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BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia. METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis. RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis. LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed. CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia., This study was supported by the following funding: The 2021 Shanghai “Science and Technology Innovation Action Plan” (Project Number: 21XD1432900), the Research Project Plan of the Shanghai Municipal Health Commission (Project Number: 202150019), the Project of Hospital Management from Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Project Number: YGA202308), and the 2022 Medical and Health Science and Technology Plan of Zhoushan City, China (Project Number: 2022JYB05).

Background and purpose: Rituximab (RTX) is frequently used off-label in multiple sclerosis. However, studies on the risk–benefit profile of RTX in pediatric-onset multiple sclerosis are scarce. Methods: In this multicenter retrospective cohort study, patients with pediatric-onset multiple sclerosis from Sweden, Austria and Germany, who received RTX treatment were identified by chart review. Annualized relapse rates, Expanded Disability Status Scale scores and magnetic resonance imaging parameters (new T2 lesions and contrast-enhancing lesions) were assessed before and during RTX treatment. The proportion of patients who remained free from clinical and disease activity (NEDA-3) during RTX treatment was calculated. Side effects such as infusion-related reactions, infections and laboratory abnormalities were assessed. Results: Sixty-one patients received RTX during a median (interquartile range) follow-up period of 20.9 (35.6) months. The annualized relapse rate decreased from 0.6 (95% confidence interval [CI] 0.38–0.92) to 0.03 (95% CI 0.02–0.14). The annual rate of new T2 lesions decreased from 1.25 (95% CI 0.70–2.48) to 0.08 (95% CI 0.03–0.25) and annual rates of new contrast-enhancing lesions decreased from 0.86 (95% CI 0.30–3.96) to 0. Overall, 70% of patients displayed no evidence of disease activity (NEDA-3). Adverse events were observed in 67% of patients. Six patients discontinued treatment due to ongoing disease activity or adverse events. Conclusion: Our study provides class IV evidence that RTX reduces clinical and radiological activity in pediatric-onset multiple sclerosis.

Background: This study, conducted on a Swedish population cohort, explores how internalized (depressive and functional somatic) and externalized (smoking, drinking, truancy, vandalism, delinquency) mental health symptoms, as well as close interpersonal relations (family climate and school connectedness) reported during adolescence, influence the work-life course up to late midlife. Methods: We examined repeated measurements of labour market status from age 16 to 56 using sequence analyses. We identified five different labour market attachment (LMA16-56) trajectories, namely ‘strong,’ ‘early intermediate,’ ‘early weak,’ ‘late weak,’ and ‘constantly weak.’ Multinomial logistic regressions were employed to relate each of the nine determinants to the identified trajectories. Results: When compared to the risk of ‘strong’ LMA16-56, adversity in all conditions, except for vandalism, entailed a higher risk of the ‘constantly weak’ trajectory. Moreover, all conditions, except for functional somatic symptoms, entailed a higher risk of the ‘late weak’ LMA16-56. The risk of the ‘early intermediate’ LMA16-56 was non-significant across all the conditions. Conclusions: This study contributes to existing knowledge through its novel exploration of labour market attachment and the revelation of the significance of proximal interpersonal relationships in attachment outcomes. Additionally, the study reaffirms the importance of externalizing behaviour, while suggesting that internalized symptoms in adolescence might have a less influential, though not negligible, role. These results underscore the importance of addressing acting out behaviour and nurturing human relationships during compulsory basic education, when the entire age group is still within reach. This approach aims not only to reduce frictions in the school-to-work transition but also to prevent midlife labour market attachment problems that may arise with delayed intervention.

One of the main tasks of the armed forces is to recruit and select future soldiers and to identify potential officers. However, these procedures may have a wider societal impact beyond the borders of the military organization itself. This study aims to examine how compatible assessments of military leadership potential are with those in the labor market. Using longitudinal data concerning a large cohort of Swedish males who underwent mustering during the early 1970s, we analyzed the association between officer suitability assessments and managerial role occupancy at age 50 to 55, while controlling for socio-demographic factors in childhood and adulthood. We found a high level of predictability, whereby those who were ranked highest were four times more likely to hold managerial positions than those with the lowest ranking. Results are discussed in relation to perceptions about leadership skills and possible institutional isomorphism between the armed forces and other societal organizations.

AIMS: We have evaluated long-term weighted mean HbA1c (wHbA1c), HbA1c variability, diabetes duration, and lipid profiles in relation to the development of diabetic peripheral neuropathy (DPN), nephropathy, and retinopathy in childhood-onset type 1 diabetes. MATERIALS AND METHODS: In a longitudinal cohort study, 49 patients (21 women) with childhood-onset type 1 diabetes were investigated with neurophysiological measurements, blood tests, and clinical examinations after a diabetes duration of 7.7 (±3.3) years (baseline) and followed with repeated examinations for 30.6 (±5.2) years. We calculated wHbA1c by integrating the area under all HbA1c values since the diabetes diagnosis. Lipid profiles were analysed in relation to the presence of DPN. Long-term fluctuations of HbA1c variability were computed as the standard deviation of all HbA1c measurements. Data regarding the presence of other diabetes complications were retrieved from medical records. RESULTS: In this follow-up study, 51% (25/49) of the patients fulfilled electrophysiological criteria for DPN. In nerve conduction studies, there was a deterioration in the amplitudes and conduction velocities for the median, peroneal, and sural nerves over time. Patients with DPN had a longer duration of diabetes, higher wHbA1c, and increased HbA1c variability. The lowest wHbA1c value associated with the development of DPN was 62 mmol/mol (7.8%). The presence of albuminuria and retinopathy was positively correlated with the presence of neuropathy. CONCLUSIONS: More than half of the patients had developed DPN after 30 years. None of the patients who developed DPN had a wHbA1c of less than 62 mmol/mol (7.8%)., Financial support was received from Linköping University, Sweden, ALF grants (Swedish governmental funding of clinical research), and the Medical Research Council of Southeast Sweden.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease., This study was supported by grants from the Swedish Research Council for Health, Working Life and Welfare (Forte) (grant number 2019-01236), Nyckelfonden and the UK Economic and Social Research Council (ESRC) to the International Centre for Life Course Studies (ES/R008930/1).

