Prediction model for future OHCAs based on geospatial and demographic data: An observational study.

This study used demographic data in a novel prediction model to identify areas with high risk of out-of-hospital cardiac arrest (OHCA) in order to target prehospital preparedness. We combined data from the nationwide Danish Cardiac Arrest Registry with geographical- and demographic data on a hectare level. Hectares were classified in a hierarchy according to characteristics and pooled to square kilometers (km2). Historical OHCA incidence of each hectare group was supplemented with a predicted annual risk of at least 1 OHCA to ensure future applicability. We recorded 19,090 valid OHCAs during 2016 to 2019. The mean annual OHCA rate was highest in residential areas with no point of public interest and 100 to 1000 residents per hectare (9.7/year/km2) followed by pedestrian streets with multiple shops (5.8/year/km2), areas with no point of public interest and 50 to 100 residents (5.5/year/km2), and malls with a mean annual incidence per km2 of 4.6. Other high incidence areas were public transport stations, schools and areas without a point of public interest and 10 to 50 residents. These areas combined constitute 1496 km2 annually corresponding to 3.4% of the total area of Denmark and account for 65% of the OHCA incidence. Our prediction model confirms these areas to be of high risk and outperforms simple previous incidence in identifying future risk-sites. Two thirds of out-of-hospital cardiac arrests were identified in only 3.4% of the area of Denmark. This area was easily identified as having multiple residents or having airports, malls, pedestrian shopping streets or schools. This result has important implications for targeted intervention such as automatic defibrillators available to the public. Further, demographic information should be considered when implementing such interventions.

Oral anticoagulation therapy initiation in patients with atrial fibrillation in relation to world region of origin: a register-based nationwide study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia and results in a high risk of stroke. The number of immigrants is increasing globally, but little is known about potential differences in AF care across migrant populations. AIM: To investigate if initiation of oral anticoagulation therapy (OAC) differs for patients with incident AF in relation to country of origin. METHODS: A nationwide register-based study covering 1999-2017. AF was defined as a first-time diagnosis of AF and a high risk of stroke. Stroke risk was defined according to guidelines from the European Society of Cardiology (ESC). Poisson regression adjusted for sex, age, socioeconomic position and comorbidity was made to compute incidence rate ratios (IRR) for initiation of OAC. RESULTS: The AF population included 254 586 individuals of Danish origin, 6673 of Western origin and 3757 of non-Western origin. Overall, OAC was initiated within -30/+90 days relative to the AF diagnosis in 50.3% of individuals of Danish origin initiated OAC, 49.6% of Western origin and 44.5% of non-Western origin. Immigrants from non-Western countries had significantly lower adjusted IRR of initiating OAC according to all ESC guidelines compared with patients of Danish origin. The adjusted IRRs ranged from 0.73 (95% CI: 0.66 to 0.80) following the launch of the 2010 ESC guideline to 0.89 (95% CI: 0.82 to 0.97) following the launch of the 2001 ESC guideline. CONCLUSION: Patients with AF with a high risk of stroke of non-Western origin have persistently experienced a lower chance of initiating OAC compared with patients of Danish origin during the last decades.

Prodromal complaints and 30-day survival after emergency medical services-witnessed out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a frequent and lethal condition with a yearly incidence of approximately 5000 in Denmark. Thirty-day survival is associated with the patient's prodromal complaints prior to cardiac arrest. This paper examines the odds of 30-day survival dependent on the reported prodromal complaints among OHCAs witnessed by the emergency medical services (EMS). METHODS: EMS-witnessed OHCAs in the Capital Region of Denmark from 2016-2018 were included. Calls to the emergency number 1-1-2 and the medical helpline for out-of-hours were analyzed according to the Danish Index; data regarding the OHCA was collected from the Danish Cardiac Arrest Registry. We performed multiple logistic regression to calculate the odds ratio (OR) of 30-day survival with adjustment for sex and age. RESULTS: We identified 311 eligible OHCAs of which 79 (25.4%) survived. The most commonly reported complaints were dyspnea (n = 209, OR 0.79 [95% CI 0.46: 1.36]) and 'feeling generally unwell' (n = 185, OR 1.07 [95% CI 0.63: 1.81]). Chest pain (OR 9.16 [95% CI 5.09:16.9]) and heart palpitations (OR 3.15 [95% CI 1.07:9.46]) had the highest ORs, indicating favorable odds for 30-day survival, while unresponsiveness (OR 0.22 [95% CI 0.11:0.43]) and blue skin or lips (OR 0.30, 95% CI 0.09, 0.81) had the lowest, indicating lesser odds of 30-day survival. CONCLUSION: Experiencing chest pain or heart palpitations prior to EMS-witnessed OHCA was associated with higher 30-day survival. Conversely, complaints of unresponsiveness or having blue skin or lips implied reduced odds of 30-day survival.

