Swedish Cohort Research Articles

Adverse pregnancy outcomes attributable to overweight and obesity across maternal birth regions: a Swedish population-based cohort study

Whether there are differences in the contribution of overweight and obesity to adverse pregnancy outcomes between migrant and non-migrant women in high-income countries, which might increase health inequalities, remains unclear. Therefore, in this study, we aimed to estimate the contribution (including the proportion and number of attributable cases) of overweight and obesity to a wide range of adverse pregnancy outcomes in Swedish-born and migrant women. This population-based cohort study used nationwide population registries in Sweden. All outcomes and covariates were collected from the Medical Birth Register (delivery and maternal characteristics), National Patient Register (inpatient and specialised outpatient care), the Cause of Death Register (all deaths in Sweden), the Longitudinal Integrated Database for Health Insurance and Labour Market Studies (socioeconomic data), and the Total Population Register (maternal birth country data). Women with missing records of BMI at the first antenatal visit, country of birth, or covariates, were excluded from the study. BMI was measured during the first antenatal visit. Maternal country of birth was categorised into Sweden and seven super-regions. The proportion (ie, population attributable fractions [PAFs]) and the number of adverse pregnancy outcomes attributable to overweight and obesity were calculated, adjusting for maternal age, gestational age at first antenatal visit, maternal parity, smoking status, maternal somatic conditions, child's sex, socioeconomic and demographic variables. We identified 2 228 416 singleton pregnancies between Jan 1, 2000, and Dec 31, 2020 of 1 245 273 women. 254 778 (11·4%) pregnancies with missing records of BMI at the first antenatal visit, country of birth, or covariates were excluded, which resulted in a final analytical cohort of 1 973 638 pregnancies carried by 1 164 783 women. The overall mean maternal age of the study population was 30·8 years (SD 5·1). As estimated by PAFs, overweight and obesity contributed to a large proportion of adverse pregnancy outcomes: gestational diabetes (52·1% [95% CI 51·0-53·2]), large-for-gestational age (36·9% [36·2-37·6]), pre-eclampsia (26·5% [25·7-27·3]), low Apgar score (14·7% [13·5-15·9]), infant mortality (12·7% [9·8-15·7]), severe maternal morbidity (henceforth referred to as a near-miss event; 8·5% [6·0-11·0]), and preterm birth (5·0% [4·4-5·7]) in the total study population. PAFs varied between maternal birth regions. Interventions to reduce overweight and obesity have the potential to mitigate the burden of adverse pregnancy outcomes and possibly reduce inequalities in reproductive health. Therefore, public health practice and policy should prioritise efforts to prevent overweight and obesity among women of childbearing age. Swedish Research Council.

Asthma and allergy trajectories in children based on combined parental report and register data.

Trajectories of asthma and allergy in children are heterogeneous and commonly derived from parental report of disease or clinical records. This study combined parental-reported and register-based dispensed medication data to characterize childhood trajectories of co-existing asthma, allergic rhinitis, and eczema. From a Swedish population-based birth cohort (N = 5654), survey responses collected at the age of 1, 4.5, 8, and 12 years were linked to dispensed medication register data for the period of 2-13 years. Trajectories were identified with latent class analysis. Statistical metrics and clinical interpretability guided the model selection. Nine distinct trajectories were identified: three asthma-dominated (early-onset remitting [n = 189, 3.3%], late-onset [n = 117, 2.1%], and persistent [n = 149, 2.6%]), two eczema-dominated (persistent [n = 190, 3.4%] and remitting [n = 432, 7.6%]), one allergic rhinitis-dominated (late-onset [n = 259, 4.6%]), two multimorbidity (mid-childhood asthma and late-onset allergic rhinitis [n = 144, 2.5%], and persistent eczema and late-onset allergic rhinitis [n = 90, 1.6%]), and one low-disease burden trajectory (n = 4084, 72.2%). Differences were seen across the trajectories in the proportion of parental report of disease and dispensed medication as well as by class and quantity of medication dispensed. Combined parental-reported and dispensed medication data enriches characterization of longitudinal trajectories of asthma and allergy in children by merging subjective experience of disease with healthcare utilization. The identified trajectories were characterized by distinct disease development and prescription patterns suggesting clinically differential morbidity burden.

