Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Outbreak of equine herpesvirus 4 (EHV-4) in Denmark: tracing patient zero and viral characterization.

BACKGROUND: Equine herpesvirus 4 (EHV-4) causes respiratory disease in horses, and the virus is considered endemic in the global equine population. However, outbreaks can occur when several horses are gathered in relation to shows, competitions, breeding units and at hospitals. In the spring year 2022, an EHV-4 outbreak occurred at the Large Animal Teaching Hospital, University of Copenhagen, Denmark. Nine horses were tested EHV-4 positive during the outbreak, which lasted approx. seven weeks. In addition, a tenth horse "Eq10" tested EHV-4 positive almost three weeks after the last of the outbreak horses tested positive. Detailed clinical registrations were obtained from all ten horses as well as their location and movement during hospitalization. Nasal swabs were obtained throughout the outbreak and tested by qPCR for EHV-4. Additionally, pre- and post-infection sera were tested for the presence of EHV-4 antibodies. Selected samples were characterized by partial and full genome sequencing. RESULTS: The most common clinical signs of the EHV-4 infected horses during this outbreak were pyrexia, nasal discharge, mandibular lymphadenopathy and increased lung sounds upon auscultation. Based on the locations of the horses, EHV-4 detection and antibody responses the most likely "patient zero" was identified as being "Eq1". Partial genome sequencing revealed that Eq10 was infected by another wild type EHV-4 strain, suggesting that the hospital was able to eliminate the outbreak by testing and reinforcing biosecurity measures. The complete genome sequence of the outbreak strain was obtained and revealed a closer relation to Australian and Japanese EHV-4 strains rather than to other European EHV-4 strains, however, very limited sequence data are available from Europe. CONCLUSION: The study illustrated the transmission of EHV-4 within an equine facility/hospital and provided new insights into the viral shedding, antibody responses and clinical signs related to EHV-4 infections. Finally, sequencing proved a useful tool in understanding the transmission within the hospital, and in characterizing of the outbreak strain.

Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer's disease: a nationwide nested case-control study.

BACKGROUND: Patients with young onset Alzheimer's disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis. METHODS: In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016-2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals. RESULTS: The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05-1.31), increasing to 1.57 (95% CI 1.39-1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users. CONCLUSIONS: In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.

Inverse probability weighting for self-selection bias correction in the investigation of social inequality in mortality.

BACKGROUND: Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage. METHODS: The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009-11 (ages 49-63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population. RESULTS: Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29]). CONCLUSIONS: Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors.

Short-term and long-term stroke risk following SARS-CoV-2 infection in relation to disease severity: a Danish national cohort study.

OBJECTIVES: Studies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke in SARS-CoV-2 test-positive individuals compared with test-negative individuals stratified by disease severity during acute infection and post infection. DESIGN: A register-based cohort study. SETTING: A Danish nationwide study. PARTICIPANTS: All Danish adults who had PCR tests for SARS-CoV-2 performed between 1 March 2020 and 30 November 2021. Test-positive individuals were included at their first positive test. For individuals tested prior to 30 November 2021, we randomly sampled an index date from the distribution of test dates among SARS-CoV-2 test-positive individuals. Test-positive individuals were followed during the acute phase of infection (days 0-14) and post infection (180 days after the acute phase). Test-negative individuals were followed in equivalent time periods. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident ischaemic stroke risk in SARS-CoV-2 test-positive individuals compared with test-negative individuals during acute infection and post infection. We calculated subdistribution HRs (SHR) with death as a competing risk using propensity score weighting as confounder control. The risk was stratified according to disease severity: community managed, hospitalised, or admission to the intensive care unit. RESULTS: Among 3 910 219 SARS-CoV-2 PRC-tested individuals, 356 421 test-positive and 3 067 456 test-negative individuals were included. A positive SARS-CoV-2 test was associated with an SHR of 3.32 (95% CI 2.60 to 4.25) overall for stroke compared with test negative in the acute phase. In the postinfection period, the risk of stroke remained increased in individuals hospitalised during the acute phase (SHR 1.85, 95% CI 1.45 to 2.37). Individuals with community-managed SARS-CoV-2 had no increased long-term risk of stroke (SHR 1.01, 95% CI 0.88 to 1.16). CONCLUSION: SARS-CoV-2 infection is associated with increased stroke risk. Disease severity seems to be an important factor. Individuals with community-managed SARS-CoV-2 had no increased stroke risk.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort.

