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Abstract Background Studies of time trends in Nordic adolescents' mental health have often relied on analyses of adolescents’ psychosomatic symptoms. In this study, we examine adolescents' self-reports on mental health in the context of the dual factor model, which encompasses both overt manifestations of mental health symptoms and subjective perception of one's health status. Method The objective of this study was to employ a person-oriented approach utilizing cluster analysis to discern time trends in mental health profiles of Nordic adolescents, using their psychosomatic complaints and their perception of their overall health as cluster variables. The resulting health profiles were then subjected to a comparative analysis with regard to different measures of psychological and social adjustment. The mental health profiles were based on data from the Health Behaviour in School-aged Children (HBSC) survey, which was conducted among almost 50000 15-year-olds in five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) between 2002 and 2022. Results Mental health profiles exhibiting comparable content were observed in all Nordic countries, including profiles indicating adequate health, perceived good health, perceived poor health, high psychosomatic complaints, and dual health problems (defined as both high psychosomatic complaints and perceived poor health). These health profiles showed similar trends over time in the Nordic countries. Significant gender differences were observed. In 2002, adequate health was the dominant profile for both sexes. After 20 years, however, the high psychosomatic profile became the most common profile among girls. Among the three risk profiles, namely perceived poor health, high psychosomatic complaints and dual health problems, adolescents in the dual problems profile had the most psychological and social adjustment problems. Conclusions The comparatively lower incidence of adjustment problems among adolescents in the high psychosomatic profile relative to the dual mental health group challenges the prevailing view that there has been a sharp increase in mental health problems among Nordic adolescents. This view was largely based on the observed rise in psychosomatic symptoms. Indeed, there was a doubling in the proportion of adolescents in the high psychosomatic complaints profile between 2002 and 2022. This increase was considerably more pronounced than that observed for the dual health problems profile which exhibited most problems.

Summary: Background: Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers. Methods: Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight measurement), we calculated hazard ratios (HRs) for the association between BMI and the risk of 122 cancers and cancer subtypes, grouped by topography and morphology. Cancers with a positive association (i.e., HR >1) at an α-level of 0.05 for obesity (BMI ≥30 kg/m2) vs. normal weight (BMI 18.5–24.9 kg/m2) or per 5 kg/m2 higher BMI, for which obesity is not an established risk factor, were considered potentially obesity related. Findings: After 100.2 million person-years of follow-up, 332,501 incident cancer cases were recorded. We identified 15 cancers in men and 16 in women as potentially obesity related. These were cancers of the head and neck, gastrointestinal tract, malignant melanoma, genital organs, endocrine organs, connective tissue, and haematological malignancies. Among these, there was evidence of differential associations with BMI between subtypes of gastric cancer, small intestine cancer, cervical cancer, and lymphoid neoplasms (P values for heterogeneity in HRs

Abstract Long-read genome sequencing (lrGS) is a promising method in genetic diagnostics. Here we investigate the potential of lrGS to detect a disease-associated chromosomal translocation between 17p13 and the 19 centromere. We constructed two sets of phased and non-phased de novo assemblies; (i) based on lrGS only and (ii) hybrid assemblies combining lrGS with optical mapping using lrGS reads with a median coverage of 34X. Variant calling detected both structural variants (SVs) and small variants and the accuracy of the small variant calling was compared with those called with short-read genome sequencing (srGS). The de novo and hybrid assemblies had high quality and contiguity with N50 of 62.85 Mb, enabling a near telomere to telomere assembly with less than a 100 contigs per haplotype. Notably, we successfully identified the centromeric breakpoint of the translocation. A concordance of 92% was observed when comparing small variant calling between srGS and lrGS. In summary, our findings underscore the remarkable potential of lrGS as a comprehensive and accurate solution for the analysis of SVs and small variants. Thus, lrGS could replace a large battery of genetic tests that were used for the diagnosis of a single symptomatic translocation carrier, highlighting the potential of lrGS in the realm of digital karyotyping.

