Aarhus University Hospital

Purpose Delivering optimal care to patients with seizures and epilepsy requires all EEGs to be interpreted accurately and reliably. This study investigated neurology professionals' opinions on the ideal standards for EEG in clinical care. Methods We developed an anonymous e-survey targeting practicing and trainee neurologists focused on participants' demographics, clinical practice characteristics, and views on optimal EEG standards of care—including whether an EEG certification test is needed and whether postresidency/fellowship training in EEG/epilepsy is necessary for neurologists who interpret outpatient/routine EEGs in practice. The survey was hosted by the Neurology Clinical Practice—Practice Current, and it was distributed online through the American Academy of Neurology, American Epilepsy Society, American Clinical Neurophysiology Society, and International League Against Epilepsy, and through social media. Results Two hundred eighty-three responses were included: 119 from EEG/epilepsy-trained neurologists, 83 from non-EEG/epilepsy-trained neurologists, 75 from trainees, and 6 from advanced care providers. Most participants (78%) agreed that “an objective certification test of ability to interpret EEGs is needed for all those who interpret EEGs in clinical practice.” Most participants (71%) believed that outpatient/routine EEGs may be read only by neurologists with EEG/epilepsy training; this opinion was more prevalent among EEG/epilepsy-trained (83%) versus non-EEG/epilepsy-trained neurologists (55%). Conclusions Our neurology community should discuss the need to develop and implement a certification test of ability for all neurologists who wish to interpret EEGs in clinical practice. In addition, it is imperative to improve in-residency EEG education to ensure that neurology graduates achieve EEG competence before entering the workforce.

Parasitic helminths secrete extracellular vesicles (EVs) into their host tissues to modulate immune responses, but the underlying mechanisms are poorly understood. We demonstrate that Ascaris EVs are efficiently internalised by monocytes in human peripheral blood mononuclear cells and increase the percentage of classical monocytes. Furthermore, EV treatment of monocytes induced a novel anti‐inflammatory phenotype characterised by CD14⁺, CD16⁻, CC chemokine receptor 2 (CCR2⁻) and programmed death‐ligand 1 (PD‐L1)⁺ cells. In addition, Ascaris EVs induced T cell anergy in a monocyte‐dependent mechanism. Targeting professional phagocytes to induce both direct and indirect pathways of immune modulation presents a highly novel and efficient mechanism of EV‐mediated host‐parasite communication. Intra‐peritoneal administration of EVs induced protection against gut inflammation in the dextran sodium sulphate model of colitis in mice. Ascaris EVs were shown to affect circulating immune cells and protect against gut inflammation; this highlights their potential as a subject for further investigation in inflammatory conditions driven by dysregulated immune responses. However, their clinical translation would require further studies and careful consideration of ethical implications.

Importance Integration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences. Observations Distinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated. Conclusions and Relevance The results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual’s predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.

Objective We aimed to 1) identify distinct segments within the general population characterized by various combinations of stressors (stressor profiles) and to 2) examine the socio-demographic composition of these segments and their associations with perceived stress levels. Methods Segmentation was carried out by latent class analysis of nine self-reported stressors in a representative sample of Danish adults (N = 32,417) aged 16+ years. Perceived stress level was measured by the Perceived Stress Scale (PSS). Results Seven classes were identified: Class 1 was labeled Low Stressor Burden (64% of the population) and the remaining six classes, which had different stressor combinations, were labeled: 2) Burdened by Financial, Work, and Housing Stressors (10%); 3) Burdened by Disease and Death among Close Relatives (9%); 4) Burdened by Poor Social Support and Strained Relationships (8%); 5) Burdened by Own Disease (6%); 6) Complex Stressor Burden Involving Financial, Work, and Housing Stressors (2%); and 7) Complex Stressor Burden Involving Own Disease and Disease and Death among Close Relatives (2%). Being female notably increased the likelihood of belonging to Classes 2, 3, 5, and 7. Higher age increased the likelihood of belonging to Class 3. Low educational attainment increased the likelihood of belonging to Classes 5 and 6. A significant difference was observed in perceived stress levels between the seven latent classes. Average PSS varied from 9.0 in Class 1 to 24.2 in Class 7 and 25.0 in Class 6. Conclusion Latent class analysis allowed us to identify seven population segments with various stressor combinations. Six of the segments had elevated perceived stress levels but differed in terms of socioeconomic composition and stressor combinations. These insights may inform a strategy aimed at improving mental health in the general population by targeting efforts to particular population segments, notably segments experiencing challenging life situations.

