), but lower rates compared with survivors of STEMI (HR 0.34 [0.20-0.56]). Propensity-score matched analyses yielded similar results.CONCLUSIONS: Survivors of TTS had significantly higher associated mortality rates than the background population and survivors of STEMI. Survivors of TTS had lower HF hospitalization rates than survivors of STEMI, but the rates were higher than those of the background population.

Peter Ascanius Jacobsen,1,2 Kristian Kragholm,2,3 Christian Torp-Pedersen,4 Ulla Møller Weinreich1,2 1Department of Respiratory Diseases, Aalborg University Hospital, Aalborg, Denmark; 2The Clinical Institute, Aalborg University, Aalborg, Denmark; 3Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; 4Department of Clinical Research, Hillerød Hospital, Hillerød, DenmarkCorrespondence: Peter Ascanius Jacobsen, Department of Respiratory Diseases, Aalborg University Hospital, Mølleparkvej 4, Aalborg, DK-9100, Denmark, Tel +4597664800, Email Mail:peter.jacobsen@rn.dkIntroduction: Many chronic obstructive pulmonary disease (COPD) patients below retirement age are outside the workforce. The existing knowledge about association between acute exacerbation of COPD (AECOPD) and disability retirement is limited.Aim: The aim of this study is to explore disability retirement in COPD patients 3 years following first-ever AECOPD.Methods: This retrospective registry-based follow-up cohort study design is based on nationwide Danish registry data. Patients admitted to the hospital for the first time between 1999 and 2017 with AECOPD and age between 35 and 59 years, active in the workforce, were included in the study. Socio-demographics, comorbidities and inhaled medication use were explored. COPD patients’ hazard ratio of disability retirement during 3-year follow-up was calculated. Cox regression was used to examine the effects of covariates on disability retirement.Results: A total of 4032 patients were included in the study. During follow-up, 17.2% (692/4032) experienced disability retirement from the workforce. Factors associated with disability retirement were expressed as hazard ratio (95% confidence intervals): Higher age (ref. age 46– 50: Age 51– 55, 1.42, (1.12– 1.81); age 56– 59, 1.37 (1.08– 1.74)); living alone (1.34 (1.14– 1.56)); number of comorbidities for 1, 2, and 3 comorbidities (1.36 (1.14– 1.62), 1.57 (1.19– 2.07), 1.77 (1.20– 2.60)); emphysema (2.01 (1.44– 2.79)); depression (1.60 (1.12– 2.28)); cardiac comorbidity (1.38 (1.07– 1.78)); triple inhalation therapy (2.76 (2.20– 3.47)); ICS + LAMA or ICS + LABA treatment (1.82 (1.48– 2.23)); and ICS treatment (1.49 (1.17– 1.90)). Higher educational level was associated with a significantly reduced risk of disability retirement, medium, short higher and long higher educational level, relative to low education level (0.78 (0.67– 0.91), 0.63 (0.48– 0.83) and 0.27 (0.12– 0.60)).Conclusion: Patients vulnerable to disability retirement are patients with markers of severe COPD, comorbidities, and social vulnerability.Keywords: chronic obstructive pulmonary disease, return to work, early retirement, comorbidities

AimWe investigated temporal trends in major cardiovascular events following first-time myocardial infarction (MI) and trends in revascularization and pharmacotherapy from 2000 to 2017.Methods and resultsUsing nationwide registries, we identified 120 833 Danish patients with a first-time MI between 2000 and 2017. We investigated 30-day and 1-year mortality and the 1-year risk of first-time admission for heart failure (HF) and recurrent MI. Patients were younger with a higher prevalence of hypertension and diabetes in 2015–2017 compared with 2000–2002. The patients were predominantly male (65.6%), and the median age declined by 3 years through the periods. Percutaneous coronary interventions within 7 days after first-time MI increased significantly (2000: 11.4% vs. 2017: 68.6%; Ptrend < 0.001). Cardiovascular medication after first-time MI changed significantly in the same period. Absolute risks and adjusted rates of outcomes were significantly lower in 2015–2017 compared with 2000–2002: 30-day mortality: 6.5% vs. 14.1% [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.48–0.55); 1-year mortality 10.7% vs. 21.8% (HR 0.52, 95% CI: 0.50–0.55); recurrent MI: 4.0% vs. 7.8% (HR 0.56, 95% CI: 0.51–0.62); and first-time admission for HF: 2.9% vs. 3.7% (HR 0.82, 95% CI: 0.73–0.92). The rates of 30-day/1-year mortality and recurrent MI showed significantly decreasing trends (Ptrend < 0.001). The rates of first-time admission for HF were borderline significant (Ptrend = 0.045).ConclusionFrom 2000 to 2017, we observed a decreasing risk of recurrent MI, first-time admission for HF, and all-cause mortality in patients with a first-time MI. In the same period, we observed a high rate of guideline-recommended pharmacological treatment after first-time MI as well as increasing rate of early revascularization in Denmark.Translational perspectivesThe results from the current study portrait the risk of all-cause mortality, recurrent MI, and first-time admission for HF in a real-life setting with a very high utilization of early revascularization and guideline-recommended pharmacological therapy. We observed a temporal trend of improved survival, reduced risk of recurrent MI, as well as reduced risk of first-time admission for HF after first-time MI from 2000 through 2017. We observed an increase in the overall use of revascularization, as well as early revascularization and use of guideline-recommended pharmacotherapy. Our study reveals important results from real-life, nationwide data, showing a reduced risk of cardiovascular outcomes after first-time MI during the past 20 years. Current guidelines are based on results from clinical trials. Our real-life results add additionally important knowledge on patients’ prognosis after first-time MI and underline the importance of treating MI according to guideline recommendations. AimWe investigated temporal trends in major cardiovascular events following first-time myocardial infarction (MI) and trends in revascularization and pharmacotherapy from 2000 to 2017.Methods and resultsUsing nationwide registries, we identified 120 833 Danish patients with a first-time MI between 2000 and 2017. We investigated 30-day and 1-year mortality and the 1-year risk of first-time admission for heart failure (HF) and recurrent MI. Patients were younger with a higher prevalence of hypertension and diabetes in 2015–2017 compared with 2000–2002. The patients were predominantly male (65.6%), and the median age declined by 3 years through the periods. Percutaneous coronary interventions within 7 days after first-time MI increased significantly (2000: 11.4% vs. 2017: 68.6%; Ptrend < 0.001). Cardiovascular medication after first-time MI changed significantly in the same period. Absolute risks and adjusted rates of outcomes were significantly lower in 2015–2017 compared with 2000–2002: 30-day mortality: 6.5% vs. 14.1% [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.48–0.55); 1-year mortality 10.7% vs. 21.8% (HR 0.52, 95% CI: 0.50–0.55); recurrent MI: 4.0% vs. 7.8% (HR 0.56, 95% CI: 0.51–0.62); and first-time admission for HF: 2.9% vs. 3.7% (HR 0.82, 95% CI: 0.73–0.92). The rates of 30-day/1-year mortality and recurrent MI showed significantly decreasing trends (Ptrend < 0.001). The rates of first-time admission for HF were borderline significant (Ptrend = 0.045).ConclusionFrom 2000 to 2017, we observed a decreasing risk of recurrent MI, first-time admission for HF, and all-cause mortality in patients with a first-time MI. In the same period, we observed a high rate of guideline-recommended pharmacological treatment after first-time MI as well as increasing rate of early revascularization in Denmark.Translational perspectivesThe results from the current study portrait the risk of all-cause mortality, recurrent MI, and first-time admission for HF in a real-life setting with a very high utilization of early revascularization and guideline-recommended pharmacological therapy. We observed a temporal trend of improved survival, reduced risk of recurrent MI, as well as reduced risk of first-time admission for HF after first-time MI from 2000 through 2017. We observed an increase in the overall use of revascularization, as well as early revascularization and use of guideline-recommended pharmacotherapy. Our study reveals important results from real-life, nationwide data, showing a reduced risk of cardiovascular outcomes after first-time MI during the past 20 years. Current guidelines are based on results from clinical trials. Our real-life results add additionally important knowledge on patients’ prognosis after first-time MI and underline the importance of treating MI according to guideline recommendations.