Abstract Background Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection. Methods We used data from the Stockholm Diabetes Prevention Programme (SDPP) cohort together with information from national and regional registers. Individuals without T2D aged 35–56 years at baseline were followed up after two ten-year periods. The proportion of diagnosed T2D was based on register information for 7664 individuals during period 1 and for 5148 during period 2. Undiagnosed T2D was assessed by oral glucose tolerance tests at the end of each period. With logistic regression, we analysed factors associated with being diagnosed among individuals with T2D. Results At the end of the first period, the proportion of individuals with T2D who had been diagnosed with T2D or not was similar (54.0% undiagnosed). At the end of the second period, the proportion of individuals with T2D was generally higher, but they were less likely to be undiagnosed (43.5%). The likelihood of being diagnosed was in adjusted analyses associated with overweight (OR=1.85; 95% CI 1.22–2.80), obesity (OR=2.73; 95% CI 1.76–4.23), higher fasting blood glucose (OR=2.11; 95% CI 1.67–2.66), and self-estimated poor general health (OR=2.42; 95% CI 1.07–5.45). Socioeconomic factors were not associated with being diagnosed among individuals with T2D. Most individuals (>71%) who developed T2D belonged to risk groups defined by having at least two of the prominent risk factors obesity, hypertension, daily smoking, prediabetes, or family history of T2D, including individuals with T2D who had not been diagnosed by healthcare. Conclusions Nearly half of individuals who develop T2D during 10 years in Stockholm County are undiagnosed, emphasizing a need for intensified screening of T2D within primary healthcare. Screening can be targeted to individuals who have at least two prominent risk factors.

This study examines whether youth's goals for their future societal engagement affect their future political activities. We hypothesized, first, that youth's political interest would be a central predictor of their future political activities and, second, that their goals for future societal engagement would moderate their political interest. The greatest future political activity would be among youth who were both politically interested and had set high goals. A community sample of about 400 16-year-olds (M[subscript age]=16.62, SD=0.71, 50.8% females) was followed over four years. The theory of planned behavior was applied. Different types of political action were predicted: offline political activities, online political activities, membership of a political/civic organization, and taking a stance in public for a party pre and post voting in a national election. Age-16 political interest significantly predicted all age-20 political activities, except for being a member of political/civic organizations and actual voting. In line with the second hypothesis, significant interactions were found between political interest and setting societal goals for all the future political activities except voting. It was concluded that youth's early-developed agency in setting goals for their societal engagement has widespread predictive utility for their political activities over a lengthy period.

Background: Variable-oriented analyses of time trends in the ease of communicating with mothers and fathers in the Swedish HBSC (Health and Behavior in School-aged Children) dataset show that communication problems with fathers, but not with mothers, positively predict mental health problems among adolescents. This similarity across years is likely to lead to high structural stability in person-oriented analyses across survey years, providing opportunities to uncover typical communication patterns in a robust way. A person-oriented method, cluster analysis, was used in this study to clarify these variable-oriented findings on the prediction of mental health problems. Methods: The Swedish HBSC dataset of 15-year-olds for 2002, 2006, 2010, 2014, and 2018, with a total of 9255 participants, was used for variable- and person-oriented analyses. Results: Person-oriented analyses of ease of communication with the mother and ease of communication with the father show that poor communication with both parents is associated with the worst mental health problems. They also show that when there is poor communication with mothers, in most cases, adolescents also have poor communication with fathers. The variable-oriented analyses do not show that mental health problems are highest when adolescents find it difficult to communicate with both parents. Conclusions: Person-oriented analyses offer the possibility of drawing more specific conclusions about family conditions that affect adolescents’ mental health. More generally, person-oriented analyses are likely to clarify the results of variable-oriented analyses in many other areas also.

AbstractObjective Describe a method in a real-world setting to identify persons with undiagnosed prediabetes and type 2 diabetes through an interprofessional collaboration between Public Dental Services and Primary Health Care in Regions Stockholm.Design A descriptive observational study.Setting The study was conducted at seven sites in the region of Stockholm, Sweden. Each collaborating site consisted of a primary health clinic and dental clinic.Subjects Study participants included adults over 18 years of age who visited the Public Dental Services and did not have a medical history of prediabetes or type 2 diabetes.Main outcome measures Selective screening is conducted in accordance with a risk assessment protocol at the Public Dental Services. In the investigated method, DentDi (Dental and Diabetes), adults diagnosed with caries and/or periodontitis over a cut-off value are referred to the Primary Health Care clinic for screening of prediabetes and type 2 diabetes.Results DentDi, introduced at seven sites, between the years 2017 and 2020, all of which continue to use the method today. A total of 863 participants from the Public Dental Services were referred to the Primary Health Care. Of those 396 accepted the invitation to undergo screening at the primary health care centre. Twenty-four individuals did not meet the inclusion criteria, resulting in a total of 372 persons being included in the study. Among the 372 participants, 27% (101) had elevated glucose levels, of which 12 were diagnosed with type 2 diabetes and 89 with prediabetes according to the study classification.Conclusions DentDi is a feasible method of interprofessional collaboration where each profession contributes with the competence included in everyday clinical practice for early identification of persons with prediabetes and type 2 diabetes with a complete chain of care. The goal is to disseminate this method throughout Stockholm County and even other regions in Sweden.

