Danish Cohort Study Research Articles

Winter, spring, summer or fall: temporal patterns in placenta-mediated pregnancy complications—an exploratory analysis

PurposePlacenta-mediated pregnancy complications, like growth restriction and hypertensive disorders, are leading causes of maternal, fetal and neonatal morbidity and mortality in high-income countries. The purpose was to investigate if there is a seasonal variation in placenta-mediated pregnancy complications (small for gestational age, intrauterine growth restriction, preeclampsia, preterm birth and intrauterine fetal death).MethodsThis is a Danish cohort study including all singleton deliveries at gestational week 22 up to and including week 41 conceived from December 2006 to November 2016 (N = 555,459). We used statistical process control charts to visualize data and to test for patterns of non-random variation in data over time for pregnancies with risk factors (BMI, diabetes, in vitro fertilization, maternal age > 40 years, primipara, previous caesarean and smoking) and each of the following outcome: fetal growth restriction, hypertensive disorders, preterm birth and intrauterine fetal death. The study was approved by the Danish Data Protection agency; REG-039-2019.ResultsWe found a seasonal pattern in hypertensive disorders during pregnancy with dips in pregnancies conceived in the fall season and highest risk by conception in the spring and summer season. We found no apparent seasonality in cases of preterm delivery, small for gestational age and intrauterine mortality. Individual risk factors (e.g. smoking and obesity) for placenta-mediated complicated over time were in consistency with the general trends.ConclusionsWe found a significant seasonal variation in the risk of hypertensive disorders of pregnancy with highest risk by conception in the spring and summer season. This study found no seasonal variation in other placenta-mediated complications.

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 μm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 μg·m-3) and NO2 (per 3.59 μg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

The magnitude and severity of paediatric RSV infections in 2022-2023: A Danish nationwide cohort study.

Acta PaediatricaAccepted Articles BRIEF REPORT The magnitude and severity of pediatric RSV infections in 2022-23. A Danish nationwide cohort study Ulrikka Nygaard, Corresponding Author Ulrikka Nygaard [email protected] orcid.org/0000-0002-2093-5909 Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Correspondence Ulrikka Nygaard, consultant, ass. professor, MD, MPhil, PhD; Department of Paediatrics and Adolescent Medicine; Copenhagen University Hospital, Rigshospitalet; Blegdamsvej 9, DK-2100 Copenhagen Ø; Denmark; Email: [email protected]Search for more papers by this authorJens Nielsen, Jens Nielsen Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, DenmarkSearch for more papers by this authorJeppe Sylvest Angaard Nielsen, Jeppe Sylvest Angaard Nielsen Department of Paediatric and Neonatal Intensive Care, Copenhagen University HospitalSearch for more papers by this authorAstrid Thaarup Matthesen, Astrid Thaarup Matthesen Department of Paediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, DenmarkSearch for more papers by this authorKia Hee Schultz Dungu, Kia Hee Schultz Dungu Department of Paediatrics and Adolescent Medicine, Copenhagen University HospitalSearch for more papers by this authorUlla Birgitte Hartling, Ulla Birgitte Hartling Department of Paediatrics and Adolescent Medicine, Hans Christian Andersen Children's Hospital, Odense, DenmarkSearch for more papers by this authorMette Holm, Mette Holm Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, DenmarkSearch for more papers by this author Ulrikka Nygaard, Corresponding Author Ulrikka Nygaard [email protected] orcid.org/0000-0002-2093-5909 Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Correspondence Ulrikka Nygaard, consultant, ass. professor, MD, MPhil, PhD; Department of Paediatrics and Adolescent Medicine; Copenhagen University Hospital, Rigshospitalet; Blegdamsvej 9, DK-2100 Copenhagen Ø; Denmark; Email: [email protected]Search for more papers by this authorJens Nielsen, Jens Nielsen Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, DenmarkSearch for more papers by this authorJeppe Sylvest Angaard Nielsen, Jeppe Sylvest Angaard Nielsen Department of Paediatric and Neonatal Intensive Care, Copenhagen University HospitalSearch for more papers by this authorAstrid Thaarup Matthesen, Astrid Thaarup Matthesen Department of Paediatrics and Adolescent Medicine, Aalborg University Hospital, Aalborg, DenmarkSearch for more papers by this authorKia Hee Schultz Dungu, Kia Hee Schultz Dungu Department of Paediatrics and Adolescent Medicine, Copenhagen University HospitalSearch for more papers by this authorUlla Birgitte Hartling, Ulla Birgitte Hartling Department of Paediatrics and Adolescent Medicine, Hans Christian Andersen Children's Hospital, Odense, DenmarkSearch for more papers by this authorMette Holm, Mette Holm Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, DenmarkSearch for more papers by this author First published: 17 June 2023 https://doi.org/10.1111/apa.16877 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/apa.16877. AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Accepted ArticlesAccepted, unedited articles published online and citable. The final edited and typeset version of record will appear in the future. RelatedInformation