Early clinical outcomes in men and women undergoing proximal thoracic aortic surgery – A Swedish population-based cohort study

ObjectiveTo investigate the association between female sex and 30-day mortality and postoperative complications in patients undergoing scheduled proximal thoracic aortic surgery in Sweden. MethodsIn a nationwide population-based cohort study, all patients who underwent scheduled proximal thoracic aortic surgery in Sweden between 2016 and 2020 were included. The primary outcome measure was 30-day mortality. Secondary outcome measure included a combined endpoint including 30-day all-cause mortality, postoperative new onset dialysis, perioperative stroke or a prolonged need of postoperative ventilation (>48 hours). Logistic regression models and propensity score matching were used to estimate the association between female sex and primary and secondary outcomes adjusted for differences in baseline characteristics. Results2000 patients (29% women) were analyzed. The crude 30-day all-cause mortality rate was higher in women compared to men (3.1 vs. 1.4%, p<0.001). Women were older at time of surgery (65.6 vs. 60.2 years, p<0.001), had more comorbidities and a larger maximum indexed aortic diameter (cm/m body height) at time of surgery (3.4 ± 0.56 vs. 3.0 ± 0.48, p<0.001). The adjusted risk for 30-day mortality for women compared to men was not significant (OR 1.41 CI 95% (0.70-2.83)), neither was the secondary composite endpoint (OR 0.89 CI 95% (0.62-1.27)). The propensity score matched analysis showed similar results. ConclusionsWomen who underwent proximal thoracic aortic surgery had a two-fold higher unadjusted 30-day mortality risk, but the mortality risk was not significantly higher when age and comorbidities was taken into consideration.

Cardiovascular events following coronavirus disease 2019 vaccination in adults: a nationwide Swedish study.

While the rationale for coronavirus disease 2019 (COVID-19) vaccination is to reduce complications and overall mortality, some cardiovascular complications from the vaccine itself have been demonstrated. Myocarditis and pericarditis are recognized as rare acute adverse events after mRNA vaccines in young males, while evidence regarding other cardiovascular events remains limited and inconsistent. This study assessed the risks of several cardiovascular and cerebrovascular events in a Swedish nationwide register-based cohort. Post-vaccination risk of myocarditis/pericarditis, dysrhythmias, heart failure, myocardial infarction, and cerebrovascular events (transient ischaemic attack and stroke) in several risk windows after each vaccine dose were assessed among all Swedish adults (n = 8 070 674). Hazard ratios (HRs) with 95% confidence intervals (95% CIs) compared with unvaccinated were estimated from Cox regression models adjusted for potential confounders. For most studied outcomes, decreased risks of cardiovascular events post-vaccination were observed, especially after dose three (HRs for dose three ranging from .69 to .81), while replicating the increased risk of myocarditis and pericarditis 1-2 weeks after COVID-19 mRNA vaccination. Slightly increased risks, similar across vaccines, were observed for extrasystoles [HR 1.17 (95% CI 1.06-1.28) for dose one and HR 1.22 (95% CI 1.10-1.36) for dose two, stronger in elderly and males] but not for arrhythmias and for transient ischaemic attack [HR 1.13 (95% CI 1.05-1.23), mainly in elderly] but not for stroke. Risk of myopericarditis (mRNA vaccines only), extrasystoles, and transient ischaemic attack was transiently increased after COVID-19 vaccination, but full vaccination substantially reduced the risk of several more severe COVID-19-associated cardiovascular outcomes, underscoring the protective benefits of complete vaccination.

What do we know now about evidence-based treatment for psychosis and aggressive behaviour or criminality that we did not know when community care was implemented?