Introduction: Drawing upon the framework of life course epidemiology, this study aligns with research on the mental health consequences of significant social transitions during early adulthood. The focus is on the variation in initial labour market attachment and the development of depressiveness, assuming that a firm attachment is associated with decreasing depressiveness. Methods: The baseline investigation of the studied cohort (n = 1,001) took place during their final year of compulsory schooling at age 16. Follow-up surveys were conducted at ages 18, 21, 30, and 43. Depressiveness was measured with a five-item score. Multiple trajectory analysis, incorporating five labour market statuses observed over seven half-year periods from ages 18 to 21, was employed to categorize the cohort into six distinct groups. Among these, ‘All-time education,’ ‘From education to employment,’ ‘Education and employment,’ and ‘From employment to education’ were considered to demonstrate firm labour market attachment. Meanwhile, ‘Active labour market policy’ and ‘Unemployment’ represented less firm attachment. Results: The trajectory of depressive symptoms among the total cohort from age 16 to age 43 exhibited a ‘broken stick’ pattern, reaching its lowest point at age 21. This pattern was evident in all groups classified as having a firm attachment. A substantial decrease in depressiveness was also observed in the relatively weakly attached ‘Active labour market policy’ group, whereas no ‘broken stick’ pattern emerged in the ‘Unemployment’ group. The disparities in the levels of depressiveness observed at age 21 remained relatively stable across the measurements at ages 30 and 43. Discussion: The results were as expected, except for the observed improvement in mental health within the ‘Active labour market policy’ group. Supported labour market attachment during emerging adulthood can enhance mental well-being similarly to regular mainstream attachment. In terms of policy recommendat

Cutaneous malignant melanoma (CMM) is the cancer type in Sweden with the most rapidly increasing incidence. This thesis investigated if whole-body imaging improves the follow-up scheme post-surgery in high-risk CMM patients and explored the long-term outcomes for early-stage melanoma patients compared to the general population. We launched the nationwide randomized phase III study: “Trial to assess the Role of Imaging after radical surgery of CMM stage IIB-C and III (TRIM study, NCT 03116412)” with allocation to physical examinations for three years according to Swedish national guidelines +/- five scheduled whole-body imaging procedures. Primary endpoint is overall survival (OS) at five years. Secondary endpoints include Health-Related Quality of Life (HRQoL) outcomes. In paper I, the TRIM study protocol and the recruitment status were described and evaluated. Based on enrollment of more than 550 patients at 19 centra, we found the study protocol feasible and identified some obstacles for optimal inclusion rate. In paper II, we evaluated HRQoL and anxiety/depression in > 200 patients in the TRIM study who responded to the Hospital Anxiety and Depression (HAD) scale and the EORTC Quality of Life Questionnaire (QLQ)-C30 at baseline and after one year. No statistically significant differences were found between the study arms. Levels of anxiety and depression symptoms were generally low. The Malignant Melanoma Database Sweden (MMBaSe) was created by record linkages between the Swedish Melanoma Register and several population-based registers. The MMBaSe includes 67 000 individuals diagnosed with CMM or melanoma in situ (MIS) between 1996 and 2018 and matched, randomly selected, melanoma-free comparators representing the general population. Overall survival and mortality risks were assessed in two cohort studies in patients with MIS (paper III) and thin CMM (≤ 1 mm) (paper IV) in comparison to their matched comparators. Mortality risks were adjusted for socioeconomic

Purpose: We examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD). Methods: We analysed 2169 patients from the Alpha Omega Cohort (aged 60–80 years, 81% male). Dietary intake was assessed at baseline (2002–2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS. Results: The average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and − 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS. Conclusion: The DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.

This study aimed to evaluate short-term outcomes of the HEAL™ing Mental Health program, an 8-week intervention for change in functional, behavioural and physiological health and wellbeing designed for people living with mental health conditions in rural or regional areas of Australia. A prospective cohort study was completed, reporting on 19 items (pre-program) and 15 (post-participation change), organised across seven domains. Participants took part in an Accredited Exercise Physiologist/Nurse led supervised group exercise (60 minutes) and healthy lifestyle education program (60 minutes). Separate linear mixed models with restricted maximum likelihood were used to examine the primary research question considering the effect of the program on: walking (min/week); planned, incidental and total physical activity (min/week); sitting time; active days; fruit and vegetable intake; body mass index; waist circumference; blood pressure; 6 minute walk distance; 30 second sit-to-stand; psychological distress symptoms; and stage of behaviour change. There were 99 participants (31 males, 68 females) out of 117 participants completed more than 50% of program sessions. Twelve of 15 measures achieved their desired target change and a statistically significant change toward the desired outcome was reported for 14 of 15 measures. Positive results were obtained for participants completing more than 50% of sessions, suggesting that HEAL™ ing Mental Health program is effective to increase physical activity and healthy lifestyle choices in individuals who self-report a mental health disorder.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Type 2 diabetes (T2D) is a major health threat of our era and has become a health priority worldwide. Emerging evidence suggests that T2D is a main post-COVID-19 metabolic sequela, further exacerbating its epidemic. Inflammation and metabolic disorders are two hallmarks of T2D, and both have been shown to heighten the risk of incident diabetes. However, there are significant heterogeneities in the risks of incident diabetes with exposure to each of them. Notably, accumulated evidence suggests a closely intertwined biological process between them. It is unknown whether elevated inflammation could interact with metabolic disorders acting on diabetogenesis and explain the diabetic risk heterogeneity in metabolic disorders. Furthermore, different levels of inflammation have distinct sources. Low-grade systemic inflammation commonly results from metabolic disorders, whereas highgrade inflammation is indicative of an acute phase response, mainly initiated from acute infectious processes and acute stress. Currently, mainstream knowledge excludes highgrade inflammation for addressing the risk of cardiometabolic diseases and has seldom linked it to the pathophysiology of diabetes. Nonetheless, the alarmingly high incidence of T2D postacute SARS-CoV-2 infections has awakened a need to link infectious diseases to the development of T2D. This thesis aims to provide data-based epidemiological insights into the combined effect of different sources and levels of inflammation with a wide range of metabolic disorders on the development of diabetes and specifically considers the potential interactive effects between them. This thesis is composed of nine chapters: an overview of the thesis (Chapter 1); a comprehensive literature review (Chapter 2); six results chapters (Chapters 3–8); and a final chapter with a general discussion of the main findings and future directions (Chapter 9). The first chapter of the thesis includes an introduction and overview of the entire thesis. This is t