Bleeding risk in female patients undergoing intravesical injection of onabotulinumtoxinA for overactive bladder: a Danish retrospective cohort study

Introduction and hypothesisWe aimed to examine the risk of bleeding in female patients undergoing intravesical onabotulinumtoxinA (BTX-A) treatments and provide clinical recommendations for the perioperative management of patients on antithrombotic therapy prior to BTX-A treatments.MethodsThis was a retrospective cohort of Danish female patients, who had their first BTX-A treatment because of an overactive bladder at the Department of Gynecology and Obstetrics, Herlev and Gentofte University Hospital, between January 2015 and December 2020. Data extraction was from an electronic medical journal system. BTX-A, Botox® Allergan was injected in the detrusor at 10–20 sites. Significant bleeding during or after a BTX-A treatment was defined as persistent macroscopic hematuria. Bleeding reporting was based on information obtained from journal notes.ResultsWe included 400 female patients, who had a total of 1,059 BTX-A treatments. Median age at first BTX-A treatment was 70 years (IQR 21), and median number of BTX-A treatments was 2 (range 1–11). In total, 27.8% (n=111) received antithrombotic therapy. Within this group, 30.6% and 69.4% were on anticoagulant and antiplatelet therapy. No cases of hematuria were reported in our cohort. We found that no patients stopped their antithrombotic therapy, were bridged, or monitored by International Normalized Ration (INR) levels.ConclusionsWe suggest that BTX-A treatments might be classified as low-risk procedures. Discontinuation of antithrombotic therapy is not required in the perioperative management of this patient group.

Comorbidity and risk of infection among patients with hip fracture: a Danish population-based cohort study

SummaryImpact of comorbidity on infection risk among hip fracture patients is unclear. We found high incidence of infection. Comorbidity was an important risk factor for infection up to 1 year after surgery. Results indicates a need for additional investment in pre- and postoperative programs that assist patients with high comorbidity.PurposeComorbidity level and incidence of infection have increased among older patients with hip fracture. The impact of comorbidity on infection risk is unclear. We conducted a cohort study examining the absolute and relative risks of infection in relation to comorbidity level among hip fracture patients.MethodsUtilizing Danish population-based medical registries, we identified 92,600 patients aged ≥ 65 years undergoing hip fracture surgery between 2004 and 2018. Comorbidity was categorized by Charlson comorbidity index scores (CCI): none (CCI = 0), moderate (CCI = 1–2), or severe (CCI ≥ 3). Primary outcome was any hospital-treated infection. Secondary outcomes were hospital-treated pneumonia, urinary tract infection, sepsis, reoperation due to surgical-site infection (SSI), and a composite of any hospital- or community-treated infection. We calculated cumulative incidence and hazard ratios (aHRs) adjusted for age, sex, and surgery year, including 95% confidence intervals (CIs).ResultsPrevalence of moderate and severe comorbidity was 40% and 19%, respectively. Incidence of any hospital-treated infection increased with comorbidity level within 0–30 days (none 13% vs. severe 20%) and 0–365 days (none 22% vs. 37% severe). Patients with moderate and severe comorbidity, compared to no comorbidity, had aHRs of 1.3 (CI: 1.3–1.4) and 1.6 (CI: 1.5–1.7) within 0–30 days, and 1.4 (CI: 1.4–1.5) and 1.9 (CI: 1.9–2.0) within 0–365, respectively. Highest incidence was observed for any hospital- or community-treated infection (severe 72%) within 0–365 days. Highest aHR was observed for sepsis within 0–365 days (severe vs. none: 2.7 (CI: 2.4–2.9)).ConclusionComorbidity is an important risk factor for infection up to 1 year after hip fracture surgery.

