Swedish Population-based Cohort Study Research Articles

#1271 Risk of primary infections in patients with IgA nephropathy: a Swedish population-based cohort study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common global kidney disease with a highly variable clinical presentation. Diagnosis IgAN requires a biopsy, and the immunohistologic examination is dominated by depositions of aberrant IgA1 antibodies. Since IgA antibodies are mainly produced by the mucosal associated lymphoid tissue the relationship between the mucosal immune system and IgAN has long been considered. The current theories on the origin of the disease involve genetic and environmental factors, with mucosal infections potentially playing a role. In some IgAN patients gastrointestinal and/or upper respiratory infections can aggravate the disease with episodic macrohematuria and/or increased proteinuria. Coincidently, these infections are also more common among patients with selective IgA deficiency. The aim of this study was to investigate whether the presence of IgAN confers an increased risk of infections in general to the IgAN patient. Method IgAN was defined by a computerized biopsy record from 1997 to 2011 in Sweden. Each IgAN patient was matched with up to five reference individuals based on age, sex, calendar year, and county of residence. Exclusions included those with organ transplants, HIV, immunodeficiency, or end-stage kidney disease before study entry, and follow-up data were censored for subsequent occurrences. Linear and Cox regressions, adjusted for age, sex, and education, were performed to analyze total infections and antimicrobial treatments in both patient and reference groups. Sibling analyses were also performed, adjusted for baseline age, sex and educational attainment. Results The linear regression analysis revealed a significant association between IgA nephropathy (IgAN) and the overall frequency of infections compared to the general population (β = 0.45; 95% CI: 0.37–0.54), women (β = 0.35; 95% CI: 0.19–0.50), men (β = 0.50; 95% CI: 0.40–0.60), and siblings (β = 0.37; 95% CI: 0.25–0.49) for women (β = 0.24; 95% CI: 0.06–0.41) and men (β = 0.43; 95% CI: 0.27–0.60). Similarly, a significant association was found for the frequency of prescribed antimicrobial agents compared to the general population (β = 0.66; 95% CI: 0.51–0.82), women (β = 0.92; 95% CI: 0.56–1.27), men (β = 0.55; 95% CI: 0.39–0.71), with similar estimates in the sibling analyses. The subtypes with the strongest association were urinary tract infections (β = 0.09; 95% CI: 0.07–0.11), ENT (ear, nose, and throat) infections (β = 0.08; 95% CI: 0.04–0.12), muscular infections (β = 0.08; 95% CI: 0.05–0.12), and infections in the GI (gastrointestinal) tract (β = 0.06; 95% CI: 0.04–0.09). Infections in the lower respiratory tract, skin and mycoses also had a significant positive association, however, no associations to infections in the central nervous system or infections caused by helminths and protozoans were identified. Cox regression showed an elevated risk of any infection with an adjusted hazard ratio (HR) of 2.05 (95% CI: 1.88–2.23), especially for sepsis (aHR = 3.13; 95% CI: 2.14–4.59), and time to the first prescription of antimicrobials with an aHR of 1.37 (95% CI: 1.30–1.45). Linear regression of prescribed antimicrobial treatments showed an overall β = 0.67; 95% CI: 0.51–0.82, and specifically for antibiotics (β = 0.64; 95% CI: 0.49–0.78). Conclusion Our study demonstrates an increased prevalence of infections and antibiotic prescriptions in IgAN patients compared to the general population and their siblings. Further studies on the potential impact of IgAN and its immunological aberrations on overall infection susceptibility is warranted.

Psychotropic drugs in patients with Addison's disease: A Swedish population-based cohort study

Psychotropic drugs in patients with Addison's disease: A Swedish population-based cohort study

The incidence of cancers in patients with non-functional adrenal tumors: a swedish population-based national cohort study

The incidence of cancers in patients with non-functional adrenal tumors: a swedish population-based national cohort study

Association between parental psychiatric disorders and risk of offspring autism spectrum disorder: a Swedish and Finnish population-based cohort study

