Melatonin use and the risk of self-harm and unintentional injuries in youths with and without psychiatric disorders.

BACKGROUND: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury. METHODS: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin-treatment initiation. RESULTS: While body injuries, falls and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users. CONCLUSIONS: Decreased risk of intentional self-harm was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-harm in this population.

Association of severe childhood infections with depression and intentional self-harm in adolescents and young adults.

Early-life infections have been linked with subsequent depression and self-harm. Examination of specific groups of infections and the role of familial factors may elucidate this observed relationship. We addressed these considerations in our investigations of the association of severe childhood infections with the risks of depression and self-harm in adolescence and early-adulthood. This population-based cohort study included all individuals born in Sweden between 1982 and 1996, with follow-up through 2013 (N = 1,506,070). Severe childhood infections were identified using inpatient and outpatient diagnoses from birth through age 12. Any infection as well as specific groups of infections were investigated. We examined diagnoses of depression and self-harm within inpatient and outpatient care and death by self-harm between ages 13 and 31. Cox proportional hazards regression models were used to estimate absolute risks, hazard ratios (HRs), and 95% CIs. When adjusting for sex and birth year, individuals exposed to any childhood infection demonstrated increased absolute risk differences for both outcomes (2.42% [95% CI, 0.41-4.43%] of being diagnosed with depression up until age 31, and 0.73% [-2.05% to 3.51%] of self-harm up until age 31) and increased relative risks (HR, 1.22 [1.20-1.24] for depression and HR, 1.29 [1.25-1.32] for self-harm). When controlling for unmeasured factors shared between family members by comparing discordant siblings, no strong association persisted. Our findings show that childhood infections may not be involved in the etiology of later depression and self-harm, and highlight the importance of identifying these genetic and environmental familial risk factors, which may serve as targets for interventions.

Clinical and societal burden of incident major depressive disorder: A population-wide cohort study in Stockholm.

OBJECTIVE: Major depressive disorder (MDD) is a highly prevalent condition and a significant contributor to global disability. The vast majority of MDD is handled by primary care, but most real-life studies on MDD only include data from secondary care. The aim of this study was therefore to estimate the total clinical and societal burden of incident MDD including data from all healthcare levels in a large well-defined western European healthcare region. METHODS: Population-wide observational study included healthcare data from Region Stockholm, Sweden's largest region with approximately 2.4 million inhabitants. All patients in Region Stockholm having their first unipolar MDD episode between January 1, 2012, and December 31, 2018, were included. The sample also included matched study population controls. Outcomes were psychiatric and non-psychiatric comorbid conditions, antidepressant therapy use, healthcare resource utilization, work loss, and all-cause mortality. RESULTS: In the study period, 137,822 patients in Region Stockholm were diagnosed with their first unipolar MDD episode. Compared with matched controls, MDD patients had a higher burden of non-psychiatric and psychiatric comorbid conditions, 3.2 times higher outpatient healthcare resource utilization and 8.6 times more work loss. MDD was also associated with a doubled all-cause mortality compared with matched controls (HR: 2.2 [95% CI: 2.0-2.4]). CONCLUSIONS: The high mortality, morbidity, healthcare resource utilization, and work loss found in this study confirms that MDD is associated with individual suffering and low functioning leading to substantial costs for patients and society. These findings should motivate additional efforts in improving outcomes for MDD patients.

Cardiovascular, bone, and metabolic health in men with castrate-resistant prostate cancer treated with androgen deprivation: a matched cohort study.