Long-term aspirin adherence following myocardial infarction and risk of cardiovascular events.

BACKGROUND AND AIMS: Aspirin is considered mandatory after myocardial infarction (MI). However, its long-term efficacy has been questioned. This study investigated the effectiveness of long-term aspirin after MI. METHODS: Patients ≥ 40 years with MI from 2004-2017 who were adherent to aspirin one year after MI were included from Danish nationwide registries. At 2, 4, 6, and 8 years after MI, continued adherence to aspirin was evaluated. Absolute and relative risks of MI, stroke, or death at 2 years from each timepoint were calculated using multivariable logistic regression analysis with average treatment effect modeling standardized for age, sex, and comorbidities. Subgroup analyses were stratified by sex and age > and ≤ 65 years. RESULTS: Among 40 114 individuals included, the risk of the composite endpoint was significantly higher for nonadherent patients at all timepoints. The absolute risk was highest at 2-4 years after MI for both adherent (8.34%, 95% confidence interval [CI]: 8.05-8.64%) and nonadherent patients (10.72%, 95% CI: 9.78-11.66%). The relative risk associated with nonadherence decreased from 4 years after index-MI and onwards: 1.41 (95% CI: 1.27-1.55) at 4-6 years and 1.21 (95% CI: 1.06-1.36) at 8-10 years (Ptrend = 0.056). Aspirin nonadherence in women and individuals > 65 years was not associated with increased risk. Pinteraction at each of the timepoints: Age-<0.001, <0.001, 0.002, 0.51; Sex - 0.25, 0.02, 0.02, 0.82. CONCLUSION: Nonadherence to long-term aspirin was associated with increased risk of MI, stroke, or death, but not in women or individuals > 65 years. The risk decreased from 4 years after MI with near statistical significance.

Patients with eosinophilic oesophagitis in Denmark have higher use of psychotropic drugs: A Danish nationwide study of psychotropic drug use in 3367 patients and 16,835 matched comparators.

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated disease of the oesophagus. Eosinophilic oesophagitis is associated with a substantial disease burden affecting the quality of life and affecting mental health. There are limited data describing the incidence of psychiatric disorders and the use of psychotropic drugs (PDs) in EoE patients. OBJECTIVES: The aim was to investigate whether EoE patients in Denmark have higher use of PDs, contacts with the department of psychiatry, and attempts of suicide or intentional self-harm compared with the general population after being diagnosed with EoE. METHODS: This study was a nationwide, population-based register study including 3367 EoE patients and 16,835 age- and sex-matched comparators. A register-based EoE definition was used to identify cases. Incident PD use was extracted from the prescription register and information regarding psychiatric contacts was retrieved from the Danish Psychiatric Central Research Register. RESULTS: The 5-year incidence of PD use in EoE patients was 13.8% compared to 7.1% of the matched comparators (Hazard ratio 1.83; confidence interval 1.6-2.0; p ≤ 0.001). Antidepressants were the most frequently prescribed PD, whereas antipsychotics were the least prescribed PD. Increasing age, lower educational level, and comorbidity (Charlson Comorbidity Index score ≥1) were associated with the prescription of PDs. The risk of PD use was lower in men than in women with EoE. CONCLUSION: Treatment with PDs were more common in EoE patients after they were diagnosed than in the general Danish population, indicating that EoE patients have an increased risk of psychiatric disorders.

Incidence of atrial fibrillation and flutter in Denmark in relation to country of origin: a nationwide register-based study.

