Klaus Rostgaard

This cross‐sectional study investigated associations between screening positive for attention‐deficit/hyperactivity disorder (ADHD) and quality of life (QoL), as well as real‐life functioning, in 235 adults with neurofibromatosis 1 (NF1). Self‐reported data included ADHD symptoms (Adult Self‐Report ADHD Scale v1.1), QoL (PedsQL NF1 Module), partner status, and need for daily support, supplemented by registry data on education and employment. Adults screening positive for ADHD (14%) had a mean QoL score that was 16.0 points lower (95% confidence interval [CI]: −20.2 to −11.7) than that of adults who screened negative. Each 1‐point increase in inattention or hyperactivity/impulsivity score was associated with a mean decrease in QoL of 0.9 (95% CI: −1.1, −0.7) and 0.5 (95% CI: −0.7, −0.3). Screening positive for ADHD was associated with lower odds of having a medium/long education (odds ratio [OR]: 0.24, 95% CI: 0.10–0.56) and being employed (OR: 0.20, 95% CI: 0.10–0.50), but not with having a partner (OR: 0.73, 95% CI: 0.34–1.56). ADHD was also associated with a greater need for daily support, including physical (OR: 8.7, 95% CI: 3.6–21.1), family‐related (OR: 5.7, 95% CI: 2.4–13.3), and psychological (OR: 5.0, 95% CI: 2.2–11.3) support. These results support assessment of ADHD symptoms in adults with NF1 to facilitate timely treatment and care.

Hormonal contraceptive (HC) use is known to be associated with elevated CRP levels. However, evidence on the effect of HC on several circulating inflammatory biomarkers in healthy humans is limited. The aim of this study was to examine the association between hormonal contraceptives and circulating biomarker levels and differential cell counts. A cross‐sectional observational study design with biomarker measurements from 4,160 healthy females was used, coupled with registered HC prescriptions. We compared 752 high and low dose combined oral contraceptive (COC) users, 77 progestin‐only pill users, 417 levonorgestrel intrauterine device users, 65 hormonal therapy users, and 1,523 post‐menopausal women with a control group of 1,326 women below 50 years. Repeated differential cell counts from a different dataset of 16,231 females were analyzed for the effects of HC. Data were analyzed using various regression models. COC use was associated with higher vascular marker levels but lower chemokine levels. We found no association with progestin‐only use. The association with differential cell counts was limited for most HC types. This study emphasizes the widespread impact of HC on the immune and vascular systems and how the impact may differ between HC types. The biomarker associations found could be targets for elucidation in functional studies.

Summary: Diffuse large B‐cell lymphoma (DLBCL) type Richter transformation (DLBCL‐RT) in patients with chronic lymphocytic leukaemia (CLL) has a worse prognosis compared to de novo DLBCL (dnDLBCL). We investigated outcomes of patients with DLBCL‐RT with or without previous CLL‐directed therapy compared to dnDLBCL between 2002 and 2022. We included 6525 patients with dnDLBCL and 383 patients with DLBCL‐RT, of whom 260 had Richter transformed treatment‐naïve CLL (RT:TN‐CLL) and 123 had Richter transformed treatment exposed CLL (RT:TE‐CLL). Median time to next treatment or death (TTNTd) was 4.83 years, 1.43 years and 0.46 years for patients with dnDLBCL, RT:TN‐CLL and RT:TE‐CLL respectively. Median overall survival (OS) following first‐line treatment was 9.42, 5.22 and 0.72 years for dnDLBCL, RT:TN‐CLL and RT:TE‐CLL respectively ( p < 0.001). In a high‐validity subcohort, OS did not differ significantly between RT:TN‐CLL and dnDLBCL (median OS 9.85 years [CI: 9.16–10.70] for dnDLBCL, 6.07 years [CI: 4.23–not estimable] for RT:TN‐CLL and 1.15 years [CI: 0.76–3.66] for RT:TE‐CLL). In conclusion, patients with RT:TE‐CLL had inferior TTNTd and OS compared to RT:TN‐CLL and dnDLBCL. RT:TN‐CLL demonstrated inferior TTNTd compared to dnDLBCL, but OS approached that of dnDLBCL. This indicates that for patients with RT:TN‐CLL, chemoimmunotherapy may still be an effective modality, while patients with RT:TE‐CLL need novel treatment options.

Background and Objectives: The demand for plasma‐derived medicinal products underscores the need to assess health effects of plasma donation. This study examines the association between plasma donation rates and infection risk in a country with voluntary, non‐remunerated donation. Materials and Methods: From 2016 to 2024, 45,615 first‐time plasma donors were enrolled in a cohort study with time‐varying exposure. Follow‐up began 90 days after the first plasma donation, with donation rates recalculated every 90 days. Donation rates were categorized as 0, 1 (reference), 2–3, 4–5 or 6–8 donations. Infection was defined using Danish health registers. Survival models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: The median plasma donation rate was 2 (Q1, 1; Q3, 4). During follow‐up, 15,498 donors experienced an infection. A trend of decreasing HRs for infection was observed with higher donation rates compared with a single donation (0 donations: HR: 0.89, 95% CI: 0.86–0.93; 2–3 donations: HR: 0.85, 95% CI: 0.81–0.89; 4–5 donations: HR: 0.65, 95% CI: 0.59–0.72; and 6–8 donations: HR: 0.48, 95% CI: 0.36–0.62). Findings were consistent across multiple regression models. Conclusion: In this study, higher plasma donation rates were associated with lower infection risk. Importantly, this inverse association is likely due to bias inherent to observational designs, particularly the internal healthy donor effect, which limits interpretation. Thus, no causal relationship between plasma donation rates and infection risk can be inferred. This underscores the challenges of assessing plasma donation safety using non‐randomized data.