Purpose Community care replaced institutional care for people with psychosis without guidance about what constituted effective treatment. In a Swedish birth cohort, many of those who developed schizophrenia or bipolar disorder as community care was being implemented were subsequently convicted of violent and non-violent crimes. Studies from other countries that were implementing community care at this time also reported elevated proportions of patients acquiring criminal convictions. Since community care was first implemented, much has been learned about factors that promote and treatments that limit aggressive/antisocial behaviour/criminality (AABC) among people with psychosis. Without the benefit of this knowledge, did mental health policy and practices that were in place as the asylums were closed inadvertently contribute to criminality? Material and methods This article provides a narrative review of current evidence of effective treatments and management strategies to reduce AABC among patients with psychosis. Results Reductions in AABC are associated with stable contact with psychiatric services, second-generation antipsychotic medication, clozapine for patients with schizophrenia and elevated levels of hostility and/or a history of childhood conduct disorder, abstinence from substances, avoidance of trauma, and constant monitoring of both illness symptoms and AABC. Conclusions Failure to adopt evidence-based practices allows the problem of AABC to persist, prevents patients from experiencing independent, safe, community tenure, and puts those around them at risk. Many challenges remain, including implementing effective assessment and interventions at first-episode and convincing patients with antisocial attitudes and behaviours to participate in treatment programs to reduce AABC and to learn prosocial behaviours.

Gene-variant specific effects of plasma amyloid-β levels in Swedish autosomal dominant Alzheimer disease

BackgroundSeveral blood-based biomarkers offer the opportunity of in vivo detection of brain pathology and neurodegeneration in Alzheimer disease with high specificity and sensitivity, but the performance of amyloid-β (Aβ) measurements remains under evaluation. Autosomal dominant Alzheimer disease (ADAD) with mutations in PSEN1, PSEN2 and APP can be studied as a model for sporadic Alzheimer disease. However, clarifying the genetic effects on the Aβ-levels in different matrices such as cerebrospinal fluid or plasma is crucial for generalizability and utility of data. We aimed to explore plasma Aβ concentrations over the Alzheimer disease continuum in a longitudinal cohort of genetic Alzheimer disease.Methods92 plasma samples were collected from at-risk individuals (n = 47) in a Swedish cohort of ADAD, including 18 mutation carriers (13 APPswe (p.KM670/671NL) MC), 5 PSEN1 (p.H163Y) MC) and 29 non-carriers (NC) as the reference group. Concentrations of Aβ1–38, Aβ1–40 and Aβ1–42 were analyzed in plasma using immunoprecipitation coupled to tandem liquid chromatography mass spectrometry (IP-LC-MS/MS). Cross-sectional and repeated-measures data analyses were investigated family-wise, applying non-parametric tests as well as mixed-effects models.ResultsCross-sectional analysis at baseline showed more than a 3-fold increase in all plasma Aβ peptides in APPswe MC, regardless of clinical status, compared to controls (p < 0.01). PSEN1 (p.H163Y) presymptomatic MC had a decrease of plasma Aβ1–38 compared to controls (p < 0.05). There was no difference in Aβ1–42/1–40 ratio between APPswe MC (PMC and SMC), PSEN1 MC (PMC) and controls at baseline. Notably, both cross-sectional data and repeated-measures analysis suggested that APPswe MC have a stable Aβ1–42/1–40 ratio with increasing age, in contrast to the decrease seen with aging in both controls and PSEN1 (p.H163Y) MC.ConclusionThese data show very strong mutation-specific effects on Aβ profiles in blood, most likely due to a ubiquitous production outside of the CNS. Hence, analyses in an unselected clinical setting might unintentionally disclose genetic status. Furthermore, our findings suggest that the Aβ ratio might be a poor indicator of brain Aβ pathology in selected genetic cases. The very small sample size is a limitation that needs to be considered but reflects the scarcity of longitudinal in vivo data from genetic cohorts.

Chemical Exposomics in Human Plasma by Lipid Removal and Large-Volume Injection Gas Chromatography-High-Resolution Mass Spectrometry.