BACKGROUND: Descriptive data on late effects associated with castrate-resistant prostate cancer (CRPC) are sparse. We aimed to define the timing and incidence of cardiovascular disease (CVD), fractures, and diabetes in a patient population with CRPC. METHODS: In the population-based STHLM0 cohort 1464 men with CRPC were identified and matched with three men free from prostate cancer (PC) in the Stockholm region of Sweden. Kaplan-Meier estimates of net survival were used to describe time to CVD, fracture, and diabetes. Cox regression was used to compare incidence rates (IRRs) for the respective late effects. Cumulative incidence analyses of late effects in the presence of the competing risk of death were performed to estimate absolute risks. RESULTS: The Kaplan Meier estimates demonstrated a higher net probability for CVD, fracture, and diabetes among men diagnosed with CRPC compared to the matched comparators. The IRRs were 1.94 (95% CI: 1.79-2.12) for CVD, 2.08 (95% CI: 1.70-2.53) for fracture, and 2.00 (95% CI: 1.31-3.05) for diabetes, respectively, comparing men diagnosed with CRPC to men free from PC. The cumulative incidence of CVD at 12 months of follow-up was higher in men diagnosed with CRPC compared to healthy controls regardless of age with a difference in cumulative incidence being 0.20 for men aged <65 and 0.11 for men aged >84. CONCLUSIONS: In this cohort, the incidence of CVD was significantly higher among men with CRPC compared to healthy controls. Despite having this end-stage disease this finding proves that clinicians must recognize this late effect in men diagnosed with CRPC to improve preventive actions. These men did not have a higher absolute risk of fractures and diabetes after accounting for deaths due to any cause compared to healthy controls.

Overview of CAPICE-Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe-an EU Marie Sklodowska-Curie International Training Network.

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).

Observational evidence from patients diagnosed with chronic lymphocytic leukaemia (CLL) in Finland between 2005-2015 show improved survival over time.

OBJECTIVES: We aimed to describe treatment patterns of chronic lymphocytic leukaemia (CLL) patients in routine practice settings, compare overall survival and time-to-next-treatment among patients treated in different time periods (2005-2008, 2009-2013, 2014-2015), and explore associated factors. METHODS: This retrospective cohort study included adult CLL patients from the Finnish Hematology Registry. RESULTS: In total, 124 and 64 CLL patients received first- and second-line treatments, respectively. The use of first- and second-line treatments with bendamustine-rituximab (BR) increased, while chlorambucil-based treatments decreased over time. Patients treated in more recent years showed a trend towards longer first- and second-line survival. A trend towards inferior overall survival was detected in first- and second-line treatment with B/BR. First-line time-to-next-treatment was longer for patients treated in the later years towards 2015, while second-line time-to-next-treatment did not improve over time. CONCLUSIONS: This study identified that improved treatment outcomes over time were likely influenced by patient characteristics and treatments, but also through other factors unexplored in this study. Hence, further research on the factors influencing patients' survival over time is needed. In particular, research on using B/BR in clinical practice is warranted.

Real-time real-world analysis of seasonal influenza vaccine effectiveness: method development and assessment of a population-based cohort in Stockholm County, Sweden, seasons 2011/12 to 2014/15.

Real-world estimates of seasonal influenza vaccine effectiveness (VE) are important for early detection of vaccine failure. We developed a method for evaluating real-time in-season vaccine effectiveness (IVE) and overall seasonal VE. In a retrospective, register-based, cohort study including all two million individuals in Stockholm County, Sweden, during the influenza seasons from 2011/12 to 2014/15, vaccination status was obtained from Stockholm's vaccine register. Main outcomes were hospitalisation or primary care visits for influenza (International Classification of Disease (ICD)-10 codes J09-J11). VE was assessed using Cox multivariate stratified and non-stratified analyses adjusting for age, sex, socioeconomic status, comorbidities and previous influenza vaccinations. Stratified analyses showed moderate VE in prevention of influenza hospitalisations among chronically ill adults ≥ 65 years in two of four seasons, and lower but still significant VE in one season; 53% (95% confidence interval (CI): 33-67) in 2012/13, 55% (95% CI: 25-73) in 2013/14 and 18% (95% CI: 3-31) in 2014/15. In conclusion, seasonal influenza vaccination was associated with substantial reductions in influenza-specific hospitalisation, particularly in adults ≥ 65 years with underlying chronic conditions. With the use of population-based patient register data on influenza-specific outcomes it will be possible to obtain real-time estimates of seasonal influenza VE.

Association of varying number of doses of quadrivalent human papillomavirus vaccine with incidence of condyloma.

IMPORTANCE: Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine. OBJECTIVE: To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS: An open cohort of all females aged 10 to 24 years living in Sweden (n = 1,045,165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers. MAIN OUTCOMES AND MEASURES: Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting. RESULTS: A total of 20,383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100,000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100,000 person-years. CONCLUSIONS AND RELEVANCE: Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.

Association between neighborhood socioeconomic status and healthcare utilization among individuals with a first diagnosis of major depressive disorder in primary care in the Stockholm region.

