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Background: Patients with idiopathic inflammatory myopathies (IIM) have an increased risk of cancer, but their cancer‐related disease burden remains unclear. Objectives: To explore how cancer might impact the mortality of patients with IIM and examine the associated prognostic factors for cancer and death. Methods: We identified patients with IIM diagnosed between 1998 and 2020 and ascertained their cancer and death records via linkage to the Swedish healthcare and population registers. Transition hazards from IIM diagnosis to cancer and death were estimated in multistate models using flexible parametric methods. We then predicted the probability of having cancer or death, and the duration of staying alive at a given time from IIM and cancer diagnoses from a crude model. We also explored prognostic factors for progression to cancer and death in a multivariable model. Results: Of 1826 IIM patients, 310 (17%) were diagnosed with cancer before and 306 (17%) after IIM diagnosis. In patients diagnosed with cancer after IIM, the 5‐year probability of death from cancer and from other causes was 31% and 18%, respectively, compared to 7% and 15% in patients without cancer after IIM. We reported several factors associated with risk of progression to cancer and death. Specifically, patients with first cancer after IIM who were older at IIM diagnosis, had cancer history, dermatomyositis and a cancer diagnosis within 1 year following IIM faced a greater cancer‐specific mortality. Conclusion: We observed a substantial increase in mortality from cancer, compared to before, rather than other causes after a cancer diagnosis following IIM, suggesting an unmet medical need for effective cancer management in IIM patients. This finding, along with the identified prognostic factors, provides useful insight into future research directions for improving cancer management in IIM patients. [ABSTRACT FROM AUTHOR]

Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. There is little information in Sweden or elsewhere on the spatial variation in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing prior to a prostate cancer diagnosis in the Stockholm region at the municipality and small area levels. A population-based register study comprised men aged 40 years and over living in the Stockholm region during 2007–2016. For Stockholm in 2016, we reported the proportion of men who had a PSA test for the preceding one, two, five and ten years by ten-year age groups. The age-standardised proportion of men having a PSA test was reported for municipalities by calendar years. We used spatial smoothing for calculating the age-standardised proportion of men having a PSA test in a small area for each calendar year. In 2016, 74.0% and 77.8% of men aged 60–69 and 70–79 years respectively had taken a PSA test in the previous ten years. The municipalities of Danderyd and Ekerö showed high proportions of PSA testing. A marked heterogeneity in such proportions within each municipality was observed. The odds ratio for having a PSA test for those born in Sweden was 2.22 (95% CI 2.00–2.52). Opportunistic PSA testing is widespread with three quarters of men in their sixties and seventies having had a test in the preceding decade. We found evidence for marked geographical heterogeneity, where more affluent and metropolitan areas had higher levels of testing. Variations in PSA testing was associated with socio-economic position and demographic factors including education, income and country of birth. [ABSTRACT FROM AUTHOR]