Cardiovascular mortality in patients with advanced chronic kidney disease with and without diabetes: a nationwide cohort study

BackgroundCardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels.MethodsIn a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m2 between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort.ResultsWe included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6–10.0) and 7.4% (95% CI 7.3–7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1–3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes.ConclusionsDiabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.

#3938 THE ASSOCIATION BETWEEN HEMOGLOBIN A1C LEVEL AND COMPLICATIONS IN PATIENTS WITH DIABETES AND ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Although the global prevalence of advanced diabetic kidney disease is increasing, the optimum glycemic target remains uncertain. Specifically, data pertaining to the association of hemoglobin A1c (HbA1c) level with micro- and macrovascular outcomes in patients with advanced diabetic kidney disease remain inconclusive. We examined the association between HbA1c levels and complications in patients with diabetes and chronic kidney disease (CKD) stage 4 and 5. Method In a Danish nationwide registry-based retrospective cohort study, we included persons ≥18 years of age with diabetes, an estimated glomerular filtration rate (eGFR) &amp;lt;30 mL/min/1.73m2 and a concurrent measured HbA1c between 2010 and 2022. Complications were categorized as 1) major adverse cardiovascular events (MACE) defined as a composite endpoint of acute myocardial infarction, stroke, and all-cause mortality; 2) microvascular complications defined as a composite endpoint of diabetic retinopathy, major lower extremity amputation, and start of dialysis; 3) hospitalization with hypoglycemia. Multiple outcome-specific Cox regressions stratified by HbA1c levels were performed to calculate the 1-year risk of complications standardized to the distribution of risk factors of all patients in the sample. The analyses regarding the risk of hypoglycemia were further stratified according to insulin treatment at baseline. Results In total, 34,046 patients were included. The median age was 76.2 (IQR 69.1-82.7) years and 54.6% were men. The median eGFR and HbA1c level was 26.4 (IQR 21.9-28.5) mL/min/1.73m2 and 53 (IQR 46-63) mmol/mol, respectively. Figure 1 depicts the 1-year risks of MACE and microvascular complications stratified by HbA1c level. We found a U-shaped association between HbA1c level and MACE where patients with an HbA1c level between 45-50 mmol/mol had the lowest risk. The risk increased significantly with an HbA1c level below 45 mmol/mol or above 65 mmol/mol compared with 45-50 mmol/mol (P&amp;lt;0.001). The risk of microvascular complications was lowest at an HbA1c level between 35-40 mmol/mol. The risk increased significantly with increasing levels of HbA1c above 50 mmol/mol compared with 35-40 mmol/mol (P&amp;lt;0.05). The 1-year risks of hospitalization with hypoglycemia stratified according to HbA1c level and insulin treatment are illustrated in Figure 2. For both groups, the risk was lowest at an HbA1c level between 30-40 mmol/mol and increased with increasing HbA1c levels. Conclusion In patients with diabetes and CKD stage 4 and 5, HbA1c levels &amp;gt;65 mmol/mol and &amp;lt;45 mmol/mol were associated with an increased risk of MACE, whereas HbA1c levels &amp;gt;50 mmol/mol were associated with a higher risk of microvascular complications. Our findings suggest that appropriate glycemic control can reduce adverse outcomes in patients with advanced CKD without increasing the risk of hypoglycemia, but also suggest that intensive glycemic control (HbA1c &amp;lt;45 mmol/mol) might be associated with an increased risk of MACE.

Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort study.