For comprehensive chemical exposomics in blood, analytical workflows are evolving through advances in sample preparation and instrumental methods. We hypothesized that gas chromatography-high-resolution mass spectrometry (GC-HRMS) workflows could be enhanced by minimizing lipid coextractives, thereby enabling larger injection volumes and lower matrix interference for improved target sensitivity and nontarget molecular discovery. A simple protocol was developed for small plasma volumes (100-200 μL) by using isohexane (H) to extract supernatants of acetonitrile-plasma (A-P). The HA-P method was quantitative for a wide range of hydrophobic multiclass target analytes (i.e., log Kow > 3.0), and the extracts were free of major lipids, thereby enabling robust large-volume injections (LVIs; 25 μL) in long sequences (60-70 h, 70-80 injections) to a GC-Orbitrap HRMS. Without lipid removal, LVI was counterproductive because method sensitivity suffered from the abundant matrix signal, resulting in low ion injection times to the Orbitrap. The median method quantification limit was 0.09 ng/mL (range 0.005-4.83 ng/mL), and good accuracy was shown for a certified reference serum. Applying the method to plasma from a Swedish cohort (n = 32; 100 μL), 51 of 103 target analytes were detected. Simultaneous nontarget analysis resulted in 112 structural annotations (12.8% annotation rate), and Level 1 identification was achieved for 7 of 8 substances in follow-up confirmations. The HA-P method is potentially scalable for application in cohort studies and is also compatible with many liquid-chromatography-based exposomics workflows.

Prediction of suicide attempt in a Swedish population-based cohort.

Suicidal behaviors are prevalent public health concerns, and we need to improve our predictive ability to better inform prevention efforts. Using nationwide longitudinal Swedish registers, we included 344,490 males and 323,177 females born 1982-1990 with information on genetic liability and environmental exposures from birth to age 16: perinatal variables, parental psychopathology (suicide attempt, substance use disorder, major depression), family status, socioeconomic difficulties, peers' psychopathology, and school grades. We conducted sex-specific analysis and developed data-driven predictive models including risk factors that occurred between ages 0 and 16 using structural equation modeling. In both females and males, the best-fitting models reveal a complex risk pathway to suicide attempt. In females, the model indicates four direct effects on suicide attempt risk: the occurrence of suicide attempt in parents during childhood (β = 0.159, 95% CI: 0.118; 0.199) and adolescence (β = 0.115, 95% CI: 0.077; 0.153), suicide attempt in peers (β = 0.068, 95% CI: 0.057; 0.079), and low academic achievement (β = 0.166, 95% CI: 0.156; 0.175). In males, aggregate genetic liability for suicide attempt (β = 0.130, 95% CI: 0.111; 0.148), suicide attempt in parents during adolescence (β = 0.099, 95% CI: 0.074; 0.124), suicide attempt in peers (β = 0.118, 95% CI: 0.108; 0.129), and low academic achievement (β = 0.61, 95% CI: 0.152; 0.171) were related to later suicide attempt. These factors also acted as mediators to explain the association between environmental exposures in childhood and later suicide attempt. These findings illustrate sex-specific pathways to suicide attempt by including risk factors that occur during the development. Results highlight the importance of genetic and family environment but also the prominent role of academic achievement.

Potentially inappropriate prescribing in polymedicated older adults with atrial fibrillation and multimorbidity: a Swedish national register-based cohort study.