A protective effect of childhood vaccinations on leukemia risk, particularly acute lymphoblastic leukemia (ALL), has been hypothesized, though findings are inconsistent. We used a nationwide cohort of Danish children born 1997–2018 (n = 1,360,230), to examine associations between childhood vaccinations and leukemia (<20 years) using registry data (follow‐up: December 31, 2018). Cox proportional hazard models with age as the underlying time estimated hazard ratios (HRs) for leukemia (any, ALL, acute myeloid [AML], and other), comparing vaccinated with unvaccinated children. We also accessed the effect of each additional vaccine dose. During 14,536,819 person‐years, 771 children were diagnosed with leukemia (74% ALL, 16% AML, and 10% other). Any vaccination was associated with an increased HR for ALL (HR: 2.76; 95% CI: 0.66–11.58), compared to unvaccinated children, with a change in HR of 1.01 (95% CI: 0.96–1.05) per dose. The corresponding HRs for any leukemia, AML, and other leukemia were 1.04 (95% CI: 0.50–2.17), 0.67 (95% CI: 0.18–2.59) and 0.29 (95% CI: 0.09–0.99), with a change in HR of 0.97 (95% CI: 0.94–1.02), 0.92 (95% CI: 0.84–1.00, p = .062) and 0.88 (95% CI: 0.78–1.00, p = .044) per dose. No significant associations were found for vaccination types, except for the pneumococcal vaccine which was associated with a decreased risk of other leukemia (HR: 0.32; 95% CI: 0.14–0.74). In six‐months lag analyses, no significant associations were observed, and decreased risks were attenuated. The results provide no strong evidence that childhood vaccinations reduce leukemia risk. The limited number of unvaccinated cases and wide confidence intervals suggest cautious interpretation of some findings.

To assess tumour factors that reduce primary technical efficacy (PTE) from CT-guided renal cryoablation. Patients were taken from the EuRECA registry between December 2014 and November 2020. To focus on tumour factors rather than individual technique, this study was limited to cases using CT and excluded procedures using cone beam, US, MRI, or laparoscopy. PTE was assessed per tumour and defined as complete ablation of the target on enhanced CT or MRI by 90 days. Residual unablated tumour (RUT) was defined as focal persistent tumour enhancement within 90 days. A total of 1,424 tumours from 11 different centres were eligible; 38 episodes of RUT were detected giving an overall PTE of 97.3%. The factors most likely to be associated with RUT were as follows and persisted in multivariate logistic regression. Tumour contact with a central artery or vein; increased OR of 5.29 (CI 2.59–10.81 p < 0.001), PTE was 89.8% in this group. Tumours size; T1b vs T1a increased OR of 2.31 (CI 1.10–4.87 p = 0.0276), T1b PTE was 94.1% vs T1a PTE 97.9%. Close proximity to the collecting system (< 4 mm) was significant at univariate logistic regression (OR 2.87, P = 0.028), as was a RENAL complexity score of 10 or above (OR 2.71, p = 0.0147), but neither was significant in the multivariate analysis. Overall, CT-guided percutaneous renal cryoablation has a high PTE at 97.3%. In this analysis, the most significant risk factor for RUT is central renal vessel contact. T1b tumours are also noted to have an increased risk of RUT compared to T1a.

Background Intergenerational transmission of mental disorders has been well established, but it is unclear whether exposure to a child's mental disorder increases parents' subsequent risk of mental disorders. Aims We examined the association of mental disorders in children with their parents' subsequent mental disorders. Method In this population-based cohort study, we included all individuals with children born in Finland or Denmark in 1990–2010. Information about mental disorders was acquired from national registers. The follow-up period began when the parent's eldest child was 5 years old (for ICD-10 codes F10–F60) or 1 year old (for codes F70–F98) and ended on 31 December 2019 or when the parent received a mental disorder diagnosis, died, or emigrated from Finland or Denmark. The associations of mental disorders in children with their parents' subsequent mental disorders were examined using Cox proportional hazards models. Results The study cohort included 1 651 723 parents. In total, 248 328 women and 250 763 men had at least one child who had been diagnosed with a mental disorder. The risk of a parent receiving a mental disorder diagnosis was higher among those who had a child with a mental disorder compared with those who did not. For both parents, the hazard ratios were greatest in the first 6 months after the child's diagnosis (hazard ratio 2.04–2.54), followed by a subtle decline in the risk (after 2 years, the hazard ratio was 1.33–1.77). Conclusion Mental disorders in children are associated with a greater risk of subsequent mental disorders among their parents. Additional support is needed for parents whose children have been recently diagnosed with a mental disorder.