Roughly more than one in six adults worldwide suffer from psychiatric conditions. Sporadic studies have associated parental psychiatric disorders with autism spectrum disorder in offspring. Comprehensively examining the association between parental psychiatric disorders and offspring autism spectrum disorder is needed to guide health policies, and to inform etiologic studies. We included all children born in Sweden and Finland 1997-2016. Diagnoses were clinically ascertained from National Registers through 2017. We calculated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for autism spectrum disorder in offspring of fathers and mothers with psychiatric disorders, in both parents jointly and across co-occurring conditions. Among 2,505,842 children, 33,612 were diagnosed with autism spectrum disorder, of which 20% had a parent with psychiatric disorders. The risk of autism spectrum disorder was increased across all psychiatric disorders in fathers (Sweden: aHR=2.02, 95% CI=1.92-2.12; Finland: aHR=1.63, 95% CI=1.50-1.77), mothers (Sweden: aHR=2.34, 95% CI=2.24-2.43; Finland aHR=2.12, 95% CI=1.92-2.28), or both parents (Sweden: aHR=3.76, 95% CI=3.48-4.07; Finland aHR=3.61, 95% CI=3.20-4.07), compared to neither parents. Co-occurrence of parental psychiatric disorders further increased risk (e.g., Sweden: for one, two or≥three different diagnostic categories compared to no diagnosis, in fathers aHR=1.81, 2.07, 2.52; in mothers aHR=2.05, 2.63, 3.57). Psychiatric disorders in both parents conveyed the highest risk of offspring autism spectrum disorder, followed by mothers and then fathers. The risk increased with number of co-occurring disorders. All parental psychiatric disorders were associated with increased the risk of autism spectrum disorder. To reliably assess the risk of autism spectrum disorder in children, a comprehensive history incorporating the full range of parental psychiatric disorders is needed beyond solely focusing on familial autism spectrum disorder. Swedish-Research-Council-2021-0214.

Incidence of oncogenic HPV infection in women with and without mental illness: A population-based cohort study in Sweden.

Women with mental illness experience an increased risk of cervical cancer. The excess risk is partly due to low participation in cervical screening; however, it remains unknown whether it is also attributable to an increased risk of infection with human papillomavirus (HPV). We aimed to examine whether women with mental illness had an increased infection rate of HPV compared to women without mental illness. Using a cohort design, we analyzed all 337,116 women aged 30 to 64 and living in Stockholm, who had a negative test result of 14 high-risk HPV subtypes in HPV-based screening, during August 2014 to December 2019. We defined women as exposed to mental illness if they had a specialist diagnosis of mental disorder or had a filled prescription of psychotropic medication. We identified incident infection of any high-risk HPV during follow-up and fitted multivariable Cox models to estimate hazard ratios (HR) with 95% confidence intervals (CI) for HPV infection. A total of 3,263 women were tested positive for high-risk HPV during follow-up (median: 2.21 years; range: 0 to 5.42 years). The absolute infection rate of HPV was higher among women with a specialist diagnosis of mental disorder (HR = 1.45; 95% CI [1.34, 1.57]; p < 0.001) or a filled prescription of psychotropic medication (HR = 1.67; 95% CI [1.55, 1.79]; p < 0.001), compared to women without such. The increment in absolute infection rate was noted for depression, anxiety, stress-related disorder, substance-related disorder, and ADHD, and for use of antidepressants, anxiolytics, sedatives, and hypnotics, and was consistent across age groups. The main limitations included selection of the female population in Stockholm as they must have at least 1 negative test result of HPV, and relatively short follow-up as HPV-based screening was only introduced in 2014 in Stockholm. Mental illness is associated with an increased infection rate of high-risk HPV in women. Our findings motivate refined approaches to facilitate the WHO elimination agenda of cervical cancer among these marginalized women worldwide.

Physical activity is associated with a lower risk of contracting and dying in infection and sepsis: a Swedish population-based cohort study