Migraine carries risk of myocardial infarction (MI) and stroke. The risk of premature MI (i.e., among young adults) and stroke differs between men and women; previous studies indicate that migraine is mainly associated with an increased risk of stroke among young women. The aim of this study was to examine impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women. Using Danish medical registries, we conducted a nationwide population-based cohort study (1996 to 2018). Redeemed prescriptions for migraine-specific medication were used to identify women with migraine (n = 179,680) and men with migraine (n = 40,757). These individuals were matched on sex, index year, and birth year 1:5 with a random sample of the general population who did not use migraine-specific medication. All individuals were required to be between 18 and 60 years old. Median age was 41.5 years for women and 40.3 years for men. The main outcome measures to assess impact of migraine were absolute risk differences (RDs) and hazard ratios (HRs) with 95% confidence intervals (CIs) of premature MI, ischemic, and hemorrhagic stroke, comparing individuals with migraine to migraine-free individuals of the same sex. HRs were adjusted for age, index year, and comorbidities. The RD of premature MI for those with migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.3% (95% CI [-0.1%, 0.6%]; p = 0.061) for men. The adjusted HR was 1.22 (95% CI [1.14, 1.31]; p < 0.001) for women and 1.07 (95% CI [0.97, 1.17]; p = 0.164) for men. The RD of premature ischemic stroke for migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.5% (95% CI [0.1%, 0.8%]; p < 0.001) for men. The adjusted HR was 1.21 (95% CI [1.13, 1.30]; p < 0.001) for women and 1.23 (95% CI [1.10, 1.38]; p < 0.001) for men. The RD of premature hemorrhagic stroke for migraine versus no migraine was 0.1% (95% CI [0.0%, 0.2%]; p = 0.011) for women and -0.1% (95% CI [-0.3%, 0.0%]; p = 0.176) for men. The adjusted HR was 1.13 (95% CI [1.02, 1.24]; p = 0.014) for women and 0.85 (95% CI [0.69, 1.05]; p = 0.131) for men. The main limitation of this study was the risk of misclassification of migraine, which could lead to underestimation of the impact of migraine on each outcome. In this study, we observed that migraine was associated with similarly increased risk of premature ischemic stroke among men and women. For premature MI and hemorrhagic stroke, there may be an increased risk associated with migraine only among women.

Sudden Sensorineural Hearing Loss Following Immunization With BNT162b2 or mRNA-1273: A Danish Population-Based Cohort Study.

To compare the occurrence of sudden sensorineural hearing loss following immunization with BNT162b2 (Comirnaty®; Pfizer BioNTech) or mRNA-1273 (Spikevax®; Moderna) to the occurrence among unvaccinated individuals. Cohort study. Nationwide Danish health care registers comprised all Danish residents living in Denmark on October 1, 2020, who were 18 years or older or turned 18 in 2021. We compared the occurrence of sudden sensorineural hearing loss following immunization with BNT162b2 (Comirnaty®; Pfizer BioNTech) or mRNA-1273 (Spikevax®; Moderna) (first, second, or third dose) against unvaccinated person time. Secondary outcomes were a first-ever hospital diagnosis of vestibular neuritis and a hearing examination, by an ear-nose-throat (ENT) specialist, followed by a prescription of moderate to high-dose prednisolone. BNT162b2 or mRNA-1273 vaccine was not associated with an increased risk of receiving a discharge diagnosis of sudden sensorineural hearing loss (adjusted hazard ratio [HR]: 0.99, confidence interval [CI]: 0.59-1.64) or vestibular neuritis (adjusted HR: 0.94, CI: 0.69-1.24). We found a slightly increased risk (adjusted HR: 1.40,CI, 1.08-1.81) of initiating moderate to high-dose oral prednisolone following a visit to an ENT specialist within 21 days from receiving a messenger RNA (mRNA)-based Covid-19 vaccine. Our findings do not suggest an increased risk of sudden sensorineural hearing loss or vestibular neuritis following mRNA-based COVID-19 vaccination. mRNA-Covid-19 vaccination may be associated with a small excess risk of a visit to an ENT specialist visit followed by a prescription of moderate to high doses of prednisolone.

Long-term risk of atrial fibrillation or flutter after transcatheter patent foramen ovale closure: a nationwide Danish study.