Aims To compare the effectiveness and safety of clopidogrel, ticagrelor, and prasugrel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods and results Nationwide, registry-based study of STEMI patients treated with primary PCI (2011–17) and subsequently with aspirin and a P2Y12 inhibitor. The effectiveness outcome was major adverse cardiovascular events (MACE) defined as a composite of recurrent myocardial infarction, repeat revascularization, stroke, or cardiovascular death at 12 months. The safety outcome was bleeding requiring hospitalization at 12 months. Multivariable logistic regression with average treatment effect modeling was used to calculate absolute and relative risks for outcomes standardized to the distributions of demographic characteristics of all included subjects. We included 10 832 patients; 1 697 were treated with clopidogrel, 7 508 with ticagrelor, and 1,627 with prasugrel. Median ages were 66, 63, and 59 years (P Conclusion Ticagrelor and prasugrel were associated with lower risks of MACE after STEMI than clopidogrel, and ticagrelor was associated with a marginal reduction compared with prasugrel. The risk of bleeding was lower with ticagrelor compared with clopidogrel, but did not significantly differ between ticagrelor and prasugrel.

Histamine receptor 2 (HR

Clinical Scenario: Chronic ankle instability (CAI) is a condition that involves feelings of the ankle “giving way,” pain, and decreased self-reported function. Individuals with CAI often demonstrate persistent biomechanical impairments during gait that are associated with repetitive lateral ankle sprains (LAS) and the development of early onset ankle posttraumatic osteoarthritis (OA). Traditional rehabilitation strategies have not successfully improved these reported aberrant gait biomechanics; thus, traditional rehabilitation may not effectively reduce the risk of recurrent LAS and ankle OA among individuals with CAI. Conversely, targeted gait training with biofeedback may be effective at decreasing the risk of recurring LAS and ankle OA if these rehabilitation strategies can promote individuals with CAI to develop a gait strategy that protects against subsequent LAS and ankle OA. Clinical Question: Can targeted gait biofeedback interventions cause individuals with CAI to implement a walking gait pattern that is not associated with recurrent LAS and ankle OA? Summary of Findings: Five studies assessed gait biofeedback interventions targeting plantar pressure and/or ankle kinematics involving visual biofeedback (n = 3), auditory biofeedback (n = 1), and haptic biofeedback (n = 1). Plantar pressure was medially shifted during a single session while receiving biofeedback (n = 2), immediately after biofeedback (n = 1), and 5 minutes after receiving biofeedback (n = 1) in 3 studies. One study demonstrated reduced ankle inversion after 8 sessions of biofeedback training. One study did not substantially improve plantar pressure while receiving visual feedback. Clinical Bottom Line: Targeted gait training strategies appear effective in acutely altering gait biomechanics in individuals with CAI while receiving, and immediately after, biofeedback has been removed. Long-term outcomes are not currently established for gait training strategies in those with CAI. Strength of Recommendation: Limited evidence (grade B) suggests that targeted gait biofeedback strategies can alter specific CAI gait biomechanics to a strategy not associated with recurrent LAS, and ankle OA immediately, and after, multiple sessions of gait training.

First-line treatments for lymphomas often include high doses of prednisolone, but the risks of new-onset diabetes mellitus (DM) or worsening of preexisting DM following treatment with cyclic high dose corticosteroids is unknown. This cohort study matched non-Hodgkin lymphoma (NHL) patients treated with steroid-containing immunochemotherapy (ie, R-CHOP[-like] and R-CVP) between 2002 and 2015 to individuals from the Danish population to investigate the risks of new-onset DM. For patients with preexisting DM, the risks of insulin dependency and anthracycline-associated cardiovascular diseases (CVDs) were assessed. In total, 5672 NHL patients and 28 360 matched comparators were included. Time-varying incidence rate ratios (IRRs) showed increased risk of DM in the first year after treatment compared with matched comparators, with the highest IRR being 2.7. The absolute risks were higher among patients in the first 2 years, but the difference was clinically insignificant. NHL patients with preexisting DM had increased risks of insulin prescriptions with 0.5-, 5-, and 10-year cumulative risk differences of insulin treatment of 15.3, 11.8, and 6.0 percentage units as compared with the DM comparators. In a landmark analysis at 1 year, DM patients with lymphoma had decreased risks of insulin dependency compared with comparators. Time-varying IRRs showed a higher CVD risk for NHL patients with DM as compared with comparators in the first year after treatment. NHL patients treated with steroid-containing immunochemotherapy regimens have a clinically insignificant increased risk of DM in the first year following treatment, and patients with preexisting DM have a temporary increased risk of insulin prescriptions and CVD.

AimsTo date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants.Methods and resultsAll immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000–2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8–1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2–4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively).ConclusionNo overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants. AIMS: To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. METHODS AND RESULTS: All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000-2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8-1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2-4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). CONCLUSION: No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.

AimsWhile 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.ObjectiveTo assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate.Methods and resultsECGs recorded at the Copenhagen General Practitioners Laboratory (2001–15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70–85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71–101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100–110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10–1.95) and 2.41 (CI: 1.94–3.00) respectively for new-onset HF, compared with 60–79 bpm. Similarly, patients with AF ventricular rates 100–110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13–1.82) and 1.34 (CI: 1.08–1.65) respectively for all-cause mortality, compared with 60–79 bpm.ConclusionsVentricular rates ≥100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality. Aims 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. Objective To assess 1-year risk of new-onset diagnosed HF and all-cause mortality among rate-control treated patients presenting with atrial fibrillation (AF) on an electrocardiogram (ECG) according to ventricular rate. Methods and results ECGs recorded at the Copenhagen General Practitioners Laboratory (2001-15) were used to identify patients with AF. Multivariate Cox proportional hazard regression models were used to compare risk of new-onset HF and all-cause mortality after first ECG presenting with AF according to ventricular rate on ECG [ 110 beats per minute (bpm)]. We identified 7408 patients in treatment with rate control drugs at time of first ECG presenting with AF [median age 78 years (Q1,Q3 = 70-85 years)], 45.8% male, median ventricular rate 83 bpm, (Q1,Q3 = 71-101 bpm)]. During 1-year follow-up, 666 (9.0%) of all patients with AF developed HF and 858 (11.6%) died. Patients with AF ventricular rates 100-110 bpm and >110 bpm had a hazard ratio (HR) of 1.46 (CI: 1.10-1.95) and 2.41 (CI: 1.94-3.00) respectively for new-onset HF, compared with 60-79 bpm. Similarly, patients with AF ventricular rates 100-110 bpm and >110 bpm had a HR of 1.44 (CI: 1.13-1.82) and 1.34 (CI: 1.08-1.65) respectively for all-cause mortality, compared with 60-79 bpm. Conclusions Ventricular rates >= 100 bpm among patients presenting with AF on ECG in treatment with rate control drugs were associated with greater risk of both new-onset HF and all-cause mortality.

