Long-Term Risk of Type 2 Diabetes After Preterm Delivery or Hypertensive Disorders of Pregnancy.

OBJECTIVE: To examine long-term diabetes risk after preterm delivery or hypertensive disorders of pregnancy in a large population-based cohort. METHODS: This retrospective cohort study included all women with a singleton delivery in Sweden during 1973-2015 and no preexisting diabetes mellitus. Participants were followed up for development of type 2 diabetes identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute hazard ratios (HRs) for the association between preterm delivery or hypertensive disorders of pregnancy and type 2 diabetes with adjustment for gestational diabetes and other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic or environmental) factors. RESULTS: Overall, 2,184,417 women were included. Within 10 years after delivery, adjusted HRs for type 2 diabetes associated with specific pregnancy outcomes were as follows: any preterm delivery (before 37 weeks of gestation), 1.96 (95% CI, 1.83-2.09); extremely preterm delivery (22-27 weeks), 2.53 (95% CI, 2.03-3.16); and hypertensive disorders of pregnancy, 1.52 (95% CI, 1.43-1.63). All HRs remained significantly elevated (1.1-1.7-fold) 30-46 years after delivery. These findings were largely unexplained by shared familial factors. CONCLUSION: In this large national cohort, preterm delivery and hypertensive disorders of pregnancy were associated with increased risk for type 2 diabetes up to 46 years later. Women with these pregnancy complications are candidates for early preventive actions and long-term monitoring for type 2 diabetes.

Adverse Pregnancy Outcomes and Long-Term Mortality in Women.

Importance: Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions. Objective: To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women. Design, Setting, and Participants: This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had a singleton delivery during 1973 to 2015. All 2 195 667 such women with information for pregnancy duration and infant birth weight were included in the study. Data were analyzed from March to September 2023. Exposure: Adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes), identified from nationwide birth records. Main Outcome and Measures: All-cause and cause-specific mortality through December 31, 2018. Cox regression was used to compute hazard ratios (HRs) for mortality associated with specific adverse pregnancy outcomes, adjusted for other maternal factors. Cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors. Results: In 56 million person-years of follow-up to a median (IQR) age of 52 (42-61) years, 88 055 women (4%) died (median [IQR] age at death, 59 [50-67] years). All 5 adverse pregnancy outcomes were independently associated with increased mortality. Across the entire follow-up (≤46 years after delivery), adjusted HRs for all-cause mortality associated with specific adverse pregnancy outcomes were as follows: gestational diabetes, 1.52 (95% CI, 1.46-1.58); preterm delivery, 1.41 (95% CI, 1.37-1.44); small for gestational age, 1.30 (95% CI, 1.28-1.32); other hypertensive disorders, 1.27 (95% CI, 1.19-1.37); and preeclampsia, 1.13 (95% CI, 1.10-1.16). All HRs remained significantly elevated even 30 to 46 years after delivery. These effect sizes were only partially (0%-45%) reduced after controlling for shared familial factors in cosibling analyses. Women who experienced multiple adverse pregnancy outcomes had further increases in risk. Several major causes of death were identified, including cardiovascular and respiratory disorders and diabetes. Conclusions and Relevance: In this large national cohort study, women who experienced any of 5 major adverse pregnancy outcomes had increased mortality risks that remained elevated more than 40 years later. Women with adverse pregnancy outcomes need early preventive evaluation and long-term follow-up for detection and treatment of chronic disorders associated with premature mortality.

Mortality Risks Associated with Depression in Men with Prostate Cancer.

BACKGROUND: Men diagnosed with prostate cancer (PC) have an increased risk of depression; however, it is unclear to what extent depression affects long-term survival. A better understanding of such effects is needed to improve long-term care and outcomes for men with PC. OBJECTIVE: To determine the associations between major depression and mortality in a national cohort of men with PC. DESIGN, SETTING, AND PARTICIPANTS: A national cohort study was conducted of all 180 189 men diagnosed with PC in Sweden during 1998-2017. Subsequent diagnoses of major depression were ascertained from nationwide outpatient and inpatient records through 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Deaths were identified from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) for all-cause mortality associated with major depression, adjusting for sociodemographic factors and comorbidities. Subanalyses assessed differences by PC treatment during 2005-2017. PC-specific mortality was examined using competing risks models. RESULTS AND LIMITATIONS: In 1.3 million person-years of follow-up, 16 134 (9%) men with PC were diagnosed with major depression and 65 643 (36%) men died. After adjusting for sociodemographic factors and comorbidities, major depression was associated with significantly higher all-cause mortality in men with high-risk PC (HR, 1.50; 95% confidence interval [CI], 1.44-1.55) or low- or intermediate-risk PC (1.64; 1.56-1.71). These risks were elevated regardless of PC treatment or age at PC diagnosis, except for youngest men (<55 yr) in whom the risks were nonsignificant. Major depression was also associated with increased PC-specific mortality in men with either high-risk PC (HR, 1.35; 95% CI, 1.28-1.43) or low- or intermediate-risk PC (1.42; 1.27-1.59). This study was limited to Sweden and will need replication in other countries when feasible. CONCLUSIONS: In this national cohort of men with PC, major depression was associated with ∼50% higher all-cause mortality. Men with PC need timely detection and treatment of depression to support their long-term outcomes and survival. PATIENT SUMMARY: In this report, we examined the effects of depression on survival in men with prostate cancer. We found that among all men with prostate cancer, those who developed depression had a 50% higher risk of dying than those without depression. Men with prostate cancer need close monitoring for the detection and treatment of depression to improve their long-term health outcomes.

