Danish National Research Articles

Trigeminal neuralgia and its comorbidities: a nationwide disease trajectory study.

There is a limited understanding of risk factors and comorbidities in trigeminal neuralgia, a disease characterized by paroxysms of severe unilateral facial pain and a higher incidence in women. We aim to identify temporally associated comorbidities involving trigeminal neuralgia by analyzing nationwide disease trajectories. Using data from 7.2 million unique individuals in the Danish National Patient Register between 1994 and 2018, each individual diagnosed with trigeminal neuralgia was compared with 10,000 matched controls to identify co-occurring diseases. The sequential disease associations were identified in sex-stratified disease trajectories. A Cox-regression analysis investigated whether treatment with carbamazepine or oxcarbazepine, as compared with gabapentin, pregabalin, or lamotrigine, was associated with stroke risk. Finally, we investigated the stroke polygenic risk score and its association with stroke incidence in a subset of genotyped individuals with trigeminal neuralgia. We included 7141 individuals with trigeminal neuralgia (64.2% female, mean age at diagnosis 58.7 years) and identified 18 diseases associated with subsequent trigeminal neuralgia. After diagnosis, trigeminal neuralgia was associated with 9 diseases, including ischemic stroke (relative risk 1.55). Carbamazepine or oxcarbazepine treatment increased the ischemic stroke risk (hazard ratio 1.78; 95% confidence interval 1.47-2.17); however, the polygenic risk of stroke showed no association. In the Danish population, a trigeminal neuralgia diagnosis is temporally associated with 27 diseases revealed in systematic disease trajectories. Trigeminal neuralgia itself and its first-line treatment, but not a stroke polygenic risk score, was associated with an increased risk of ischemic stroke indicating that vascular risk factors should be routinely assessed in individuals with trigeminal neuralgia.

Validity of a Hypertrophic Cardiomyopathy Diagnosis in Adult Patients in the Danish National Patient Register.

To assess the positive predictive value (PPV) of the diagnostic codes for hypertrophic cardiomyopathy (HCM) in the Danish National Patient Register (DNPR) and identify factors affecting the PPV. We randomly sampled 200 patients registered in DNPR with the diagnostic codes DI421 (obstructive) or DI422 (non-obstructive) HCM, from Eastern Denmark, between December 1st, 2017, and September 16th, 2021. We assessed patients' medical records and classified whether the diagnosis of HCM was correct, incorrect, or uncertain according to the European Society of Cardiology (ESC) guidelines. Overall PPVs were estimated for all hospitals irrespective of specialty and for dedicated centers for inherited cardiac diseases. Of the 200 patients, seven were excluded; six were younger than 18 years when initially diagnosed and one adult patient had requested that their medical records be unavailable for research purposes. Of the 193 patients (median age 61 years, Interquartile range (IQR) 50-70, 40% female) with medical records available for assessment, 148 (77%) patients were registered correctly, 41 (21%) were incorrectly registered and for four (2%) patients there was insufficient data to determine if the diagnosis was correct. The overall PPV was 0.77 (95% confidence interval (CI) 0.70-0.82). The PPV for patients diagnosed in dedicated centers for inherited cardiac diseases was 0.91 (95% CI 0.84-0.95). For patients diagnosed in a dedicated center for inherited cardiac diseases with more than one clinical visit, the PPV increased to 0.99 (95% CI 0.93-1), however with the risk of a reduced sensitivity as these patients constituted only 52% of the correctly registered patients. The overall PPV of the HCM diagnostic codes in the DNPR was 0.77 (95% CI 0.70-0.82). The validity of the diagnosis was higher at dedicated centers for inherited cardiac diseases. These findings may prove useful for future register-based research.

Semaglutide treatment for PRevention Of Toxicity in high-dosE Chemotherapy with autologous haematopoietic stem-cell Transplantation (PROTECT): study protocol for a randomised, double-blind, placebo-controlled, investigator-initiated study

IntroductionCancer treatment with high-dose chemotherapy damages the mucosal barrier of the gastrointestinal (GI) tract and is associated with severe toxicity involving mucositis, severe inflammation and organ dysfunction. Currently, there is...

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline.

It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife. The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression. In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance. Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study

ObjectiveTo assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent...

Incidence of Graves' Disease with Validation and Completeness of the Diagnosis for Registry Extracts in the Danish National Patient Register.