BACKGROUND: Population-based surveys suggest that low socioeconomic status (SES) is associated with higher prevalence of depressive symptoms, while their healthcare utilization is not necessarily higher. OBJECTIVE: To investigate the association between neighborhood socioeconomic status (NSES) and healthcare utilization among individuals diagnosed with major depressive disorder (MDD). METHOD: This was a retrospective longitudinal study of all adults with a first MDD diagnosis within primary care during 2010-2018. NSES was defined by the household area of residence using the Mosaic™ classification. Outcomes were AD (antidepressants) (N06A) dispensation and psychiatric outpatient visit, both of which are outlined as options in depression guidelines. Cox multivariable regression was used for the time to event analyses. RESULTS: A total of 117,193 individuals were included, of which 87,499 (75 %) were dispensed an AD and 35,989 (31 %) had a recorded psychiatric outpatient visit. Low NSES was associated with lower rate of AD dispensation in the first-year post-diagnosis (HR: 0.95, 95 % CI: 0.93-0.96, p < 0.001) and higher rate of psychiatric visit (HR: 1.10, 95 % CI: 1.07-1.12, p < 0.001) compared with high NSES. LIMITATIONS: Data sources have high coverage. A minority of psychiatric care provided by non-publicly financed providers was not included. It was not possible to adjust for depression severity. CONCLUSION: Socioeconomic status as measured by the neighborhood of residency was associated with AD dispensation and psychiatric outpatient visit in MDD, also in a healthcare system with virtually free access. This is of relevance for clinical practice, considering the focus on equity of care and the increase in depression prevalence worldwide.

Incidence of genital warts in Sweden before and after quadrivalent human papillomavirus vaccine availability.

BACKGROUND: More than 90% of genital warts (GW) cases are caused by human papillomavirus (HPV) types 6 and 11. The introduction of HPV vaccines necessitates the estimation of the population-based incidence of GW immediately before and after vaccination uptake. METHODS: Incidence proportions were calculated using the entire population aged 10­44 years living in Sweden during 2006­2010. The Prescribed Drug Register and the National Patient Register were used to define GW episodes. Time trends were estimated using Poisson regression. RESULTS: In 2010, age-stratified incidence proportions of GW were highest for 20-year-old women (956 cases/100 000), while the incidence proportion among males was greatest at the slightly older age of 24 years (1137 cases/100 000). Crude rates were marginally higher among males than among females during 2006­2007 and appeared to later diverge. Between 2008 and 2010, the overall incidence appeared to increase among males, and the incidence among females declined. Females aged 17 and 18 years had a >25% decline in GW rates between 2006 and 2010, with significant decreases through the age of 25 years. CONCLUSIONS: This study provides a reasonable estimation of the incidence of GW in the Swedish population by use of register data, with results comparable to those from previous smaller studies. There was a downward trend of GW incidence among younger females between 2006 and 2010.

Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder.

Importance: Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples. Objective: To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines. Design, Setting, and Participants: This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022. Exposures: Patients with MDD with and without records of suicidal behavior. Main Outcomes and Measures: The main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated. Results: A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed. Conclusions and Relevance: This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study.

Importance: The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited. Objective: To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use. Design, Setting, and Participants: This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022. Main Outcomes and Measures: Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD. Results: A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69). Conclusions and Relevance: In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.

Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression: A Nationwide Swedish Study of Siblings.

OBJECTIVE: Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence. METHODS: This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves' disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences. RESULTS: Individuals with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves' disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes. CONCLUSIONS: These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets.

How can young women be encouraged to attend cervical cancer screening? Suggestions from face-to-face and internet focus group discussions with 30-year-old women in Stockholm, Sweden.