BACKGROUND: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. METHODS: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. RESULTS: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e - 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. CONCLUSIONS: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Exploring the course of functional somatic symptoms (FSS) from pre- to late adolescence and associated internalizing psychopathology - an observational cohort-study.

BACKGROUND: Functional somatic symptoms (FSS), which commonly cannot be attributed to well-defined organic pathology, often co-occur with internalizing psychopathology and fluctuate throughout different life stages. We examined FSS courses throughout adolescence, and the association between preadolescent FSS, FSS severity and internalizing psychopathology at late adolescence. METHODS: Data from the Copenhagen Child Cohort (CCC2000) were utilized from assessments at ages 11-12 years (preadolescence; T0) and 16-17 years (late adolescence; T1). Self-report questionnaire and interview data on FSS, internalizing psychopathology, chronic medical conditions, and sociodemographic data from Danish national registers were available for 1285 youths. FSS courses were categorized into persistent (high FSS at T0 & T1), remission (high FSS only at T0), incident (high FSS only at T1) or no FSS (no FSS at T0 & T1). Multiple linear and multinomial logistic regressions were conducted to investigate the FSS/psychopathology association. RESULTS: 1.8% of adolescents fell into the persistent FSS course group throughout adolescence. Higher preadolescent FSS predicted FSS (b = 0.07, p < .001), anxiety (b = 0.05, p < .001) and depression (b = 0.06, p < .001) at age 16/17, even after controlling for sex, parental education, a chronic medical condition and internalizing psychopathology in preadolescence. Persistent, incident, and remittent FSS courses were associated with significantly higher mean levels of anxiety and depression compared to the reference group (no FSS). CONCLUSIONS: FSS during pre- and late adolescence might increase and co-occur with anxiety and depression throughout adolescence, potentially due to shared underlying risk factors and processes.

ProtecT-2-D trial protocol: cardiovascular protection in patients with type 2 diabetes and established heart and/or vascular disease at a cardio-metabolic clinic-a randomized controlled trial.

BACKGROUND: Cardiovascular disease remains the primary cause of morbidity and mortality despite advancements in the treatment of patients with type 2 diabetes. Effective diabetes management extends beyond blood glucose control and includes cardiovascular prevention and treatment. However, the conventional healthcare model often emphasizes single-disease-specific management, leading to fragmented care. We aim to establish an affordable Cardio-Metabolic Clinic (CMC) that can provide comprehensive assessment and specialized care with a focus on cardiovascular protection. METHODS: The ProtecT-2-D study is a prospective, randomized control trial at the Cardiovascular Research Unit, Odense University Hospital Svendborg, Denmark. In this study, 1500 participants with type 2 diabetes and cardiovascular disease will be randomly assigned in a 2:1 ratio to receive either the intervention: treatment in the CMC, or the control: standard of care. The Cardio-Metabolic Clinic applies a decision-making algorithm coded with the latest guidelines to evaluate lifestyle factors and manage medical treatment. Health examinations are conducted at baseline and after three years, and clinical events will be assessed through registry and journal audits after five and ten years. The primary outcome is the time to the first occurrence of a composite of cardiovascular deaths, non-fatal acute myocardial infarctions, non-fatal stroke, or hospitalization due to heart failure at a time frame of five years. DISCUSSION: The Cardio-Metabolic Clinic represents a pioneering approach to diabetes management that aims to improve patient outcomes by reducing the cardiovascular disease burden. This study could transform diabetes care and offer a multidisciplinary, cost-effective, and specialized treatment. We need to establish the efficacy and feasibility of a CMC to integrate comparable clinics into broader healthcare systems, and potentially enhance cardiovascular health in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT06203860.

Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. However, the routes of transmission of the virus to, and from, the mink have been unclear. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. Detailed analysis of changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants with the Y453F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early in the outbreak. However, further introductions of the virus, by variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of viral genome data, we estimate, using a conservative approach, that about 17 separate examples of mink to human transmission occurred in Denmark but up to 59 such events (90% credible interval: (39-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using Bayesian methods. Using the latter approach, 136 jumps (90% credible interval: (117-164)) from humans to mink were found, which may underlie the farm-to-farm spread. Thus, transmission of SARS-CoV-2 from humans to mink, mink to mink, from mink to humans and between humans were all observed.

Direct factor Xa inhibitors and the risk of cancer and cancer mortality: A Danish population-based cohort study.

BACKGROUND: Preclinical animal studies have suggested that myeloid cell-synthesized coagulation factor X dampens antitumor immunity and that rivaroxaban, a direct factor Xa inhibitor, can be used to promote tumor immunity. This study was aimed at assessing whether patients with atrial fibrillation taking direct factor Xa inhibitors have lower risk of cancer and cancer-related mortality than patients taking the direct thrombin inhibitor dabigatran. METHODS AND FINDINGS: This nationwide population-based cohort study in Denmark included adult patients with atrial fibrillation and without a history of cancer, who started taking a factor Xa inhibitor or dabigatran between 2011 and 2015. Data on medical history, outcomes, and drug use were acquired through Danish healthcare registries. The primary outcome was any cancer. Secondary outcomes were cancer-related mortality and all-cause mortality. Outcome events were assessed during 5 years of follow-up in an intention-to-treat analysis. The propensity score-based inverse probability of treatment weighting was used to compute cumulative incidence and subdistribution hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs), with death as a competing event. Propensity scores were estimated using logistic regression and including in the model sex, age group at index date, comorbidities, and use of comedications. A total of 11,742 patients with atrial fibrillation starting a factor Xa inhibitor and 11,970 patients starting dabigatran were included. Mean age was 75.2 years (standard deviation [SD] 11.2) in the factor Xa cohort and 71.7 years (SD 11.1) in the dabigatran cohort. On the basis of the propensity score-weighted models, after 5 years of follow-up, no substantial difference in the cumulative incidence of cancer was observed between the factor Xa inhibitor (2,157/23,711; 9.11%, 95% CI [8.61%,9.63%]) and dabigatran (2,294/23,715; 9.68%, 95% CI [9.14%,10.25%]) groups (SHR 0.94, 95% CI [0.89,1.00], P value 0.0357). We observed no difference in cancer-related mortality (factor Xa inhibitors cohort 1,028/23,711; 4.33%, 95% CI [4.02%,4.68%]. Dabigatran cohort 1,001/23,715; 4.22%, 95% CI [3.83%,4.66%]; SHR 1.03, 95% CI [0.94,1.12]), but all-cause mortality was higher in the factor Xa inhibitor cohort (factor Xa inhibitors cohort 7,416/23,711; 31.31%, 95% CI [30.37%,32.29%]. Dabigatran cohort 6,531/23,715; 27.56%, 95% CI [26.69%,28.45%]; HR 1.17, 95% CI [1.13,1.21]). The main limitations of the study were the possibility of residual confounding and the short follow-up period. CONCLUSIONS: In this population based cohort study, factor Xa inhibitor use was not associated with an overall lower incidence of cancer or cancer-related mortality when compared to dabigatran. We did observe an increase in all-cause mortality in the factor Xa inhibitor cohort.

Colorectal cancer and association with anaerobic bacteraemia: A Danish nationwide population-based cohort study.

OBJECTIVES: We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer. METHODS: A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference. RESULTS: Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference). CONCLUSION: This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Potential of the Danish Comorbidity Index for Acute Myocardial Infarction to discriminate mortality in patients with infective endocarditis.