Graves' disease (GD) is one of the most common causes of thyrotoxicosis. It has been proposed to identify incident GD by using the GD-specific code, E05.0, of the 10th revision of the International Classification of Disease (ICD-10) in the Danish National Patient Register (DNPR). We aimed to report the incidence of GD and to investigate the validity and completeness of E05.0 registration using Aalborg University Hospital (AaUH) as a single centre-sample. The study included registry data from 2020 to 2022. The study population (n=2,893) comprised all people (15-99 years) in the catchment area of AaUH (n=244,872) with either positive anti-thyroid stimulating hormone receptor antibodies (TRAb), or registered with a thyroid disease related ICD-10 code E03.0-E07.9, O99.2 or O90.5 at the Department of Endocrinology, AaUH. To identify incident cases, all subjects occurring for the first time in 2020 were excluded (n=2,339). The incident subjects were categorized into a general practice (n=63) or hospital care group (n=491) and underwent GD verification by biochemical tests and thyroid imaging. Validity was evaluated by positive (PPV) and negative (NPV) predictive values and completeness of E05.0 registration was estimated to the total number of verified GD subjects in hospital care only and in overall (groups combined). One hundred thirty-one incident GD subjects were identified corresponding to an incidence of 26.8 per 100,000/year. E05.0had a PPV of 90% [95% CI: 81;96] and a NPV of 90% [95% CI: 85;93] to identify incident cases of GD. Completeness was estimated to be 73% [95% CI: 63;82] in hospital care and 50-60% [95% CI: 41;68] in overall. We report on a similar incidence of GD as previous studies in Denmark. Despite a high PPV, incident cases of GD could not adequately be identified by E05.0 in DNPR due to low completeness. Researchers should rely on biochemical test results to identify incident GD.

The incidence of atypical fibroxanthoma and pleomorphic dermal sarcoma in Denmark from 2002 to 2022

BackgroundThe purpose of this study was to assess trends in the incidence rates and overall survival of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) in the Danish population from 2002 to 2022. MethodsWe included all patients diagnosed with AFX or PDS in the Danish National Pathology Register (DNPR) during the study period. We computed the age-adjusted incidence rate (AAIR) per 100,000 and the average annual percent change (AAPC) and developed an age-period-cohort (APC) model of incidence. ResultsWe included a total of 1118 patients, 78.3 % of whom were men. The median age upon diagnosis for AFX and PDS was 77.6 and 78.4 years, respectively. 84.5 % of the 1118 patients received an AFX diagnosis, while 15.5 % received a PDS diagnosis. The AAIR rose from 0.2 per 100,000 individuals in 2002 to 0.5 per 100,000 by 2022, with a peak increase of 0.75 per 100,000 in 2014. The AAPC for both tumors was 5.3 (95 % CI 2.9 %–7.7 %). We found a significant difference in overall survival between AFX and PDS, with PDS having worse overall survival than AFX. ConclusionThis study, which included the largest non-selected national population to date, found a significant increase in the incidence of AFX and PDS between 2002 and 2015, followed by a decrease.

Actionable alterations in glioblastoma: Insights from the implementation of genomic profiling as the standard of care from 2016 to 2023

Abstract Background In 2016, genomic profiling was implemented for patients with grade 4 primary brain tumors at Rigshospitalet, Denmark. The aim of this study was to discover actionable alterations and to match these with targeted therapies. Methods Between January 2016 and December 2023, 483 brain tumor patients were profiled. We retrieved clinical data and molecular data. Whole exome, whole genome, or panel sequencing, along with SNP array analyses, and RNA-seq were performed on resected primary tumor tissue. Alterations were classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) following the European Association of Neuro-Oncology (EANO) guideline on rational molecular testing. Results A total of 200 (41.4%) patients’ tumors harbored an alteration of interest according to the EANO guideline. Twenty (4.1%) patients had an ESCAT high-tier alteration (tier I or II), while 155 patients (32.1%) had an alteration corresponding to ESCAT IIIA. Thirty-five patients (7.2%) had an actionable alteration, and 15 (3.1%) received targeted therapy. The treated targets were BRAFV600E mutations, FGFR alterations, NTRK fusions, PDGFRA fusions, PTPRZ1-MET fusions, and TMB-high. The overall response rate was 20%, with a median duration of response of 12 months, and 47% achieved stable disease as the best response. Conclusions Genomic profiling uncovers alterations of interest in a substantial number of patients, but only a minority are considered by the Danish National Molecular Tumor Board to have actionable alterations, and even fewer receive targeted therapy. Nevertheless, factors, such as promising targets and the increasing availability of trials, may contribute to a future increase in the number of patients benefiting from targeted therapies based on genomic profiling.