Background Employment is important for physical and mental health and self-esteem and provides financial independence. However, little is known on the prognostic value of employment status prior to admission with acute myocardial infarction (MI). Methods and results Using Danish nationwide registries, all patients between 18 and 60 years with a first-time MI admission (2010–2018) and alive at discharge were included. Rates of all-cause mortality and recurrent MI according to workforce attachment at the time of the event was compared using multivariable Cox regression. Of the 16 060 patients included in the study, 3520 (21.9%) patients were not part of the workforce. Patients who were not part of the workforce were older (52 vs. 51 years), less often men (63% vs. 77%), less likely to have higher education, more often living alone (47% vs. 29%), and more often had comorbidities, including heart failure, atrial fibrillation, hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease. The absolute 5-year risk of death was 3.3% and 12.8% in the workforce and non-workforce group, respectively. The corresponding rates of recurrent MI were 7.5% and 10.9%, respectively. In adjusted analyses, not being part of the workforce was associated with a significantly higher rate of all-cause mortality [HR: 2.39 (95% CI: 2.01–2.83)] and recurrent MI [1.36 (1.18–1.57)]. Conclusion Among patients of working age who were admitted with MI and alive at discharge, not being part of the workforce was associated with a higher long-term rate of all-cause mortality and recurrent MI.

AimsReduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality.Methods and resultsAll Danish patients diagnosed with BrS (2006–2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46–8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42–13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death.ConclusionApproximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety. AimsReduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality.Methods and resultsAll Danish patients diagnosed with BrS (2006–2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46–8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42–13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death.ConclusionApproximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.

Background Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. Methods This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. Results Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56–1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48–2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %–6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %–6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51–0.66]). Conclusion Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671–35,943), 34,801 (95% CI: 34,180–35,432), and 35,708 (95% CI: 35,085–36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620–38,929), 36,956 (95% CI: 36,323–37,600), 37,475 (95% CI: 36,838–38,122), and 38,536 (95% CI: 37,798–39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38–46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18–32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical. A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671–35,943), 34,801 (95% CI: 34,180–35,432), and 35,708 (95% CI: 35,085–36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620–38,929), 36,956 (95% CI: 36,323–37,600), 37,475 (95% CI: 36,838–38,122), and 38,536 (95% CI: 37,798–39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38–46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18–32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Background The World Health Organization (WHO) Classification of Tumours, also known as WHO Blue Books, represents an international standardised tool in the diagnostic work-up of tumours. This classification system is under continuous revision, and progress in the molecular classification of tumours in the central nervous system (CNS) enforced an update of the WHO 2016 classification, and the fifth edition, WHO CNS5, was published in 2021. The aim of this minireview is to highlight important changes in this new edition relevant for the practicing neurosurgeon. Methods The sixth volume of the fifth edition of the WHO Blue Books of CNS tumours and related papers formed the basis for this minireview. Results Major changes encompass standardisation of tumour grading and nomenclature as well as increased incorporation of molecular markers in the classification of CNS tumours. Conclusion Advances in molecular genetics have resulted in more accurate diagnosis and prognosis of CNS tumours, and this minireview summarises important changes implemented in the last edition of WHO classification of CNS tumours important for the practicing neurosurgeon.

Objectives To examine long-term cardiovascular outcomes and temporal trends among patients with ANCA-associated vasculitis (AAV) using Danish nationwide registries. Methods Using a cohort design, we examined patients with granulomatosis with polyangiitis (ICD-10: DM31.3) and microscopic polyangiitis (ICD-10: DM3.17) in Denmark from 1996–2018. Hazard ratios (HRs) of cardiovascular outcomes were compared between patients with AAV and age and gender-matched controls. Counterfactual G-estimation of HRs was performed to estimate 5-year absolute risks. Temporal trends were obtained by grouping cohorts into evenly distributed tertiles according to inclusion year. Results A total of 2306 patients with AAV (median age: 62.9yrs, 52.6% male) were matched with 6918 controls. Median follow-up was 9.5yrs. Patients with AAV had a higher rate of ischaemic heart disease [HR 1.86 (1.62–2.15)], myocardial infarction [HR 1.62 (1.26–2.09)], coronary angiogram [HR 1.64 (1.37–1.96)], percutaneous coronary intervention [HR 1.56 (1.17–2.07)] and ventricular arrhythmias/implantable-cardioverter-defibrillator (ICD)-implantations [HR 2.04 (1.16–3.57)]. Similarly, an increased rate of heart failure [HR 2.12 (1.77–2.54)], deep vein thrombosis [HR 3.13 (2.43–4.05)], pulmonary embolism [HR 4.04 (3.07–5.32)], atrial fibrillation [HR 2.08 (1.82–2.39)], ischaemic stroke [HR 1.58 (1.31–1.90)] and in-hospital cardiac arrest [HR 2.27 (1.49–3.48)] was observed. The 5-year risk of all outcomes were significantly higher (excluding ventricular arrhythmia/ICD-implantations). For temporal trends among patients with AAV, a decreased 3-year risk of cardiovascular mortality was observed over time. Conclusions Patients with AAV are at increased risk of heart failure, atrial-/ventricular arrhythmias, venous thrombotic events, ischaemic stroke and myocardial infarction. Furthermore, patients with AAV were more frequently examined with coronary procedures and underwent more coronary revascularizations. No temporal changes in ischaemic cardiovascular outcomes were observed, albeit the cardiovascular mortality has decreased over time.

There is a risk of gaseous and solid micro-embolus formation during transcatheter cardiac interventions and surgery in children with congenital heart disease (CHD). Our aim was to study the burden of high-intensity transient signals (HITS) during these procedures in infants. We used a novel color M-mode Doppler (CMD) technique by NeoDoppler, a non-invasive ultrasound system based on plane wave transmissions for transfontanellar continuous monitoring of cerebral blood flow in infants. The system displays CMD with 24 sample volumes and a Doppler spectrogram. Infants with CHD undergoing transcatheter interventions (n = 15) and surgery (n = 13) were included. HITS were manually detected based on an “embolic signature” in the CMD with corresponding intensity increase in the Doppler spectrogram. Embolus-to-blood ratio (EBR) defined HITS size. A total of 1169 HITS with a median EBR of 9.74 dB (interquartile range [IQR]: 5.10–15.80 dB) were detected. The median number of HITS in the surgery group was 45 (IQR: 11–150), while in the transcatheter group the median number was 12 (IQR: 7–24). During cardiac surgery, the highest number of HITS per hour was seen from initiation of cardiopulmonary bypass to aortic X-clamp. In this study we detected frequent HITS and determined the feasibility of using NeoDoppler monitoring for HITS detection.

Aims To search for sequence variants associated with ACEi discontinuation and to test their association with ACEi-associated adverse drug reactions (ADRs). Methods and results A genome-wide association study (GWAS) on ACEi discontinuation was conducted, including 33 959 ACEi-discontinuers and 44 041 controls. Cases were defined as persons who switched from an ACEi treatment to an angiotensin receptor blocker. Controls were defined as persons who continued ACEi treatment for at least 1 year. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed for ACEi discontinuation risk by mixed model regression analysis. Summary statistics from the individual cohorts were meta-analyzed with a fixed-effects model. To test for association with specific ACEi-associated ADRs, any genome-wide significant (P < 5 × 10-8) ACEi discontinuation variants was tested for association with ACEi-associated cough and angioedema. A polygenetic risk score (PRS) based on ACEi discontinuation GWAS data was constructed and tested for association with ACEi-associated cough and angioedema in two population-based samples. In total, seven genetic genome-wide loci were identified, of which six were previously unreported. The strongest association with ACEi discontinuation was at 20q13.3 (NTSR1; OR: 1.21; 95% CI: 1.17–1.24; P = 2.1 × 10–34). Five of seven lead variants were associated with ACEi-associated cough, whereas none were associated with ACEi-associated angioedema. The ACEi discontinuation PRS was associated with ACEi-associated cough in a dose–response manner but not with ACEi-associated angioedema. ACEi discontinuation was genetically correlated with important causes for cough, including gastro-esophageal reflux disease, allergic rhinitis, hay fever, and asthma, which indicates partly shared genetic underpinning between these traits. Conclusion This study showed the advantage of using prescription patterns to discover genetic links with ADRs. In total, seven genetic loci that associated with ACEi discontinuation were identified. There was evidence of a strong association between our ADR phenotype and ACEi-associated cough. Taken together, these findings increase insight into the pathophysiological processes that underlie ACEi-associated ADRs.