INTRODUCTION: Current risk score models for predicting mortality in infective endocarditis (IE) include data often unavailable in registries, limiting their use for confounding adjustment in population-based research. METHODS: This study assessed the Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI) for its ability to predict 30-day, 1-year, and 5-year mortality in IE patients, compared to the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The study included all adult Danish patients with first-time IE from 1995 to 2021. The area under the receiver operating characteristic curve (AUC) was estimated using logistic regression to measure discriminatory performance for all-cause and cardiovascular mortality at the specified time intervals. A baseline model included age and sex, while extended models incorporated continuous comorbidity scores. RESULTS: We identified 8966 patients with IE. Mortality rates were 12% at 30 days, 26% at 1 year, and 36% at 5 years. For all-cause mortality, AUCs for the baseline versus DANCAMI models were 0.64 vs. 0.69 at 30 days, 0.66 vs. 0.73 at 1 year, and 0.72 vs. 0.79 at 5 years. For cardiovascular mortality, AUCs for baseline versus DANCAMI models were 0.67 vs. 0.69 at 30 days, 0.67 vs. 0.69 at 1 year, and 0.70 vs. 0.71 at 5 years. CCI and ECI demonstrated comparable AUCs to the DANCAMI model. CONCLUSION: DANCAMI improved discrimination of short- and long-term mortality in IE patients and may be used for confounder adjustment similarly to CCI and ECI.

Cardiovascular events according to blood pressure thresholds recommended by ACC/AHA.

AIM: The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome. METHODS: In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP <120 mmHg and DBP <80 mmHg, Elevated: SBP 120-129 mmHg and DBP <80 mmHg, Stage 1: SBP 130-139 mmHg or DBP 80-89 mmHg, Stage 2: SBP ≥140 mmHg or DBP ≥90 mmHg. Absolute 10-year risk was calculated taking repeated examinations, covariates, and competing risk into account. RESULTS: For all outcomes, the 10-year risk in stage 1 hypertension did not differ significantly from risk in subjects with normal BP: The 10-year risk of cardiovascular events in stage 1 hypertension was 14.1% [95% CI 13.2;15.0] and did not differ significantly from the risk in normal BP at 12.8% [95% CI 11.1;14.5] (p = 0.19). The risk was highest in stage 2 hypertension 19.4% [95% CI 18.9;20.0] and differed significantly from normal BP, elevated BP, and stage 1 hypertension (p < 0.001). The 10-year risk of cardiovascular death was 6.6% [95% CI 5.9;7.4] in stage 1 hypertension and did not differ significantly from the risk in normal BP at 5.7% [95% CI 4.1;7.3] (p = 0.33). CONCLUSIONS: Stage 1 hypertension as defined by the ACC/AHA guidelines has the same risk for future cardiovascular events as normal BP. In contrast, the definition of hypertension as suggested by ESC/ESH identifies patients with elevated risk of cardiovascular events.

Until 2017, there was worldwide agreement on defining hypertension at systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.In 2017, the American Cardiology Societies (ACC and AHA) lowered the threshold for defining hypertension at SBP 130-139 mmHg or DBP 80-89 mmHg.Lowering the threshold might make healthy persons sick if the thresholds do not identify persons at high risk.Unnecessary medical treatment is associated with high economic cost for the health care systems.We wanted to explore whether applying the American BP definition in a Scandinavian population identified persons with elevated risk for cardiovascular disease.As part of the Copenhagen City Heart study, 19,721 men and women aged 20-98 years were followed from 1976.They went through up to five examinations between 1976 and 2018 including BP measurements.We applied the American BP thresholds and followed the persons until death or 2018.In Denmark all citizens have a unique identification number which is linked to all health care contacts and administrative registers.We used advanced statistical methods and linked the BP measurements with the data for cardiovascular disease and death date from the Danish registries for each person.The results showed that the American definition of hypertension has same risk for future cardiovascular disease as the definition of normal BP.This means that healthy persons will be diagnosed with hypertension if the US guidelines were applied in Denmark.

Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study.

OBJECTIVES: To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during the first trimester of pregnancy. DESIGN: Prospective Nordic registry based study. SETTING: Sweden, Denmark, and Norway. PARTICIPANTS: 343 066 liveborn singleton infants in Sweden, Denmark, and Norway, with an estimated start of pregnancy between 1 March 2020 and 14 February 2022, identified using national health registries. MAIN OUTCOME MEASURE: Major congenital anomalies were categorised using EUROCAT (European Surveillance of Congenital Anomalies) definitions. The risk after covid-19 infection or vaccination during the first trimester was assessed by logistic regression, adjusting for maternal age, parity, education, income, country of origin, smoking, body mass index, chronic conditions, and estimated date of start of pregnancy. RESULTS: 17 704 (5.2%) infants had a major congenital anomaly. When evaluating risk associated with covid-19 infection during the first trimester, the adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 to 1.40) for eye anomalies to 1.12 (0.68 to 1.84) for oro-facial clefts. Similarly, the risk associated with covid-19 vaccination during the first trimester ranged from 0.84 (0.31 to 2.31) for nervous system anomalies to 1.69 (0.76 to 3.78) for abdominal wall defects. Estimates for 10 of 11 subgroups of anomalies were less than 1.04, indicating no notable increased risk. CONCLUSIONS: Covid-19 infection and vaccination during the first trimester of pregnancy were not associated with risk of congenital anomalies.

The "true" 1-year incidence of dislocation after primary total hip arthroplasty: validation of an algorithm identifying dislocations in the Danish National Patient Register based on 5,415 patients from the Danish Hip Arthroplasty Register.

BACKGROUND AND PURPOSE: Dislocations continue to be a serious complication after primary total hip arthroplasty (THA). Our primary aim was to report the "true" incidence of dislocations in Denmark and secondarily to validate a previously developed algorithm designed to identify THA dislocations in the updated version of the Danish National Patient Register (DNPR), based on data from the Danish Hip Arthroplasty Register (DHR). METHODS: We included 5,415 primary THAs from the DHR performed from July 1 to December 31, 2019. Version 3 of the DNPR was launched in February 2019, and a combination of data from the DNPR and a comprehensive national review of 1,762 hospital contacts enabled us to identify every dislocation occurring during the 1st year after THA to determine the "true" 1-year incidence of dislocation. The results were presented as proportions with 95% confidence intervals (CI), and validation was performed by calculating sensitivity and predictive values. RESULTS: The "true" 1-year incidence of dislocation was 2.8% (CI 2.4-3.3). Of these, 37% suffered recurrent dislocations during the follow-up period. Between-hospital variation ranged from 0.0% to 9.6%. The algorithm demonstrated a sensitivity close to 95%, while maintaining a positive predictive value of above 94%. CONCLUSION:  The "true" 1-year incidence of dislocation of 2.8% is comparable to earlier findings, and large variation among hospitals continues to be evident. We have proven the algorithm to be valid in the latest DNPR (version 3), enabling it to be employed as a new quality indicator in future annual DHR reports.

High revision rate of metal-backed glenoid component and impact on the overall revision rate of stemless total shoulder arthroplasty: a cohort study from the Danish Shoulder Arthroplasty Registry.