Patients' use of Danish emergency medical services before and during the COVID-19 pandemic: a register-based study

BackgroundDuring the COVID-19 pandemic, disturbing images of ambulances unable to respond to the demands for prehospital assistance appeared from several parts of the world. In Denmark, however, a notion occurred that the demands for emergency medical assistance declined. The purpose of this study was to compare the patients' use of the Danish Emergency Medical Services (EMS) before and during the COVID-19 pandemic. Furthermore, we investigated the overall mortality of the ambulance population, the main reason for calling the emergency medical dispatch centre, and the diagnosis assigned to the admitted patients.MethodsThe study was a nationwide registry-based cohort study based on the national prehospital medical records and the Danish National Patient Registry. The primary outcome was the requested number of ambulances. Secondary outcomes included the primary reason for contact with the dispatch centre (reflected by the dispatch criteria), patient mortality, and the diagnoses assigned to the patients transported to the hospital by ambulance during the COVID-19 pandemic in Denmark in March–December 2020. Comparisons were made using a similar period in 2019 before the pandemic.ResultsIn comparison with the baseline values before the pandemic, the total number of patients treated by the EMS was reduced by 4.5% during the COVID-19 pandemic. The number of patients transported to the hospital during the pandemic was similarly reduced by 3.5%. Compared with baseline values, fewer were patients hospitalised with respiratory diseases during the pandemic (a reduction of 53.3% from April 2019 to April 2020).Compared to the baseline period, there were significant increases in both the 48-h mortality (from 1.4% to 1.5%) and the 30-day mortality (from 4.9% to 5.4%) (p < 0.03 and p < 0.001, respectively), in patients hospitalised during the pandemic.ConclusionDuring the first wave of the COVID-19 pandemic, the Danish EMS experienced an overall reduction in the requests for and the use of ambulances and, especially, in the number of patients admitted to hospitals for respiratory diseases. Despite the overall reduction in EMS requests, the mortality of the ambulance population increased, indicating that despite the reduced ambulance use, the prehospital population was more severely ill during the pandemic.

Female Infertility and Neurodevelopmental Disorders in Children: associations and evidence for familial confounding in Denmark.

Existing research suggests the impact of infertility on the risk of neurodevelopmental disorders in children, however, studies to date have failed to separate the impact of male and female infertility, often blurring the lines with proxies that encompass all forms of infertility. Moreover, while both health conditions co-occurring with infertility and genetic factors operating upstream have been suggested to influence the association between infertility and child outcomes, their roles and potential impact on observed associations remain unclear. The objectives of this study are to investigate the relationship between female infertility and autism in the child, differentiating it from the effects of male and the couple infertility; consider the role of various maternal and birth factors in the association; and examine the effects of shared familial confounders on the association. Danish population-based cohort study, including all singleton live births in Denmark 1998-2015, their parents and parents' siblings. The cohort was followed up until December 31, 2016. The exposure was a history of female infertility in the mother and the mother's sister. We examined four definitions of female infertility based on the ICD-10 codes derived from the Danish National Patient Register - any female infertility; specified female infertility; female exclusive infertility; and female or male infertility. The outcome was diagnosis of autism spectrum disorder (ASD) in the Danish Psychiatric Central Research Register or the national patient register. A multivariable Cox regression model was used to estimate the associations between female infertility and autism, accounting for child's sex, year of birth, maternal age, education level, chronic comorbidities, and pregnancy and birth complications. The effects of shared familial factors on the association were analyzed using exposure information from the child's maternal aunt. The cohort included 1,131,899 mother-child pairs, among which 18,374 children with ASD diagnosis. History of female infertility in the mother (all definitions) was significantly associated with autism in the child, with the association remaining robust after adjustment for covariates (HRadj=1.14 (95% CI, 1.03-1.26) for specified infertility). The diagnosis of infertility in a child's maternal aunt was also significantly linked to the child's autism risk, even after adjustment for maternal infertility (HRadj=1.10 (95% CI, 1.00-1.20). in This population-based birth cohort study, we found a slightly higher risk of autism in children born to mothers with a history of infertility, with the association remaining consistent across various definitions of female infertility and robust to adjustments for demographic, child, and maternal factors. The study suggests for the first time that shared familial factors, possibly both genetic and non-genetic, could be influencing both female infertility and the risk of autism in children, indicating a need for further investigation into these familial effects.