Hypertension is the most common comorbidity in patients with chronic lymphocytic leukemia (CLL), but its impact on the disease course of CLL remains poorly understood. In this nationwide cohort study of Danish patients with incident CLL (2008-2022), we examined the association between hypertension and survival from CLL diagnosis and treatment, and compare with the general population. Cox proportional hazard regression was applied for survival analyses, and the Aalen-Johansen estimator for cumulated incidence. At diagnosis of CLL, the hypertension prevalence was 46% in the CLL cohort and 45% in the general population. Hypertension was associated with shorter overall survival (OS) following CLL diagnosis (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.00-1.20) and first-line treatment (HR, 1.48; 95% CI, 1.18-1.86), primarily driven by infections and cardiocerebrovascular causes of death. The difference was seen for patients aged <75 years both following diagnosis (HR, 1.43; 95% CI, 1.25-1.64) and first-line treatment (HR, 1.89; 95% CI, 1.34-2.66). For patients treated with Bruton tyrosine kinase inhibitors, we observed a trend toward poorer OS in patients with hypertension (HR, 1.97; 95% CI, 0.90-4.34). No interaction between CLL in general and hypertension was observed (HR, 0.89; 95% CI, 0.79-1.02), meaning that hypertension did not confer a higher additional risk in patients with CLL than in individuals without CLL. This study identifies an important subgroup of patients with CLL aged <75 years with coexisting hypertension who have a poorer prognosis. Our findings support encouraging patients to maintain regular contact with primary care and adhere to preventative health measures, as hypertension and related comorbidities remain important for survival even after CLL diagnosis.

Background: Sex differences in cancer incidence and survival have been documented, but underlying mechanisms remain unclear. We examined sex differences in incidence and survival for non-sex-specific cancers and the role of socioeconomic factors and comorbidity. Methods: All individuals living in Denmark from 2004–2020 were included. Incidence rate ratios (IRRs) and excess mortality ratios (EMRs) for 35 cancers were estimated using Poisson regression adjusted for age and year. Modification of associations between sex and death by cohabitation, education and comorbidity was assessed. Results: A total of 7,339,667 individuals were followed for 99,832,998 person-years, during which 355,339 were registered with a primary malignancy (197,375 males, 157,964 females). Males had a 52% higher risk of cancer and upon cancer diagnosis 10% higher mortality than females. IRRs were elevated (with confidence intervals excluding the null) for 24 cancers and EMRs for 16 cancers in males. One in six cancers and one in five cancer deaths in males could have been avoided if male rates matched female rates. Disparities were greatest among males living alone, particularly for alcohol- and smoking-related cancers. Conclusion: Sex differences in cancer must be addressed and translated into interventions that promote equality between sexes, specifically focusing on socioeconomically vulnerable males.

Background and purpose: Bone sarcomas are important contributors to early-life cancer mortality and morbidity. Optimisation of treatment regimens has improved survival, but the survival disparity between children, adolescents and young adults has widened. Population-based studies are needed to understand and address these disparities. This is the first comprehensive study of early-life bone sarcomas in Denmark.Patient/material and methods: We combined population-wide data from national registers from 1990 to 2024 with clinical data from patient records. We calculated age-standardised incidence rates, 5-year relative survival rates stratified by several clinical factors, and Aalen-Johansen estimators for relapse/progression and death within 5 years.Results: A total of 578 patients under 40 years of age were diagnosed with either osteosarcoma (n = 336) or Ewing sarcoma of bone (n = 242) in Denmark between 1990 and 2024. Five-year relative survival improved for patients aged 0–24 years but stagnated for those aged 25–39 years. We observed age-dependent differences in the distribution of tumours and in relative survival across anatomical sites, tumour sizes, and treatment regimens. Metastatic disease or a tumour diameter of > 8 cm reduced relative survival by 19 to 45 percentage points.Interpretation: Survival disparities between children, adolescents, and young adults with bone sarcomas are likely multifactorial. Age-dependent differences in the distribution of tumours across anatomical sites and in tumour size appear to play a role. The incidence of and survival from relapse/progression also appear to favour younger patients. Including patients in international, joint paediatric-adult treatment protocols remains a high priority.

A bstract: Selective participation in biobanks often compromises inference to the general population, particularly when selection occurs across multiple stages, whether at recruitment or during subsequent participation. Inverse probability (IP) weighting can reduce systematic differences using suitable external benchmarks, but most applications assume a single selection process. Here, we present a multi-stage IP-weighting framework and apply it to the Danish Blood Donor Study (DBDS), a nationwide biobank embedded in Denmark’s blood-donation infrastructure. Using national registers, we estimated year-specific probabilities of (i) donation activity and (ii) DBDS enrolment conditional on donation activity, yielding two-stage inclusion weights for 169,893 participants. These weights reduced inclusion-associated imbalance across the 52 auxiliary variables in the probability models by 97.6% (median) and, despite strong health selection under donation-based recruitment, reduced relative-prevalence discrepancies across held-out prescription phenotypes by 69.7% (median). The effective sample size after weighting was 30,627 (18.0% of 169,893). Combining the inclusion weights with questionnaire-specific response weights across five DBDS questionnaires (>500 questions) produced the largest changes from unweighted to weighted responses for health behaviours and symptom severity, including tobacco and alcohol consumption, menstrual-pain severity, restless-legs severity, nocturia, sleep disturbance, and fatigue. These findings support multi-stage IP-weighting to improve population alignment in biobanks with staged selection.