Background [beta]-blockers are widely used for treating cardiac conditions and are suggested for the treatment of anxiety and aggression, although research is conflicting and limited by methodological problems. In addition, [beta]-blockers have been associated with precipitating other psychiatric disorders and suicidal behaviour, but findings are mixed. We aimed to examine associations between [beta]-blockers and psychiatric and behavioural outcomes in a large population-based cohort in Sweden. Methods and findings We conducted a population-based longitudinal cohort study using Swedish nationwide high-quality healthcare, mortality, and crime registers. We included 1,400,766 individuals aged 15 years or older who had collected [beta]-blocker prescriptions and followed them for 8 years between 2006 and 2013. We linked register data on dispensed [beta]-blocker prescriptions with main outcomes, hospitalisations for psychiatric disorders (not including self-injurious behaviour or suicide attempts), suicidal behaviour (including deaths from suicide), and charges of violent crime. We applied within-individual Cox proportional hazards regression to compare periods on treatment with periods off treatment within each individual in order to reduce possible confounding by indication, as this model inherently adjusts for all stable confounders (e.g., genetics and health history). We also adjusted for age as a time-varying covariate. In further analyses, we adjusted by stated indications, prevalent users, cardiac severity, psychiatric and crime history, individual [beta]-blockers, [beta]-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years and over, and 52.2% (n = 731,322) were women. During the study period, 6.9% (n = 96,801) of the [beta]-blocker users were hospitalised for a psychiatric disorder, 0.7% (n = 9,960) presented with suicidal behaviour, and 0.7% (n = 9,405) were charged with a violent crime. There was heterogeneity in the direction of results; within-individual analyses showed that periods of [beta]-blocker treatment were associated with reduced hazards of psychiatric hospitalisations (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.91 to 0.93, p < 0.001), charges of violent crime (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased hazards of suicidal behaviour (HR: 1.08, 95% CI: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalisations during [beta]-blocker treatment were mainly driven by lower hospitalisation rates due to depressive (HR: 0.92, 95% CI: 0.89 to 0.96, p < 0.001) and psychotic disorders (HR: 0.89, 95% CI: 0.85 to 0.93, p < 0.001). Reduced associations with violent charges remained in most sensitivity analyses, while associations with psychiatric hospitalisations and suicidal behaviour were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment, unless measured and adjusted for in the model. Conclusions In this population-wide study, we found no consistent links between [beta]-blockers and psychiatric outcomes. However, [beta]-blockers were associated with reductions in violence, which remained in sensitivity analyses. The use of [beta]-blockers to manage aggression and violence could be investigated further., Author(s): Yasmina Molero 1,2, Sam Kaddoura 3,4,5, Ralf Kuja-Halkola 2, Henrik Larsson 2,6, Paul Lichtenstein 2, Brian M. D'Onofrio 2,7, Seena Fazel 8,9,* Introduction Beta adrenergic-blocking agents, or [beta]-blockers, act [...]

Background and Hypothesis Recent research showed that young people who presented to hospital with self-harm in Finland had a significantly elevated risk of later psychosis. We investigated the prospective relationship between hospital presentation for self-harm and risk of psychosis in an unprecedentedly large national Swedish cohort. Study Design We used inpatient and outpatient healthcare registers to identify all individuals born between 1981 and 1993 who were alive and living in Sweden on their 12th birthday and who presented to hospital one or more times with self-harm. We compared them with a matched cohort, followed up for up to 20 years, and compared the cumulative incidence of psychotic disorders. Furthermore, we examined whether the strength of the relationship between hospital presentation for self-harm and later psychosis changed over time by examining for cohort effects. Study Results In total, 28 908 (2.0%) individuals presented to hospital with self-harm without prior psychosis diagnosis during the follow-up. For individuals who presented to hospital with self-harm, the cumulative incidence of diagnosed psychosis was 20.7% at 20 years follow-up (hazard radio = 13.9, 95% CI 13.3–14.6, P -value <5 × 10−308). There was no evidence of a dilution of the effect over time: while the incidence of hospital self-harm presentation increased, this did not result in an attenuation over time of the strength of the relationship between hospital self-harm presentation and subsequent psychosis. Conclusions Individuals who present to hospital with self-harm in their teens and 20s represent an important risk group for psychosis prediction and prevention. [ABSTRACT FROM AUTHOR]

