Nationwide Register-based Cohort Study Research Articles

The PATCH study: Prevalence of Hearing Loss During Ageing and Treatment Choices in Osteogenesis Imperfecta: A Danish Nationwide Register-Based Cohort Study.

Osteogenesis imperfecta (OI) is a group of rare hereditary collagen disorders. Hearing loss (HL) is a known complication linked to changes in the bones of the middle ear seen in OI. We aimed to determine the prevalence, age at debut, incidence, and risk of HL, surgery on bones of the middle ear, and use of hearing aids. A Danish nationwide, register-based cohort study. Data were extracted from the Danish National Patient register. Anyone with an OI diagnosis between January 1st 1977 and December 31st 2018, matched 1:5 with a reference population (Ref.Pop) on birthyear and sex, were included. 864 persons (487 women) with OI were included in the study and 4276 (2330 women) in the Ref.Pop. The sub-hazard ratio (SHR) for any HL was 4.56 [95% CI 3.64-5.71], with a prevalence of 17.0% and 4.0% in the OI cohort and Ref.Pop. Median age at debut was 42 and 58 years, respectively. The risk of otosclerosis and/or surgery was higher in the OI cohort (SHR 22.51 [95% CI 12.62-40.14]), with a median age at debut of 43 and 32 years in the OI cohort and Ref.Pop, respectively. Hearing aid use was more frequent in the OI cohort (SHR 4.16 [95% CI 3.21-5.40]) than in the Ref.Pop. The median age at debut was 45 and 60 years in the OI cohort and Ref.Pop, respectively. Persons with OI have a higher risk and prevalence of HL, hearing aids, and surgery, debuting younger, and prevalence increases with age.

Drug survival and risk factors for ADHD medication discontinuation in adults: A Danish Nationwide Registry-based cohort study.

Attention deficit hyperactivity disorder (ADHD) medication has proven effective for treating ADHD in adults, nonetheless previous studies have shown high rates of medication discontinuation. To assess drug survival and identify risk factors associated with discontinuation of ADHD medication. A nationwide registry-based cohort study in Danish adults who redeemed a prescription for ADHD medication for the first time between 2010 and 2015. All patients were followed for 5 years from the first redeemed prescription. Discontinuation was defined as a gap of 12 months between redemptions. Logistic regression analysis with odds ratio (OR) and Kaplan Meier analysis were used to examine risk factors (sex, age, socioeconomic status, substance use disorders, and comorbidities) associated with discontinuation. Twenty three thousand nine-hundred and sixteen patients with ADHD were identified. The 5-year overall drug survival was 29% in women vs. 23.5% in men. The risk of medication discontinuation was significantly higher in men compared to women, OR 1.26 (95% CI 1.19-1.34, p < 0.001). Adults aged 31-50 years had a significantly decreased risk of medication discontinuation compared to adults aged 18-30 years, OR 0.57 (95% CI 0.53-0.61, p < 0.001). Switching ADHD medication two times or three times or more significantly decreased the risk of discontinuation; OR 0.53 (95% CI 0.49-0.56, p < 0.001) and OR 0.26 (95% CI 0.23-0.30, p < 0.001), respectively. Substance use disorders and certain comorbidities were associated with medication discontinuation. Eating disorders, OR 0.71 (95% CI 0.64-0.78, p < 0.001), intellectual disabilities, OR 0.65 (95% CI 0.59-0.73, p < 0.001) and sleep disorders, OR 0.42 (95% CI 0.37-0.49, p < 0.001) were associated with continuation of ADHD medication. The 5-year overall drug survival was longer in women compared to men. Women with ADHD; adults aged 31-50; and patients with comorbid eating disorder; intellectual disability; sleep disorder and medication switching were individually associated with continuation of ADHD medication. Various factors were associated with medication discontinuation. Discontinuation should be acknowledged as a common phenomenon in patients with ADHD and calls for increased attention from the treatment responsible prescriber or team. Moreover, our findings suggest that timely, frequent medication switching, or temporary regimens may indeed represent optimal management strategies for a significant proportion of the ADHD population.