BACKGROUND: cervical cancer screening (CCS) using Pap-smears has been carried out for decades and is still an essential tool for secondary cancer prevention. Focus has traditionally been on what hinders women's attendance, instead of researching this issue from a positive standpoint, i.e. what factors encourage women to take a Pap-smear? In this article, we therefore explore issues that 30-year-old women have addressed as encouraging CCS attendance, with particular focus on aspects susceptible to intervention. MATERIAL AND METHODS: through the population-based cervical cancer screening (PCCSP) registry in Stockholm, Sweden, a stratified random sampling technique was used to recruit women from the same birth cohort with varied CCS histories and results. Nine face-to-face focus groups discussions (FGDs) and 30 internet-based FGDs were conducted with a total of 138 women aged 30. Qualitative analysis was inspired by interpretative description, to generate clinically relevant and useful data. RESULTS: in general, these women expressed positive views about the PCCSP as an existing service, regardless of screening history. They described a wide range of factors encompassing the entire screening trajectory from invitation through follow-up which could motivate young women to CCS participation, including social marketing. Many of the suggestions related to individualization of the PCCSP, as well as a need to understand the relationship between human papilloma virus (HPV) and cervical cancer. DISCUSSION: [corrected these results are discussed in terms of the inherent tension between population-based public health initiatives and individually-oriented health care provision. Many suggestions given are already incorporated into the existing Stockholm-Gotland screening program, although this information may not reach women who need it. New research should test whether systematic information on HPV may provide a missing link in motivating young women to attend CCS, and which of their suggestions can serve to increase CCS participation.

Association of Youth Depression With Subsequent Somatic Diseases and Premature Death.

Importance: Early-onset depression has been linked to poor health outcomes. However, it is unclear the extent to which this disorder is associated with specific diseases and premature death and whether these associations remain after controlling for psychiatric comorbidity. Objective: To quantify the association of youth depression with subsequent diagnoses of numerous somatic diseases and mortality. Design, Setting, and Participants: A population-based cohort study was conducted using Swedish national registers containing data on all individuals born in Sweden between 1982 and 1996. A total of 1 487 964 participants were followed up from age 5 years through 2013 if no censoring occurred. Data analysis was performed from January 15, 2019, to August 10, 2020. Exposures: Youth depression was defined as having received at least 1 diagnosis of depression from inpatient or outpatient care between ages 5 and 19 years. Main Outcomes and Measures: This study examined 69 somatic conditions diagnosed after youth depression, as well as all-cause and cause-specific mortalities. Overall and sex-specific hazard ratios (HRs), together with 95% CIs, were estimated using Cox proportional hazards regression with attained age as underlying timescale and time-varying exposure, and adjusted for birth year and sex. All analyses were repeated controlling for psychiatric comorbidities. Absolute risk differences were calculated using standardization with Cox proportional hazards regression. Results: Of 1 487 964 individuals included in the analysis, 51.2% were male. A total of 37 185 patients (2.5%; 67.4% female) had an inpatient or outpatient contact for depression between ages 5 and 19 years (mean [SD] age at first recorded diagnosis of depression, 16.7 [2.1] years for males and 16.7 [1.8] years for females). Age at the end of follow-up ranged between 17 and 31 years. Individuals with youth depression had higher relative risks for 66 of the 69 somatic diagnoses. Strong associations were observed for certain injuries, especially self-harm in females (HR, 14.4; 95% CI, 13.8-15.1), sleep disorders (HR, 8.1; 95% CI, 7.6-8.7), viral hepatitis (HR, 6.1; 95% CI, 5.4-6.8), all-cause mortality (HR, 5.9; 95% CI, 5.3-6.6), and cause-specific mortalities, especially death by intentional self-harm (HR, 14.6; 95% CI, 12.6-16.9). Most associations were attenuated but persisted after adjusting for psychiatric comorbidity. The absolute risk difference of a specific disease within 12 years from the first diagnosis of depression during youth ranged from -0.2% (95% CI, -1.0% to 0.6%) for arthropathies among males to 23.9% (95% CI, 22.7%-25.0%) for the broader category of injuries among females. Conclusions and Relevance: In this Swedish population cohort study, patients with depression diagnosed during their youth appeared to have increased risks for many somatic diseases as well as for mortality, even after controlling for other psychiatric disorders. These findings suggest that several medical conditions should be considered when investigating youth depression.

Real world treatment utilization patterns in patients with castration-resistant prostate cancer.