Clinical Outcomes of Continuation and Maintenance Electroconvulsive Therapy

Large-scale evidence for the efficacy of continuation and maintenance electroconvulsive therapy (c/mECT) is lacking. To provide an exhaustive and naturalistic insight into the real-world outcomes and the cost-effectiveness of c/mECT in a large dataset. This cohort study included all patients in the Danish National Patient Registry who initiated treatment with ECT from 2003 through 2022. The data were analyzed from October 2023 to February 2024. ECT. An algorithm to identify c/mECTs in the dataset was developed: (>3 treatments with ≥7 and <90 days between adjacent treatments, occurring within a time frame of 180 days [cECT] or more [mECT] after an acute [aECT] series). The association of c/mECT with subsequent 6- to 12-month risk of hospitalization or suicidal behavior using Cox proportional hazard regression with multiple adjustments and aECT only as a reference, propensity score matching, and self-controlled case series analysis using a Poisson regression model. A cost-effectiveness analysis based on hospitalization and ECT expenses was made. A total of 19 944 individuals were treated with ECT (12 157 women [61%], 7787 men [39%]; median [IQR] age, 55 [41-70] years). Of these, 1533 individuals (7.7%) received c/mECT at any time point (1017 [5.1%] cECT only and 516 [2.6%] mECT). Compared with patients receiving aECT only, c/mECT patients more frequently experienced schizophrenia (odds ratio [OR], 2.14; 95% CI, 1.86-2.46) and schizoaffective disorder (OR, 2.42; 95% CI, 1.90-3.09) and less frequently unipolar depression (OR, 0.56; 95% CI, 0.51-0.62). In all models, c/mECT was associated with a lower rate of hospitalization after finishing aECT (eg, 6-month adjusted hazard ratio, 0.68; 95% CI, 0.60-0.78 [Cox regression]; 6-month incidence rate ratio, 0.51; 95% CI, 0.41-0.62 [Poisson regression]). There was no significant difference in the risk of suicidal behavior. Compared with the periods before the end of aECT, c/mECT was associated with a substantial reduction in total treatment costs. In a nationwide and naturalistic setting, c/mECT after aECT was infrequently used but associated with a lower risk of readmission than aECT alone. The totality of the evidence indicates that c/mECT should be considered more often to prevent relapse after successful aECT in patients whose condition does not respond sufficiently to other interventions.

Temporal Trend in Hospitalization Among Patients With Congenital Heart Disease: ADanish Nationwide Study.

The congenital heart disease (CHD) population is growing and aging. We aim to examine the impact by describing the temporal trend and causes of lifetime hospitalization burden among the CHD population. From the Danish National Patient Registry, 23 141 patients with CHD and their hospitalizations from 1977 to 2018 were identified, excluding patients with extracardiac malformation. Patients with CHD were categorized into major CHD and minor CHD, and each patient was matched with 10 controls by sex and year of birth. The rate of all-cause hospitalization increased over time from 28.3 to 36.4 hospitalizations per 100 person-years (PY) with rate difference (RD) per decade of 2.5 (95% CI, 2.0-3.1) hospitalizations per 100 PY for the patients with CHD, compared with the increase from 10.8 to 17.0 per 100 PY (RD per decade, 2.0 [95% CI, 1.8-2.2] per 100 PY) for the control group (RD for CHD versus control, P=0.08). The all-cause hospitalization rate remained constant for the major CHDs (RD per decade, -0.2 [95% CI, -1.2 to 0.9] per 100 PY) but increased for the minor CHDs (RD per decade, 5.2 [95% CI, 4.3-6.0] per 100 PY). For all patients with CHD, the cardiovascular hospitalization rate remained constant over time (RD per decade, 0.2 [95% CI, -0.3 to 0.6] per 100 PY) whereas the noncardiovascular hospitalization rate increased (RD per decade, 2.1 [95% CI, 1.6-2.7] per 100 PY). The length of all-cause hospital stays for all patients with CHD decreased from 2.7 (95% CI, 2.6-2.8) days per PY in 1977 to 1987 to 1.6 (95% CI, 1.6-1.7) days per PY in 2008 to 2018. Compared with previous decades, patients with CHD have an increasing hospitalization rate, similar to the general population, but a decreasing length of hospital stay. The increase in hospitalization rate was driven by noncardiovascular hospitalizations, with the patients with minor CHD being the key contributor to the increasing rate.