Results: A total of 8.9 mill

Objectives: To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively. Methods: We performed a nationwide population-based matched cohort study (Denmark, 1993–2021). We included 52 200 Bb-seropositive individuals (stratified as only Bb-IgM-seropositive [n = 26 103], only Bb-IgG-seropositive [n = 18 698], and Bb-IgM-and-IgG-seropositive [n = 7399]) and two age- and sex-matched comparison cohorts: 104 400 Bb-seronegative individuals and 261 000 population controls. We investigated the risk associated with being tested for serum Bb antibodies and being Bb seropositive. Outcomes were atrioventricular block and other conduction disorders. We calculated short-term odds ratios (aOR) (within 1 month), and long-term hazard ratios (aHR) (after 1 month) adjusted for age, sex, diabetes, chronic heart failure, and kidney disease with 95% CI. Results: Compared with population controls, individuals tested for Bb antibodies had increased short- and long-term risks of atrioventricular block (aOR 47.9, 95% CI: 30.0–76.7, aHR 1.3, 95% CI:1.2–1.3), and other conduction disorders (aOR 18.2, 95% CI: 10.1–32.8, aHR 1.2, 95% CI: 1.1–1.4). Compared with Bb-seronegative individuals, only Bb-IgM-and-IgG-seropositive individuals had increased short-term risk of atrioventricular block (aOR: 2.1, 95% CI: 1.5–3.1). Discussion: The results suggest that Bb antibody testing is included in the diagnostic work-up of conduction disorders. Finally, that Bb seropositivity is not associated with other conduction disorders than atrioventricular block or with increased long-term risk of conduction disorders.

Introduction Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study., Introduction: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. Methods: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. Results: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0–12.8). Conclusion: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study.

Objectives In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. Patients and methods Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0–10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. Results We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84–1.02]). Conclusion In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders., Objectives: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. Patients and methods: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0–10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. Results: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84–1.02]). Conclusion: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.

Background: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. Objective: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman’s general smoking habits. Methods: The study cohort included all Danish women, pregnant in the period 1991–2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. Results: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32–1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08–1.76), n = 110). Conclusion: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk., Background: The association between intra-uterine exposure to maternal smoking and risk of multiple sclerosis (MS) has been little studied and with conflicting results. Objective: To examine the risk of MS in offspring exposed intra-uterine to maternal smoking. In addition, to re-examine prior observations of an elevated risk of MS among smokers, assuming that self-reported smoking during pregnancy reflects the woman’s general smoking habits. Methods: The study cohort included all Danish women, pregnant in the period 1991–2018, (n = 789,299) and singletons from these pregnancies (n = 879,135). Nationwide information on maternal smoking during pregnancy and MS cases in the study cohort were obtained from the Medical Birth Register and the National Patient Register. Cox regression analysis was used to estimate hazard ratios (HRs) for the association between smoking and MS risk. Results: Women who smoked during pregnancy had a 42% increased risk of developing MS compared with non-smoking women (HR = 1.42 (1.32–1.52), n = 1,296). The risk of MS among singletons of women who smoked during pregnancy was 38% higher than that among singletons born to non-smoking women (HR = 1.38 (1.08–1.76), n = 110). Conclusion: Our observations add further to the evidence implicating smoking in the development of MS and suggest that intra-uterine exposure to tobacco smoke may increase MS risk.

Objective Patients with autoimmune disease may have impaired cancer survival. The aim was to investigate the association between autoimmune disease and ovarian cancer survival. Methods From the Extreme study, we included women diagnosed with epithelial ovarian cancer (EOC) in Denmark during 1990–2014 (n = 11,870). Information on exposure and covariates was retrieved from nationwide registries. Using pseudo-values, we estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) for autoimmune diseases combined and for the four most common individual disorders in our study population, namely type 1 diabetes, rheumatoid arthritis, Graves' disease, and inflammatory bowel disease. Results The overall 5- and 10-year absolute survival probabilities were 35% and 24%, respectively, in women with EOC without autoimmune disease. Autoimmune diseases combined was not significantly associated with survival among women with EOC (5-year adjusted relative survival probability = 1.01, 95% CI: 0.94–1.09; 10-year adjusted relative survival probability = 0.90, 95% CI: 0.81–1.00). However, stratification by disease stage showed an impaired 10-year survival in women with autoimmune disease and a localized EOC (relative survival probability = 0.86, 95% CI: 0.76–0.97). None of the individual autoimmune diseases were statistically significantly associated with EOC survival. Conclusions Only among women with localized EOC, there seemed to be a long-term survival loss associated with a history of autoimmune disease. In contrast, no significant association between a history of autoimmune disease and survival was observed in women with nonlocalized EOC where the survival is already low., Objective: Patients with autoimmune disease may have impaired cancer survival. The aim was to investigate the association between autoimmune disease and ovarian cancer survival. Methods: From the Extreme study, we included women diagnosed with epithelial ovarian cancer (EOC) in Denmark during 1990–2014 (n = 11,870). Information on exposure and covariates was retrieved from nationwide registries. Using pseudo-values, we estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) for autoimmune diseases combined and for the four most common individual disorders in our study population, namely type 1 diabetes, rheumatoid arthritis, Graves' disease, and inflammatory bowel disease. Results: The overall 5- and 10-year absolute survival probabilities were 35% and 24%, respectively, in women with EOC without autoimmune disease. Autoimmune diseases combined was not significantly associated with survival among women with EOC (5-year adjusted relative survival probability = 1.01, 95% CI: 0.94–1.09; 10-year adjusted relative survival probability = 0.90, 95% CI: 0.81–1.00). However, stratification by disease stage showed an impaired 10-year survival in women with autoimmune disease and a localized EOC (relative survival probability = 0.86, 95% CI: 0.76–0.97). None of the individual autoimmune diseases were statistically significantly associated with EOC survival. Conclusions: Only among women with localized EOC, there seemed to be a long-term survival loss associated with a history of autoimmune disease. In contrast, no significant association between a history of autoimmune disease and survival was observed in women with nonlocalized EOC where the survival is already low.