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: a nationwide register-based cohort study from 1991 through 2021

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: a nationwide register-based cohort study from 1991 through 2021

Incidence and clinical significance of non-tuberculous mycobacteria among migrants in Denmark: a nationwide register-based cohort study from 1991 through 2021

BackgroundThere is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. MethodNationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. Results433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR]=2.1, 95%CI 1.9-2.3, p<0.001), possible disease (IRR=2.4, 95%CI 2.0-3.0, p<0.001), and isolation (IRR=4.6, 95%CI 3.9-5.4, p<0.001) compared to Danish-born, but not of definite disease (IRR=1.1, 95%CI 0.9-1.3, p=0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8%/year, p=0.133). ConclusionsMigrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for M. tuberculosis. Also, microbiologically classified definite NTM disease is not substantially more common among migrants.

Neurological function before and after an in-hospital cardiac arrest – A nationwide registry-based cohort study

BackgroundAccording to the Utstein Registry Template for in-hospital cardiac arrest (IHCA), a good neurological outcome is defined as either Cerebral Performance Category (CPC) 1–2 at discharge from hospital or unchanged CPC compared to baseline. However, the latter alternative has rarely been described in IHCA. This study aimed to examine CPC at admission to hospital, the occurrence of post-arrest neurological deterioration, and the factors associated with such deterioration. MethodsWe studied adult IHCA survivors registered in the Swedish Registry of Cardiopulmonary Resuscitation between 2007 and 2022. The CPC was assessed based on information from admission and discharge from hospital. The data were analyzed using descriptive statistics and significance tests. ResultsOne in ten IHCA had a CPC score > 1 at admission to hospital. Out of 7,677 IHCA who survived until hospital discharge and had full CPC data, 6,774 (88%) had preserved CPC, 150 (2%) had improved CPC, and 753 (10%) had deteriorated CPC. Among the factors significantly associated with deteriorated neurological function are IHCA in a general ward or intensive care unit, non-shockable rhythm, no ECG surveillance, and a higher proportion of intra-arrest and post-resuscitation treatments (all p-values < 0,05). ConclusionMost patients had preserved neurological function compared to admission. Factors associated with deteriorated neurological function are mainly concordant with established risk factors for adverse outcomes and are primarily intra-arrest and post-resuscitation, making deterioration hard to predict. Further, every tenth survivor was admitted with CPC more than 1, stressing the use of unchanged CPC as an outcome in IHCA.

Imprinting disorders in children conceived with assisted reproductive technology in Sweden

ObjectiveTo assess whether the use of assisted reproductive technology for conception is associated with imprinting disorders in children and the impact of parental factors related to infertility. DesignA nationwide register-based cohort study. SubjectsAll liveborn singletons in Sweden (N = 2 084 127) between 1997-2017 with follow-up to December 31, 2018. ExposureThe use of specific methods implemented in the assisted reproductive technology Main Outcome MeasuresThe International Classification of Diseases version 10 was used to identify three distinct imprinting disorder groups: Prader-Willi/Silver-Russell syndrome, Beckwith-Wiedemann syndrome, and central precocious puberty. The Cox model combined with inverse probability treatment weights were used to estimate weighted hazard ratio (wHR) with 95% confidence interval (CI), accounting for multiple confounders. ResultsA total of 1044 children were diagnosed with the disorders of interest, and 52 of them were conceived with assisted reproductive technology. The overall risk of being diagnosed with any of the studied imprinting disorders was elevated in children conceived with ART compared to all other children (HR 1.84, 95% CI: 1.38-2.45). After adjusting for parental background factors, the association was partially attenuated (wHR 1.50, 95% CI: 0.97-2.32), but remained also in the weighted comparison restricted to children of couples with known infertility (wHR 1.52, 95% CI: 1.05-2.21). For the specific diagnoses of Prader-Willi/Silver-Russell syndrome and Beckwith-Wiedemann syndrome, compared to children of couples with known infertility, children conceived with assisted reproductive technology showed a small excess risk, which could not be distinguished from the null (wHR 1.56 [95% CI: 0.93-2.62] and 1.80 [95% CI: 0.99-3.28], respectively). Further subgroup analysis showed that the combined use of intra-cytoplasmic sperm injection and cryopreserved embryos was associated with higher risk of both Prader-Willi/Silver-Russell syndrome (wHR 4.60, 95% CI: 1.72-12.28) and Beckwith-Wiedemann syndrome (wHR 6.69, 95% CI: 2.09-21.45). The number of central precocious puberty cases in children conceived with assisted reproductive technology was too small (N=3) to make any meaningful inference. ConclusionThe combined use of intra-cytoplasmic sperm injection and cryopreserved embryos was associated with small elevated risks of Prader-Willi/Silver-Russell syndrome and Beckwith-Wiedemann syndrome in children, independent of parental factors related to infertlity.