BACKGROUND: Studies describing treatment utilization for castration-resistant prostate cancer (CRPC) are limited. We aimed to describe the treatment utilization of a contemporary population-based CRPC cohort between 2006 and 2016. METHODS: We identified 1699 men with a PC diagnosis between 2005 and 2015, who developed CRPC between 2006 and 2015 in the Stockholm region of Sweden. Demographic information, stage and grade at PC diagnosis, stage at CRPC, prostate-specific antigen (PSA) nadir, PSA doubling time, treatment utilization rate within 1 year of CRPC diagnosis, reason for stopping therapy, treatment sequence trajectory, overall and PC specific survival was described. RESULTS: Treatment for men with de novo metastatic disease (n = 463) was 32%, treatment for men with progressive metastatic disease after PC diagnosis (n = 66) was 44%, treatment for men with nonmetastatic CRPC (n = 113) was 34% and treatment for those with an unknown stage at time of CRPC diagnosis (n = 857) was 12%. Docetaxel was used in 39%, abiraterone acetate plus prednisone in 15%, enzalutamide in 13%, cabazitaxel in 11% and radium-223 in 5% of treatments. Treatment increased from 22% in 2006-2009 for metastatic cancer to 50% in 2013-2015 (p < .001). Factors associated with treatment were an unknown stage at diagnosis (OR: 0.3, 95% CI: 0.2-0.4), age ≥75 years (OR: 0.2, 95% CI: 0.1 - 0.3), PSA doubling time >3 months (OR: 0.4, 95% CI: 0.3 - 0.6) and a diagnosis between 2013 and 2015 (OR: 3.4, 95% CI: 2.0 - 5.8). CONCLUSIONS: Despite treatment availability, in this large real-world cohort we found treatment utilization to remain low.

Survival in patients diagnosed with castration-resistant prostate cancer: a population-based observational study in Sweden.

Background: This study investigated prostate cancer (PC)-specific survival and overall survival (OS) in a population-based castration-resistant PC (CRPC) cohort.Methods: Data from Stockholm Prostate-Specific Antigen (PSA) and Biopsy Register patients with increasing PSA despite gonadotropin-releasing hormone treatment or surgical castration (n = 1,712) included PSA values and biopsies from 2003 to 2015 and were linked to the National Prostate Cancer Register and Prescribed Drug Register. Kaplan-Meier method estimated PC-specific survival and OS, stratified by metastasis at PC diagnosis, and Cox regression estimated hazard ratios (HRs) for Gleason score and T-stage at PC diagnosis and for age and calendar period at CRPC onset by metastasis status at diagnosis.Results: Median OS after CRPC onset was 23.2 months (95% CI = 21.0-25.9) among patients without metastases (M0) at primary diagnosis, and 13.2 months (11.3-14.5) among patients with metastases (M1). Median PC-specific survival from CRPC onset was 30.3 (27.5-34.1) months and 13.3 (12.1-15.8) months for M0 and M1 patients, respectively. Biopsy Gleason score ≥ 8 was associated with higher all-cause mortality than ≤6 (HR = 2.07 [95% CI = 1.43-3.01]) and PC-specific mortality (2.07 [1.27-3.40]) after CRPC among patients with M0 disease. Patients developing CRPC from 2012 onward had lower all-cause mortality (HR = 0.71 [95% CI = 0.60-0.85] [M0]; 0.60 [0.47-0.77] [M1]) and PC-specific mortality (0.73 [0.57-0.94] [M0]; 0.62 [0.46-0.84] [M1]) compared with those prior to 2012.Conclusions: M1 disease at PC diagnosis was associated with worse survival after CRPC onset versus M0. Higher Gleason score at diagnosis was associated with higher mortality after CRPC onset in M0 patients at diagnosis.

Health and work disability outcomes in parents of patients with schizophrenia associated with antipsychotic exposure by the offspring.

This study aimed to identify if antipsychotic exposure in offspring is associated with psychiatric and non-psychiatric healthcare service use and work disability of their parents. This Swedish population-based cohort study was based on data comprising 10,883 individuals with schizophrenia, who had at least one identifiable parent in the nationwide registers, and their parents (N = 18,215). The register-based follow-up during 2006-2013 considered the level of antipsychotic exposure and persistence of use of the offspring, further categorized into first (FG) and second generation (SG) antipsychotics, and orals versus long-acting injections (LAIs). The main outcome measure was parental psychiatric healthcare service use, secondary outcomes were non-psychiatric healthcare use and long-term sickness absence. SG-LAI use was associated with a decreased risk (relative risks [RR] 0.81-0.85) of parental psychiatric healthcare use compared with not using SG-LAI, whereas oral antipsychotics were associated with an increased risk (RRs 1.10-1.29). Both FG- and SG-LAI use by the offspring were associated with a lower risk of long-term sickness absence (range of odds ratios 0.34-0.47) for the parents, compared with non-use of these drugs. The choice of antipsychotic treatment for the offspring may have an impact on work disability and healthcare service use of their parents.