Objective To examine the association between the de Morton Mobility Index (DEMMI) score on admission in geriatric patients and readmission and mortality within 30, 180, and 365 days after discharge, and discharge to a post-acute care facility. Methods A nationwide register-based cohort study including 23,941 geriatric in-patients aged ≥65 years admitted to a geriatric ward between 2014 and 2017 and included in the Danish National Database for Geriatrics. The DEMMI score was categorized into four subcategories: very low mobility (DEMMI=0–24), low mobility (DEMMI=27–39), moderately reduced mobility (DEMMI=41–57), and independent mobility (DEMMI=62–100). Patients were followed 30, 180 and 365 days after discharge for readmission and mortality. Their risk of being discharged to a post-acute care facility was examined. Adjusted hazard ratios (HRs) and odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Results HRs for readmission within 30-days were 1.36 (1.24–1.48) for very low mobility, 1.30 (1.20–1.42) for low mobility and 1.17 (1.08–1.28) for moderately reduced compared with independent mobility. Similar results were seen for readmission within 180- and 365-days. For mortality, HR for 30-day mortality ranged from1.93 and 5.66, 180-day mortality between 1.62 and 3.19, and 365-day mortality between 1.54 and 2.81 compared with patients with independent mobility. OR for discharge to a post-acute care facility was 8.76 (7.29–10.53) for lowest compared with the highest DEMMI mobility subcategory. Conclusion In geriatric in-patients, lower DEMMI scores on hospital admission are associated with increased rates of discharge to a post-acute care facility, and for readmission, and mortality within one year., Objective: To examine the association between the de Morton Mobility Index (DEMMI) score on admission in geriatric patients and readmission and mortality within 30, 180, and 365 days after discharge, and discharge to a post-acute care facility. Methods: A nationwide register-based cohort study including 23,941 geriatric in-patients aged ≥65 years admitted to a geriatric ward between 2014 and 2017 and included in the Danish National Database for Geriatrics. The DEMMI score was categorized into four subcategories: very low mobility (DEMMI=0–24), low mobility (DEMMI=27–39), moderately reduced mobility (DEMMI=41–57), and independent mobility (DEMMI=62–100). Patients were followed 30, 180 and 365 days after discharge for readmission and mortality. Their risk of being discharged to a post-acute care facility was examined. Adjusted hazard ratios (HRs) and odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Results: HRs for readmission within 30-days were 1.36 (1.24–1.48) for very low mobility, 1.30 (1.20–1.42) for low mobility and 1.17 (1.08–1.28) for moderately reduced compared with independent mobility. Similar results were seen for readmission within 180- and 365-days. For mortality, HR for 30-day mortality ranged from1.93 and 5.66, 180-day mortality between 1.62 and 3.19, and 365-day mortality between 1.54 and 2.81 compared with patients with independent mobility. OR for discharge to a post-acute care facility was 8.76 (7.29–10.53) for lowest compared with the highest DEMMI mobility subcategory. Conclusion: In geriatric in-patients, lower DEMMI scores on hospital admission are associated with increased rates of discharge to a post-acute care facility, and for readmission, and mortality within one year.

Objectives In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals. Methods We identified all Bb seropositive individuals in Denmark (1993–2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex. We stratified seropositive individuals on only Bb-IgM seropositive (n = 26 103), only Bb-IgG seropositive (n = 18 698), and Bb-IgM-and-IgG seropositive (n = 7399). Results Compared with the background population, individuals tested for Bb antibodies had increased short-term (aOR: 12.6, 95% CI: 10.1–15.6) and long-term (aHR: 1.3, 95% CI: 1.2–1.4) risk of haematologic cancers. The Bb seropositive individuals had no increased risk of haematologic cancers compared with those who tested negative for Bb, except that Bb-IgM-and-IgG seropositive individuals had increased long-term risk of chronic lymphatic leukaemia (aHR: 2.0, 95% CI: 1.2–3.4). Discussion Our results suggest that Bb antibody testing is included in the work-up of unspecific symptoms preceding diagnosis of haematologic cancers. Bb-IgM-and-IgG seropositivity was associated with a two-fold increased long-term risk of chronic lymphatic leukaemia, which warrants further investigation., Objectives: In a nationwide, matched cohort study, we aimed to investigate risks of haematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals. Methods: We identified all Bb seropositive individuals in Denmark (1993–2020) (n = 52 200) and constructed two age- and sex-matched comparison cohorts: (a) Bb seronegative controls (n = 104 400) and (b) background population controls (n = 261 000). We calculated short-term OR (aOR) (<1 month of study inclusion), and long-term hazard ratios (aHR) (>1 month after study inclusion) adjusted for age and sex. We stratified seropositive individuals on only Bb-IgM seropositive (n = 26 103), only Bb-IgG seropositive (n = 18 698), and Bb-IgM-and-IgG seropositive (n = 7399). Results: Compared with the background population, individuals tested for Bb antibodies had increased short-term (aOR: 12.6, 95% CI: 10.1–15.6) and long-term (aHR: 1.3, 95% CI: 1.2–1.4) risk of haematologic cancers. The Bb seropositive individuals had no increased risk of haematologic cancers compared with those who tested negative for Bb, except that Bb-IgM-and-IgG seropositive individuals had increased long-term risk of chronic lymphatic leukaemia (aHR: 2.0, 95% CI: 1.2–3.4). Discussion: Our results suggest that Bb antibody testing is included in the work-up of unspecific symptoms preceding diagnosis of haematologic cancers. Bb-IgM-and-IgG seropositivity was associated with a two-fold increased long-term risk of chronic lymphatic leukaemia, which warrants further investigation.

Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I). In 2021, re-investigations were performed (PFT-II). We investigated changes in percent predicted (%pred) lung function from PFT-I to PFT-II. Patients were categorized into a pediatric group (age under 18 at PFT-I) and an adult group (age 18 or older at PFT-I). Out of the 81 patients completing PFT-I, 48 completed PFT-II. In the pediatric group (32 patients), there were significant declines in %pred forced expiratory volume in 1s (99.7 (92.4, 104.4)–89.3 (84.9, 97.2), p < 0,001), forced vital capacity (98.3 (87.8, 106.1)–96.7 (86.7, 100.6), p = 0.008), and alveolar volume (95.5 (89.5, 101.6)–89.5 (79.7, 93.2), p < 0.001). The corresponding measurements remained stable in the adult group. However, the median %pred DLNO significantly declined in the adult group (58.4 (53.3, 63.5)–53.7 (44.1, 57.3), p = 0.005). Over a 10-year period, several lung function parameters declined significantly in the younger Fontan patients, suggesting possible impairments in lung development during growth. The decline in %pred DLNO in the adult patient group indicates deterioration of the membrane component of diffusion capacity, implying that the Fontan circulation might negatively affect the alveolar membrane over time. © 2024, The Author(s)., Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I). In 2021, re-investigations were performed (PFT-II). We investigated changes in percent predicted (%pred) lung function from PFT-I to PFT-II. Patients were categorized into a pediatric group (age under 18 at PFT-I) and an adult group (age 18 or older at PFT-I). Out of the 81 patients completing PFT-I, 48 completed PFT-II. In the pediatric group (32 patients), there were significant declines in %pred forced expiratory volume in 1s (99.7 (92.4, 104.4)–89.3 (84.9, 97.2), p < 0,001), forced vital capacity (98.3 (87.8, 106.1)–96.7 (86.7, 100.6), p = 0.008), and alveolar volume (95.5 (89.5, 101.6)–89.5 (79.7, 93.2), p < 0.001). The corresponding measurements remained stable in the adult group. However, the median %pred DLNO significantly declined in the adult group (58.4 (53.3, 63.5)–53.7 (44.1, 57.3), p = 0.005). Over a 10-year period, several lung function parameters declined significantly in the younger Fontan patients, suggesting possible impairments in lung development during growth. The decline in %pred DLNO in the adult patient group indicates deterioration of the membrane component of diffusion capacity, implying that the Fontan circulation might negatively affect the alveolar membrane over time.

Infection with BK polyomavirus (BKPyV) is a common opportunistic infection after kidney transplantation (KT) and may affect graft function. We aimed to determine the incidence, risk factors, and clinical outcomes of BKPyV DNAemia in a prospective cohort of 601 KT recipients transplanted from 2012 to 2020. BKPyV PCR on plasma was performed at days 60, 90, 180, 270, and 360 post-KT. Any BKPyV DNAemia was defined as a single BKPyV DNA of ≥1000 copies/mL. Severe BKPyV DNAemia was defined as two consecutive BKPyV DNA of ≥10,000 copies/mL. Cumulative incidences were investigated using the Aalen–Johansen estimator, and the risk factors were investigated in Cox proportional hazard models. The incidence of any BKPyV DNAemia and severe BKPyV DNAemia was 21% (18–25) and 13% (10–16) at one year post-KT, respectively. Recipient age > 50 years (aHR, 1.72; 95% CI 1.00–2.94; p = 0.049), male sex (aHR, 1.96; 95% CI 1.17–3.29; p = 0.011), living donors (aHR, 1.65; 95% CI 1.03–2.74; p = 0.045), and >3 HLA-ABDR mismatches (aHR, 1.72; 95% CI 1.01–2.94; p = 0.046) increased the risk of severe BKPyV DNAemia. Any BKPyV DNAemia was associated with an increased risk of graft function decline (aHR, 2.26; 95% CI 1.00–5.12; p = 0.049), and severe BKPyV DNAemia was associated with an increased risk of graft loss (aHR, 3.18; 95% CI 1.06–9.58; p = 0.039). These findings highlight the importance of BKPyV monitoring post-KT.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