PURPOSE: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis.METHODS: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model.RESULTS: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p CONCLUSION: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257.TRIAL REGISTRY: POET ClinicalTrials.gov number, NCT01375257.

Aims A few studies suggested that epilepsy and antiepileptic drugs with sodium channel-blocking properties were independently associated with out-of-hospital cardiac arrest (OHCA). However, these findings have not yet been replicated. Methods Using Danish registries, we conducted a nested case–control study in a cohort of individuals between 1 June 2001 and 31 December 2015. Cases were defined as OHCA from presumed cardiac causes, and were matched with non-OHCA-controls based on sex, and age on the date of OHCA. Exposure of interest was epilepsy or antiepileptic drug use. To study the association between individual antiepileptic drug use and the rate of OHCA, we compared each antiepileptic drug with valproic acid. Cox regression with time-dependent covariates was conducted to calculate hazard ratio (HR) and 95% confidence interval (CI). Results We identified 35 195 OHCA-cases and 351 950 matched non-OHCA controls. Epilepsy (cases: 3.58%, controls: 1.60%) was associated with increased rate of OHCA compared with the general population (HR: 1.76, 95%CI: 1.64–1.88) when common OHCA risk factors were taken into account. When we studied antiepileptic drug use, we found that 2 antiepileptic drugs without sodium channel blockage, clonazepam (HR: 1.88, 95%CI: 1.45–2.44) and pregabalin (HR: 1.33, 95%CI: 1.05–1.69), were associated with OHCA, whereas none of the antiepileptic drugs with sodium channel blockage were associated with OHCA. Conclusion Epilepsy is associated with increased rate of OHCA. Our findings do not support a possible association between antiepileptic drugs with sodium channel-blocking properties and OHCA.

Randomized controlled trials have shown a reduced risk of ischemic events and an increased risk of bleeding in patients treated with prolonged dual anti-platelet therapy (DAPT) beyond 12 months following acute coronary syndrome (ACS). We aimed to investigate outcomes of prolonged DAPT vs aspirin monotherapy (ASA) in a real-world population.Using nationwide registries, we identified all patients with ACS who underwent percutaneous coronary intervention and received 12-month DAPT between January 2013 and October 2016. Patients still on DAPT were compared to patients on ASA at index date (15 months after ACS-date) and followed for up to 2 years. Cox regression models were employed to calculate standardized risks of all-cause mortality, major adverse cardiovascular event (MACE), and major bleeding. The study included 7,449 patients, 1,901 on DAPT (median age 66, 72.1% male) and 5,548 on ASA (median age 65, 75.1% male). Standardized absolute 2-year risk of all-cause mortality, MACE, and major bleeding was 2.7%, 3.7%, and 5.4% for DAPT vs 2.2%, 3.8%, and 1.3% for ASA. DAPT was not associated with a significant standardized 2-year risk difference (SRD) of all-cause mortality (SRD: 0.5%, 95% confidence interval [CI]: -0.9 to 1.7) or MACE (SRD: -0.1%, 95% CI -1.8 to 1.6), but a significantly higher risk of major bleeding (SRD: 4.1%, 95% CI 1.8-6.6).In a nationwide cohort of ACS patients undergoing percutaneous coronary intervention, prolonged DAPT was not significantly associated with a reduced risk of all-cause mortality or MACE, but an increased risk of major bleeding. Future randomized controlled trials should investigate the optimal anti-platelet regimen in this patient group.

OBJECTIVES: Malnutrition in pulmonary fibrosis may influence clinical outcomes negatively. This project aimed to investigate if weight, unintended weight loss (UWL) at baseline and weight development, and signs of sarcopenia measured by the strength, assistance with the walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) are associated with hospital admissions and mortality for idiopathic pulmonary fibrosis outpatients in ≤1 y as well as referral to pulmonary rehabilitation.METHODS: At baseline, prevalence of weight and UWL were sought in a cross-sectional questionnaire study, consecutively, including 100 patients in an outpatient clinic. Medical records were sought for time from diagnosis and comorbidities. One year after inclusion weight, UWL and SARC-F were collected by phone interviews, and medical records were revisited for clinical outcomes.RESULTS: Of the 100 patients, two patients died and seven were lost to follow-up. The prevalence of UWL increased within the year (10-13%), and the amount of UWL increased (9.1-11.8 kg). Patients with a UWL at baseline had a significantly higher risk of mortality (odds ratio = 29.8; P = 0.037). UWL at baseline was associated with risk of hospital admissions (odds ratio = 14.7; P = 0.009). Based on the results from SARC-F, 20.9% have signs of sarcopenia. UWL at follow-up was associated with the risk of sarcopenia by SARC-F. Patients with risk of sarcopenia and those with body mass index ≥30 kg/m2 were to a higher degree offered pulmonary rehabilitation; however, participation was low.CONCLUSIONS: UWL at baseline was significantly associated with risk of hospital admissions and mortality in ≤1 y in idiopathic pulmonary fibrosis outpatients. Patients with signs of sarcopenia and body mass index ≥30 kg/m2 were most often referred to pulmonary rehabilitation.

ObjectivesIn the randomized controlled trial PANTHEM, the prophylactic effect of oral amoxicillin or clindamycin is investigated in patients receiving chronic haemodialysis (HD). However, data on plasma concentrations of these antibiotics during HD are sparse. This study aims to determine if the plasma concentration of amoxicillin and clindamycin is sufficient during HD after oral administration of amoxicillin and clindamycin at three different time intervals prior to the HD procedure.MethodsAdult patients receiving chronic HD were investigated twice with an interval of at least 7 days starting with either a tablet of 500/125 mg amoxicillin/clavulanic acid or a tablet of 600 mg clindamycin. Patients were randomized to take the antibiotics either 30, 60 or 120 min prior to the HD procedure. Plasma antibiotic concentrations were measured at start, midway and at the end of HD. A lower threshold was set at 2.0 mg/L for amoxicillin and at 1.0 mg/L for clindamycin. In addition, a population pharmacokinetic (PK) analysis was performed, assessing PTA.ResultsIn the amoxicillin cohort (n = 37), 84% of patients and 95% of all plasma amoxicillin concentrations were above or at the threshold throughout the dialysis procedure. In the clindamycin cohort (n = 33), all concentrations were above the threshold throughout the dialysis procedure. Further, in all patients, the mean plasma concentration of both amoxicillin and clindamycin across the HD period was well above the threshold. Finally, the PK model predicted a high PTA in the majority of patients.DiscussionIn patients on chronic HD, oral administration of amoxicillin/clavulanic acid (500/125 mg) or clindamycin (600 mg) within 30–120 min prior to HD leads to a sufficient prophylactic plasma concentration across the HD period.