BackgroundSepsis is a condition where the immune response to infection becomes dysregulated and life-threatening. It is not known whether lifestyle factors influence the risk of sepsis. The aim of the present study is to investigate the association between physical activity and the risk of acquiring and dying in infection or sepsis.MethodsThe population-based Swedish Mammography Cohort and Cohort of Swedish Men sent participants lifestyle questionnaires in 1997 and have subsequently followed participants in national Swedish registers, including the National Patient Register, the Swedish Intensive Care Registry and the Cause of Death Register. The risk of contracting infection and sepsis, the risk of intensive care unit admission and the risk of death were estimated using multivariable Cox regression.ResultsAmong 64,850 cohort participants, 26,124 individuals suffered at least one episode of infection or sepsis and 4708 individuals died of infection or sepsis during the study period. In adjusted analyses, compared to exercising less than one hour per week, stated exercise one hour per week was associated with lower risk of contracting infection or sepsis, hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.90–0.97), and lower risk of dying in infection or sepsis, HR 0.87 (95% CI 0.80–0.96). Further exercise was associated with even lower risk, and similar patterns were observed for walking. The population-attributable risks of contracting and dying in infection or sepsis for not exercising were 2.6% and 4.5%, respectively.ConclusionsExercise and walking demonstrate inverse dose–response associations with both the risk of contracting and dying in infection and sepsis, presenting possible preventative interventions for this critical condition.

Real-world overall survival and characteristics of patients with ER-zero and ER-low HER2-negative breast cancer treated as triple-negative breast cancer: a Swedish population-based cohort study

Estrogen receptor-low (ER-low) HER2-negative breast cancer has similar pathological and molecular characteristics as triple-negative breast cancer (TNBC), and it is questionable whether it should be considered a separate entity. When the international guidelines lowered the cutoff for ER positivity to ≥1% in 2010, the ≥10% threshold was kept in Sweden. ER-low breast cancer (ER 1-9%) is thus in Sweden treated as TNBC. We aimed to describe patient and tumor characteristics, treatment patterns and overall survival in a Swedish population-based cohort of patients with ER-zero and ER-low HER2-negative breast cancer treated as TNBC. All TNBC cases diagnosed in Sweden 2008-2020 were included in a population-based cohort study. Patient, tumor and treatment characteristics were analyzed by ER-status (ER 0% vs 1-9%), and associations between subgroups compared using χ2 test. Survival endpoint was overall survival (OS), and Kaplan-Meier curves were estimated. Cox proportional hazards models were used to estimate adjusted hazard ratios comparing ER-low to ER-zero. Of the 5655 tumors, 90.1% had an ER expression of 0%, while 9.9% were ER-low. ER-low tumors were grade III in 69.4% (80.8% in ER-zero tumors, p-value=0.001), with a median Ki67 of 60% (63% in ER-zero tumors, p-value=0.005). There were no significant differences in given chemotherapy (p=0.546). A pathological complete response (pCR) was achieved in 28.1% of ER-low tumors (25.1% in ER-zero tumors). In the unadjusted analysis of OS, women with ER-low disease had a borderline but not significantly better OS than those with ER-zero disease (HR 0.84 (95% CI 0.71-1.00), p=0.052). ER-status 1-9% vs 0% was not associated with OS in the multivariable analysis (HR 1.11 (0.90-1.36)). Distant disease-free survival did not differ by ER-status 0% vs 1-9% (HR 0.97 for ER-zero vs ER-low (0.62-1.53), p=0.905). After preoperative treatment, the impact of pCR for OS did not significantly differ between ER-zero or ER-low disease. ER-low HER2-negative breast cancer has characteristics and prognosis similar to TNBC, when treated in the same way. Therefore, it seems reasonable to use a ≥10% threshold for ER positivity. This would provide patients with ER-low tumors the same treatment opportunities as patients with TNBC, within studies and within clinical routine. This work was financially supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, in accordance with terms and conditions of a Master Collaboration Agreement between the company and Karolinska Institutet.

Long-term risk of neoplastic events after childhood growth hormone treatment: a population-based cohort study in Sweden.