Time-to-event Outcomes in Men with Nonmetastatic Castrate-resistant Prostate Cancer-A Systematic Literature Review and Pooling of Individual Participant Data.

CONTEXT: Until recently, there has been a lack of evidence-based treatment alternatives in men with nonmetastatic castrate-resistant prostate cancer (NM-CRPC). However, new evidence-based treatment alternatives are emerging. OBJECTIVE: We aimed to describe time-to-event outcomes in NM-CRPC patients based on evidence from both prospective and retrospective studies. Second, we aimed to describe predictors of these outcomes in the same patient population. EVIDENCE ACQUISITION: A systematic review was conducted to identify clinical studies (both prospective and retrospective) in NM-CRPC patients. All published Kaplan-Meier curves were digitized, and individual participant data were extracted using a published and validated R code. The following outcomes were considered: overall survival (OS), bone metastasis-free survival (BMFS), time to bone metastasis (TTBM), metastasis-free survival, time to metastasis, time to progression (TTP), progression-free survival, and time to prostate-specific antigen (PSA) progression. Second, we described all predictor/outcome relationships. EVIDENCE SYNTHESIS: Median survival times, in months, for OS, BMFS, TTBM, and TTP in placebo arms of randomized clinical trials are 45.3 (95% confidence interval [CI]: 43.5-46.8), 31.5 (95% CI: 28-33.4), 28.8 (95% CI: 25.2-31.6), and 22.2 (95% CI: 19.3-24.8), respectively. In general, reported outcomes in retrospective studies seemed to be longer than those reported in clinical trials. Baseline PSA nadir levels, PSA doubling time, PSA velocity, and alkaline phosphatase velocity are reliable predictors of time-to-event outcomes in NM-CRPC patients, whereas Gleason score is not. CONCLUSIONS: NM-CRPC is a long-standing condition where effective treatments to slow down disease progression historically have been lacking. Compared with prospective studies, retrospective studies have had limited ability to correctly identify NM-CRPC patients and estimate time to different outcomes in NM-CRPC patients. PATIENT SUMMARY: For patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC), currently no effective treatments resulting in longer survival compared with watchful waiting are available. On average, without additional treatment, half of these patients survive <45 mo after NM-CRPC diagnosis.

Burden for Parents of Patients With Schizophrenia-A Nationwide Comparative Study of Parents of Offspring With Rheumatoid Arthritis, Multiple Sclerosis, Epilepsy, and Healthy Controls.

BACKGROUND: The study aimed to (1) compare the risk of health care use, adverse health status, and work productivity loss of parents of patients with schizophrenia to parents of patients with multiple sclerosis (MS), rheumatoid arthritis (RA), epilepsy, and healthy controls; and (2) evaluate such outcome measures while considering disease severity of schizophrenia. METHODS: Based on linkage of Swedish registers, at least one parent was included (n = 18215) of patients with schizophrenia (information 2006-2013, n = 10883). Similarly, parental information was linked to patients with MS, RA, epilepsy, and matched healthy controls, comprising 11292, 15516, 34715, and 18408 parents, respectively. Disease severity of schizophrenia was analyzed. Different regression models yielding odds ratios (OR), hazard ratios (HR), or relative risks (RR) with 95% confidence intervals (CI) were run. RESULTS: Psychiatric health care use, mainly due to anxiety and affective disorders, showed a strongly increasing trend for parents of patients with schizophrenia throughout the observation period. During the follow-up, these parents had an up to 2.7 times higher risk of specialized psychiatric health care and receipt of social welfare benefits than other parents. Parents of the moderately severely ill patients with schizophrenia had higher risk estimates for psychiatric health care (RR: 1.12; 95% CI: 1.07-1.17) compared with parents of least severely ill patients. CONCLUSIONS: Parents of patients with schizophrenia have a considerably higher risk of psychiatric health care and social welfare benefit receipt than other parents. Psychiatric health care use worsens over time and with increasing disease severity of the offspring.