Risk of depression in persons with Alzheimer's disease: A national cohort study.

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia. DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression. Highlights: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.

Alcohol use disorder and risk of specific methods of suicide death in a national cohort.

INTRODUCTION: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. METHODS: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932-1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. RESULTS: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006-1.040 for females, 0.046-0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). CONCLUSIONS: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.

Hypertension in Pregnancy Among Immigrant and Swedish Women: A Cohort Study of All Pregnant Women in Sweden.

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.

Risk of Alzheimer's Disease and Related Dementias in Persons with Glaucoma: A National Cohort Study.

PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies that potentially may be associated with other cerebral neurodegenerative processes leading to dementia. However, prior studies have been inconsistent. We examined dementia risks after glaucoma diagnosis in a large population-based cohort. DESIGN: National matched cohort study. PARTICIPANTS: A total of 324 730 persons diagnosed with glaucoma during 1995-2017 in Sweden and 3 247 300 age- and sex-matched population-based controls without prior dementia. METHODS: Cox regression was used to compute hazard ratios (HRs) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia in persons with glaucoma compared with controls, adjusting for sociodemographic factors and comorbidities. MAIN OUTCOME MEASURES: Alzheimer's disease, VaD, and all-cause dementia identified from nationwide inpatient and outpatient diagnoses through 2018. RESULTS: In 16 million person-years of follow-up, 32 339 persons (10%) with glaucoma and 226 896 controls (7%) were diagnosed with dementia. Persons with glaucoma had increased risks for AD (adjusted HR, 1.39; 95% confidence interval [CI], 1.35-1.43), VaD (1.66; 1.61-1.72), and all-cause dementia (1.57; 1.54-1.59). Among glaucoma subtypes, both primary open-angle and normal-tension glaucoma were associated with increased risk for AD (adjusted HR, 1.31; 95% CI, 1.27-1.36; and 1.28; 1.20-1.36, respectively) and VaD (1.61; 1.54-1.68; and 1.39; 1.28-1.50, respectively), whereas primary angle-closure glaucoma was associated with VaD (1.26; 1.02-1.56) but not AD (0.98; 0.82-1.18). These findings were similar in men and women. All risks were highest in persons diagnosed with glaucoma at ages ≥ 70 years and were not elevated for ages < 60 years. CONCLUSIONS: In this large national cohort, persons with glaucoma had increased risks for AD, VaD, and all-cause dementia, particularly those diagnosed with glaucoma at older ages. Persons with glaucoma may need increased monitoring for dementia to facilitate earlier detection and treatment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Divorce and risk of suicide attempt: a Swedish national study.

BACKGROUND: Prior research has reported an association between divorce and suicide attempt. We aimed to clarify this complex relationship, considering sex differences, temporal factors, and underlying etiologic pathways. METHODS: We used Swedish longitudinal national registry data for a cohort born 1960-1990 that was registered as married between 1978 and 2018 (N = 1 601 075). We used Cox proportional hazards models to estimate the association between divorce and suicide attempt. To assess whether observed associations were attributable to familial confounders or potentially causal in nature, we conducted co-relative analyses. RESULTS: In the overall sample and in sex-stratified analyses, divorce was associated with increased risk of suicide attempt (adjusted hazard ratios [HRs] 1.66-1.77). Risk was highest in the year immediately following divorce (HRs 2.20-2.91) and declined thereafter, but remained elevated 5 or more years later (HRs 1.41-1.51). Divorcees from shorter marriages were at higher risk for suicide attempt than those from longer marriages (HRs 3.33-3.40 and 1.20-1.36, respectively). In general, HRs were higher for divorced females than for divorced males. Co-relative analyses suggested that familial confounders and a causal pathway contribute to the observed associations. CONCLUSIONS: The association between divorce and risk of suicide attempt is complex, varying as a function of sex and time-related variables. Given evidence that the observed association is due in part to a causal pathway from divorce to suicide attempt, intervention or prevention efforts, such as behavioral therapy, could be most effective early in the divorce process, and in particular among females and those whose marriages were of short duration.