A recent hypothesis suggests that maternal hormonal contraception use has contributed to the increasing incidence of autism spectrum disorders (ASD). We used a nationwide population-based cohort (the PECH cohort) including 1,056,149 Danish children born in the period January 1, 1998, to December 31, 2014, to assess associations between maternal hormonal contraception use and childhood ASD (end of follow-up: December 31, 2017). Maternal hormonal contraception use was grouped as “recent use” (≤ 3 months before pregnancy start or during pregnancy), “previous use” (>3 months before pregnancy start) and “never use”, except for few products. Incidence rate ratios (IRRs) were estimated using Poisson regression. During follow-up of nearly 12 million person-years, 19,996 children were diagnosed with ASD. A slightly higher IRR was observed for maternal recent use of any hormonal contraception, compared to previous use. This association was largely driven by the non-oral progestin-only products, and associations were especially seen for infantile autism and other/unspecified ASD. An increased IRR of infantile autism was also observed for recent use of the oral progestin-only products, compared to previous use. Our results suggest that maternal use of hormonal contraception may be associated with ASD risk in children, especially for the progestin-only products., A recent hypothesis suggests that maternal hormonal contraception use has contributed to the increasing incidence of autism spectrum disorders (ASD). We used a nationwide population-based cohort (the PECH cohort) including 1,056,149 Danish children born in the period January 1, 1998, to December 31, 2014, to assess associations between maternal hormonal contraception use and childhood ASD (end of follow-up: December 31, 2017). Maternal hormonal contraception use was grouped as “recent use” (≤ 3 months before pregnancy start or during pregnancy), “previous use” (>3 months before pregnancy start) and “never use”, except for few products. Incidence rate ratios (IRRs) were estimated using Poisson regression. During follow-up of nearly 12 million person-years, 19,996 children were diagnosed with ASD. A slightly higher IRR was observed for maternal recent use of any hormonal contraception, compared to previous use. This association was largely driven by the non-oral progestin-only products, and associations were especially seen for infantile autism and other/unspecified ASD. An increased IRR of infantile autism was also observed for recent use of the oral progestin-only products, compared to previous use. Our results suggest that maternal use of hormonal contraception may be associated with ASD risk in children, especially for the progestin-only products.

Objectives: The association of migraine with the risk of certain cancer has been reported. The aim of this pilot study was to examine the associations between migraine and the onset of head and neck cancers (HNC). Materials and Methods: A total of 1755 individuals were identified through a nationwide population-based cohort registry in Taiwan between 2000 and 2013. The primary end point variable was new-onset head and neck cancers in patients with migraine versus non-migraine controls. Cox proportional hazard regression was used to derive the risk of HNC. Subgroup analyses were performed to determine subpopulations at risk of migraine-associated HNC. Sub-outcome analyses were carried out to provide the subtypes of migraine-associated HNC. Propensity score matching was utilized to validate the findings. Results: A total of four patients out of 351 patients with migraine and seven out of 1404 non-migraine controls developed HNC. The incidence of HNC was higher in patients with migraine than that in non-migraine controls (108.93 vs. 48.77 per 100,000 person-years) (adjusted hazard ratio, aHR = 2.908, 95% CI = 0.808–10.469; p = 0.102). The risk of HNC in patients with migraine with aura (aHR = 5.454, 95% CI = 0.948–26.875; p = 0.264) and without aura (aHR = 2.777, 95% CI = 0.755–8.473; p = 0.118) was revealed. The incidence of non-nasopharyngeal HNC secondary to migraine (112.79 per 100,000 person-years) was higher than that of nasopharyngeal cancer secondary to migraine (105.33 per 100,000 person-years). Conclusion: A higher incidence of HNC was observed in a small sample of patients with migraine, especially in those with migraine with aura. Migraine-associated HNC included non-nasopharyngeal HNC. Studies with a larger sample are needed to confirm the finding of the high risk of HNC in people with migraine.

ObjectivePharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016.MethodsAll adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002–2006, 2007–2011, and 2012–2016.ResultsA total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012–2016. In 2002–2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011–2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes.ConclusionSedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift., Objective: Pharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. Methods: All adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002–2006, 2007–2011, and 2012–2016. Results: A total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012–2016. In 2002–2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011–2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. Conclusion: Sedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Background: Type 2 diabetes (T2D) is associated with an increased risk of premature death. Whether multifactorial risk factor modification could attenuate T2D-related excess risk of death is unclear. We aimed to examine the association of risk factor target achievement with mortality and life expectancy among patients with T2D, compared with individuals without diabetes. Methods: In this longitudinal cohort study, we included 316 995 participants (14 162 with T2D and 302 833 without T2D) free from cardiovascular disease (CVD) or cancer at baseline between 2006 and 2010 from the UK Biobank. Participants with T2D were categorised according to the number of risk factors within target range (non-smoking, being physically active, healthy diet, guideline-recommended levels of glycated haemoglobin, body mass index, blood pressure, and total cholesterol). Survival models were applied to calculate hazard ratios (HRs) for mortality and predict life expectancy differences. Results: Over a median follow-up of 13.8 (IQR 13.1-14.4) years, deaths occurred among 2105 (14.9%) participants with T2D and 18 505 (6.1%) participants without T2D. Compared with participants without T2D (death rate per 1000 person-years 4.51 [95% CI 4.44 to 4.57]), the risk of all-cause mortality among those with T2D decreased stepwise with an increasing number of risk factors within target range (0-1 risk factor target achieved: absolute rate difference per 1000 person-years 7.34 [4.91 to 9.78], HR 2.70 [2.25 to 3.25]; 6-7 risk factors target achieved: absolute rate difference per 1000 person-years 0.68 [-0.62 to 1.99], HR 1.16 [0.93 to 1.43]). A similar pattern was observed for CVD and cancer mortality. The association between risk factors target achievement and all-cause mortality was more prominent among participants younger than 60 years than those 60 years or older (P for interaction = 0.012). At age 50 years, participants with T2D who had 0-1 and 6-7 risk factors within target range had an average 7.