Transcatheter closure of patent foramen ovale (PFO) is the recommended stroke prevention treatment in patients ≤60 years with cryptogenic ischemic stroke and PFO. Atrial fibrillation or flutter (AF) is a known potential procedure-related complication, but long-term risk of developing AF remains unknown. This paper studied the long-term risk of developing AF following PFO closure. A Danish nationwide cohort study was conducted. During 2008-2020, this study identified a PFO closure cohort, a PFO diagnosis cohort without PFO closure, and a general population comparison cohort matched 10:1 to the PFO closure cohort on age and sex. The outcome was first-time AF diagnosis. Risk of AF and multivariable-adjusted hazard ratio (HR) of the association between PFO closure or PFO diagnosis and AF were calculated. A total of 817 patients with PFO closure, 1224 with PFO diagnosis, and 8170 matched individuals were identified. The 5 year risk of AF was 7.8% [95% confidence interval (CI): 5.5-10] in the PFO closure cohort, 3.1% (95% CI: 2.0-4.2) in the PFO diagnosis cohort, and 1.2% (95% CI: 0.8-1.6) in the matched cohort. The HR of AF comparing PFO closure with PFO diagnosis was 2.3 (95% CI: 1.3-4.0) within the first 3 months and 0.7 (95% CI: 0.3-1.7) thereafter. The HR of AF comparing PFO closure with the matched cohort was 51 (95% CI: 21-125) within the first 3 months and 2.5 (95% CI: 1.2-5.0) thereafter. Patent foramen ovale closure was not associated with any substantial increased long-term risk of developing AF beyond the well-known procedure-related short-term risk.

Cost-effectiveness of an antibacterial envelope for infection prevention in patients undergoing cardiac resynchronization therapy reoperations in Denmark.

Use of an absorbable antibacterial envelope during implantation prevents cardiac implantable electronic device infections in patients with a moderate-to-high infection risk. Previous studies demonstrated that an envelope is cost-effective in high-risk patients within German, Italian, and English healthcare systems, but these analyses were based on limited data and may not be generalizable to other healthcare settings. A previously published decision-tree-based cost-effectiveness model was used to compare the costs per quality-adjusted life year (QALY) associated with adjunctive use of an antibacterial envelope for infection prevention compared to standard-of-care intravenous antibiotics. The model was adapted using data from a Danish observational two-centre cohort study that investigated infection-risk patients undergoing cardiac resynchronization therapy (CRT) reoperations with and without an antibacterial envelope (n = 1943). We assumed a cost-effectiveness threshold of €34 125/QALY gained, based on the upper threshold used by the National Institute for Health and Care Excellence (£30 000). An antibacterial envelope was associated with an incremental cost-effectiveness ratio (ICER) of €12 022 per QALY in patients undergoing CRT reoperations, thus indicating that the envelope is cost-effective when compared with standard of care. A separate analysis stratified by device type showed ICERS of €6227 (CRT defibrillator) and €29 177 (CRT pacemaker) per QALY gained. Cost-effectiveness ratios were favourable for patients undergoing CRT reoperations in the Danish healthcare system, and thus are in line with previous studies. Results from this study can contribute to making the technology available to Danish patients and align preventive efforts in the pacemaker and ICD area.

GS-004-YI - Vulnerable offspring: a nationwide Danish cohort study of adverse health outcomes in offspring of parents with alcohol-related liver disease compared to controls

GS-004-YI - Vulnerable offspring: a nationwide Danish cohort study of adverse health outcomes in offspring of parents with alcohol-related liver disease compared to controls

Discrepancies in type of first major osteoporotic fracture and anti-osteoporotic therapy in elderly people with type 2 diabetes mellitus: A retrospective Danish cohort study.

Subjects with diabetes mellitus have an increased risk of fractures. We aimed to identify discrepancies in the first type of major osteoporotic fracture (MOF) and anti-osteoporotic therapy between subjects with type 2 diabetes (T2D) and subjects without diabetes. Methods and research design. We conducted a retrospective national cohort study by access to all discharge diagnoses (ICD-10 system) and redeemed drug prescriptions (ATC classification system). We included all subjects alive and Danish citizens in 2010 and identified subjects with T2D diagnosed after the age of 50 between 1998 and 2018. Only subjects with a MOF after the index date were included in the main analysis. The type of MOF was identified by diagnosis codes and categorized into Humerus, Forearm, Spine, and Hip. Multinomial logistic regression modeling was used to assess the predicted probability changes in MOF type between T2D and control subjects. Data on first anti-osteoporotic therapy after the MOF was assessed by redeemed drug prescriptions. Mortality and time to therapy after the MOF were evaluated by cox proportional hazards. We included 26,588 subjects with T2D and 97,982 subjects without diabetes. The mean age was age 69.33 (±10.34) for T2D and 69.85 (±10.19) for control subjects. The cohort was primarily females (67%). Subjects with T2D had a higher probability of hip (3.98% [95% CI 3.29; 4.67]) and humerus (2.82% [95% CI 2.17; 3.46]) fractures as the first MOF compared to control subjects. However, the probability of forearm fractures as the first MOF was 6.77% (95% CI 6.08; 7.46) lower among subjects with T2D. The multiple adjusted hazard ratio for anti-osteoporotic treatment after the first MOF was 0.80 (95% CI 0.77; 0.88) for T2D compared to controls among treatment-naïve subjects. Forearm fractures were the most frequent type of MOF and were more prevalent in control subjects. Subjects with T2D had a significantly higher probability of hip and humerus fractures as the first MOF but had a 20% lower chance of anti-osteoporotic treatment afterwards.