Abstract Background People with prediabetes are at high risk of developing type 2 diabetes and its complications, such as cardiovascular diseases and premature mortality. Primary prevention and health maintenance are therefore imperative. Evidence has shown that prediabetes can be prevented or delayed with behavioural change, mainly in eating habits and physical activity. Interventions that use a person-centered approach can lead to improvements in self-management, quality of life, and health outcomes. Nevertheless, there is a need for further research that engages healthcare professionals and people with prediabetes in constructing and implementing preventive programs. The purpose of this study is to explore and describe how healthcare professionals perceive prediabetes, the current challenges in its detection and treatment, and what is needed to improve quality of care. Methods This qualitative study was conducted in Region Stockholm. A total of 26 primary health care professionals participated in individual interviews: 15 diabetes nurses and/or district nurses, five general practitioners, five dietitians, and one physiotherapist. Interview transcripts were analyzed with qualitative content analysis. Results The analysis revealed two main themes that emphasize the need to make prediabetes more visible in primary health care. Despite the healthcare professionals’ engagement and their motivation to improve prediabetes care, ad hoc practices and the absence of clear screening guidelines and referral pathways made it harder to focus on primary prevention. Supporting professionals in implementing structured care for people with prediabetes might encourage more efficient interprofessional collaboration and contribute to better strategies for promoting behavioural change. Conclusions Establishing prediabetes care guidelines, supporting health care professionals´ knowledge and skills in prediabetes care, and implementing interprofessional referral pathways are some steps to enhance prediabetes detection and care precedence in primary health care. These steps could lead to more preventive care and ensure patient safety and health care equity.

Background Little is known about risks of hypertensive disorders of pregnancy in both first‐ and second‐generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first‐ and second‐generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy. Methods and Results A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% CIs while adjusting for sociodemographic factors and comorbidities. The first‐generation study included a total of 1 084 212 deliveries and 68 311 hypertension cases, and the second‐generation study included 989 986 deliveries and 67 505 hypertension cases. The fully adjusted HR (with 99% CI) for hypertension in pregnancy among first‐generation immigrant women was 0.69 (0.66–0.72), and among second‐generation immigrant women, it was 0.88 (0.86–0.91), compared with Swedish‐born women with 2 Swedish‐born parents. Women born in Finland or with parent(s) from Finland had higher risks, with fully adjusted HRs (99% CIs) of 1.30 (1.18–1.43) and 1.12 (1.07–1.17), respectively. Conclusions Both first‐ and second‐generation immigrant women had overall lower risks of hypertension in pregnancy compared with other Swedish women. However, the risk reduction was less pronounced in second‐generation compared with first‐generation immigrant women, suggesting that environmental factors in Sweden may have an important influence on risk of hypertension during pregnancy.

This study examines the idea that youth's perceptions of their political interactions with important others are influenced by their own political interest to a greater extent than the perceived political interactions that influence youth's political interest. Hence, it was proposed that youth's perceptions of important others' (parents', teachers', friends') political views, political interest, political influence, and support, as well as of being susceptible to others' political communication, are all affected by their own political interest. Community samples of 908 13-year-olds and 869 16-year-olds were followed over 1 year. Latent change models supported the idea that youth's political interest significantly affected their perceptions of important others' political views, influence, and support over time in both cohorts. In 11 out of 12 longitudinal analyses, youth's political interest strongly affected perceptions of their political interactions with others, but none of the 12 analyses showed that the perceptions of political interactions with others strongly predicted a change in youth's political interest. These results suggest that the political interest of young people is an input in their political development, making politically interested youth active agents in their political interactions with their important others.