Current research on potentially inappropriate prescribing (PIP) in polymedicated older adults with atrial fibrillation (AF) and multimorbidity is predominantly focused on PIP of oral anticoagulants (OAC). Our study aimed to assess (i) the overall prevalence of PIP in older multimorbid adults with AF, (ii) potential associated factors of PIP, and (iii) the association of PIP with adverse health outcomes in a nationwide sample of Swedish older adults. Swedish national registries were linked to establish a cohort with a 2-year follow-up of older adults (≥65y) who, on 1 January 2017, had a diagnosis of AF and had at least one comorbidity (n = 203,042). PIP was assessed using the reduced STOPP/START version 2 screening tool. The STOPP criteria identify potentially inappropriate prescribed medications (PIM), while the START criteria identify potential prescribing omissions (PPO). PIP is identified as having at least one PIM and/or PPO. Cox regression analyses were conducted to examine the association between PIP and adverse health outcomes: mortality, hospitalisation, stroke, bleeding, and falls. PIP was highly prevalent in older adults with AF, with both polypharmacy (69.6%) and excessive polypharmacy (85.9%). In the study population, benzodiazepines (22.9%), hypnotic Z-medications (17.8%) and analgesics (8.7%) were the most frequent PIM. Anticoagulants (34.3%), statins (11.1%), vitamin D and calcium (13.4%) were the most frequent PPO. Demographic factors and polypharmacy were associated with different PIM and PPO categories, with the nature of these associations differing based on the specific type of PIM and PPO. The co-occurrence of PIM and PPO, compared to appropriate prescribing, was associated with an increased risk of adverse health outcomes compared to all appropriately prescribed medications: cardiovascular (CV) (Hazard ratio (HR) [95% confidence interval] = 1.97 [1.88-2.07]) and overall mortality (HR = 2.09 [2.03-2.16]), CV (HR = 1.34 [1.30-1.37]) and overall hospitalisation (HR = 1.48 [1.46-1.51]), stroke (HR = 1.93 [1.78-2.10]), bleeding (HR = 1.10 [1.01-1.21]), and falls (HR = 1.63 [1.56-1.71]). The present study reports a high prevalence of PIP in multimorbid polymedicated older adults with AF. Additionally, a nuanced relationship between prescribing patterns, patient characteristics, and adverse health outcomes was observed. These findings emphasise the importance of implementing tailored interventions to optimise medication management in this patient population.

Parental substance use disorders and psychiatric conditions in offspring: A Swedish population-based cohort study with over 1,000,000 individuals

BackgroundExposure to parental substance use problems has been associated with offsprings poor health and adverse social outcomes. In this study, we examined the association between exposure to parental substance use disorder (SUD) during childhood, and adolescence and offspring psychiatric conditions in young adulthood. MethodThis was a register-based cohort study comprising 562,095 males and 531,130 females born between 1981 and 1990 in Sweden. Parental SUD was captured between the offspring's birth and eighteenth birthday. Cox regression models were used to estimate the Hazard Ratio (HR) of psychiatric conditions from age 18 years to a maximum age of 35 years, from January 1, 1999 to December 31, 2016. ResultsAbout 4% of the study population was exposed to parental SUD during childhood and adolescence. The HR of psychiatric diagnosis was higher in males (1.80, 95% CI = 1.77–1.85) and females (1.56, 95% CI = 1.51–1.60) who were exposed to parental SUD, compared to those who were not; after adjusting for year of birth, domicile, origin, relative poverty, and other parental psychiatric diagnoses. The risks of psychiatric conditions were higher among males and females exposed to parental SUD during childhood compared to during adolescence. ConclusionExposure to parental SUD during childhood and adolescence was associated with an increased risk of psychiatric conditions in early adulthood for both males and females. Neither origin, poverty, municipality, or other parental psychiatric diagnoses fully explained the association. These risks seemed to be somewhat higher among males, and among those exposed during childhood when compared to during adolescence.