FRI-435 - Cause-specific mortality in patients with alcohol-related liver disease: a nationwide Danish cohort study

FRI-435 - Cause-specific mortality in patients with alcohol-related liver disease: a nationwide Danish cohort study

Trends in low-density lipoprotein cholesterol goal achievement and changes in lipid-lowering therapy after incident atherosclerotic cardiovascular disease: Danish cohort study.

We aimed to investigate trends in low-density lipoprotein cholesterol (LDL-C) goal achievement (LDL-C<1.8 mmol/L, equivalent to 70 mg/dL), initiation of lipid-lowering therapy (LLT) and changes in LLT intensity in individuals with atherosclerotic cardiovascular disease (ASCVD) at very high risk of recurrent cardiovascular disease. A cohort study design was used including individuals with incident ASCVD and LDL-C≥1.8 mmol/L in 2010-2015. Data were obtained from national, population-based registers (patient, prescription, income, and laboratory). We included 11,997 individuals. Acute myocardial infarction, ischemic stroke and stable angina pectoris accounted for 79.6% of the qualifying ASCVD events. At inclusion, 37.2% were in LLT. Mean LDL-C before or during ASCVD hospitalization was 3.1 mmol/L (120 mg/dL). LDL-C goal achievement increased within the first two years after inclusion from 40.5% to 50.6%. LLT initiation within the first 90 days increased from 48.6% to 56.0%. Initiation of intensive LLT increased from 9.6% to 32.8%. The largest change in LLT intensity was seen in the period 180 days before to 90 days after discharge with 2.2% in 2010 to 12.1% in 2015. LDL-C goal achievement within the first 2 years after inclusion increased from 40.5% in 2010 to 50.6% in 2015. LLT initiation within the first year after inclusion increased, especially for intensive LLT, although only one third initiated intensive LLT in 2015. Despite trends show improvements in LDL-C goal achievement, 49.4% of individuals at very high risk of a CV event did not achieve the LDL-C goal within 2 years after ASCVD hospitalization.

Symptom-Specific Hospital Contacts in 12-18-Year-Olds Vaccinated against COVID-19: A Danish Register-Based Cohort Study.

In this register-based real-life cohort study, changes in symptom-specific hospital contacts among 12-18-year-olds following two doses of the BNT162b2 COVID-19 vaccine compared to unvaccinated peers were investigated. Using national register data, vaccinated and unvaccinated adolescents were sex and age-matched each week during the inclusion period from May to September 2021. Symptom-specific hospital contacts covering ICD-10 R diagnoses were assessed before first the vaccine dose and after the second vaccine dose. Taking previous rates of symptom-specific hospital contacts into account, differences between vaccinated and unvaccinated adolescents were found. For some hospital contacts, higher rates were seen among the vaccinated, and for others, higher rates were seen among the unvaccinated. Unspecific cognition symptoms may be important to monitor in vaccinated girls, and likewise for throat and chest pain in vaccinated boys within the first months post-vaccination. In perspective, symptom-specific hospital contacts after vaccination against COVID-19 must be assessed by taking the risk of infection and symptoms following COVID-19 infection into account.

Persistence and adherence with Latanoprost: A Danish register-based cohort study in older patients with glaucoma.