Impact of childhood traumatic brain injury on fitness for service class, length of service period, and cognitive performance during military service in Finland from 1998 to 2018: A retrospective register-based nationwide cohort study.

Traumatic brain injury (TBI) can cause neuronal damage and cerebrovascular dysfunction, leading to acute brain dysfunction and considerable physical and mental impairment long after initial injury. Our goal was to assess the impact of pediatric TBI (pTBI) on military service, completed by 65-70% of men in Finland. We conducted a retrospective register-based nationwide cohort study. All patients aged 0 to 17 years at the time of TBI, between 1998 and 2018, were included. Operatively and conservatively treated patients with pTBI were analyzed separately. The reference group was comprised of individuals with upper and lower extremity fractures. Information on length of service time, service completion, fitness for service class, and cognitive performance in a basic cognitive test (b-test) was gathered from the Finnish Military Records for both groups. Linear and logistic regression with 95% CI were used in comparisons. Our study group comprised 12 281 patients with pTBI and 20 338 reference group patients who participated in conscription. A total of 8 507 (66.5%) men in the pTBI group and 14 953 (71.2%) men in the reference group completed military service during the follow-up period. Men in the reference group were more likely to complete military service (OR 1.26, CI 1.18-1.34). A total of 31 (23.3%) men with operatively treated pTBI completed the military service. Men with conservatively treated pTBI had a much higher service rate (OR 7.20, CI 4.73-11.1). In the pTBI group, men (OR 1.26, CI 1.18-1.34) and women (OR 2.05, CI 1.27-3.36) were more likely to interrupt military service than the reference group. The PTBI group scored 0.15 points (CI 0.10-0.20) less than the reference group in cognitive b-test. PTBI groups had slightly shorter military service periods and higher interruption rate than our reference-group. There were only minor differences between groups in cognitive b-test.

Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.

The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown. In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.

Gender affirming treatment and employment rate in 3,812 Danish transgender persons and 38,120 controls. A nationwide register-based cohort study

Gender affirming treatment and employment rate in 3,812 Danish transgender persons and 38,120 controls. A nationwide register-based cohort study

Pregnancy loss in women with endocrine disorders - a nationwide registry-based cohort study of 366,548 Danish women

Pregnancy loss in women with endocrine disorders - a nationwide registry-based cohort study of 366,548 Danish women

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water

BackgroundThere is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. ObjectivesWe conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). Materials and methodsWe included all births in Sweden during 2012–2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. ResultsAmong the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01–1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DiscussionsWe observed an association of the sum of PFAS4 – especially PFOS – with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

Diverticulitis Is Associated with Increased Risk of Colon Cancer-A Nationwide Register-Based Cohort Study.