Risks of Depression, Anxiety, and Suicide in Partners of Men with Prostate Cancer: A National Cohort Study.

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress not only in a man but also his intimate partner. However, long-term risks of depression, anxiety, or suicide in partners of men with PC are largely unknown. METHODS: A national cohort study was conducted of 121,530 partners of men diagnosed with PC during 1998-2017 and 1,093,304 population-based controls in Sweden. Major depression, anxiety disorder, and suicide death were ascertained through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors. RESULTS: Partners of men with high-risk PC had increased risks of major depression (adjusted HR, 1.34; 95% CI, 1.30-1.39) and anxiety disorder (1.25; 1.20-1.30), which remained elevated ≥10 years later. Suicide death was increased in partners of men with distant metastases (adjusted HR, 2.38; 95% CI, 1.08-5.22) but not other high-risk PC (1.14; 0.70-1.88). Among partners of men with high-risk PC, risks of major depression and anxiety disorder were highest among those aged ≥80 years (adjusted HR, 1.73; 95% CI, 1.53-1.96; and 1.70; 1.47-1.96, respectively), whereas suicide death was highest among those aged <60 years (7.55; 2.20-25.89). In contrast, partners of men with low- or intermediate-risk PC had modestly or no increased risks of these outcomes. CONCLUSIONS: In this large cohort, partners of men with high-risk PC had increased risks of major depression and anxiety disorder, which persisted for ≥10 years. Suicide death was increased 2-fold in partners of men with distant metastases. Partners as well as men with PC need psychosocial support and close follow-up for psychosocial distress.

Adverse pregnancy outcomes and long-term risk of chronic kidney disease in women: national cohort and co-sibling study.

BACKGROUND: Women with adverse pregnancy outcomes may have higher subsequent risk of chronic kidney disease, but the long-term independent risks and potential causality are unclear. OBJECTIVE: This study aimed to determine long-term risks of chronic kidney disease associated with 5 major adverse pregnancy outcomes in a large population-based cohort, and to assess for familial confounding using co-sibling analyses. STUDY DESIGN: A national cohort study was conducted of all 2,201,279 women with a singleton delivery in Sweden from 1973 to 2015, followed up for chronic kidney disease identified from nationwide diagnoses through 2018. Cox regression was used to compute hazard ratios for chronic kidney disease associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. RESULTS: In 56 million person-years of follow-up, 11,572 (0.5%) women were diagnosed with chronic kidney disease (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with increased chronic kidney disease risk. Within 10 years following delivery, adjusted hazard ratios associated with specific adverse pregnancy outcomes were: 7.12 for other hypertensive disorders (95% confidence interval, 5.88-8.62), 4.38 for preeclampsia (3.72-5.16), 3.50 for preterm delivery (2.95-4.15), 3.15 for gestational diabetes (2.53-3.92), and 1.22 for small for gestational age (1.02-1.44). All hazard ratios remained significantly elevated even 30 to 46 years after delivery (gestational diabetes, 3.32 [95% confidence interval, 2.96-3.72]; other hypertensive disorders, 2.44 [1.91-3.11]; preeclampsia, 2.03 [1.90-2.16]; preterm delivery, 1.56 [1.44-1.68]; and small for gestational age, 1.24 [1.16-1.31]). These findings were only partially (0%-45%) explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk. CONCLUSION: In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for chronic kidney disease up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term monitoring to reduce risk of chronic kidney disease.

Diabetes risk during pregnancy among second-generation immigrants: A national cohort study in Sweden.

BACKGROUND AND AIMS: Gestational diabetes is more common in many first-generation immigrant women in Europe and other Western countries. Less is known about second-generation immigrant women; such knowledge is needed to understand generational influences on diabetes risk. We aimed to study second-generation immigrant women regarding the presence of all types of diabetes during pregnancy. METHODS AND RESULTS: A cohort study was conducted using 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% confidence intervals (99% CI) for any diabetes during pregnancy and specific subtypes (gestational diabetes, pre-existing diabetes type 1, pre-existing diabetes type 2) in second-generation immigrant women compared with Swedish-born women with two Swedish-born parents while adjusting for sociodemographic factors, family history of diabetes, body mass index, smoking habits, and comorbidities. The study population included a total of 989,986 deliveries and 17,938 diabetes cases. The fully adjusted HR (with 99% CI) for any type of diabetes during pregnancy among second-generation immigrant women was 1.11 (1.05-1.18). Higher risks were found in women with parents from Africa, Asia, or Eastern Europe, as well as Denmark. A lower risk for pre-existing type 1 diabetes was found overall and for women with parents from most geographic regions. CONCLUSION: In this national cohort study, the risk of all types of diabetes during pregnancy was increased in second-generation immigrant women. Diabetes prevention and treatment is especially important in these women both before and during pregnancy.