Risk of relationship separation in men with Peyronie’s disease in a matched Swedish cohort

Peyronie’s disease (PD) has detrimental effects on the quality of life, mental health, sexual functioning and several other aspects that increase the risk of relationship problems. However, no study to date has assessed the risk of relationship separation in med with PD. Herein, we utilized data from Swedish national registers to examine the risk of relationship separation in men with PD. We conducted a matched cohort study on men born 1933–1992, followed from 1997 to 2013. PD was defined as a physician-assigned diagnosis according to the International Classification of Diseases, Tenth version. Each man with PD (n = 8020) was matched with 10 comparison men. We defined relationship separation as (1) ever separated, and (2) separation rate. We used log-linear regression to estimate the risk ratio, and rate ratio of relationship separation. We adjusted for matching variables (birth year and country of birth), and an indicator of each follow-up year. We found that men with PD had a 13% increased risk of relationship separation (risk ratio 1.13, 95% confidence interval [CI] 1.08–1.17). The rate of relationship separation events, measured on a yearly basis, was increased by 18% (rate ratio 1.18, CI 1.12–1.24), and remained similar when adjusting for follow-up year and socio-economic status.

Transient colonizing microbes promote gut dysbiosis and functional impairment

Species composition of the healthy adult gut microbiota tends to be stable over time. Destabilization of the gut microbiome under the influence of different factors is the main driver of the microbial dysbiosis and subsequent impacts on host physiology. Here, we used metagenomics data from a Swedish longitudinal cohort, to determine the stability of the gut microbiome and uncovered two distinct microbial species groups; persistent colonizing species (PCS) and transient colonizing species (TCS). We validated the continuation of this grouping, generating gut metagenomics data for additional time points from the same Swedish cohort. We evaluated the existence of PCS/TCS across different geographical regions and observed they are globally conserved features. To characterize PCS/TCS phenotypes, we performed bioreactor fermentation with faecal samples and metabolic modeling. Finally, using chronic disease gut metagenome and other multi-omics data, we identified roles of TCS in microbial dysbiosis and link with abnormal changes to host physiology.

Psychiatric disorders and comorbidity in women with Turner Syndrome: a retrospective national cohort study

Turner syndrome (TS) is a genetic condition characterized by partial or complete monosomy X. A reduced life expectancy has been shown in TS, depending on an increased risk of aortic dissection, and ischemic heart disease. Studies covering the occurrence of psychiatric conditions are sparse within TS. Several case reports describe concomitant TS and neuropsychiatric abnormalities that may represent a pathogenetic link to genetics, as well as feature correlates of TS. The aim of this study was to determine the presence, and the frequency of psychiatric diagnosis in women with TS in a Swedish cohort followed during 25 years’ time. Statistics from the entire female population in Sweden of corresponding age was used as reference. Data were retrieved from clinical examinations and validated from the National Board of Health and Welfare registries for women with TS (n = 487), aged 16 to 84 years, with respect to mental health disorders. The most common diagnoses in TS were mood and anxiety disorders. There was no increase in psychiatric diagnosis within the group with time, nor correlation to specific karyotype or somatic comorbidity as congenital heart disease and hypothyroidism, hormonal treatment, or childbirth. In addition, the frequency of psychiatric diagnosis in TS was lower than in the population-based data. Further investigations are needed in the view of the fact that women with Turner syndrome should not be burdened with more severe diagnoses.

Sickness absence after work accidents and post-traumatic stress among white-collar workers in the retail and wholesale industry; a longitudinal Swedish cohort study

BackgroundMost studies about accidents and about PTSD, respectively, have been conducted either on blue-collar workers, or on the entire working population. There are very few such studies on white-collar workers.AimTo examine diagnosis-specific sickness absence (SA) and disability pension (DP) after a work accident or PTSD, respectively, among white-collar workers in the private retail and wholesale industry.MethodsA prospective population-based cohort study of all 192,077 such workers aged 18–67 (44% women) in Sweden in 2012, using linked microdata from nationwide registers. We identified individuals who had secondary healthcare due to work-related accidents (n = 1114; 31% women) or to PTSD (n = 216; 79% women) in 2012–2016. Their average number of net days of diagnosis-specific SA (in SA spells > 14 days) and DP were calculated for 365 days before and 365 days after the healthcare visit.Results35% of the women and 24% of the men had at least one new SA spell during the 365 days after healthcare due to work accidents. Among women, the average number of SA/DP days increased from 14 in the year before the visit to 31 days the year after; among men from 9 to 21 days. SA days due to fractures and other injuries increased most, while SA days due to mental diagnoses increased somewhat. 73% of women and 64% of men who had healthcare due to PTSD had at least one new SA spell in the next year. Women increased from 121 to 157 SA/DP days and men from 112 to 174. SA due to stress-related disorders and other mental diagnoses increased the most, while DP due to stress-related diagnoses and SA due to musculoskeletal diagnoses increased slightly.ConclusionsAbout a quarter of those who had secondary healthcare due to work accidents, and the majority of those with such healthcare due PTSD, had new SA in the following year. SA due to injury and mental diagnoses, respectively, increased most, however, SA/DP due to other diagnoses also increased slightly. More knowledge is needed on factors associated with having or not having SA/DP in different diagnoses after work accidents and among people with PTSD.