This study aims to assess the association between switching patterns and adherence/persistence in Danish patients over the age of 65, who started their first-ever glaucoma treatment with latanoprost eye drops. Patients were assigned to three different cohorts: (1) switchers, (2) non-switchers, and (3) preservative-free latanoprost (Monoprost®) users. Patients were followed for 1 year until the end of data coverage or censoring. Study covariates were used to compute the propensity score. In the adjusted analysis, the propensity score was added to the model as an independent variable. The Cox regression model was used to calculate the hazard ratio (HR) of discontinuation for the three cohorts (the non-switchers cohort was the reference level) in both adjusted and unadjusted analyses. Non-switchers had a statistically significant lower adherence (proportion of days covered, PDC 92%) than switchers (PDC 96%; p < 0.001) and users of Monoprost® (PDC 99%; p < 0.001). Switchers had a 53% lower risk of treatment discontinuation compared to the reference group within 1 year after the first redemption of latanoprost in both unadjusted (HR 0.47; 95% Confidence interval, 95% CI: 0.41-0.53; p < 0.001) and adjusted (HR 0.47; 95% CI: 0.42-0.53; p < 0.001) analyses. In comparison to the non-switchers, Monoprost® users had a 78% lower risk for the above result in both unadjusted (HR 0.22; 95% CI: 0.17-0.28; p < 0.001) and adjusted (HR 0.22; 95% CI: 0.17-0.29; p < 0.001) analyses. This study found increased adherence and persistence in latanoprost users among those who redeemed preservative-free latanoprost (Monoprost®) and among those who switched between different latanoprost formulations.

Triple trouble: uncovering the risks and benefits of early fetal reduction in trichorionic triplets in a large national Danish cohort study

Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent. This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies. All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first-trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses. The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton pregnancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm deliveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%). Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

Mortality in patients with incident rheumatoid arthritis and depression: a Danish cohort study of 11 071 patients and 55 355 comparators.

In patients with RA, the association between mortality and depression has been investigated only in patients with prevalent RA. In this study, we estimated the mortality risk associated with depression, defined as the first filling of a prescription for antidepressants, in patients with incident RA and background population comparators. From 2008 to 2018, we identified patients with incident RA in the nationwide Danish rheumatologic database, DANBIO. For each patient, we randomly selected five comparators. Participants were not treated with antidepressants or diagnosed with depression 3 years prior to the index date. From other registers we collected data on socioeconomic status, mortality and cause of death using unique personal identifiers. Using Cox models, we calculated hazard rate ratios (HRR) with 95% CI. In depressed patients with RA vs patients without depression, adjusted HRR for all-cause mortality was 5.34 (95% CI 3.02, 9.45) during 0-2 years and 3.15 (95% CI 2.62, 3.79) during the total follow-up period, and highest in patients <55 years with HRR 8.13 (95% CI 3.89, 17.02). In comparators with depression vs comparators without depression, the association with mortality was similar to that in patients with RA. There were no unnatural causes of death among depressed patients with RA. The most frequent natural causes of death were cancer, cardiovascular disease, stroke and pneumonia. In patients with RA, depression was a predictor of death but with a strength similar to that in matched comparators.

25-year trends in first-time hospitalizations for Parkinson's disease and subsequent mortality: A Danish nationwide cohort study

BackgroundIn most countries, incidence and mortality for Parkinson's disease (PD) have not been monitored by surveillance registries, although it could demonstrate the need for primary and tertiary prevention. ObjectiveTo examine 25-year trends in first-time hospitalizations for PD in Denmark and subsequent short and long-term mortality. MethodsIn a nationwide population-based cohort we identified all 34,947 individuals with a first-time hospitalization for PD from 1995 through 2019. We calculated standardized incidence rates of PD and 1-year and 5-year mortality by sex. Mortality rates were compared with a reference cohort randomly selected from the background population matched on sex, age, and index date. ResultsThe annual standardized incidence rate of PD was relatively stable during the study period in both men and women. The incidence of PD was higher in men than in women and with the highest incidence in those aged 70–79 years. One and 5-year mortality risk after first-time hospitalization for PD was similar for men and women, and decreased by around 30% and 20%, respectively, between 1995 and 2019. The matched reference cohort had a similar decline in mortality over time. ConclusionThe rate of first-time hospitalization for PD was relatively stable between 1995 and 2019, whereas subsequent short and long-term mortality declined during the period as in the reference cohort.