Abstract Background Insulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent. Methods We investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non‐aggressive and aggressive) and PCa death using multivariable‐adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride‐glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin. Results Higher HbA1c was related to a lower risk of non‐aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00–1.49 and 1.24, 95% CI 1.00–1.55), which further increased when restricting the analyses to glucose and TyG index measures taken

BackgroundSmoking has been associated with a higher risk of contracting pneumonia, but contradictory results have shown that smoking may or may not decrease the risk of dying in pneumonia. The aim of this study is to investigate how smoking is associated with contracting any infection and pneumonia and death.Method and findingsParticipants were drawn from the population-based Cohort of Swedish Men and the Swedish Mammography Cohort, which are representative of the Swedish population. Participants have answered detailed lifestyle questionnaires and have been followed in national registers, such as the Patient Register, Cause of Death register and Swedish Intensive Care Registry. The risks of contracting infection and pneumonia or dying in infection and pneumonia were assessed using Cox regression. Of 62,902 cohort participants, 25,297 contracted an infection of which 4,505 died; and 10,471 contracted pneumonia of which 2,851 died. Compared to never smokers, former smokers at baseline had hazard ratio (HR) 1.08 (95% confidence interval (CI) 1.05-1.12) of contracting and HR 1.19 (95% CI 1.11-1.28) of dying in infection and HR 1.17 (95% CI 1.12-1.23) of contracting and HR 1.16 (95% CI 1.06-1.27) of dying in pneumonia during follow-up. Compared to never smokers, current smokers at baseline had HR 1.17 (95% CI 1.13-1.21) of contracting infection and HR 1.64 (95% CI 1.52-1.77) dying in infection; HR 1.42 (95% CI 1.35-1.49) of contracting pneumonia and HR 1.70 (95% CI 1.55-1.87) of dying in pneumonia during follow-up. The risk of contracting and dying in infection and pneumonia increased in a dose-response manner with number of pack years smoked and decreased with years since smoking cessation.ConclusionSmoking is associated with contracting and dying in any infection and pneumonia and the risk increases with pack years smoked, highlighting the importance of both primary prevention and smoking cessation.

Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

This study aimed to analyze affiliations with violent peers as an underlying mechanism that associates ethnic harassment with violent behaviors among immigrant youth (N = 365; M[subscript age] = 13.93, SD = 0.80), and also identify the risk factors in this relation. The results revealed that identification with an immigrant peer crowd at school made ethnically harassed immigrant adolescents more inclined to associate with violent peers and, in turn, engage in violent behaviors over time. Immigrant youth's orientation toward the mainstream culture was not found to either elevate or buffer the effect of ethnic harassment on youth's affiliation with violent peers. Yet, ethnically harassed immigrant adolescents were shown to be more prone to violent behaviors over time when they were less orientated toward Swedish culture. The findings suggest that preventing ethnicity-based harassment and diversifying adolescents' peer groups at schools may be a way to prevent immigrant adolescents' involvement in violent behaviors.

Background: Little is known about disease trajectories for men with castration-resistant prostate cancer (CRPC). Objective: To create a state transition model that estimates time spent in the CRPC state and its outcomes. Design, setting, and participants: The model was generated using population-based prostate-specific antigen data from 40% of the Swedish male population, which were linked to nationwide population-based databases. We compared the observed and predicted cumulative incidence of transitions to and from the CRPC state. Outcome measurements and statistical analysis: We measured time spent in the CRPC state and the proportion of men who died of prostate cancer during follow-up by CRPC risk category. Results and limitations: Time spent in the CRPC state varied from 1.1 yr for the highest risk category to 3.9 yr for the lowest risk category. The proportion of men who died from prostate cancer within 10 yr ranged from 93% for the highest risk category to 54% for the lowest. There was good agreement between the model estimates and observed data. Conclusions: There is large variation in the time spent in the CRPC state, varying from 1 yr to 4 yr according to risk category. Patient summary: It is possible to accurately estimate the disease trajectory and duration for men with castration-resistant prostate cancer.

BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p

BackgroundStudies of secular trends in mental unhealth indicate that adolescents in the Nordic countries, especially girls, have an increased reported prevalence of mental health problems the last decades. This increase needs to be seen in the light of the adolescents' assessments of their perceived overall health.ObjectiveTo investigate whether a person-centered approach to research can enhance understanding of changes over time in the distribution of mental health problems among Swedish adolescents.MethodA dual-factor approach was used to study changes over time in mental health profiles among nationally representative 15-year-old adolescent samples from Sweden. Cluster analyses of subjective health symptoms (psychological and somatic) and perceived overall health from the Swedish Health Behavior in School-aged Children (HBSC) surveys of 2002, 2006, 2010, 2014, and 2018 were used to identify these mental health profiles (n = 9,007).ResultsFour mental health profiles were identified by a cluster analysis which combined all five data collections—Perceived good health, Perceived poor health, High psychosomatic symptoms, and Poor mental health. There were no significant differences in the distributions of these four mental health profiles between the survey years 2002 and 2010, but substantial changes took place between 2010 and 2018. Here, particularly the High psychosomatic symptoms profile increased among both boys and girls. The Perceived good health profile decreased among both boys and girls, and the Perceived poor health profile decreased among girls. The profile involving the most pronounced mental health problems, the Poor mental health profile (perceived poor health, high psychosomatic problems), was stable from 2002 to 2018 among both boys and girls.ConclusionThe study shows the added value of using person-centered analyses to describe differences in mental health indicators between cohorts of adolescents over longer periods of time. In contrast to the long-term increase in mental health problems seen in many countries, this Swedish study did not find an increase among young persons, both boys and girls, with the poorest mental health, the Poor mental health profile. Rather, the most substantial increase over the survey years, predominantly between 2010 and 2018, was found among the 15-year-olds with High psychosomatic symptoms only.

Abstract Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.

Abstract The cartilage aggrecan proteoglycan is crucial for both skeletal growth and articular cartilage function. A number of aggrecan (ACAN) gene variants have been linked to skeletal disorders, ranging from short stature to severe chondrodyplasias. Osteochondritis dissecans is a disorder where articular cartilage and subchondral bone fragments come loose from the articular surface. We previously reported a missense ACAN variant linked to familial osteochondritis dissecans, with short stature and early onset osteoarthritis, and now describe three novel ACAN gene variants from additional families with this disorder. Like the previously described variant, these are autosomal dominant missense variants, resulting in single amino acid residue substitutions in the C-type lectin repeat of the aggrecan G3 domain. Functional studies showed that neither recombinant variant proteins, nor full-length variant aggrecan proteoglycan from heterozygous patient cartilage, were secreted to the same level as wild-type aggrecan. The variant proteins also showed decreased binding to known cartilage extracellular matrix ligands. Mapping these and other ACAN variants linked to hereditary skeletal disorders showed a clustering of osteochondritis dissecans-linked variants to the G3 domain. Taken together, this supports a link between missense ACAN variants affecting the aggrecan G3 domain and hereditary osteochondritis dissecans.

Abstract Background Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden. Methods Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference ≤ 3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation. Results The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09–1.15) for > 3–6 months’ duration, 0.21 (0.06–0.69) for > 6–9 months and 0.16 (0.05–0.55) for > 9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27–1.66), 0.80 (0.31–2.07), and 1.19 (0.47–3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation. Conclusion The greatest possible benefit in reducing recurrent VTE risk occurred with > 9 months anticoagulation for PE and > 3–6 months for DVT, but larger studies are needed to confirm this. Risks of major bleeding were low overall.

Abstract Introduction For clinical decision-making, an estimate of remaining lifetime is needed to assess benefit against harm of a treatment during the remaining lifespan. Here, we describe how to predict life expectancy based on age, Charlson Comorbidity Index (CCI) and a Drug Comorbidity Index (DCI), whilst also considering potential future changes in CCI and DCI using population-based data on Swedish men. Methods Simulations based on annual updates of vital status, CCI and DCI were used to estimate life expectancy at population level. The probabilities of these transitions were determined from generalised linear models using prostate cancer-free comparison men in PCBaSe Sweden. A simulation was performed for each combination of age, CCI, and DCI. Survival curves were created and compared to observed survival. Life expectancy was then calculated as the area under the simulated survival curve. Results There was good agreement between observed and simulated survival curves for most ages and comorbidities, except for younger men. With increasing age and comorbidity, there was a decrease in life expectancy. Cross-validation based on six regions in Sweden also showed that simulated and observed survival was similar. Conclusion Our proposed method provides an alternative statistical approach to estimate life expectancy at population level based on age and comorbidity assessed by routinely collected information on diagnoses and filled prescriptions available in nationwide health care registers.

The present study aims to investigate whether support from a friend protects against the negative effects of ethnic harassment on engagement in delinquent and violent behaviors among immigrant adolescents in Sweden (n = 365; X = 13.93, SD = 0.80). We found that when ethnically harassed immigrant adolescents received friend support, they were less likely to engage in problem behaviors concurrently. Yet, friend support did not moderate the longitudinal associations between ethnic harassment and problem behaviors. These findings highlight the important role of supportive friendship relations in counteracting the detrimental effects of ethnic harassment on externalizing problems, particularly in the short term.