Objective: Most mental disorders, when examined individually, are associated with an increased risk of cardiometabolic complications. However, these associations might be attributed to a general liability to psychopathology or confounded by unmeasured familial factors. The authors investigated the association between psychiatric conditions in young adulthood and the risk of cardiometabolic complications in middle adulthood, up to 40 years later. Methods: This cohort study (N=672,823) identified all individuals and their siblings born in Sweden between 1955 and 1962 and followed the cohort through 2013. Logistic regression models were used to estimate the bivariate associations between 10 psychiatric conditions or criminal convictions and five cardiometabolic complications in individuals. A general factor model was used to identify general, internalizing, externalizing, and psychotic factors based on the comorbidity among psychiatric conditions and criminal convictions. The cardiometabolic complications were then regressed on the latent general factor and three uncorrelated specific factors within a structural equation modeling framework in individuals and across sibling pairs. Results: Each psychiatric condition significantly increased the risk of cardiometabolic complications. These associations appeared nonspecific, as multivariate models indicated that most were attributable to the general factor of psychopathology, rather than to specific psychiatric conditions. There were no or only small associations between individuals' general psychopathology and their siblings' cardiometabolic complications. The same pattern was evident for the specific internalizing and psychotic factors. Conclusions: Associations between mental disorders in early life and later long-term risk of cardiometabolic complications appeared to be attributable to a general liability to psychopathology. Familial coaggregation analyses suggested that the elevated risk could not be attributed to confounders shared within families. One possibility is that lifestyle-based interventions may reduce the risk of later cardiometabolic complications for patients with several mental disorders. [ABSTRACT FROM AUTHOR]

This cohort study investigates the association of adverse childhood experiences with adult psychiatric disorders after adjusting for familial confounding. Key Points: Question: Are adverse childhood experiences (ACEs) associated with poor mental health in adulthood after adjustment for familial confounding due to shared genetic and environmental factors? Findings: In this cohort study using twin data, there were associations between ACEs and adult mental health outcomes in dizygotic and monozygotic twin pairs, while odds ratios were attenuated compared with the full cohort. Twins who were exposed to ACEs compared with co-twins who were not exposed had increased odds of clinically confirmed adult psychiatric disorders, particularly after sexual abuse or multiple ACEs. Meaning: These findings support an association between ACEs and poor mental health in adulthood, notwithstanding evidence for familial confounding from shared genetic and environmental factors. Importance: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. Objective: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. Design, Setting, and Participants: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. Exposures: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Main Outcomes and Measures: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Results: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). Conclusions and relevance: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology. [ABSTRACT FROM AUTHOR]

Epigenetics plays an important role in the aging process, but it is unclear whether epigenetic factors also influence frailty, an age‐related state of physiological decline. In this study, we performed a meta‐analysis of epigenome‐wide association studies in four samples drawn from the Swedish Adoption/Twin Study of Aging (SATSA) and the Longitudinal Study of Aging Danish Twins (LSADT) to explore the association between DNA methylation and frailty. Frailty was defined using the frailty index (FI), and DNA methylation levels were measured in whole blood using Illumina's Infinium HumanMethylation450K and MethylationEPIC arrays. In the meta‐analysis consisting of a total of 829 participants, we identified 589 CpG sites that were statistically significantly associated with either the continuous or categorical FI (false discovery rate <0.05). Many of these CpGs have previously been associated with age and age‐related diseases. The identified sites were also largely directionally consistent in a longitudinal analysis using mixed‐effects models in SATSA, where the participants were followed up to a maximum of 20 years. Moreover, we identified three differentially methylated regions within the MGRN1, MIR596, and TAPBP genes that have been linked to neuronal aging, tumor growth, and immune functions. Furthermore, our meta‐analysis results replicated 34 of the 77 previously reported frailty‐associated CpGs at p < 0.05. In conclusion, our findings demonstrate robust associations between frailty and DNA methylation levels in 589 novel CpGs, previously unidentified for frailty, and strengthen the role of neuronal/brain pathways in frailty. [ABSTRACT FROM AUTHOR]

Background: Evidence for substance use‐related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use‐related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population‐based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use‐related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use‐related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol‐related somatic disease, conviction for a substance‐related crime, and substance‐related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use‐related problem compared to the general population (HR, 1.81; 95% CI, 1.72–1.91), both in males (HR, 1.76; 95% CI, 1.65–1.89) and females (HR, 1.89; 95% CI, 1.74–2.05). The risks of substance use‐related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21–8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use‐related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use‐related problems. [ABSTRACT FROM AUTHOR]