BACKGROUND: Atrial fibrillation and flutter (AF) is the most common sustained arrhythmia with an increasing prevalence in Western countries. However, little is known about AF among immigrants compared to non-immigrants. AIM: To examine the incidence of hospital-diagnosed AF according to country of origin. METHOD: Immigrants were defined as individuals born outside Denmark by parents born outside Denmark. AF was defined as first-time diagnosis of AF. All individuals were followed from the age of 45 years from 1998 to 2017. The analyses were adjusted for sex, age, comorbidity, contact with the general practitioner and socioeconomic variables. Adjustment was conducted using standardised morbidity ratio weights, standardised to the Danish population in a marginal structural model. RESULTS: The study population consisted of 3,489,730 Danish individuals free of AF and 108,914 immigrants free of AF who had emigrated from the 10 most represented countries. A total of 323,005 individuals of Danish origin had an incident hospital diagnosis of AF, among the immigrants 7,300 developed AF. Adjusted hazard rate ratios (HRRs) of AF for immigrants from Iran (0.48 [95%CI:0.35;0.64]), Turkey (0.74 [95%CI:0.67;0.82]) and Bosnia-Herzegovina (0.42 [95%CI:0.22;0.79]) were low compared with Danish individuals. Immigrants from Sweden, Germany and Norway had an adjusted HRR of 1.13 [95%CI:1.03;1.23], 1.12 [95%CI:1.05;1.18] and 1.11 [95%CI:1.03;1.21], respectively (Danish individuals as reference). CONCLUSIONS: Substantial variation in the incidence of hospital-diagnosed AF according to country of origin was observed. The results may reflect true biological differences but could also reflect barriers to AF diagnosis for immigrants. Further efforts are warranted to determine the underlying mechanisms.

Risk of dementia among older patients with lymphoma: A Danish nationwide matched cohort study.

INTRODUCTION: Treatment of lymphoma can be associated with cognitive challenges, and some patients may fear development of dementia as long-term complication. Studies report a lower risk of dementia after cancer. Some believe this difference to be a protective mechanism of cancer, others believe it to be driven by bias. The risk of developing dementia after lymphoma has not been investigated in a population-based setting. The aim of this study was to identify the risk of being diagnosed with dementia after lymphoma treatment. MATERIALS AND METHODS: This Danish nationwide matched cohort study included patients aged ≥65 years with a first-time diagnosis of a non-central nervous system lymphoma between 2005 and 2018 in complete remission after treatment with chemotherapy. Patients diagnosed with dementia or treated with dementia medication before lymphoma diagnosis were excluded. Each patient was matched 1:5 on sex, year of birth, and a modified Charlson comorbidity index. Patients and matched comparators were followed from the corresponding patient's date of complete remission. The risk of developing dementia was calculated using cause-specific hazard ratios (HR), and the cumulative risk was estimated by Aalen-Johansen with death as the competing risk. RESULTS: A total of 3,244 patients and 16,220 matched comparators were included in the study. There was no difference in risk of all-cause dementia among patients with lymphoma compared to matched comparators with cause-specific HR of 0.85 (95% confidence interval [CI]: 0.70;1.04). The risk of both Alzheimer's disease and non-Alzheimer's dementia was equal among patients and comparators: HR 0.89 (95% CI: 0.66;1.21) and 0.82 (95% CI: 0.63;1.07), respectively. Stratified by lymphoma subtype, age, or year of diagnosis, the risk of all-cause dementia remained equal among patients and matched comparators. The cumulative risk of all-cause dementia was significantly lower among patients with lymphoma compared to matched comparators (Gray's test p < 0.001), probably reflecting higher mortality in patients with lymphoma. DISCUSSION: The risk of all-cause dementia, Alzheimer's disease, and non-Alzheimer's dementia was equal among older patients with lymphoma compared to matched comparators. Our data suggests that risk of developing dementia is not changed after lymphoma treatment.

Association between mortality and phone-line waiting time for non-urgent medical care: a Danish registry-based cohort study.