Background: An association between diverticulitis and colon cancer has been proposed. The evidence is conflicting, and the guidelines differ regarding recommended follow-up with colonoscopy after an episode of diverticulitis. To guide regimes for follow-up, this study aimed to investigate if patients with diverticulitis have an increased risk of colon cancer. Methods: This study is reported according to the RECORD statement. We performed a cohort study with linked data from nationwide Danish registers. The inclusion period was 1997-2009, and the complete study period was 1995-2013. The primary outcome was the risk of developing colon cancer estimated using a Cox regression analysis with time-varying covariates. We performed a sensitivity analysis on a cohort of people with prior colonoscopies, comparing the risk of colon cancer between the diverticulitis group and the control group. Results: We included 29,173 adult males and females with diverticulitis and 145,865 controls matched for sex and age. The incidence proportion of colon cancer was 2.1% (95% confidence interval (CI) 1.9-2.3) in the diverticulitis group and 1.5% (95% CI 1.4-1.5) in the matched control group (hazard ratio 1.6; 95% CI 1.5-1.8). The risk of having a colon cancer diagnosis was significantly increased in the first six months after inclusion (hazard ratio 1.7; 95% CI 1.5-1.8), and hereafter there was a lower risk in the diverticulitis group compared with controls (hazard ratio 0.8; 95% CI 0.7-0.9). This protective effect lasted eight years. The increased risk of colon cancer during the first six months after diverticulitis was also found in the cohort with prior colonoscopies. Conclusions: The risk of a colon cancer diagnosis was significantly increased for patients with diverticulitis 0-6 months after the diagnosis of diverticulitis. Hereafter, we found a protective effect of diverticulitis until eight years later, possibly due to a screening effect. We recommend a follow-up colonoscopy after the first diagnosis of diverticulitis.

Risk of Venous Thromboembolism in Patients With Stage III and IV Non–Small-Cell Lung Cancer: Nationwide Descriptive Cohort Study

BackgroundVenous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non–small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. Materials and MethodsA nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen–Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. ResultsAmong the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. ConclusionVTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.

Pediatric traumatic brain injury and early age multiple sclerosis in Finland: A nationwide register-based cohort study.

Examine the link between pediatric traumatic brain injury (pTBI) and early-onset multiple sclerosis in Finland. Conducted nationwide register study (1998-2018) with 28,750 pTBI patients (<18) and 38,399 pediatric references with extremity fractures. Multiple sclerosis diagnoses from Finnish Social Insurance Institution. Employed Kaplan-Meier and multivariable Cox regression for probability assessment, results presented with 95% CI. Of 66 post-traumatic multiple sclerosis cases, 30 (0.10%) had pTBI, and 36 (0.09%) were in the reference group. Cumulative incidence rates (CIR) in the first 10 years were 46.5 per 100,000 (pTBI) and 33.1 per 100,000 (reference). Hazard ratio (HR) for pTBI was 1.10 (95% CI: 0.56-1.48).Stratified by gender, women's CIR was 197.9 per 100,000 (pTBI) and 167.0 per 100,000 (reference) after 15 years. For men, CIR was 44.6 per 100,000 (pTBI) and 34.7 per 100,000 (reference). In the initial 3 years, HR for female pTBI was 1.75 (95% CI: 0.05-6.32), and between years 3 and 20, it was 1.08 (95% CI: 0.51-1.67). For male patients, HR was 1.74 (95% CI: 0.69-4.39). We did not find evidence of an association between pTBI and early-onset multiple sclerosis 20 years post-initial trauma.

Association of celiac disease with eosinophilic esophagitis: Nationwide register-based cohort study with sibling analyses

Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE). We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings. Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n= 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding. The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51). In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.

Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study

Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.

Adult offspring's education and parental mortality: A nationwide cohort study of the mediating role of lifestyle-related diseases.