Mental disorders are associated with elevated mortality rates and reduced life expectancy. However, it is unclear whether these associations differ by socioeconomic position (SEP). The aim of this study was to explore comprehensively the role of individual‐level SEP in the associations between specific types of mental disorders and mortality (due to all causes, and to natural or external causes), presenting both relative and absolute measures. This was a cohort study including all residents in Denmark on January 1, 2000, following them up until December 31, 2020. Information on mental disorders, SEP (income percentile, categorized into low, <20%; medium, 20‐79%; and high, ≥80%), and mortality was obtained from nationwide registers. We computed the average reduction in life expectancy for those with mental disorders, relative and absolute differences in mortality rates, and proportional attributable fractions. Subgroup analyses by sex and age groups were performed. Overall, 5,316,626 individuals (2,689,749 females and 2,626,877 males) were followed up for 95.2 million person‐years. People with mental disorders had a shorter average life expectancy than the general population regardless of SEP (70.9‐77.0 vs. 77.2‐85.1 years, depending on income percentile). Among individuals with a mental disorder, the subgroup in the top 3% of the income distribution had the longest average life expectancy (77.0 years), and this estimate was lower than the shortest life expectancy in the general Danish population (77.2 years for individuals in the bottom 6% income distribution). The mortality rate differences were larger in the low‐income than the high‐income group (19.6 vs. 13.3 per 1,000 person‐years). For natural causes of death, a socioeconomic gradient for differences in life expectancy and mortality rates was observed across most diagnoses, both sexes, and all age groups. For external causes, no such gradient was observed. In the low‐SEP group, 10.1% of all deaths and 23.7% of those related to external causes were attributable to mental disorders, compared with 3.5% and 8.7% in the high‐SEP group. Thus, our data indicate that people with mental disorders have a shorter life expectancy even than people with the lowest SEP in the general population. The socioeconomic gradients in mortality rates due to natural causes highlight a greater need for coordinated care of physical diseases in people with mental disorders and low SEP.

Background We aimed to investigate if iron deficiency was associated with infection susceptibility in a large cohort of healthy individuals. Study Design and Methods The Danish Blood Donor Study is a national ongoing prospective study of blood donors. We included 94,628 donors with 338,290 ferritin measurements from March 2010 to October 2022. We performed sex‐stratified multivariable Cox regression to estimate the risk of infection for iron‐deficient donors compared with iron‐replete donors. Infection was defined as either a filled prescription of antibiotics registered in the Danish National Prescription Registry (NPR), or a hospital contact with infection registered in the Danish National Patient Registry (DNPR). Results Iron deficiency was associated with an overall increased risk of infection (defined as prescriptions of antibiotics) for women (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02–1.15). Subgroup analyses showed an increased risk of respiratory tract infections (HR 1.16, 95% CI 1.05–1.28) and urinary tract infections (HR 1.16, 95% CI 1.04–1.29). Iron deficiency was not associated with overall risk of infection for men (HR 1.02, 95% CI 0.82–1.28). For both men and women, no association was found between iron deficiency and hospital contacts for infections. Conclusion Iron deficiency was associated with an increased risk of infection in female blood donors. However, effect sizes were small, and there was no association between iron deficiency and hospital contacts for infection. Consequently, risk of infection should not be considered an apprehension regarding blood donation. These findings support the role of iron in immune function and monitorization of iron stores in female blood donors.

Background The use of patient-reported outcome (PRO) measures is an emerging field in health care. In the Central Denmark Region, epilepsy outpatients can participate in remote PRO-based follow-up by completing a questionnaire at home instead of attending a traditional outpatient appointment. This approach aims to encourage patient engagement and is used in approximately half of all epilepsy outpatient consultations. However, dropout in this type of follow-up is a challenging issue. Objective This study aimed to examine the association between potential self-reported determinants and dropout in remote PRO-based follow-up for patients with epilepsy. Methods This prospective cohort study (n=2282) explored the association between dropout in remote PRO-based follow-up for patients with epilepsy and 9 potential determinants covering 3 domains: health-related self-management, general and mental health status, and patient satisfaction. The associations were examined using multiple logistic regression analyses with adjustment for sex, age, education, and cohabitation. Results A total of 770 patients (33.7%) dropped out of remote PRO-based follow-up over 5 years. Statistically significant associations were identified between all potential determinants and dropouts in PRO-based follow-up. Patients with low social support had an odds ratio of 2.20 (95% CI 1.38-3.50) for dropout. Patients with poor health ratings had an odds ratio of 2.17 (95% CI 1.65-2.85) for dropout. Similar estimates were identified for the remaining determinants in question. Conclusions Patients with reduced self-management, poor health status, and low patient satisfaction had higher odds of dropout in remote PRO-based follow-up. However, further research is needed to determine the reasons for dropout.