BACKGROUND AND IMPORTANCE: Telephone calls are often patients' first healthcare service contact, outcomes associated with waiting times are unknown. OBJECTIVES: Examine the association between waiting time to answer for a medical helpline and 1- and 30-day mortality. DESIGN, SETTING AND PARTICIPANTS: Registry-based cohort study using phone calls data (January 2014 to December 2018) to the Capital Region of Denmark's medical helpline. The service refers to hospital assessment/treatment, dispatches ambulances, or suggests self-care guidance. EXPOSURE: Waiting time was grouped into the following time intervals in accordance with political service targets for waiting time in the Capital Region: <30 s, 0:30-2:59, 3-9:59, and ≥10 min. OUTCOME MEASURES AND ANALYSIS: The association between time intervals and 1- and 30-day mortality per call was calculated using logistic regression with strata defined by age and sex. MAIN RESULTS: In total, 1 244 252 callers were included, phoning 3 956 243 times, and 78% of calls waited <10 min. Among callers, 30-day mortality was 1% (16 560 deaths). For calls by females aged 85-110 30-day mortality increased with longer waiting time, particularly within the first minute: 9.6% for waiting time <30 s, 10.8% between 30 s and 1 minute and 9.1% between 1 and 2 minutes. For calls by males aged 85-110 30-day mortality was 11.1%, 12.9% and 11.1%, respectively. Additionally, among calls with a Charlson score of 2 or higher, longer waiting times were likewise associated with increased mortality. For calls by females aged 85-110 30-day mortality was 11.6% for waiting time <30 s, 12.9% between 30 s and 1 minute and 11.2% between 1 and 2 minutes. For calls by males aged 85-110 30-day mortality was 12.7%, 14.1% and 12.6%, respectively. Fewer ambulances were dispatched with longer waiting times (4%/2%) with waiting times <30 s and >10 min. CONCLUSION: Longer waiting times for telephone contact to a medical helpline were associated with increased 1- and 30-day mortality within the first minute, especially among elderly or more comorbid callers.

Ambulance response times and 30-day mortality: a Copenhagen (Denmark) registry study.

BACKGROUND AND IMPORTANCE: Ensuring prompt ambulance responses is complicated and costly. It is a general conception that short response times save lives, but the actual knowledge is limited. OBJECTIVE: To examine the association between the response times of ambulances with lights and sirens and 30-day mortality. DESIGN: A registry-based cohort study using data collected from 2014-2018. SETTINGS AND PARTICIPANTS: This study included 182 895 individuals who, during 2014-2018, were dispatched 266 265 ambulances in the Capital Region of Denmark. OUTCOME MEASURES AND ANALYSIS: The primary outcome was 30-day mortality. Subgroup analyses were performed on out-of-hospital cardiac arrests, ambulance response priority subtypes, and caller-reported symptoms of chest pain, dyspnoea, unconsciousness, and traffic accidents. The relation between variables and 30-day mortality was examined with logistic regression. RESULTS: Unadjusted, short response times were associated with higher 30-day mortality rates across unadjusted response time quartiles (0-6.39 min: 9%; 6.40-8.60 min: 7.5%, 8.61-11.80 min: 6.6%, >11.80 min: 5.5%). This inverse relationship was consistent across subgroups, including chest pain, dyspnoea, unconsciousness, and response priority subtypes. For traffic accidents, no significant results were found. In the case of out-of-hospital cardiac arrests, longer response times of up to 10 min correlated with increased 30-day mortality rates (0-6.39 min: 84.1%; 6.40-8.60 min: 86.7%, 8.61-11.8 min: 87.7%, >11.80 min: 85.5%). Multivariable-adjusted logistic regression analysis showed that age, sex, Charlson comorbidity score, and call-related symptoms were associated with 30-day mortality, but response time was not (OR: 1.00 (95% CI [0.99-1.00])). CONCLUSION: Longer ambulance response times were not associated with increased mortality, except for out-of-hospital cardiac arrests.

Myocarditis and pericarditis in individuals exposed to the Ad26.COV2.S, BNT162b2 mRNA, or mRNA-1273 SARS-CoV-2 vaccines.