An algorithm for drug-resistant epilepsy in Danish national registers.

Patients with drug-resistant epilepsy (DRE) have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life. Identification of persons with DRE in administrative data can allow for effective large-scale research, and we therefore aimed to construct an algorithm for identification of DRE in Danish nation-wide health registers. We used a previously generated sample of 525 persons with medical record-validated incident epilepsy between 2010-2019, of which 80 (15%) fulfilled International League Against Epilepsy (ILAE) criteria of DRE at the time of the latest contact - this cohort was considered the gold standard. We linked information in the validated cohort to Danish national health registers and constructed register-based algorithms for identification of DRE-cases. The accuracy of each algorithm was validated against the medical record-validated gold standard. We applied the best performing algorithm according to test accuracy (F1 score) to a large cohort with incident epilepsy identified in the Danish National Patient Registry between 1995 and 2013 and performed descriptive and logistic regression analyses to characterize the cohort with DRE as identified by the algorithm. The best performing algorithm in terms of F1 score was defined as 'fillings of prescriptions for ≥ 3 distinct antiseizure medications (ASMs) within 3 years or acute hospital visit with epilepsy/convulsions following fillings of prescriptions for two distinct ASMs' (sensitivity 0.59, specificity 0.93, positive predictive value 0.59, negative predictive value 0.92, area under the receiver operating characteristic curve 0.77, and F1 score 0.595). Applying the algorithm to a register-based cohort of 83,682 individuals with incident epilepsy yielded 8,650 cases (10.3 %) with DRE. In multivariable logistic regression analysis, early onset of epilepsy, focal or generalized epilepsy, somatic co-morbidity, and substance abuse, were independently associated with risk of being classified with DRE. We developed an algorithm for the identification of DRE in Danish national registers, which can be applied for a variety of research questions. We identified early onset of epilepsy, focal or generalized epilepsy, somatic co-morbidity, and substance abuse as risk factors for DRE.

Incidence and Prevalence of Concussion in Denmark from 1999-2018: A Nationwide Cohort Study.

Concussion is a common diagnosis in emergency rooms, yet contemporary incidence and prevalence estimates are sparse and rely on self-reported data. A nationwide cohort study was conducted to provide up-to-date information, covering the entire Danish population from 1999 to 2018. Hospital contacts with a concussion diagnosis, including emergency room visits, hospital admissions, and outpatient contacts, were retrieved from the Danish National Patient Registry (DNPR), and incidence rates were age-standardized and stratified. The 20-year prevalence was defined as the percentage of Danes alive in 2018 who had experienced a concussion since 1999. The diagnostic codes used were the ICD-10 code S06.0 and a local Danish code for 'observation for concussion' (DZ033D). Additional data on activities related to concussion injuries were obtained from the Accident Analysis Group at Odense University Hospital through DNPR. Findings from the study indicated that during the period 1999-2018, the total age-standardized concussion incidence rate increased by 10% to 308 per 100,000 person-years (95% confidence interval (CI): 304-313). Notable time trends included 1) a reduced sex difference from 40% to 6% (95% CI: 3%-9%), 2) a doubled incidence rate in children aged 0-1 and in seniors aged over 80, 3) an increased utilization of head imaging across all age groups, except children, 4) a decline in the proportion of traffic-related concussions, and 5) a prevalence of concussion of 4.9% (95% CI: 4.89% - 4.93%) in 2018. The increasing incidence of concussions among the elderly is concerning in light of an aging population, and warrants further investigation, as evidence-based preventive interventions for falls exist. Additionally, the increased utilization of head imaging across all age groups except children calls for attention toward avoidance of unnecessary radiation exposure. Despite a drop in traffic-related cases, concussions remain highly prevalent. In conclusion, these findings indicate that concussions are an important public health concern, necessitating ongoing surveillance, research, and targeted resource allocation to address concussion management and prevention effectively.