Aim: The mechanisms behind the association between adult offspring's socioeconomic position and their parents' mortality are not well understood. This study investigates lifestyle-related diseases as a potential mediating pathway between adult offspring's education and parental mortality. Methods: This nationwide register-based cohort study consists of 963,742 older adults aged 65 years between 2000 and 2018. Lifestyle-related diseases were measured between 60 and 65 years and those with prior lifestyle-related diseases were excluded. Natural Effect Models were performed to assess potential mediation through lifestyle-related diseases of the association between offspring's education and parental mortality measured by additive hazard estimates with 95% confidence intervals (CIs). Results: Between 60 and 65 years, 150,501 (15.6%) older adults were diagnosed with lifestyle-related diseases and 149,647 (15.5%) died during follow-up. Compared with having offspring with long education, short education was associated with 631 (95% CI: 555; 707) and 581 (95% CI: 525; 638) additional deaths per 100,000 person-years for women and men, respectively, of which 15.4% (95% CI: 9.0; 21.6) and 16.8% (95% CI: 14.6; 18.9) were mediated by lifestyle-related diseases. The corresponding numbers for medium education were 276 (95% CI: 205; 347) and 299 (95% CI: 255; 343) with 26.2% (95% CI: 12.0; 40.6) and 27.6% (95% CI: 25.1; 31.8) mediated by lifestyle-related diseases. Conclusions: Lifestyle-related diseases accounted for 15-28% of the association between offspring's education and parental mortality for both men and women.

Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes

ImportanceIndividuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.ObjectiveTo investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.Design, Setting, and ParticipantsThis nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.ExposureUse of specific ADHD medications.Main Outcomes and MeasuresThe main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.ResultsA total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).Conclusions and RelevanceIn this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.

Stable glioma incidence and increased patient survival over the past two decades in Norway: a nationwide registry-based cohort study.

Surveillance of incidence and survival of central nervous system tumors is essential to monitor disease burden and epidemiological changes, and to allocate health care resources. Here, we describe glioma incidence and survival trends by histopathology group, age, and sex in the Norwegian population. We included patients with a histologically verified glioma reported to the Cancer Registry of Norway from 2002 to 2021 (N = 7,048). Population size and expected mortality were obtained from Statistics Norway. Cases were followed from diagnosis until death, emigration, or 31 December 2022, whichever came first. We calculated age-standardized incidence rates (ASIR) per 100,000 person-years and age-standardized relative survival (RS). Results: The ASIR for histologically verified gliomas was 7.4 (95% CI: 7.3-7.6) and was higher for males (8.8; 95% CI: 8.5-9.1) than females (6.1; 95% CI: 5.9-6.4). Overall incidence was stable over time. Glioblastoma was the most frequent tumor entity (ASIR = 4.2; 95% CI: 4.1-4.4). Overall, glioma patients had a 1-year RS of 63.6% (95% CI: 62.5-64.8%), and a 5-year RS of 32.8% (95% CI: 31.6-33.9%). Females had slightly better survival than males. For most entities, 1- and 5-year RS improved over time (5-year RS for all gliomas 29.0% (2006) and 33.1% (2021), p < 0.001). Across all tumor types, the RS declined with increasing age at diagnosis. The incidence of gliomas has been stable while patient survival has increased over the past 20 years in Norway. As gliomas represent a heterogeneous group of primary CNS tumors, regular reporting from cancer registries at the histopathology group level is important to monitor disease burden and allocate health care resources in a population.

Cancer risk with tocilizumab/sarilumab, abatacept, and rituximab treatment in patients with rheumatoid arthritis: a Danish cohort study.

To investigate cancer risk in rheumatoid arthritis (RA) patients treated with tocilizumab/sarilumab, abatacept, or rituximab compared with those who received tumour necrosis factor inhibitors (TNFi) and compared with biological disease-modifying anti-rheumatic drugs (bDMARD) naïve RA patients. Nationwide registry-based cohort study of RA patients initiating treatment with tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive patients their second type of conventional synthetic DMARD (csDMARD). Patients were identified in DANBIO and followed for cancer from 2006-2020. Patients could contribute multiple treatments, with person years (PYRS), deaths, and cancers allocated to each treatment group in a 'latest type of treatment' manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept, and rituximab group compared with TNFI and bDMARD naïve groups, respectively. In total, 21 982 treatment initiations, 96 475 PYRS, and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept, or rituximab treatment groups (HRs ranged from 0.7-1.1). More than five years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% confidence intervals CI 0.74-2.71). For hematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi (HR 0.09; 95%CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95%CI 0.00-1.89). Treatment with tocilizumab/sarilumab, abatacept, or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.