Aims To investigate the association between the arrival of smartphone-activated volunteer responders before the Emergency Medical Services (EMS) and bystander defibrillation in out-of-hospital cardiac arrest (OHCA) at home and public locations. Methods and results This is a retrospective study (1 September 2017–14 May 2019) from the Stockholm Region of Sweden and the Capital Region of Denmark. We included 1271 OHCAs, of which 1029 (81.0%) occurred in private homes and 242 (19.0%) in public locations. The main outcome was bystander defibrillation. At least one volunteer responder arrived before EMS in 381 (37.0%) of OHCAs at home and 84 (34.7%) in public. More patients received bystander defibrillation when a volunteer responder arrived before EMS at home (15.5 vs. 2.2%, P < 0.001) and in public locations (32.1 vs. 19.6%, P = 0.030). Similar results were found among the 361 patients with an initial shockable heart rhythm (52.7 vs. 11.5%, P < 0.001 at home and 60.0 vs. 37.8%, P = 0.025 in public). The standardized probability of receiving bystander defibrillation increased with longer EMS response times in private homes. The 30-day survival was not significantly higher when volunteer responders arrived before EMS (9.2 vs. 7.7% in private homes, P = 0.41; and 40.5 vs. 35.4% in public locations, P = 0.44). Conclusion Bystander defibrillation was significantly more common in private homes and public locations when a volunteer responder arrived before the EMS. The standardized probability of bystander defibrillation increased with longer EMS response times in private homes. Our findings support the activation of volunteer responders and suggest that volunteer responders could increase bystander defibrillation, particularly in private homes.

ObjectiveSarcoidosis is over-represented among victims of cardiac arrest. We aimed to establish whether sarcoidosis is associated with out-of-hospital cardiac arrest (OHCA) in the general population.MethodsWe conducted a nested case–control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. OHCA cases from presumed cardiac causes were matched 1:10 by sex and age on OHCA date with non-OHCA controls from the general population. The association between sarcoidosis and OHCA was assessed using Cox regression by calculating HR and 95% CIs. Models were adjusted for cardiovascular disease. Finally, stratified analyses were performed according to sex, heart failure and ischaemic heart disease.Results We identified 35 195 OHCA cases and 351 950 matched controls without OHCA (median age 72 years and 66.8% male). Patients with sarcoidosis had higher rate of OHCA compared with the general population after adjustments for common OHCA risk factors (HR 1.51, 95% CI 1.19 to 1.92). This increased OHCA rate occurred in women (HR 2.11, 95% CI 1.42 to 3.12) but not in men (HR 1.27, 95% CI 0.93 to 1.72; p value interaction=0.033), and was larger in patients with than without heart failure (HRheart failure: 2.59, 95% CI 1.42 to 4.73; HRno heart failure: 1.33, 95% CI 1.01 to 1.74; p value interaction: 0.007). The HR associated with sarcoidosis did not vary by the presence of ischaemic heart disease.Conclusion Patients with sarcoidosis have a higher OHCA rate than the general population. This increased OHCA rate occurred in women but not in men, and was larger in patients with than without heart failure. Objective Sarcoidosis is over-represented among victims of cardiac arrest. We aimed to establish whether sarcoidosis is associated with out-of-hospital cardiac arrest (OHCA) in the general population. Methods We conducted a nested case-control study in a nationwide cohort of individuals between 1 June 2001 and 31 December 2015 in Denmark. OHCA cases from presumed cardiac causes were matched 1:10 by sex and age on OHCA date with non-OHCA controls from the general population. The association between sarcoidosis and OHCA was assessed using Cox regression by calculating HR and 95% CIs. Models were adjusted for cardiovascular disease. Finally, stratified analyses were performed according to sex, heart failure and ischaemic heart disease. Results We identified 35 195 OHCA cases and 351 950 matched controls without OHCA (median age 72 years and 66.8% male). Patients with sarcoidosis had higher rate of OHCA compared with the general population after adjustments for common OHCA risk factors (HR 1.51, 95% CI 1.19 to 1.92). This increased OHCA rate occurred in women (HR 2.11, 95% CI 1.42 to 3.12) but not in men (HR 1.27, 95% CI 0.93 to 1.72; p value interaction=0.033), and was larger in patients with than without heart failure (HR heart failure: 2.59, 95% CI 1.42 to 4.73; HR no heart failure: 1.33, 95% CI 1.01 to 1.74; p value interaction: 0.007). The HR associated with sarcoidosis did not vary by the presence of ischaemic heart disease. Conclusion Patients with sarcoidosis have a higher OHCA rate than the general population. This increased OHCA rate occurred in women but not in men, and was larger in patients with than without heart failure.

Background Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown. Methods and results Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1–7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0–30 and 31–365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31–365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0–30 days: 4.3%, 31–365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0–30 days: 0.1%, 31–365 days: 0.9%) and did not depend on relative or absolute changes between measurements. Conclusions Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements.

Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%-\18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).

Population ageing has resulted in an increasing number of older people living with chronic diseases (multimorbidity) requiring five or more medications daily (polypharmacy). Ageing produces important changes in the cardiovascular system and represents the most potent single cardiovascular risk factor. Cardiovascular diseases (CVDs) constitute the greatest burden for older people, their caregivers, and healthcare systems. Cardiovascular pharmacotherapy in older people is complex because age-related changes in body composition, organ function, homeostatic mechanisms, and comorbidities modify the pharmacokinetic and pharmacodynamic properties of many commonly used cardiovascular and non-cardiovascular drugs. Additionally, polypharmacy increases the risk of adverse drug reactions and drug interactions, which in turn can lead to increased morbi-mortality and healthcare costs. Unfortunately, evidence of drug efficacy and safety in older people with multimorbidity and polypharmacy is limited because these individuals are frequently underrepresented/excluded from clinical trials. Moreover, clinical guidelines are largely written with a single-disease focus and only occasionally address the issue of coordination of care, when and how to discontinue treatments, if required, or how to prioritize recommendations for patients with multimorbidity and polypharmacy. This review analyses the main challenges confronting healthcare professionals when prescribing in older people with CVD, multimorbidity, and polypharmacy. Our goal is to provide information that can contribute to improving drug prescribing, efficacy, and safety, as well as drug adherence and clinical outcomes.

The prognostic importance of new-onset type 2 diabetes (T2D) in heart failure (HF) remains unknown. We aimed to describe the cardiovascular outcome profile in HF patients with new-onset, no and prevalent T2D.We constructed a cohort of patients with first HF admission between 1998 and 2016 from nationwide Danish registers. Outcomes were ischemic event, HF event, and death from other causes. The landmarking approach and the Aalen Johansen estimator were used together to estimate 5-year absolute and 5-year relative risk of the outcomes in HF patients with new-onset, no and prevalent T2D. Risk among subgroups were investigated by stratification.A total of 139 264 HF patients were included between 1998 and 2016, of which 29 078 patients had prevalent T2D. A total of 11 819 developed new-onset T2D. The 5-year risks of ischemic event in new-onset, no, and prevalent T2D were: 17.9% [17.2; 18.6], 18.8% [18.6; 19.0], and 26.1% [25.6; 26.7]. The 5-year risks of HF event were: 31.5% [30.6; 32.3], 30.7% [30.5; 31.0], and 33.6% [33.0; 34.2]. For other causes of death, the 5-year risks were: 20.9% [20.2; 21.7], 18.6% [18.4; 18.8], and 18.9% [18.4; 19.3]. The 5-year risk ratios of HF event or death from other causes versus ischemic event were: 2.9 [2.8; 3.1], 2.6 [2.6; 2.7], and 2.0 [2.0; 2.1] in patients with new-onset, no, and prevalent T2D.In patients with new-onset T2D, death from other causes were more likely to occur than an ischemic event, whereas in patients with prevalent T2D and no T2D, ischemic events were more common.