Background and purpose: Disease- or procedure-specific registers offer valuable information but are costly and often inaccurate regarding outcome measures. Alternatively, automatically collected data from administrative systems could be a solution, given their high completeness. Our primary aim was to validate a method for identifying secondary surgical procedures (reoperations) in the Danish National Patient Register (DNPR) within the first year following primary fracture surgery. The secondary aim was to evaluate the accuracy of the diagnosis and procedure codes used to determine the causes of these reoperations. Finally, we developed algorithms to enhance precision in identifying the reasons for reoperations.Methods: In a national cohort of 11,551 patients with primary fracture surgery, reoperations were identified through subsequent surgical procedure codes in the DNPR. Each patient record was reviewed to confirm the reoperations and causes. To improve accuracy, a stepwise algorithm was developed for each cause.Results: We identified 2,347 possible reoperations; 2,212 were validated as true reoperations by review of patient record, i.e., a 94% positive predictive value (PPV). However, the coding for the causes of these reoperations was inaccurate. Our algorithm identified major reoperations with a sensitivity/PPV of 89/77%, minor reoperations 99%/89%, infections 77/85%, nonunion 82/56%, early re-osteosynthesis 90/75%, and secondary arthroplasties 95/87%.Conclusion: While the overall reported reoperations in the DNPR had a high PPV, the predefined diagnosis and procedure codes alone were not sufficient to accurately determine the causes of these reoperations. An algorithm was developed for this purpose, yielding acceptable results for all causes except nonunion.

Background and purpose Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. We aimed to evaluate: (I) bone healing, (II) complications and reoperations, (III) limb salvage, and (IV) survival. Methods We present a retrospective evaluation of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (interquartile range [IQR] 10–18), and the median follow-up was 82 months (IQR 32–101). Patients were analyzed overall, as well as in subgroups based on tumor location (upper versus lower extremity) and pathology (osteosarcoma versus Ewing sarcoma). Results The primary rate of graft union was 63%, and after secondary procedures the overall rate of graft union was 67%, with a median time to union of 13 months (IQR 9–17). The reoperation rate was 74%, while the limb salvage rate was 93%. The 5-year overall survival rate was 81% (95% confidence interval [CI] 61–92). Patients with upper extremity tumors were more likely to attain graft union (risk ratio [RR] 5.5, CI 1.3–31.5) and less likely to undergo multiple reoperations (RR 0.3, CI 0.8–0.9) than patients with lower extremity tumors. Conclusion Vascularized fibular grafting following tumor resection was associated with a graft union rate of 67%, a high frequency of reoperations, a high limb salvage rate (93%), and a 5-year survival rate of 81%.

Aim Estimate the incidence of asthma among children aged 0 to 15 years in Denmark, Finland, Norway and Sweden during 2000–2017. Methods Cases of preschool asthma (up to 6 years) and school‐age asthma (from 6 years) were identified through national registers using an algorithm including hospital diagnoses and prescription medicines. The respective cumulative incidence (CI) was estimated in 1‐year age intervals for each country and birth year. Results The CI of algorithm‐based preschool asthma peaked for the birth cohorts 2008 or 2009 at 14.8% in Denmark, 11.0% in Finland, 15.1% in Norway and 13.7% in Sweden. For later birth cohorts, a slight decrease was observed. The CI of school‐age asthma was 7.1% in Denmark, 10.5% in Finland, 9.7% in Norway and 10.2% in Sweden (children born in 2002). A slight decline over time was seen in Denmark and Norway, and a slight increase in Sweden and Finland. Conclusion Finland had a markedly lower CI of preschool asthma and Denmark lower CI of school‐age asthma as estimated by prescriptions and hospital diagnoses. Preschool asthma may have plateaued in the Nordic countries. For school‐age asthma trends over time varied by country. Differences in diagnostic and prescription practices may have influenced the results.

To investigate if progression of coronary artery calcification (CAC) in patients with systemic lupus erythematosus (SLE) is associated with renal and traditional cardiovascular risk factors as well as incidence of myocardial infarctions. CAC progression was evaluated by cardiac computed tomography (CT) at baseline and after 5 years. Multivariable Poisson regression was applied to investigate associations between CAC progression and baseline values for traditional cardiovascular risk factors, CAC, SLE disease duration, lupus nephritis, and renal function. Regarding renal function, three groups were defined based on eGFR. Further, we analysed association between CAC progression and myocardial infarction during follow-up. Of the 147 SLE patients, 99 had cardiac CT at baseline and 5-year follow-up, with a total of 502 patient-years. At baseline, their median age was 47 years, median SLE disease duration was 14 years, 88% were women, 58% had lupus nephritis, and the median eGFR was 99 mL/min/1.73m². 38/99 (39%) had CAC progression. CAC progression was associated with smoking (ever) (relative risk [RR] 1.69, CI95% 1.19–2.40), SLE disease duration (RR per year 1.03, CI95% 1.01–1.04), and CAC presence (RR 2.52, CI95% 1.68–3.78) at baseline. During follow-up, myocardial infarction occurred in three (7.9%) CAC progressors and in two (3.3%) patients who did not have CAC at any time (RR 2.1, CI95% 0.0-5.5). In this study, progression of CAC was associated with smoking, SLE disease duration and the prior presence of CAC, but it was inconclusive as to associations with renal involvement and incidence of MI.