Importance: There is a high level of public and professional interest related to potential safety issues of the COVID-19 vaccines; however, no serious adverse cardiovascular events were reported in phase 3 randomized controlled trials of their safety and efficacy. Moreover, none of the case series from the United States (US) of these potential complications have been population-based. Objectives: To estimate the reporting rates of myocarditis and pericarditis in the US using the Vaccine Adverse Event Reporting System (VAERS), and to assess if these adverse events were disproportionally reported among the different COVID-19 vaccines. Design setting and participants: All cases of myocarditis and pericarditis from VAERS reported up to July 28, 2021. Exposure: Single-dose Ad26.COV2.S, BNT162b2 mRNA, or mRNA-1273 SARS-CoV-2 vaccinations. Main outcomes and measures: Reporting rates were computed by dividing the total number of cases of myocarditis and pericarditis (combined) by the total number of vaccine doses administered. Disproportionality analyses were performed to evaluate disproportional reporting of myocarditis and pericarditis for the Ad26.COV2.S and mRNA-1273 vaccines vs. the BNT162b2 mRNA vaccine. Results: By July 28, 2021, 1392, 699, and 68 cases of myocarditis or pericarditis had been reported out of 1.91, 1.38, and 1.33 million administered doses of the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines, respectively. Median times to event were 3 days, 3 days, and 9 days for the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines. The reporting rates for myocarditis or pericarditis were 0.00073 (95% confidence interval, 95% CI 0.00069-0.00077), 0.00051 (95% CI 0.00047-0.00055), and 0.00005 events per dose (95% CI 0.00004-0.00006) for the BNT162b2 mRNA, mRNA-1273, and Ad26.COV2.S COVID-19 vaccines, respectively. Myocarditis and pericarditis were disproportionally reported following the BNT162b2 mRNA vaccine when compared with the other vaccines, using both disproportionality measures. Conclusions and relevance: We found reporting rates of myocarditis and pericarditis to be less than 0.1% after COVID-19 vaccination. Rates were highest for the BNT162b2 mRNA vaccine, followed by the mRNA-1273 and Ad26.COV2.S, respectively. However, the reporting rates of myocarditis and pericarditis secondary to vaccination remains less common than those seen for SARS-CoV-2 infection.

Gastrointestinal bleeding with direct oral anticoagulants in patients with atrial fibrillation and anaemia.

INTRODUCTION: A high risk of gastrointestinal bleeding has been reported with the use of some direct oral anticoagulants (DOACs). This risk may be of particular concern in individuals with associated anaemia. The aim of this study is to investigate potential differences in the risks of gastrointestinal bleeding and stroke among the four available DOACs in patients with atrial fibrillation (AF) and moderate or severe anaemia. MATERIALS AND METHODS: All Danish patients diagnosed with incident AF who had a baseline haemoglobin measurement and subsequently initiated DOAC therapy between 2012 and 2021 were identified through administrative registries. Only patients with moderate or severe anaemia (N = 7269) were included and evaluated regarding the risk of hospitalization for gastrointestinal bleeding and stroke. Standardized absolute 1-year risks of stroke and gastrointestinal bleeding were calculated from multivariable Cox regression analyses. DOACs were compared pairwise RESULTS: Compared with apixaban, both dabigatran and rivaroxaban were associated with a significantly increased risk of gastrointestinal bleeding with standardized 1-year risk ratios of 1.73 (95 % confidence interval [CI], 1.10-2.35) and 1.56 (95 % CI, 1.18-1.93), respectively, while no significant difference was seen in the comparison of apixaban with edoxaban 1.32 (95 % CI, 0.41-2.32). No significant differences in gastrointestinal bleeding were observed with pairwise comparisons of dabigatran, rivaroxaban and edoxaban. Finally, no significant difference in stroke risk among the four DOACs was observed. CONCLUSION: In AF patients with moderate or severe anaemia, apixaban was associated with a significantly lower risk of gastrointestinal bleeding than dabigatran and rivaroxaban. No significant difference in stroke risk was observed across all four available DOACs.

Education level and the use of coronary computed tomography, functional testing, coronary angiography, revascularization, and outcomes-a 10-year Danish, nationwide, registry-based follow-up study.

BACKGROUND AND AIMS: Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored. METHODS: This nationwide register-based cohort study assessed all residents in Denmark between 2008-2018 without coronary artery disease (CAD) and 50-80 years of age (n = 1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged ≥ 50-59, AR 3.62% individuals aged ≥ 60-69, AR 2.19% individuals aged ≥ 70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n = 50 234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE. CONCLUSION: Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. ICA utilization, revascularization and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare.