Background The aim was to analyse whether scoliosis or windswept hip deformity (WSH) occurs first for children with cerebral palsy (CP). Methods This longitudinal cohort study using data from 1994 − 2020 (26 years) involved 41,600 measurements of 4148 children (2419 [58.3%] boys) with CP born 1990 − 2018 and registered into the Swedish CP follow-up program. Children were followed from a mean age of 2.8 [SD 1.4] years, until they developed either scoliosis or WSH or were removed at surgery. Results WSH developed first in 16.6% of the children (mean age 8.1 [SD 5.0] years), and scoliosis in 8.1% (mean age 8.1 [SD 4.9] years). The incidence of WSH was higher than scoliosis across all levels I–V of the Gross Motor Function Classification System (GMFCS), both sexes, and for those with dyskinetic (20.0%) or spastic (17.0%) CP. The incidence of scoliosis was highest (19.8%) and developed earliest in children with GMFCS level V (mean age 5.5 [SD 3.5] years), and in children with dyskinetic (17.9%) CP (mean age 7.0 [SD 4.7] years). Conclusions WSH presents earlier than scoliosis in most children with CP. Children with higher GMFCS level or dyskinetic CP are more likely to develop these deformities at a younger age., Jackie Casey, Andreas Rosenblad, Atli Agustsson and Henrik Lauge-Pedersen are co-authors.

Introduction Primary brain tumors are a common cause of morbidity and mortality in children and young people (CYP) globally. Impaired neurocognitive function is a potential severe consequence in primary brain tumor (PBT) survivors. There are no in-depth studies from low- and middle-income countries (LMICs) to inform management and follow-up. The research questions of this study were as follows: Are the sociodemographic factors (lower age of CYP, female gender, low socioeconomic status, low parental education), disease-related factors (high grade of tumor, presence of seizures, presence of hydrocephalous), and treatment-related factors (adjuvant therapy, no surgical intervention, post-treatment seizures, placement of shunts) associated with decline in neurcognition outcomes 12 months post-treatment in CYP with PBTs? Methods A prospective cohort study was conducted from November 2020 to July 2023 at the Aga Khan University Hospital and Jinnah Postgraduate Medical Centre, tertiary care hospitals in Karachi, Pakistan. All CYP aged 5 to 21 years with a newly diagnosed PBTs were eligible. The neurocognition assessment was undertaken by a psychologist at two points, i.e., pre-treatment and at 12 months post-treatment using validated tools. The verbal intelligence was assessed by Slosson Intelligence tool, revised 3rd edition (SIT-R3), perceptual reasoning by Raven’s Progressive Matrices (RPM), and the Processing Speed Index by Wechsler Intelligence Scale (WISC V) and Wechsler Adult Intelligence Scale (WAIS-IV). The data were analyzed by STATA version 12 software. Generalized estimating equation (GEE) was used to determine the factors associated with the mean change in 12 months post-treatment verbal and non-verbal neurocognition scores. Unadjusted and adjusted beta coefficients with their 95% confidence intervals were reported. Results A total of 48 CYPs with PBTs were enrolled, 23 (48%) of them were lost to follow-up and 10 (21%) died. The remaining 25 (52%) were reassess

Background There are limited data available, particularly in low- and middle-income countries (LMICs), on the long-term quality of life (QoL) and family functioning of primary caregivers of children and young people (CYPs) affected by primary brain tumors (PBTs). This study aimed to assess the factors associated with the mean change in QoL and family functioning scores of primary caregivers of CYP patients with PBTs 12 months posttreatment. Methods This prospective cohort study enrolled CYPs aged 5–21 years with newly diagnosed PBTs and their primary caregivers. The study was carried out between November 2020 and July 2023. The primary caregivers of CYPs were recruited from two major tertiary care centers in Karachi, Pakistan. The primary caregivers QoL were assessed by the Pediatric Quality of Life Inventory (PedsQL) Family Impact Module. The assessment was undertaken by a psychologist at the time of diagnosis and 12 months posttreatment. The data were analyzed with STATA version 12. Results Forty-eight CYPs with newly diagnosed PBTs and their primary caregivers (46 mothers and 2 fathers) were enrolled. At 12 months posttreatment, 25 (52%) CYPs and their primary caregivers (mothers) were reassessed, and 23 (48%) were lost to follow-up. On multivariable analysis, a significant decrease in mothers’ mean 12-month posttreatment QoL and family functioning scores was associated with CYP having posttreatment seizures (beta= -10.2; 95% CI: -18.4 to -2.0) and with the financial burden associated with the CYP’s illness (beta= -0.3; 95% CI: -0.4 to -0.1). However, in those cases where CYP had higher posttreatment quality of life scores (beta = 0.4; 95% CI = 0.1, 0.6) and posttreatment higher verbal intelligence scores (beta = 0.1; 95% CI = 0.01, 0.3), the mothers’ QoL and family functioning scores were significantly greater. Conclusion We found a significant decrease in QoL of mothers who had a high financial burden and whose CYP had posttreatment seizures. However, those who

Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer's disease (AD). Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to antiherpesvirus treatment and potential APOE epsilon 4 carriership interaction. Methods: This studywas conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001-2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied. Results: CumulativeADand all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE epsilon 4 or anti-CMV IgG. Similar results were obtained for HSV-1. Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624–2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818–2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance. Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed., Depto. de Farmacología, Farmacognosia y Botánica, Fac. de Farmacia, TRUE, pub