BACKGROUND: Bystander-initiated basic life support (BLS) plays an important role in improving survival after out-of-hospital cardiac arrest. In 2009, laws mandating BLS course participation when acquiring a driver's licence were implemented in Denmark. The aim of this study was to characterise Danish BLS course participants.METHODS: This study is a Danish, registry-based, follow-up study that examined all Danish BLS course participants from 2016 to 2019. Data concerning BLS course participation were supplied by the major Danish BLS course providers. Socio-economic and healthcare data on all Danish inhabitants were assessed using national registers from Statistics Denmark.RESULTS: Between January 1, 2016, and January 1, 2020, 3.6% of the entire adult population of Denmark attended certified BLS courses annually. Since the implementation of a law mandating BLS course participation when acquiring a driver licence in 2009, approximately 44% of the adult population has participated in a BLS course. BLS course participants were commonly younger and healthier than the general population (mean 31.3 years old vs. 51.3 years old, P < 0.001). Furthermore, law-mandated BLS course participants had a lower disposable income (adjusted OR: 0.23; 95% CI: 0.23-0.23; P < 0.001) and were more likely to live in rural areas (adjusted OR: 0.57; 95% CI: 0.57-0.58; P < 0.001).CONCLUSION: In Denmark, 3.6% of the entire adult population attend certified courses annually. BLS participants are commonly male, younger, healthier, less likely to have small children in the household, and more likely to live in rural areas. Law-mandated BLS course participation prior to acquiring a driver's licence has been successful in reaching segments of the society that are known to have limited participation.

Objective: A transient rise in the occurrence of hyperthyroidism ensued the introduction of iodine fortification (IF) of salt in Denmark. Older adults are at risk of complications to hyperthyroidism that could prove fatal to vulnerable individuals. We evaluated the association between thyroid function and mortality in older adults before and after nationwide implementation of IF. Design: Retrospective cohort study. Patients: All 68-year-olds from the general population in the city of Randers were invited to participate in a clinical study in 1988 and followed until death, emigration or end of study (31 December 2017) using Danish registries. Measurements: Baseline measures comprised of a questionnaire, physical examination and blood and urine samples. Kaplan–Meier survival curves and Cox regression were used to determine the association between thyroid function and death before and after IF. Time-stratification of results before and after IF was employed due to violation of proportional hazards assumptions in Cox regression. Results: Median urinary iodine concentration was 42 µg/L at baseline consistent with moderate iodine deficiency. Hyperthyroidism (thyrotropin < 0.4 mIU/L) occurred in 37 (9.1%) participants. Kaplan–Meier survival curves showed an increase in mortality among participants with hyperthyroidism after IF. There was no significant association between hyperthyroidism and mortality before IF compared to euthyroid participants, but after IF hyperthyroid subjects had an increased mortality (adjusted hazard ratio: 2.22, 95% confidence interval: 1.44–3.44). Conclusions: IF was associated with raised mortality among older adults with a history of hyperthyroidism and moderate iodine deficiency. Our results highlight the need for cautious iodine supplementation and for monitoring of IF.

Objectives: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control. Background: The sex-specific epidemiology of AF in HF is sparse. Methods: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018. Results: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability–weighted models across all strata and in both sexes (hazard ratio: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03). Conclusions: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.

BackgroundPatients with Brugada syndrome (BrS) are recommended to avoid drugs that may increase their risk of arrhythmic events. We examined treatment with such drugs in patients with BrS after their diagnosis.Methods and ResultsAll Danish patients diagnosed with BrS (2006–2018) with >12 months of follow‐up were identified from nationwide registries. Nonrecommended BrS drugs were grouped into drugs to “avoid” or “preferably avoid” according to http://www.brugadadrugs.org. Cox proportional hazards analyses were performed to identify factors associated with any nonrecommended BrS drug use, and logistic regression analyses were performed to examine associated risk of appropriate implantable cardioverter defibrillator therapy, mortality, and a combined end point indicating an arrhythmic event of delayed implantable cardioverter defibrillator implantation, appropriate implantable cardioverter defibrillator therapy, and mortality. During a median follow‐up of 6.8 years, 93/270 (34.4%) patients with BrS (70.4% male, median age at diagnosis 46.1 years [interquartile range, 32.6–57.4]) were treated with ≥1 nonrecommended BrS drugs. No difference in any nonrecommended BrS drug use was identified comparing time before BrS diagnosis (12.6%) with each of the 5 years following BrS diagnosis (P>0.05). Factors associated with any nonrecommended BrS drug use after diagnosis were female sex (hazard ratio [HR]) 1.83 [95% CI, 1.15–2.90]), psychiatric disease (HR, 3.63 [1.89–6.99]), and prior use of any nonrecommended BrS drug (HR, 4.76 [2.45–9.25]). No significant association between any nonrecommended BrS drug use and implantable cardioverter defibrillator therapy (n=20/97, odds ratio [OR], 0.7 [0.2–2.4]), mortality (n=10/270, OR, 3.4 [0.7–19.6]), or the combined end point (n=38/270, OR, 1.7 [0.8–3.7]) was identified.ConclusionsOne in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescription patterns. More awareness of nonrecommended drug use among patients with BrS is needed. BackgroundPatients with Brugada syndrome (BrS) are recommended to avoid drugs that may increase their risk of arrhythmic events. We examined treatment with such drugs in patients with BrS after their diagnosis.Methods and ResultsAll Danish patients diagnosed with BrS (2006–2018) with >12 months of follow‐up were identified from nationwide registries. Nonrecommended BrS drugs were grouped into drugs to “avoid” or “preferably avoid” according to http://www.brugadadrugs.org. Cox proportional hazards analyses were performed to identify factors associated with any nonrecommended BrS drug use, and logistic regression analyses were performed to examine associated risk of appropriate implantable cardioverter defibrillator therapy, mortality, and a combined end point indicating an arrhythmic event of delayed implantable cardioverter defibrillator implantation, appropriate implantable cardioverter defibrillator therapy, and mortality. During a median follow‐up of 6.8 years, 93/270 (34.4%) patients with BrS (70.4% male, median age at diagnosis 46.1 years [interquartile range, 32.6–57.4]) were treated with ≥1 nonrecommended BrS drugs. No difference in any nonrecommended BrS drug use was identified comparing time before BrS diagnosis (12.6%) with each of the 5 years following BrS diagnosis (P>0.05). Factors associated with any nonrecommended BrS drug use after diagnosis were female sex (hazard ratio [HR]) 1.83 [95% CI, 1.15–2.90]), psychiatric disease (HR, 3.63 [1.89–6.99]), and prior use of any nonrecommended BrS drug (HR, 4.76 [2.45–9.25]). No significant association between any nonrecommended BrS drug use and implantable cardioverter defibrillator therapy (n=20/97, odds ratio [OR], 0.7 [0.2–2.4]), mortality (n=10/270, OR, 3.4 [0.7–19.6]), or the combined end point (n=38/270, OR, 1.7 [0.8–3.7]) was identified.ConclusionsOne in 3 patients with BrS were treated with a nonrecommended BrS drug after BrS diagnosis, and a BrS diagnosis did not change prescription patterns. More awareness of nonrecommended drug use among patients with BrS is needed.