Increased risk of neoplastic events after recombinant human growth hormone (rhGH) treatment in childhood has been an ongoing concern but long-term safety data are limited. A nationwide population-based cohort study in Sweden of patients treated with rhGH during childhood between 1985-2010, due to isolated growth hormone deficiency (GHD), small for gestational age (SGA) and idiopathic short stature (ISS). The comparison group consisted of 15 age-, sex-, and region-matched controls per patient, randomly selected from the general population. Data on neoplastic events and covariates, such as gestational age, birth weight, birth length, socioeconomic status, and height at study start, were collected through linkage with population-based registers. The cohort was followed for neoplastic events until the end of 2020. 53,444 individuals (3,408 patients; 50,036 controls) were followed for up to 35 years, with a median follow-up of 19.8 years and a total of 1,050,977 person-years. Patients showed a moderately increased hazard ratio (HR) for neoplastic events overall compared to controls (HR 1.28, 95% CI: 1.12-1.46), but only significant for males (HR 1.39, 95% CI: 1.17-1.66) and not females (HR 1.15, 95% CI: 0.94-1.41). Longer treatment duration was associated with an increased HR, but no association was found between neoplastic events and mean or cumulative dose. No increased risk of malignant neoplasms was observed for the patients compared to matched controls (HR 0.91 95% CI: 0.66-1.26). No association was found between rhGH treatment during childhood for GHD, SGA, or ISS and malignant neoplastic events in early to mid-adulthood. A moderate increase in overall neoplastic events was observed due to an increased number of events in male patients.

Statin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma: a Swedish population-based cohort study.

Studies have suggested that medication with statins improves survival in patients with gastric cancer, but methodological issues have limited the interpretability and prohibited conclusive results. We aimed to provide valid evidence as to whether statin use improves survival of gastric adenocarcinoma. This nationwide and population-based cohort study included virtually all patients who underwent curatively intended surgery (gastrectomy) for gastric adenocarcinoma in Sweden between 2006 and 2015 with follow-up throughout 2019 for disease-specific mortality and 2020 for all-cause mortality. Data came from medical records and national healthcare registries. The exposure was statin use during the year prior to gastrectomy which was compared to no such use during the same period. The outcomes were 5-year disease-specific mortality (main) and 5-year all-cause mortality (secondary). Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, low-dose aspirin use, tumour sublocation, pathological tumour stage, neoadjuvant chemotherapy, annual surgeon volume, and surgical radicality. Among 1515 participating patients, the mean age was 69years and 58.4% were men. Statin use, identified in 399 (26.3%) patients, was not associated with any statistically significantly decreased 5-year disease-specific mortality (HR 0.99, 95% CI 0.82-1.21) or 5-year all-cause mortality (HR 0.94, 95% CI 0.79-1.12). No risk reductions were found across subgroups of age, sex, aspirin user status, or tumour stage, or in patients with long-term preoperative of postoperative use of statins, all with point estimates close to 1. Perioperative use of statins does not seem to improve the 5-year survival in patients who undergo gastrectomy with curative intent for gastric adenocarcinoma in Sweden.

Clostridioides difficile recurrence in individuals with and without cancer: a Swedish population-based cohort study

PurposePatients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored.MethodsThis Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006–2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status.ResultsCompared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73–0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43–1.74; Cancer history: OR = 1.45, 95% CI 1.36–1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76–0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97–1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found.ConclusionThe population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.

Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study

The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population. This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses. The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients. Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS. Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond, Mats and Stefan Paulsson Trust, Medicon Village, Lund and Uppsala University Hospital (ALF).

Educational attainment and symptoms of anxiety and depression in young adulthood

Abstract Background Young adulthood is a life phase when mental health problems are common. Although education is known to exert an influence on health, increased knowledge about the links between educational attainment and mental health problems in young adults is needed. The aim of this study was to analyse if educational attainment at the end of upper secondary (U.S.) school (i.e. age 19) predicted self-reported anxiety and depression symptoms two years later. Methods Data was derived from the Swedish population-based cohort study Futura01 (n = 3247; 56% women). Anxiety and depression were measured by self-reports in 2022 (age 21) through the Patient Health Questionnaire (PHQ-4). Educational attainment was measured through linked registry information from 2020 (age 19). Linear regression analysis was used. Covariates included parental country of birth, parental education and family type. Results Co-occurring symptoms of anxiety and depression were more common among young adults with a compulsory than a U.S. academic degree (women: b = 0.79, 95% CI 0.49, 1.09; men: b = 0.77, 95% CI 0.37, 1.17). Symptoms of depression only were more common among women with a compulsory degree (b = 0.60, 95% CI 0.20, 1.00), and among participants with a U.S. vocational degree (women: b = 0.51, 95% CI 0.09, 0.94; men: b = 0.50, 95% CI 0.08, 0.91), compared to those with a U.S. academic degree. Symptoms of anxiety only were, in contrast, less common among men and women with a compulsory degree compared to those with a U.S. academic degree, although statistically significant only among women (b=-0.50, 95% CI -0.88, -0.12). Conclusions Educational level in young adulthood was clearly associated with subsequent symptoms of anxiety and depression but the social patterning varied between symptoms. Lower educational level was linked to a higher reporting of co-occurring anxiety and depression and of depression only, while a higher educational level was linked to a higher reporting of anxiety only. Key messages • Young adult educational attainment was negatively associated with symptoms of co-occurring anxiety and depression and of depression only, but positively associated with symptoms of anxiety only. • In young adulthood educational level is associated with anxiety and depression in complex ways. Efforts to improve educational attainment and/or mental health need to consider this complexity.