AI-based, automated chamber volumetry from gated, non-contrast CT.

BACKGROUND: Accurate chamber volumetry from gated, non-contrast cardiac CT (NCCT) scans can be useful for potential screening of heart failure. OBJECTIVES: To validate a new, fully automated, AI-based method for cardiac volume and myocardial mass quantification from NCCT scans compared to contrasted CT Angiography (CCTA). METHODS: Of a retrospectively collected cohort of 1051 consecutive patients, 420 patients had both NCCT and CCTA scans at mid-diastolic phase, excluding patients with cardiac devices. Ground truth values were obtained from the CCTA scans. RESULTS: The NCCT volume computation shows good agreement with ground truth values. Volume differences [95% CI ] and correlation coefficients were: -9.6 [-45; 26] mL, r â€‹= â€‹0.98 for LV Total, -5.4 [-24; 13] mL, r â€‹= â€‹0.95 for LA, -8.7 [-45; 28] mL, r â€‹= â€‹0.94 for RV, -5.2 [-27; 17] mL, r â€‹= â€‹0.92 for RA, -3.2 [-42; 36] mL, r â€‹= â€‹0.91 for LV blood pool, and -6.7 [-39; 26] g, r â€‹= â€‹0.94 for LV wall mass, respectively. Mean relative volume errors of less than 7% were obtained for all chambers. CONCLUSIONS: Fully automated assessment of chamber volumes from NCCT scans is feasible and correlates well with volumes obtained from contrast study.

A novel approach for pharmacological substantiation of safety signals using plasma concentrations of medication and administrative/healthcare databases: A case study using Danish registries for an FDA warning on lamotrigine.

PHARMACOM-EPI is a novel framework to predict plasma concentrations of drugs at the time of occurrence of clinical outcomes. In early 2021, the U.S. Food and Drug Administration (FDA) issued a warning on the antiseizure drug lamotrigine claiming that it has the potential to increase the risk of arrhythmias and related sudden cardiac death due to a pharmacological sodium channel-blocking effect. We hypothesized that the risk of arrhythmias and related death is due to toxicity. We used the PHARMACOM-EPI framework to investigate the relationship between lamotrigine's plasma concentrations and the risk of death in older patients using real-world data. Danish nationwide administrative and healthcare registers were used as data sources and individuals aged 65 years or older during the period 1996 - 2018 were included in the study. According to the PHARMACOM-EPI framework, plasma concentrations of lamotrigine were predicted at the time of death and patients were categorized into non-toxic and toxic groups based on the therapeutic range of lamotrigine (3-15 mg/L). Over 1 year of treatment, the incidence rate ratio (IRR) of all-cause mortality was calculated between the propensities score matched toxic and non-toxic groups. In total, 7286 individuals were diagnosed with epilepsy and were exposed to lamotrigine, 432 of which had at least one plasma concentration measurement The pharmacometric model by Chavez et al. was used to predict lamotrigine's plasma concentrations considering the lowest absolute percentage error among identified models (14.25 %, 95 % CI: 11.68-16.23). The majority of lamotrigine associated deaths were cardiovascular-related and occurred among individuals with plasma concentrations in the toxic range. The IRR of mortality between the toxic group and non-toxic group was 3.37 [95 % CI: 1.44-8.32] and the cumulative incidence of all-cause mortality exponentially increased in the toxic range. Application of our novel framework PHARMACOM-EPI provided strong evidence to support our hypothesis that the increased risk of all-cause and cardiovascular death was associated with a toxic plasma concentration level of lamotrigine among older lamotrigine users.

Discharge time after birth is associated with parity - A retrospective cohort study.