BACKGROUND: Heavy alcohol use during pregnancy can harm the fetus, but the relation to most obstetric outcomes remains unclear. We therefore aimed to describe maternal characteristics and estimate the association between heavy prenatal alcohol exposure and 22 adverse obstetric and birth outcomes. METHODS: We carried out a Danish nationwide register-based historical cohort study, including all singleton births from Jan 1, 1996, to Dec 31, 2018. Births of women who had emigrated to Denmark were excluded from the study due to missing data and women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. Logistic regression models were used to estimate crude and adjusted odds ratios (ORs) of obstetric and birth outcomes. Heavy alcohol use was defined by hospital contacts for alcohol-attributable diagnoses given to the mother, her infant, or both, or maternal redeemed prescriptions for drugs to treat alcohol dependence within 1 year before or during pregnancy. FINDINGS: Of 1 191 295 included births, 4823 (0·40%) were defined as heavily alcohol-exposed and 1 186 472 were categorised as a reference group with no identified heavy prenatal alcohol exposure. Heavy-alcohol-exposed births more often had mothers with psychiatric diagnoses (49·8% vs 9·6%), substance use (22·0% vs 0·4%), tobacco use (64·3% vs 15·8%), and low educational level (64·1% vs 17·6%) than did the reference group. For heavy-alcohol-exposed births, significantly increased adjusted ORs were found for small for gestational age (OR 2·20 [95% CI 1·97-2·45]), preterm birth (OR 1·32 [1·19-1·46]), haemorrhage in late pregnancy (OR 1·25 [1·05-1·49]), and preterm prelabour rupture of membranes (OR 1·18 [1·00-1·39]). Decreased adjusted ORs were found for postpartum haemorrhage (500-999 mL; OR 0·80 [95% CI 0·69-0·93]), gestational diabetes (OR 0·81 [0·67-0·99]), planned caesarean section (OR 0·82 [0·72-0·94]), pre-eclampsia and eclampsia (OR 0·83 [0·71-0·96]), and abnormalities of forces of labour (OR 0·92 [0·86-0·99]). INTERPRETATION: Heavy prenatal alcohol exposure is associated with adverse obstetric and birth outcomes and high proportions of maternal low educational level, psychiatric disease, and lifestyle risk behaviours. These findings highlight a need for holistic public health programmes and policy attention on improving pre-conceptional care and antenatal care. FUNDING: The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, the A.V. Lykfeldts Foundation.

Background Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematicreview and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, andreported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcoholexposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and healthrelated problems.Methods Our Danish nationwide register-based cohort study included all singleton births. Individuals were followedup to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, andbirths of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up.Data on health and education were extracted from the Danish Medical Birth Register, the Danish National PatientRegistry, the Danish National Prescription Registry, the Danish Civil Registration System, and the PopulationEducation Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatalalcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or herchild, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy.Findings Of 1407 689 identified singleton births, 219 186 were excluded for reasons including they were born toimmigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatalalcohol exposure and 1 183704 (99·6%) were classified as non-alcohol-exposed births. 578179 (48·6%) babies werefemale and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals withfetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%,predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four higheststandardised risk differences were found for low birthweight (4·70% [95% CI 3·70–5·71]), small for gestational age(4·63% [3·72–5·55]), delayed milestone (3·81% [2·99–4·64]), and other preterm infants (2·69% [1·71–3·68]). Ofpreviously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of atleast 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities.Interpretation Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities andpreviously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue witha potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates theprofound degree to which pre-conceptional care is mandatory Background: Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. Methods: Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Findings: Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4·70% [95% CI 3·70–5·71]), small for gestational age (4·63% [3·72–5·55]), delayed milestone (3·81% [2·99–4·64]), and other preterm infants (2·69% [1·71–3·68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities. Interpretation: Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the profound degree to which pre-conceptional care is mandatory. Funding: The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.

BackgroundCardiac arrest following trauma is a leading cause of death, mandating urgent treatment. This study aimed to investigate and compare the incidence, prognostic factors, and survival between patients suffering from traumatic cardiac arrest (TCA) and non-traumatic cardiac arrest (non-TCA).MethodsThis cohort study included all patients suffering from out-of-hospital cardiac arrest in Denmark between 2016 and 2021. TCAs were identified in the prehospital medical record and linked to the out-of-hospital cardiac arrest registry. Descriptive and multivariable analyses were performed with 30-day survival as the primary outcome.ResultsA total of 30,215 patients with out-of-hospital cardiac arrests were included. Among those, 984 (3.3%) were TCA. TCA patients were younger and predominantly male (77.5% vs 63.6%, p = ConclusionSurvival from TCA is lower than in non-TCA. TCA has different predictors of outcome compared to non-TCA, illustrating the differences regarding the aetiologies of cardiac arrest. Presenting with an initial shockable cardiac rhythm might be associated with a favourable outcome in TCA. BACKGROUND: Cardiac arrest following trauma is a leading cause of death, mandating urgent treatment. This study aimed to investigate and compare the incidence, prognostic factors, and survival between patients suffering from traumatic cardiac arrest (TCA) and non-traumatic cardiac arrest (non-TCA).METHODS: This cohort study included all patients suffering from out-of-hospital cardiac arrest in Denmark between 2016 and 2021. TCAs were identified in the prehospital medical record and linked to the out-of-hospital cardiac arrest registry. Descriptive and multivariable analyses were performed with 30-day survival as the primary outcome.RESULTS: A total of 30,215 patients with out-of-hospital cardiac arrests were included. Among those, 984 (3.3%) were TCA. TCA patients were younger and predominantly male (77.5% vs 63.6%, p = CONCLUSION: Survival from TCA is lower than in non-TCA. TCA has different predictors of outcome compared to non-TCA, illustrating the differences regarding the aetiologies of cardiac arrest. Presenting with an initial shockable cardiac rhythm might be associated with a favourable outcome in TCA.

ObjectivesCallers with myocardial infarction presenting atypical symptoms in telephone consultations when calling out-of-hours medical services risk misrecognition. We investigated characteristics in callers’ interpretation of experienced conditions through communication with call-takers.MethodsRecording of calls resulting in not having an ambulance dispatched for 21 callers who contacted a non-emergency medical helpline, Copenhagen (Denmark), up to one week before they were diagnosed with myocardial infarction. Qualitative content analysis was applied.ResultsAwareness of illness, remedial actions and previous experiences contributed to callers’ interpretation of the experienced condition. Unclear symptoms resulted in callers reacting to their interpretation by being unsure and worried. Negotiation of the interpretation was seen when callers tested the call-taker’s interpretation of the condition and when either caller or call-taker suggested: “wait and see”.ConclusionCallers sought to interpret the experienced conditions but faced challenges when the conditions appeared unclear and did not correspond to the health system’s understanding of symptoms associated with myocardial infarction. It affected the communicative interaction with the call-taker and influenced the call-taker’s choice of response. OBJECTIVES: Callers with myocardial infarction presenting atypical symptoms in telephone consultations when calling out-of-hours medical services risk misrecognition. We investigated characteristics in callers' interpretation of experienced conditions through communication with call-takers. METHODS: Recording of calls resulting in not having an ambulance dispatched for 21 callers who contacted a non-emergency medical helpline, Copenhagen (Denmark), up to one week before they were diagnosed with myocardial infarction. Qualitative content analysis was applied. RESULTS: Awareness of illness, remedial actions and previous experiences contributed to callers' interpretation of the experienced condition. Unclear symptoms resulted in callers reacting to their interpretation by being unsure and worried. Negotiation of the interpretation was seen when callers tested the call-taker's interpretation of the condition and when either caller or call-taker suggested: "wait and see". CONCLUSION: Callers sought to interpret the experienced conditions but faced challenges when the conditions appeared unclear and did not correspond to the health system's understanding of symptoms associated with myocardial infarction. It affected the communicative interaction with the call-taker and influenced the call-taker's choice of response. PRACTICE IMPLICATIONS: Call-takers, as part of the decision-making process, could ask further questions about the caller's insecurity and worry. It might facilitate faster recognition of conditions warranting hospital referral.

