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Background Incidence rates in Denmark of central nervous system (CNS) tumors remain among the highest in the world. Survival rates, however, have improved in the past decades in high‐income countries. Methods We analyzed incidence and survival of childhood CNS tumors in Denmark diagnosed from 1997 to 2019 based on data from the Danish Childhood Cancer Registry and information on histological types, tumor localization, and treatment from medical records. Results From 1997 to 2019, 949 children<15 years were diagnosed with a CNS tumor. Age‐standardized incidence was 42.1 (95% CI, 39.4–44.6) per million person‐years and stable during this period. Age‐specific incidence for children aged 0–4 years was 47.7 per million. More than one‐third (n = 374, 39.4%) were treated with surgery alone. Overall survival rates 5 and 10 years after diagnosis were 77.6% (95% CI, 74.7–80.2) and 74.7% (95% CI, 71.7–77.5). Five‐year overall survival improved from 73.0% (95% CI, 68.9–76.7) in 1997–2008 to 83.2% (95% CI, 79.2–86.4) in 2009–2019 (p‐value < 0.0001) in children aged 0–4 years (p = 0.0006). Conclusion Incidence rates are stable but remain among the highest in the world. Despite improved survival rates in recent years in younger children, some subtypes still have a poor prognosis. Incidence of childhood central nervous system (CNS) tumors in Denmark from 1997 to 2019 was 42.1 per million person‐years and did not increase from 1997 to 2019. Survival has improved especially among younger children with CNS tumors. Still, some subgroups in particular have a poor prognosis.

Most research on psychosocial consequences of neurofibromatosis type 1 (NF1) has focused on the relationship between disease factors and cognitive functioning. NF1 may impair domains of learning and attention, resulting in low academic performance. This study is the first nationwide population-based cohort study to investigate educational attainment and delay in completing mandatory school by persons with NF1. Educational information was collected from 550 persons at the age of 30 (born 1965–1984). They were diagnosed with NF1 in Denmark and compared to a cohort of NF1-free persons matched on gender and age (n = 4295). Multinomial logistic models were applied to estimate odds ratios (ORs) for obtaining short (≤9 years) or medium (10–12 years) education compared to long education (>12 years) by the age of 30 years. We calculated the probability of graduating 9th year of mandatory school at different ages in 932 persons with NF1 and 7962 NF1-free persons (born 1965–2000) using quantile regression. The OR of educational completion for short- and medium-term education was three fold (95% CI 2.55–3.99) and 1.29 fold (95% CI 0.99–1.69) higher, respectively, for persons with NF1 than NF1-free persons after adjusting for birth year, gender, psychiatric and somatic morbidity and mother’s education. Persons with NF1 were significantly delayed in graduating mandatory school education compared to NF1-free persons. When 90% of persons have graduated, persons with NF1 were 1.2 times older than the NF1-free persons. Experiencing delays in mandatory school likely affect further educational achievements and may impair employment and entering work force.

Purpose The aim was to assess lifetime risk for hospitalization in individuals with neurofibromatosis 1 (NF1). Methods The 2467 individuals discharged with a diagnosis indicating NF1 or followed in a clinical center for NF1 were matched to 20,132 general population comparisons. Based on diagnoses in 12 main diagnostic groups and 146 subcategories, we calculated rate ratios (RRs), absolute excess risks (AERs), and hazard ratios for hospitalizations. Results The RR for any first hospitalization among individuals with NF1 was 2.3 (95% confidence interval 2.2–2.5). A high AER was seen for all 12 main diagnostic groups, dominated by disorders of the nervous system (14.5% of all AERs), benign (13.6%) and malignant neoplasms (13.4%), and disorders of the digestive (10.5%) and respiratory systems (10.3%). Neoplasms, nerve and peripheral ganglia disease, pneumonia, epilepsy, bone and joint disorders, and intestinal infections were major contributors to the excess disease burden caused by NF1. Individuals with NF1 had more hospitalizations and spent more days in hospital than the comparisons. The increased risk for any hospitalization was observed for both children and adults, with or without an associated cancer. Conclusion NF1 causes an overall greater likelihood of hospitalization, with frequent and longer hospitalizations involving all organ systems throughout life.

Background Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various somatic manifestations and cognitive impairments, but the latter are sparsely described in adults. This study aimed at characterizing potential impairments of neurocognitive functions using neuropsychological tests as well as a self-report questionnaire. Methods In a nationwide, population-based study including 103 adults with NF1 and 38 age- and gender-matched NF1-free comparisons, we used a comprehensive neurocognitive test battery to assess intelligence and visual short-term memory, immediate visuospatial recall, reaction time, sustained attention, motor speed, planning, planning time, working memory as well as multitasking and a questionnaire to assess executive functions. Descriptive statistics, multivariate analysis of variance (MANOVA), and general linear models with repeated measure analysis of variance (ANOVA) were used. Results We observed a statistically significant difference in overall performance-based cognitive functioning. Adults with NF1 showed significant, moderate-to-severe impairments in intelligence, visual short-term memory, immediate visuospatial recall, sustained attention ( p  < 0.0001–0.002), and some executive functions ( p  = 0.008 − 0.001), whereas other cognitive functions (multitasking, reaction time, motor speed, spatial working memory, planning time, and planning efficacy as well as some self-reported executive functions) were unimpaired. Conclusions This is the first study with a population-based sample of persons with NF1 and the results show impairments of intelligence and other cognitive functions. The pattern of both significant cognitive impairments and non-significantly different cognitive functions suggests a cognitive profile of selective rather than generalized cognitive deficits in NF1.