BACKGROUND AND PURPOSE: There is controversy regarding the results of stemmed and stemless total shoulder arthroplasty (TSA) used for osteoarthritis. Therefore, we aimed to compare revision rates of stemmed and stemless TSA and to examine the impact of metal-backed glenoid components. METHODS: We included all patients reported to the Danish Shoulder Arthroplasty Register from January 1, 2012 to December 31, 2022 with an anatomical TSA used for osteoarthritis. Primary outcome was revision (removal or exchange of components) for any reason. RESULTS: 3,338 arthroplasties were included. The hazard ratio for revision of stemless TSA adjusted for age and sex was 1.83 (95% confidence interval [CI] 1.21-2.78) with stemmed TSA as reference. When excluding all arthroplasties with a metal-backed glenoid component, the adjusted hazard ratio for revision of stemless TSA was 1.37 (CI 0.85-2.20). For the Eclipse stemless TSA system, the adjusted hazard ratio for revision of a metal-backed glenoid component was 8.75 (CI 2.40-31.9) with stemless Eclipse with an all-polyethylene glenoid component as reference. CONCLUSION:  We showed that the risk of revision of stemless TSAs was increased and that it was related to their combination with metal-backed glenoid components.

Discontinuing the recommendation of hip precautions does not increase the risk of early dislocation after primary total hip arthroplasty using 36-mm heads: a population-based study from the Danish Hip Arthroplasty Register.

BACKGROUND AND PURPOSE: Dislocation is a severe complication following total hip arthroplasty (THA). Hip precautions have been recommended in the initial postoperative period but evidence supporting this practice is limited. We therefore conducted a population-based study to evaluate the association between discontinuing recommending postoperative hip precautions and the risk of early dislocation. METHODS: This is a cohort study with data from the Danish Hip Arthroplasty Register and the Danish National Patient Register. We included patients who underwent primary THA for osteoarthritis in 2004-2019 in public hospitals in the Capital Region of Denmark. The cohort was divided into the hip precautions group, comprising patients operated on between 2004 and 2009, and the no-precautions group operated on between 2014 and 2019. The primary outcome was the difference in the absolute risk of dislocation within 3 months post-surgery. The secondary outcome assessed the same risk within 2 years. We evaluated the difference in absolute risk using absolute risk regression (ARR). RESULTS: The cumulative incidence of dislocation within 3 months was 2.9% (confidence interval [CI] 2.5-3.3) in the hip precautions group and 3.5% (CI 3.1-3.9) in the no-precautions group. The risk of dislocation was higher in the no-precautions group but failed to reach statistical significance in the crude (ARR 1.2, CI 0.9-1.6) and multivariate model (ARR 1.4, CI 0.9-2.2). CONCLUSION: We found a higher but statistically insignificant increase in the risk of early dislocation in the no-precautions group. The lack of significance in the association may be explained by the increased use of 36-mm femoral heads after the guideline revision.

Cardiovascular risk associated with changes in anticholinergic load on four different scales: a registry-based cohort study of geriatric outpatients.

BACKGROUND: Recent studies have shown that anticholinergic medications are associated with cardiovascular disease. Little is known about how discontinuation of anticholinergic medication affects this association. We investigated how baseline anticholinergic load and change in anticholinergic load associates with major adverse cardiovascular events (MACE) on four different scales. METHODS: We included all geriatric outpatients aged 65 and older in Denmark between January 2011 and December 2018. Data were sourced from Danish national registries. Anticholinergic drug exposure was assessed at first contact to the outpatient clinic (baseline) and changes were assessed at 180 days after outpatient contact. Anticholinergic scales were the CRIDECO Anticholinergic Load Scale, Anticholinergic Drugs Scale, Anticholinergic Cognitive Burden and a scale by the Danish Institute of Rational Pharmacotherapy. Multivariate analyses were conducted to investigate the 1- and 5-year risk of MACE by baseline anticholinergic load and changes in anticholinergic load after 180 days. RESULTS: We included a total of 64 378 patients in the analysis of baseline anticholinergic load and 54 010 patients remained after 180 days for inclusion in the analysis of change in anticholinergic load. At baseline the mean age was 81.7 year (SD 7.5) and 68% were women. Higher level of anticholinergic load on any scale associated with greater risk of MACE in a dose response pattern. There were no association between reduction in anticholinergic load and risk of MACE. CONCLUSION: While anticholinergic load at baseline was associated with MACE, reducing anticholinergic load did not lower the risk of MACE indicating the association may not be causal.