Differential Outcomes in Colorectal Cancer Detection: A Comparative Study of Swedish Nationwide Screening and Fast-Track Diagnostic Pathways.

In 2021, a nation-wide screening program for colorectal cancer (CRC) was step-wise implemented in Region Örebro County (RÖC) for patients aged 60 to 74 years, utilizing the fecal immunochemical test (FIT) to refer patients for colonoscopy. Concurrently, the standardized care course for colorectal cancer (SCC-CRC), initiated in 2016, employs a fast-track pathway for patients with alarm symptoms to undergo colonoscopy. This study compares CRC screening colonoscopies with SCC-CRC colonoscopies in RÖC among patients aged 60 to 67 years. An initial analysis of the Swedish colorectal screening cohort was combined with a retrospective cohort study, analyzing data from 307 CRC screening patients and 441 age-matched SCC-CRC patients in RÖC. Data included demographics, colonoscopy participation rates, and pathology findings. Statistical analyses compared outcomes between the 2 groups. Among the screening group, 2% tested positive for FIT, with an 86% colonoscopy participation rate (N=9296). In RÖC, 266 screening patients underwent colonoscopy, with 10% diagnosed with CRC, compared with 20% in the SCC-CRC group. In addition, 39% of the screening group in RÖC were diagnosed with advanced adenomas, versus 15% in the SCC-CRC group. Screening participation was high, with effectiveness aligning with international counterparts. The SCC-CRC pathway excels in diagnosing CRC among symptomatic patients, while the nationwide screening program is effective in early detection of CRC and advanced adenomas. underscoring the importance of integrating and optimizing both approaches within the Swedish health care system to optimize CRC prevention and management.

Shared genetic architecture between gastro-esophageal reflux disease, asthma, and allergic diseases

The aim is to investigate the evidence for shared genetic architecture between each of asthma, allergic rhinitis and eczema with gastro-esophageal reflux disease (GERD). Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (n = 46,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.

Personalized mixture toxicity testing: A proof-of-principle in vitro study evaluating the steroidogenic effects of reconstructed contaminant mixtures measured in blood of individual adults

Chemical risk assessments typically focus on single substances, often overlooking real-world co-exposures to chemical mixtures. Mixture toxicology studies using representative mixtures can reveal potential chemical interactions, but these do not account for the unique chemical profiles that occur in the blood of diverse individuals. Here we used the H295R steroidogenesis assay to screen personalized mixtures of 24 persistent organic pollutants (POPs) for cytotoxicity and endocrine disruption. Each mixture was reconstructed at a human exposure relevant concentration (1×), as well as at 10- and 100-fold higher concentration (10×, 100×) by acoustic liquid handling based on measured blood concentrations in a Swedish cohort. Among the twelve mixtures tested, nine mixtures decreased the cell viability by 4–18%, primarily at the highest concentration. While the median and maximum mixtures based on the whole study population induced no measurable effects on steroidogenesis at any concentration, the personalized mixture from an individual with the lowest total POPs concentration was the only mixture that affected estradiol synthesis (35% increase at the 100× concentration). Mixtures reconstructed from blood levels of three different individuals stimulated testosterone synthesis at the 1× (11–15%) and 10× concentrations (12–16%), but not at the 100× concentration. This proof-of-principle personalized toxicity study illustrates that population-based representative chemical mixtures may not adequately account for the toxicological risks posed to individuals. It highlights the importance of testing a range of real-world mixtures at relevant concentrations to explore potential interactions and non-monotonic effects. Further toxicological studies of personalized contaminant mixtures could improve chemical risk assessment and advance the understanding of human health, as chemical exposome data become increasingly available.