[Abstract] Objective. Postpartum depression is one of the most common complications after childbearing. Urinary incontinence is a frequent symptom during pregnancy and the postnatal period, often being the first time that women experience it. This systematic review and meta-analysis aimed to synthesize the evidence on the association between urinary incontinence and postpartum depression and to assess whether this association becomes weaker at 6 months after childbirth. Data Sources. MEDLINE, Embase, Cochrane Library, Web of Science, and PsycINFO were searched from inception to December 26, 2023. Study Eligibility Criteria. Cross-sectional and cohort studies addressing the association between urinary incontinence and postpartum depression were included. Methods. Pooled odds ratios and their 95% confidence intervals, and 95% prediction intervals were estimated using a DerSimonian and Laird random-effects model for the association between urinary incontinence and postpartum depression. Subgroup analyses were conducted on the basis of time after delivery (<6 or ≥6 months). The risk of bias was assessed with the National Institutes of Health Quality Assessment Tool for Observational Cohort Studies. Results. Eleven published studies were included in the systematic review and meta-analysis. Overall, the odds ratio for the association between urinary incontinence and postpartum depression was 1.45 (95% confidence interval, 1.11–1.79; 95% prediction interval, 0.49–2.40; I2=65.9%; P=.001). For the 7 cohort studies, the odds ratio was 1.63 (95% confidence interval, 1.35–1.91; 95% prediction interval, 1.14–2.13; I2=11.1%; P=.345). For the 4 cross-sectional studies, the odds ratio was 1.05 (95% confidence interval, 1.04–1.05; 95% prediction interval, 1.04–1.06; I2=0.0%; P=.413). According to the time after delivery, the odds ratio estimates for cohort studies with a postpartum period <6 months were 1.44 (95% confidence interval, 1.07–1.81; prediction interval, 0.63–2.25; I2=0.0

CHEK2 is a well-established breast cancer susceptibility gene. The most frequent pathogenic CHEK2 variant is 1100delC, a loss-of-function mutation conferring 2-fold risk for breast cancer. This gene also harbors other rare variants encountered in the clinical gene panels for hereditary cancer. One of these is CHEK2 c.1312 G > T, p.(Asp438Tyr) in the kinase domain of the protein, but due to its rarity its clinical significance for breast cancer predisposition has remained unclear. Here, we tested the prevalence of CHEK2 p.(Asp438Tyr) allele showing enrichment in the Northern Finnish population, in a total of 2284 breast cancer patients from this geographical region. Genotyping was performed for DNA samples extracted from peripheral blood using high-resolution melt analysis. Fourteen CHEK2 p.(Asp438Tyr) carriers were identified (14/2284, 0.6%, P = 0.67): two in the cohort of breast cancer cases with the indication of inherited disease susceptibility (2/281, 0.7%, P = 1.00) and twelve in the breast cancer cohort unselected for the family history of disease and age at disease onset (12/2003, 0.6%, P = 0.66). This frequency did not differ from the frequency in the general population (10/1299, 0.8%). No CHEK2 p.(Asp438Tyr) homozygotes were identified. Our results indicate that CHEK2 p.(Asp438Tyr) carriers do not have an increased risk for breast cancer and the classification of the CHEK2 p.(Asp438Tyr) variant can be changed from the variant of uncertain significance (VUS) to likely benign for breast cancer.

Purpose: This study estimated the long-term individual-level productivity costs of physical inactivity. Methods: The data were drawn from the Northern Finland Birth Cohort 1966, to which the productivity cost variables (sick leaves and disability pensions) from Finnish registries were linked. Individuals (N = 6261) were categorized into physical activity groups based on their level of physical activity, which was measured in three ways: 1) self-reported leisure-time moderate- to vigorous-intensity physical activity (MVPA) at 46 yr old, 2) longitudinal self-reported leisure-time MVPA at 31–46 yr old, and 3) accelerometer-measured overall MVPA at 46 yr old. The human capital approach was applied to calculate the observed costs (years 2012–2020) and the expected costs (years 2012–2031). Results: The results showed that the average individual-level productivity costs were higher among physically inactive compared with the costs among physically active. The results were consistent regardless of the measurement type of physical activity or the period used. On average, the observed long-term productivity costs among physically inactive individuals were €1900 higher based on self-reported MVPA, €1800 higher based on longitudinal MVPA, and €4300 higher based on accelerometer-measured MVPA compared with the corresponding productivity costs among physically active individuals. The corresponding difference in the expected costs was €2800, €1200, and €8700, respectively. Conclusions: The results provide evidence that productivity costs differ according to an individual’s level of physical activity. Therefore, investments in physical activity may decrease not only the direct healthcare costs but also the indirect productivity costs paid by the employee, the employer, and the government.

Background: Postpartum psychiatric disorders (PPD) are common complications of childbirth. A common explanation for their development is that the psychological, hormonal, and immune changes associated with pregnancy and parturition may trigger psychiatric symptoms postpartum. Rheumatoid arthritis (RA) is characterized by abnormalities in the activity of the hypothalamic-pituitary-adrenal axis and of the immune system, but its association with PPD is unknown. We analyzed whether women with RA before childbirth have an increased risk of PPD. Methods: We conducted a large population-based cohort study including mothers of singleton births in the Danish (1995-2015), Finnish (1997-2013), and Swedish Medical Birth Registers (2001-2013) (N = 3,516,849). We linked data from the Medical Birth Registers with data from several national socioeconomic and health registers. Exposure was defined as having a diagnosis of RA before childbirth, while the main outcome was a clinical diagnosis of psychiatric disorders 90 days postpartum. We analyzed the association between RA and PPD using Cox proportional hazard models, stratified by a personal history of psychiatric disorders. Results: Among women without a history of psychiatric disorders, the PPD incidence rate was 32.2 in the exposed and 19.5 per 1000 person-years in the unexposed group; women with RA had a higher risk of overall PPD than their unexposed counterparts [adjusted hazard ratio (HR) = 1.52, 95% confidence intervals (CI) 1.17 to 1.98]. Similar associations were also observed for postpartum depression (HR = 1.65, 95% CI 1.09 to 2.48) and other PPD (HR = 1.59, 95% CI 1.13 to 2.24). Among women with a history of psychiatric disorders, the incidence rate of overall PPD was 339.6 in the exposed and 346.6 per 1000 person-years in the unexposed group; RA was not associated with PPD. We observed similar associations between preclinical RA (RA diagnosed after childbirth) and PPD to those corresponding to clinical RA. Conclusions