Long term exposure to road traffic noise and air pollution and risk of infertility in men and women: nationwide Danish cohort study

ObjectiveTo investigate associations between long term residential exposure to road traffic noise and particulate matter with a diameter <2.5 µm (PM2.5) and infertility in men and women.DesignNationwide prospective cohort study.SettingDenmark.Participants526...

Fracture risk revisited: Bone mineral density T-score and fracture risk in type 2 diabetes.

To study the association between femoral neck (FN) bone mineral density (BMD) T-score and fracture risk in individuals with and without type 2 diabetes (T2D). We performed a single-centre retrospective cohort study using the Danish National Health Service. BMD of the FN was measured by dual-energy X-ray absorptiometry. Cox proportional hazards regression models were used to study the association between FN BMD T-score and fractures in individuals with and without T2D separately, adjusted for age, comorbidities and comedication. The results from this analysis were used to estimate the 10-year absolute fracture risk. In total, there were 35,129 women (2362 with T2D) and 7069 men (758 with T2D). The FN BMD T-score was significantly associated with risk of any, hip and major osteoporotic fracture in men and women with [adjusted hazard risk ratios (aHR) women, hip: 1.57; 95% confidence interval (CI) 1.24-2.00, incidence rate (IR) 8.7; aHR men, hip: 1.55; 95% CI 1.01-2.36, IR 4.6] and without T2D (aHR women, hip: 1.75; 95% CI 1.64-1.87, IR 7.0; aHR men, hip: 1.97, 95% CI 1.73-2.25, IR 6.3), and its ability to predict fracture risk was similar. Fracture IRs were not significantly different for individuals with or without T2D, nor was the estimated cumulative 10-year fracture risk. The FN BMD T-score was significantly associated with hip, non-spine and major osteoporotic fracture risk in men and women with and without T2D. Fracture risk for a given T-score and age was equal in individuals with and without T2D, as was the ability of the FN BMD T-score to predict fracture risk.

Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark.

Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark. We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry. Patients, 18 years and older between May 2012 and December 2020 with a valsartan dispensing were identified in each database. Patients were followed from the date of valsartan dispensing until discontinuation. We defined four valsartan exposure categories based on nitrosamine impurity status; recalled generic products with confirmed NDMA/NDEA levels (recalled-tested); recalled generic products that were not tested (recalled); non-recalled generic and non-recalled branded products. In Denmark, the recalled-tested category was not included due to absence of testing data. The proportion and duration of use of valsartan episodes stratified by nitrosamine-impurity status was calculated. We identified 3.3 and 2.8 million (United States) and 51.3 and 229 thousand (Canada) recalled-tested and recalled valsartan exposures. In Denmark, where valsartan exposure was generally low, there were 10 747 recalled exposures. Immediately after the recall notices were issued, there was increased rates of switching to a non-valsartan ARB. The mean duration of use of the recalled-tested products was 167 (±223.1) and 146 (±255.8) days in the United States and Canada respectively. For the recalled products, mean cumulative duration of use was 178 (±249.6), 269 (±397.3) and 166 (±251.0) days in the United States, Canada, and Denmark, respectively. In this cohort study, despite widespread use of recalled generic valsartan between 2012 and 2018, the duration of use was relatively short and probably did not pose an elevated risk of nitrosamine-induced cancer. However, since products with nitrosamine impurity could have been on the market over a 6-year period, patients exposed to these products for longer durations could have a potentially different risk of cancer.

Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark

BackgroundA considerable number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) lack a history of venous thromboembolism (VTE). ObjectivesWe aimed to examine the annual incidence and prevalence of CTEPH in Denmark and to compare the rates of VTE, bleeding, and mortality between CTEPH patients with and without a history of VTE. MethodsThe Danish National Patient Registry covering all Danish hospitals was used to identify all CTEPH cases between 2009 and 2018, based on combinations of discharge diagnoses using International Classification of Diseases, 10th Revision codes for CTEPH and relevant diagnostic and/or therapeutic interventions. Incidence rates of CTEPH per 100 000 person-years, rates of VTE and bleeding, and 5-year survival estimates were calculated. ResultsIn total, 509 CTEPH patients were identified, of whom 82% had a history of VTE. The yearly incidence rate of CTEPH was 0.5 to 0.8 per 100 000 person-years during the study period. Patients with a history of VTE experienced a 2.5-fold rate of VTE compared with those without prior VTE (2571 vs 980 per 100 000 person-years), while the rate of bleeding events was lower (5008 vs 7139 per 100 000 person-years). The 5-year survival of CTEPH patients with a VTE history was 65% (95% CI, 58%-71%) compared with 45% (95% CI, 31%-58%) in patients without a history of VTE. ConclusionThe Danish incidence rate of CTEPH was comparable with that of other European countries. We identified notable differences in the prognosis of patients with CTEPH with or without a history of VTE. These findings may support generation of hypotheses regarding the pathophysiology of CTEPH and inform current patient care.

Comparing the risk of reoperation between pneumatic tourniquet and non-tourniquet use in surgical treatment of ankle fractures.

Pneumatic tourniquets are often used during the surgical treatment of unstable traumatic ankle fractures. The aim of this study was to assess the risk of reoperation after open reduction and internal fixation of ankle fractures with and without the use of pneumatic tourniquets. This was a population-based cohort study using data from the Danish Fracture Database with a follow-up period of 24 months. Data were linked to the Danish National Patient Registry to ensure complete information regarding reoperations due to complications, which were divided into major and minor. The relative risk of reoperations for the tourniquet group compared with the non-tourniquet group was estimated using Cox proportional hazards modelling. A total of 4,050 ankle fractures treated with open reduction and internal fixation between 15 March 2012 and 31 December 2016 were included, with 669 (16.5%) undergoing surgery with a tourniquet and 3,381 (83.5%) without a tourniquet. The overall reoperation risk was 28.2% with an adjusted relative risk of 1.46 (95% CI 0.91 to 2.32) for group comparison. The reoperation risk due to major complications was 3.1% with a tourniquet and 4.4% without a tourniquet, resulting in an adjusted relative risk of 1.45 (95% CI 0.91 to 2.32). For minor complications, there were 24.7% and 23.9% reoperations, resulting in an adjusted relative risk of 0.99 (95% CI 0.84 to 1.17). We found no significant difference in the reoperation rate when comparing ankle fractures treated surgically with and without the use of pneumatic tourniquets.

Incidence of cardiovascular events in a population-based Danish cohort with atopic dermatitis

The risk of cardiovascular disease in atopic dermatitis (AD) is not well established. Our aims were to evaluate the incidence rate (IR) of venous thromboembolism (VTE) in patients with AD in a population-based cohort study and to assess atherosclerotic cardiovascular disease (ASCVD) risk factors and incidence of malignancies, major adverse cardiovascular events (MACE), and VTE in patients with AD and rheumatoid arthritis (RA) in a nested cohort analysis. Data from individuals age 12 years or older (nested cohort age≥ 18 years) from January 1, 2000, to December 31, 2018, were extracted from the Danish National Patient Registry. Patients with AD were age- and sex-matched with 10 healthy controls. ASCVD risk factors included age 65 years or older and history of smoking, coronary artery disease, stroke, deep vein thrombosis (DVT), pulmonary embolism (PE), and malignancy. The population-based cohort comprised 190,751 patients (17,341 patients with AD and 173,410 healthy controls). The IRs per 100 patient-years were comparable between the AD cohort and healthy controls for VTE (0.14 [95% CI= 0.12-0.16] vs 0.11 [95% CI= 0.11-0.12]), DVT (0.08 [95% CI= 0.06-0.09] vs 0.06 [95% CI= 0.06-0.07]), and PE (0.06 [95% CI= 0.05-0.08] vs 0.05 [95% CI= 0.05-0.05]). The IR for VTE was higher in the AD cohort age 65 years or older (0.71 [95% CI= 0.56-0.90]) than in the age-matched controls (0.50 [95% CI= 0.46-0.54]). ASCVD risk factors were more frequent in the patients with RA than in the patients with AD. The IRs for malignancies and MACE were higher with specific ASCVD risk factors. The IRs of cardiovascular events were comparable between the AD cohort and general population. The risk of VTE, malignancy, or MACE was higher with specific ASCVD risk factors, underscoring the need for patient monitoring.