Background: All healthy mothers with uncomplicated births are recommended to be discharged directly from the labour ward a few hours after birth as a change in practice in three hospitals in Denmark. However, despite this practice, there is limited knowledge about when mothers leave the hospital after birth in clinical practice. Objective: The aim of this study is to examine 1) when mothers are discharged from hospital after birth, 2) if discharge time from the hospital after birth is associated with parity, and 3) which factors are associated with discharge time. Methods: This retrospective study is based on data from the North Denmark Regional Hospital and included mothers giving vaginal birth from March 25, 2019 to April 10, 2021. Results: A total of 1990 mothers were included. Nearly 50% of the new mothers stayed at the hospital less than 6 h after birth (26% of primiparous women vs 64% of multiparous women). Primiparous women had an adjusted RR 0.44 (95% CI 0.39-0.49) for discharge ≤6 h, RR 1.71 (95% CI 1.15-2.54) for discharge >6-12 h, and RR 3.76 (95% CI 3.03-4.67) for discharge >48 h after birth compared to multiparous women. Multiparous women's adjusted RR for discharge >6-12 h was 0.15 (95% CI 0.12-0.20) and for discharge >48 h 0.16 (95% CI 0.14-0.20) compared to discharge less than 6 h after birth. Furthermore, smoking, low education level, and younger age were associated with early discharge. Conclusion: There is a significant association with parity and discharge time after birth and factors related to discharge time which healthcare professionals should be aware of when planning inpatient and outpatient care. In addition, healthcare professionals should be aware of mothers discharged early who are smoking, of younger age, lower education level or multiparity.

Work Disability and Return to Work After Lymphoma: A Danish Nationwide Cohort Study.

Purpose: Many patients diagnosed with lymphoma are of working age. Cancer patients are known to have a higher risk of sick leave and disability pension, but this has only been delineated for certain subtypes of lymphoma. Therefore, this study aimed at investigating the overall risk of disability pension for all lymphoma subtypes and at quantifying return to work for patients with lymphoma in work before diagnosis. Patients and Methods: Patients aged 18-60 years with lymphoma in complete remission (CR) diagnosed between 2000 and 2019 were included in the study. Using national registers, each patient was matched with five comparators from the general population with same sex, birth year, and level of Charlson Comorbidity Index. Risk of disability pension was calculated from 90 days after CR or end of treatment with competing events (death, retirement pension, early retirement pension, relapse for patients, or lymphoma diagnosis for comparators). Return to work for patients was calculated annually until 5 years after diagnosis for patients employed before diagnosis. Results: In total, 4072 patients and 20,360 comparators were included. There was a significant increased risk of disability pension for patients with all types of lymphoma compared to the general population (5-year risk difference: 5.3 (95% confidence interval (CI): 4.4;6.2)). Patients with non-Hodgkin lymphoma were more likely to get disability pension than patients with Hodgkin lymphoma (sex- and age-adjusted 10-year risk difference: 2.9 (95% CI: 0.3;5.5)). One year after diagnosis, 24.5% of the relapse-free patients were on sick leave. Return to work was highest 2 years after diagnosis (82.1%). Conclusion: Patients with lymphoma across all subtypes have a significantly higher risk of disability pension. Return to work peaks at 2 years after diagnosis.

Temporal trends in low-dose aspirin therapy for primary prevention of cardiovascular disease in European adults with and without diabetes.

AIMS: Aspirin therapy for primary prevention of cardiovascular disease (CVD) is controversial, and guideline recommendations have changed throughout the last decades. We report temporal trends in primary prevention aspirin use among persons with and without diabetes and describe characteristics of incident aspirin users. METHODS AND RESULTS: Using Danish nationwide registries, we identified incident and prevalent aspirin users in a population of subjects ≥40 years without CVD eligible for primary preventive aspirin therapy from 2000 through 2020. Temporal trends in aspirin users with and without diabetes were assessed, as were CVD risk factors among incident users. A total of 522 680 individuals started aspirin therapy during the study period. The number of incident users peaked in 2002 (39 803 individuals, 1.78% of the eligible population) and was the lowest in 2019 (11 898 individuals, 0.49%), with similar trends for subjects with and without diabetes. The percentage of incident users with no CVD risk factors [diabetes, hypertension, hypercholesterolemia, or chronic obstructive pulmonary disease (a proxy for smoking)] decreased from 53.9% in 2000 to 30.9% in 2020. The temporal trends in prevalent aspirin users followed a unimodal curve, peaked at 7.7% in 2008, and was 3.3% in 2020. For subjects with diabetes, the peak was observed in 2009 at 38.5% decreasing to 17.1% in 2020. CONCLUSION: Aspirin therapy for primary prevention of CVD has decreased over the last two decades. However, the drug remained used in individuals with and without diabetes, and a large proportion of individuals started on aspirin therapy had no CVD risk factors.