Associations between physical activity and ankle-brachial index: the Swedish CArdioPulmonary bioImage Study (SCAPIS)

BackgroundThe ankle–brachial index (ABI) is the ratio of the ankle and brachial systolic blood pressures. In the clinical setting, low ABI (< 0.9) is an indicator of peripheral atherosclerosis, while high ABI (> 1.4) is a sign of arterial stiffness and calcification. The purpose of the current study was to investigate the association between ABI and physical activity levels, measured by accelerometer.MethodsThe Swedish CArdioPulmonary bioImage Study (SCAPIS) is a Swedish nationwide population-based cross-sectional cohort for the study of cardiovascular and pulmonary diseases, in which individuals aged 50–64 years were randomly invited from the general population. The study population with data on ABI, physical activity, and sedentary time based on accelerometry was 27,737. Differences between ABI categories and associations to sedentary behavior, moderate to vigorous physical activity (MVPA), and other metabolic characteristics were compared. ABI was categorized as low, ABI ≤ 0.9, borderline, ABI 0.91–0.99, normal, ABI 1.0-1.39, and high, ABI ≥ 1.4.ResultsPrevalence of low ABI was higher in the most sedentary quartiles compared to the least sedentary (0.6% vs. 0.1%, p < 0.001). The most sedentary individuals also exhibited higher BMI, higher prevalence of diabetes and hypertension. The proportion of wake time spent in MVPA was lowest in those with low ABI (0.033 ± 0.004; p < 0.001) and highest in those with ABI > 1.4 (0.069 ± 0.001; p < 0.001) compared to those with normal ABI. Compared to normal ABI, the proportion of sedentary time was highest in those with low ABI (0.597 ± 0.012; p < 0.001) and lowest in those with ABI > 1.4 (0.534 ± 0.002; p = 0.004).ConclusionThis population-based study shows that middle-aged individuals with ABI > 1.4 have the highest level of physical activity, while individuals with a lower ABI, especially those with ABI < 0.9, are less active and spend more time sedentary. Future studies are needed to understand the relationships between ABI, physical activity, and the risk of peripheral arterial and cardiovascular disease in the general population.

Increased risk of bacterial pneumonia before and after respiratory syncytial virus infection in young children.

The burden of respiratory disease is great among children. This study aimed to examine the temporal relationship between hospitalisation for respiratory syncytial virus (RSV) and bacterial pneumonia. A Swedish population-based cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Children born between 1998 and 2015 were included and followed for 2 years. We examined the temporal relationship between RSV hospitalisation and bacterial pneumonia using piecewise exponential models. The final cohort comprised 1 641 747 children, 48.5% were females. There were 23 632 RSV and 4722 bacterial pneumonia hospitalisations, with mean age of 137.8 and 424.2 days, respectively. RSV hospitalisation was associated with bacterial pneumonia with an adjusted incidence rate ratio (aIRR) of 3.18. The risk was highest in the first month after RSV hospitalisation, aIRR 11.19. The risk of bacterial pneumonia was elevated for 4 months after RSV hospitalisation and before RSV hospitalisation. We found an increased risk for bacterial pneumonia hospitalisation in children hospitalised for RSV both before and after RSV hospitalisation, indicating a bidirectional relationship.

The Incidence of Cancers in Patients With Nonfunctional Adrenal Tumors: A Swedish Population-Based National Cohort Study.

It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence. To analyze the cancer incidence in patients with NFAT. In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded. Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors. The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.