O.5.1-11 Index for Promoting Sustainable, Healthy and Environment friendly Lifestyles and its association with metabolic syndrome: findings from a Swedish Population-Based Cohort Study

Abstract Purpose The purpose of this study was to investigate the association between sustainable and healthy lifestyle factors and the risk of metabolic syndrome, with a focus on promoting sustainable, healthy and environment friendly behaviours. By creating Index for Promoting Sustainable, Healthy and Environment friendly Lifestyles (IPSHEL), we aimed to assess the combined impact of various lifestyle factors on the development of metabolic syndrome. Methods A population-based cohort study was conducted in Sweden, involving a total of 5,364 participants. Lifestyle factors related to physical activity, food habits, tobacco use, alcohol, and sleep were assessed through questionnaires. To quantify the influence of these factors, an Index called IPSHEL was developed. Each lifestyle factor was graded and aggregated into an overall index score for each participant. Results The results showed a significant association between IPSHEL and the risk of metabolic syndrome. Individuals with the highest IPSHEL scores had reduced relative risk of developing metabolic syndrome compared to those with the lowest IPSHEL scores. Notable lifestyle factors strongly associated with metabolic syndrome included the intake of fast food and soda, portion sizes of meat and other protein-rich foods, intake of red and processed meat, consumption of cakes, candy, chocolate, ice-cream, chips, total sitting time, snuff use, and the climate impact from diet. Conclusions This study highlights the importance of adopting a sustainable and healthy lifestyle in reducing the risk of metabolic syndrome. The IPSHEL proved to be a valuable tool in assessing the combined impact of multiple lifestyle factors. These findings suggest the practical application of the index in public health contexts, serving as a useful tool for surveys, interventions, and evaluations targeting healthy behaviours. By promoting sustainable, healthy and environment friendly lifestyle choices, we can strive towards improved population health and the achievement of global development goals.

Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm: a Swedish population-based retrospective cohort study.

The aim of this study is to investigate how genetic variations in genes related to oxidative stress, intake of antioxidant vitamins, and any potential interactions between these factors affect the incidence of intact abdominal aortic aneurysm (AAA) and its rupture (rAAA), accounting for sex differences where possible. The present retrospective cohort study (n = 25 252) uses baseline single-nucleotide polymorphisms (SNPs) and total antioxidant vitamin intake data from the large population-based, Malmö Diet and Cancer Study. Cumulative incidence of intact AAA was 1.6% and of rAAA 0.3% after a median follow-up of 24.3 years. A variant in NOX3 (rs3749930) was associated with higher rAAA risk in males [adjusted hazard ratio (aHR): 2.49; 95% confidence interval (CI): 1.36-4.35] and the overall population (aHR: 1.88; 95% CI: 1.05-3.37). Higher intakes of antioxidant vitamins, riboflavin, and folate were associated with 20% and 19% reduced intact AAA incidence, respectively. Interestingly, the inverse associations between riboflavin and vitamin D intake with intact AAA incidence were stronger in the individuals carrying the NOX3 variant as compared with the wild-type recessive genotype, i.e. by 60% and 66%, respectively (P for interaction < 0.05). Higher riboflavin intake was associated with a 33% male-specific intact AAA risk reduction, while higher intake of vitamin B12 intake was associated with 55% female-specific intact AAA risk increase; both these associations were significantly modified by sex (P for interaction < 0.05). Our findings highlight the role of oxidative stress genetic variations and antioxidant vitamin intake in AAA. Although a low AAA/rAAA sample size limited some analyses, especially in females, our findings highlight the need for future randomized controlled trials and mechanistic studies, to explore the potential benefits of antioxidant vitamins while accounting for genetic and sex differences.