Background Little is known about employment status, occupation, and disposable income in adults with NF1. Methods From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980–2019. Results Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61–0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16–3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82–0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years. Conclusion Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.

Background: Tumors of the central nervous system (CNS) are the most common solid childhood malignancy. Over the last decades, treatment developments have strongly contributed to the improved overall five-year survival rate, which is now approaching 75%. However, children now face significant long-term morbidity with late-effects including sleep disorders that may have detrimental impact on everyday functioning and quality of life. The aims of this study were to 1) describe the symptoms that lead to polysomnographic evaluation; 2) describe the nature of sleep disorders diagnosed in survivors of childhood CNS tumor using polysomnography; and 3) explore the association between tumor location and diagnosed sleep disorder. Methods: An extensive literature search following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines (PRISMA) was conducted. Inclusion criteria were children and adolescents diagnosed with a CNS tumor age < 20 years having a polysomnography performed after end of tumor treatment. The primary outcome was sleep disorder confirmed by polysomnography. Results: Of the 1,658 studies identified, 11 met the inclusion criteria. All the included articles were appraised for quality and included in the analysis. Analyses indicated that sleep disorders commonly occur among childhood CNS tumor survivors. Symptoms prior to referral for polysomnography were excessive daytime sleepiness, fatigue, irregular breathing during sleep and snoring. The most common sleep disorders diagnosed were sleep-related breathing disorders (i.e., obstructive sleep apnea) and central disorders of hypersomnolence (i.e., narcolepsy). Conclusion: Our findings point to the potential benefit of systematically registering sleep disorder symptoms among CNS tumor patients together with tumor type and treatment information, so that at-risk patients can be identified early. Moreover, future rigorous and larger scale controlled observational studies that include possible modifiable confounders of sleep disorders such as fatigue and obesity are warranted.

Individuals with neurofibromatosis 1 (NF1) may have problems in managing the transition between childhood and adulthood, such as forming a relationship or finding a partner. We aimed to determine the association between NF1 and forming and ending marital or cohabiting relationships by comparing a large Danish population of adults with NF1 with population comparisons. In this population-based cohort study, we compared a population of Danish adults who were hospitalized for or with complications to prior diagnosed NF1 (n = 787) with population comparisons matched on gender and birth year (n = 7787) through nationwide registries with annually updated information on marriage and cohabitation. Discrete-time survival models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the formation and termination of relationships, with adjustment for birth year, gender, and somatic and psychiatric comorbidities at entry. Individuals with NF1 were significantly less likely to form a relationship (HR = 0.65; 95% CI: 0.58–0.73), with the lowest association for individuals ≥33 years (HR 0.40; 95% CI: 0.25–0.63) and the highest for those aged 18–20 years (HR 0.82; 95% CI: 0.70–0.96). No significant difference was found for ending relationships (HR 1.00; 95% CI: 0.86–1.16). In conclusion, individuals who were hospitalized for NF1 are less likely to engage in marital or cohabiting relationships than population comparisons and are older when they form their first relationship. Once a relationship has been established, however, couples with a NF1-individual are not at greater risk of ending the relationship.

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10−7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

Since the publication of the article, the authors noticed that 'NFI cohort' and 'NFI-free cohort' columns in the 'Autismg' and the 'Autism/ADHD' rows had been erroneously interchanged in Table 3. This has now been updated in the HTML and PDF of the original article.

PurposeThe Danish neurofibromatosis 1 (NF1) cohort was initiated to study health-related, socioeconomic and psychological consequences of living with the monogenetic disorder NF1 using a nationwide and population-based approach.ParticipantsThe cohort includes all 2467 individuals in Denmark who were hospitalised with or due to NF1 from 1977 to 2013 or registered in the RAREDIS Database (1995–2013), a national clinical database for rare diseases, or both. A comparison cohort matched to individuals with NF1 on sex and date of birth was identified in the Civil Registration System (n=20 132).Findings to dateAll cohort members were linked to the unique Danish registries to obtain information on hospital contacts, birth outcomes, education and partnership. A questionnaire was completed by 244 of the 629 adult cohort members with NF1 registered in the RAREDIS Database to evaluate the psychosocial and emotional burden. Further, neuropsychological tests were performed on 103 adult cohort members with NF1 and 38 adult population comparisons. To date, six studies have been published. Individuals with NF1 had an increased risk for (1) hospitalisation for disorders affecting all organ systems of the body throughout all decades of life, (2) psychiatric disorders, (3) attaining a short or medium long education and (4) not forming a life partner. Women with NF1 had an increased risk for spontaneous abortions and stillbirths. Finally, adults with NF1 had an impaired quality of life and a high need for professional support for physical, psychological and work-related problems, which was partly associated with disease severity and visibility.Future plansThe cohort will regularly be updated with newly diagnosed patients in the RAREDIS Database as well as with outcome information in the Danish registries. New studies are in progress to assess other medical and socioeconomic dimensions of living with NF1.