One sentence summaryThis study investigated the temporal trends in aspirin use for primary prevention of cardiovascular disease in individuals with and without diabetes and found that even though the number of aspirin users has declined, the drug remains prescribed, and individuals even without cardiovascular risk factors were started on aspirin therapy. Lay summary key findingsThe number of aspirin users with and without diabetes for primary prevention of cardiovascular disease has decreased over the last two decades. Nevertheless, individuals with a low burden of cardiovascular risk factors were started on aspirin therapy.Efforts to inform appropriate use of aspirin are needed.

Time trends of coronary procedures, guideline-based drugs and all-cause mortality following acute coronary syndrome in patients with bipolar disorder.

AIM: This study analyzed time trends in the use of coronary procedures, guideline-based drugs, and 1-year all-cause and presumed cardiovascular mortality (CV) following acute coronary syndrome (ACS) in patients with and without bipolar disorder (BD). METHOD: Using Danish registries 497 patients with ACS and BD in the period 1996-2016 were matched 1:2 on age, sex and year of ACS to patients without preexisting psychiatric disease. RESULTS: Patients with BD and ACS received fewer coronary angiography (CAG) compared to psychiatric healthy controls (PHC). However, the difference between the populations decreased over time. For percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) no differences in trend over time were found. In general patients with BD redeemed fewer prescriptions of guideline-based tertiary prophylactic drugs compared to PHCs. The difference remains constant over time for all drugs except for acetylsalicylic acid, lipid-lowering drugs and beta blockers, where the difference decreased. The 1-year all-cause mortality gap and the presumed CV mortality gap remained unchanged. CONCLUSION: Despite improvements in treatment disparities regarding CAG, acetylsalicylic acid, lipid-lowering drugs and beta-blockers, the treatment gap remained unchanged concerning PCI and CABG. Likewise, patients with BD experienced a lower rate of the remaining redeemed prescriptions. The overall crude mortality risk ratio for patients with BD experiencing ACS remained unchanged over the study period compared to PHC.

Hypothetical interventions on emergency ambulance and prehospital acetylsalicylic acid administration in myocardial infarction patients presenting without chest pain.

BACKGROUND: Myocardial infarction (MI) patients presenting without chest pain are a diagnostic challenge. They receive suboptimal prehospital management and have high mortality. To elucidate potential benefits of improved management, we analysed expected outcome among non-chest pain MI patients if hypothetically they (1) received emergency ambulances/acetylsalicylic acid (ASA) as often as observed for chest pain patients, and (2) all received emergency ambulance/ASA. METHODS: We sampled calls to emergency and non-emergency medical services for patients hospitalized with MI within 24 h and categorized calls as chest pain/non-chest pain. Outcomes were 30-day mortality and a 1-year combined outcome of re-infarction, heart failure admission, and mortality. Targeted minimum loss-based estimation was used for all statistical analyses. RESULTS: Among 5418 calls regarding MI patients, 24% (1309) were recorded with non-chest pain. In total, 90% (3689/4109) of chest pain and 40% (525/1309) of non-chest pain patients received an emergency ambulance, and 73% (2668/3632) and 37% (192/518) of chest pain and non-chest pain patients received prehospital ASA. Providing ambulances to all non-chest pain patients was not associated with improved survival. Prehospital administration of ASA to all emergency ambulance transports of non-chest pain MI patients was expected to reduce 30-day mortality by 5.3% (CI 95%: [1.7%;9%]) from 12.8% to 7.4%. No significant reduction was found for the 1-year combined outcome (2.6% CI 95% [- 2.9%;8.1%]). In comparison, the observed 30-day mortality was 3% among ambulance-transported chest pain MI patients. CONCLUSIONS: Our study found large differences in the prehospital management of MI patients with and without chest pain. Improved prehospital ASA administration to non-chest pain MI patients could possibly reduce 30-day mortality, but long-term effects appear limited. Non-chest pain MI patients are difficult to identify prehospital and possible unintended effects of ASA might outweigh the potential benefits of improving the prehospital management. Future research should investigate ways to improve the prehospital recognition of MI in the absence of chest pain.