OP06_5. Alcohol exposure prior to pregnancy - does risk consumption increase the risk of preeclampsia and low birth weight? a swedish population-based cohort study

OP06_5. Alcohol exposure prior to pregnancy - does risk consumption increase the risk of preeclampsia and low birth weight? a swedish population-based cohort study

Air pollution, social engagement, and depression in older adults: Results from a Swedish population-based cohort study

Although emerging research has investigated the relationship between outdoor air pollution and depression risk in older adults, the results remain inconclusive. We aimed to determine the relationship between long-term exposure to ambient air pollution and depression among older adults and explore whether active social engagement may modify this association. At baseline (2001–2004), 2812 depression-free older adults from Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were included. SNAC-K is a longitudinal population-based cohort in Stockholm, Sweden. Incident depression cases occurred during 2004–2013 were ascertained using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition. Air pollution [particulate matter (PM) and nitrogen oxides (NOx)] at the residency were estimated using dispersion models. Social engagement was measured as active participation in social activities (at least twice/week) or inactive (less than twice/week) in the last 12 months. The hazard ratios (HR) and 95% confidence intervals of depression from air pollution exposure of 3-year moving average before diagnosis (1-μg/m3 difference in PM2.5 and PM10, and 10-μg/m3 difference in NOx) were obtained from Cox models considering greenspace and noise. A product term of air pollutant and social activity was added to test the multiplicative interaction and attributable proportion due to interaction was calculated for assessing additive interaction. We identified 137 (4.9%) incident depression cases. Participants exposed to higher concentrations of PM2.5, NOx, and PM10 had 53% (HR:1.53 [1.22, 1.93]), 26% (HR:1.26 [1.01, 1.58]), and 7% (HR:1.07 [0.98, 1.18]) increased hazard of depression, respectively. These associations were largely attenuated in people with active social engagement (HR for PM2.5: 1.04 [0.70, 1.55]; HR for PM10: 0.98 [0.81, 1.18]; and HR for NOx: 1.09 [0.71, 1.66]). Our findings suggest long-term exposure to air pollution may be a risk factor for depression among older adults. An active social engagement might however decrease this risk.

Associations between cardiorespiratory fitness in youth and the incidence of site-specific cancer in men: a cohort study with register linkage

ObjectivesTo assess the associations between cardiorespiratory fitness (CRF) in young men and the incidence of site-specific cancer.MethodsA Swedish population-based cohort study with register linkage of men who underwent military conscription...

Gender differences in earnings among people with multiple sclerosis and associations with type of occupation and family composition: A population-based study with matched references.

Gender differences in earnings exist worldwide. Gender segregation or familial status have been previously stated as possible explanations for these differences as well as health differences between women and men. Women are diagnosed with multiple sclerosis (MS) as twice much as men. Moreover, MS limitations may affect the work capacity of people with MS (PwMS) implying a reduction in their earnings. We aimed to explore gender differences in earnings among people with MS and without MS and between groups of those diagnosed while also considering types of occupation and family composition, and how these possible differences relate to sickness absence (SA) and disability pension (DP). We conducted a population-based cohort study in Sweden with microdata from several nationwide registers. PwMS aged 19-57 years (n = 5128) living in Sweden and 31,767 matched references from the population without MS. Outcome measures included earnings, number of SA and DP days combined (SA/DP). A four-way weighted least-squares analysis of covariance was performed to explore the associations of gender, MS, type of occupation, and family composition with earnings. Risk of SA and DP days was assessed with logistic regression. Overall, and across all occupations, women earned less than men, although less so among managers with MS. Annual gender differences in earnings were larger if living with children at home compared to not living with children. Nevertheless, these gender differences decreased after adjusting for SA/DP, both among PwMS and references. PwMS had considerably more SA/DP days than references. Women also had more SA/DP days than men. We observed that working women earned less than working men, and that gender differences in earnings were present in all occupations, although less evident among PwMS in managerial positions. The combination of gender, occupation, family composition, and MS, was associated with earnings, even when adjusting for the number of SA and DP days.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study.

Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown. Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs. A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00-6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants. Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.