AIM: There is limited evidence regarding prodromal symptoms of out-of-hospital cardiac arrest (OHCA). We aimed to describe patient characteristics, prodromal symptoms, and prognosis of patients contacting emergency medical services (EMS) within 24 hours before OHCA.METHODS: We identified all OHCA treated by Copenhagen EMS from 2016 through 2018 using the Danish Cardiac Arrest Registry and linked them to emergency calls. We included all pre-arrest calls by patients or bystanders if they were performed 1) within 24 hours before the OHCA call or 2) during the OHCA event for EMS-witnessed OHCA. Calls were reviewed by healthcare professionals using a survey guide.RESULTS: Among 4,071 patients, 481 patients (12%) had 539 calls within 24 hours prior to OHCA (60% male, median age 74 years of age). The patient spoke on the phone in 25% of calls. The most common symptoms were breathing problems (59%), confusion (23%), unconsciousness (20%), chest pain (20%), and paleness (19%). Patients with breathing problems compared to chest pain were more likely to be ≤75 years of age (55% versus 35%), less likely to be male (52% versus 73%), have shockable rhythm (10% versus 38%), receive bystander defibrillation (6% versus 19%) or EMS defibrillation (15% versus 65%), achieve return of spontaneous circulation (37% versus 68%) and survive 30 days following OHCA (10% versus 50%).CONCLUSION: More than 10% of patients with OHCA had a call to EMS within 24 hours before OHCA. The most common symptom was breathing problems which compared to chest pain had lower 30-day survival.

Background Chronic cough, more than 8 weeks, can either be without co-morbidity called unexplained chronic cough (UCC) or with co-morbidity called refractory chronic cough (RCC). Using datasets from the Danish National Prescription Registry (Prescription Registry) and Danish National Patient Registry (Patient Registry) we wanted to investigate the prevalence and factors of importance of cough in a Nationwide registry. Material and methods Inclusion criteria were patients 18–90 years with at least one final cough diagnosis (ICD-10 DR05/DR059) in Patient registry or patients who have redeemed ≥2 prescriptions for relevant cough-medication within a 90-day harvest in the Prescription registry from 2008 to 2017. To validate this study’s chosen proxy on chronic cough an analysis of the Patient registry sub-population with a contact of ≥8 weeks and then final diagnosis code DR05/DR059 was also performed. The population was divided into UCC and RCC. Results Of the 104,216 patients from the Prescription registry, 52,727 were classified as having UCC and 51,489 were classified with RCC. From the Patient registry 34,260 were included, of whom 12,278 had UCC and 21,982 had RCC. Cough were frequently found among females (p p Conclusion Many patients suffer from chronic cough or cough requiring medications, with or without co-morbidity; frequently found among menopausal women. Most patients had a substantial work-up performed. The high frequency and the resources consuming work-up program call for systematic coding of disease, systematic patient evaluation and more specific treatment options. The study was approved (ID: no. P-2019-191).

Background Pediatric out-of-hospital cardiac arrest (POHCA) has received limited attention. All causes of POHCA and outcomes were examined during a 4-year period in a Danish nationwide register and prehospital medical records. The aim was to describe the incidence, reversible causes, and survival rates for POHCA in Denmark. Methods This is a registry-based follow-up cohort study. All POHCA for a 4-year period (2016–2019) in Denmark were included. All prehospital medical records for the included subjects were reviewed manually by five independent raters establishing whether a presumed reversible cause could be assigned. Results We identified 173 cases within the study period. The median incidence of POHCA in the population below 17 years of age was 4.2 per 100,000 persons at risk. We found a presumed reversible cause in 48.6% of cases, with hypoxia being the predominant cause of POHCA (42.2%). The thirty-day survival was 40%. Variations were seen across age groups, with the lowest survival rate in cases below 1 year of age. Defibrillators were used more frequently among survivors, with 16% of survivors defibrillated bystanders as opposed to 1.9% in non-survivors and 24% by EMS personnel as opposed to 7.8% in non-survivors. The differences in initial rhythm being shockable was 34% for survivors and 16% for non-survivors. Conclusion We found pediatric out-of-hospital cardiac arrests was a rare event, with higher incidence and mortality in infants compared to other age groups of children. Use of defibrillators was disproportionally higher among survivors. Hypoxia was the most common presumed cause among all age groups.

IntroductionNecrotising enterocolitis (NEC) remains a major contributor to preterm mortality and morbidity. Prolonged duration of antibiotic therapy after delivery is associated with later NEC development but recent evidence suggests that absence of antibiotic treatment after delivery may also increase NEC risk. We will explore this controversy using a large pre-existing dataset of preterm infants in the UK.Methods and analysisThis is a retrospective cohort study using data from UK National Neonatal Research Database (NNRD) for infants born 1 January 2012 to 31 December 2020. Eligible infants will be Ethics and disseminationWe will use deidentified data from NNRD, which holds permissions for the original data, from which parents can opt out and seek study-specific research ethics approval. The results will help to determine optimal use of early antibiotics for very preterm infants.ImplicationsThis data will help optimise early antibiotic use in preterm infants.Trial registration numberISRCTN55101779.

International studies document that medical education and the transition from student to medical doctor may be a stressful and difficult time. High anxiety levels impact professional performance and quality of life. The aim of this study was to investigate the prevalence of anxiety among Danish final-semester medical students and newly graduated medical doctors, including individual changes.This was a descriptive cohort and cross-sectional study based on a questionnaire given to medical students and newly graduated doctors between December 2020 and May 2021. The survey used the following validated anxiety scales: the Leeds Self-assessment of Anxiety scale and the State-Trait Anxiety Inventory. The data were analysed for medical students and doctors as cross-sectional analyses.A total of 175 medical students and 65 newly graduated doctors were included; 20 participated in both surveys. We found that 54 (32.5%) of the medical students and 12 (19.4%) of the newly graduated doctors scored pathologically anxious (p = 0.06). The measured anxiety level was higher than the anxiety level found in the background populations from other studies. Anxiety was related to gender and to previous treatment for stress or anxiety and it persisted from student life into life as a young doctor.A high proportion of the medical students reported anxiety, a condition which remained among the young doctors.The Emergency Medicine Research Unit, Odense University Hospital, Denmark.not relevant.

Aim To investigate temporal trends in inpatient vs. outpatient diagnosis of new-onset heart failure (HF) and the subsequent risk of death and hospitalization. Methods and results Using nationwide registers, 192 581 patients with a first diagnosis of HF (1997–2017) were included. We computed incidences of HF, age-standardized mortality rates, and absolute risks (ARs) of death and hospitalization (accounting for competing risk of death) to understand the importance of the diagnosis setting in relation to subsequent mortality and hospitalization. The overall incidence of HF was approximately the same (170/100 000 persons) every year during 1997–2017. However, in 1997, 77% of all first diagnoses of HF were made during a hospitalization, whereas the proportion was 39% in 2017. As inpatient diagnoses decreased, outpatient diagnoses increased from 23% to 61%. Outpatients had lower mortality and hospitalization rates than inpatients throughout the study period, although the 1-year age-standardized mortality rate decreased for each inpatient (24 to 14/100-person) and outpatient (11 to 7/100-person). One-year and five-year AR of death decreased by 11.1% and 17.0%, respectively, for all HF patients, while the risk of hospitalization for HF did not decrease significantly (1.13% and 0.96%, respectively). Conclusion Between 1997 and 2017, HF changed from being primarily diagnosed during hospitalization to being mostly diagnosed in the outpatient setting. Outpatients had much lower mortality rates than inpatients throughout the study period. Despite a significant decrease in mortality risk for all HF patients, neither inpatients nor outpatients experienced a reduction in the risk of an HF hospitalization.