Preterm or early term birth and risk of attention-deficit/hyperactivity disorder: a national cohort and co-sibling study.

PURPOSE: To examine risks of attention-deficit/hyperactivity disorder (ADHD) in preterm and early term birth survivors, and potential sex-specific differences. METHODS: A national cohort study was conducted of all 4061,795 singletons born in Sweden in 1973-2013 who survived infancy, followed up for ADHD identified from nationwide diagnoses and medications through 2018. Poisson regression was used to compute prevalence ratios (PRs), adjusting for sociodemographic and perinatal factors. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic or environmental) factors. RESULTS: ADHD prevalences by gestational age at birth were 12.1% for extremely preterm (22-27 weeks), 7.0% for moderately preterm (28-33 weeks), 5.7% for late preterm (34-36 weeks), 6.1% for all preterm (<37 weeks), 5.2% for early term (37-38 weeks), and 4.5% for full-term (39-41 weeks). Adjusted PRs comparing extremely preterm, all preterm, or early term versus full-term, respectively, were 2.35 (95% CI, 2.15-2.57), 1.28 (1.25-1.31), and 1.12 (1.10-1.13) among males, and 2.46 (2.17-2.78), 1.24 (1.20-1.28), and 1.08 (1.06-1.10) among females (P < .001 for each). These associations were virtually unchanged after controlling for shared familial factors. Both spontaneous and medically indicated preterm birth were associated with ADHD (adjusted PRs, 1.21; 95% CI, 1.18-1.24; and 1.39; 1.34-1.43, respectively). CONCLUSIONS: In this large cohort, preterm and early term birth were associated with increased risks of ADHD in males and females, independently of covariates and shared familial factors.

Exposure to alcohol outlets and risk of suicidal behavior in a Swedish cohort of young adults.

BACKGROUND: Greater alcohol accessibility, for example in the form of a high density of alcohol outlets or low alcohol taxation rates, may be associated with increased risk of suicidal behavior. However, most studies have been conducted at the aggregate level, and some have not accounted for potential confounders such as socioeconomic position or neighborhood quality. METHODS: In a Swedish cohort of young adults aged 18 to 25, we used logistic regressions to evaluate whether living in a neighborhood that included bars, nightclubs, and/or government alcohol outlets was associated with risk of suicide attempt (SA) or suicide death (SD) during four separate 2-year observation periods. Neighborhoods were defined using pre-established nationwide designations. We conducted combined-sex and sex-stratified analyses, and included as covariates indicators of socioeconomic position, neighborhood deprivation, and aggregate genetic liability to suicidal behavior. RESULTS: Risk of SA was increased in some subsamples of individuals living in a neighborhood with a bar or government alcohol outlet (odds ratios [ORs] = 1.05 to 1.15). Risk of SD was also higher among certain subsamples living in a neighborhood with a government outlet (ORs = 1.47 to 1.56), but lower for those living near a bar (ORs = 0.89 to 0.91). Significant results were driven by, but not exclusive to, the male subsample. Individuals with higher aggregate genetic risk for SA were more sensitive to the effects of a neighborhood government alcohol outlet, pooled across observation periods, in analyses of the sexes combined (relative excess risk due to interaction [RERI] = 0.05; 95% confidence intervals [CI] 0.01; 0.09) and in the male subsample (RERI = 0.06; 95% CI 0.001; 0.12). CONCLUSIONS: Although effect sizes are small, living in a neighborhood with bars and/or government alcohol outlets may increase suicidal behavior among young adults. Individuals with higher genetic liability for SA are slightly more susceptible to these exposures.

Neighborhood deprivation in relation to lung cancer in individuals with type 2 diabetes-A nationwide cohort study (2005-2018).

BACKGROUND: Neighborhood deprivation has been found associated with both type 2 diabetes and lung cancer. The aim of this study was to examine the potential association between neighborhood deprivation and lung cancer incidence or mortality in individuals diagnosed with type 2 diabetes. The results may identify a new risk or prognostic factor for lung cancer in this important subgroup and help develop a more contextual approach to prevention that includes neighborhood environment. METHODS AND FINDINGS: The study population included adults (n = 613,650) aged ≥ 30 years with type 2 diabetes during 2005 to 2018 in Sweden. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incidence or mortality of lung cancer associated with neighborhood deprivation. All models were conducted in both men and women and adjusted for individual-level characteristics (e.g. age, smoking- and alcohol-related comorbidities, sociodemographic factors). The cumulative incidence and mortality for lung cancer were 1.08% (95% CI, 1.06 to 1.11) and 0.93% (0.90 to 0.95), respectively, in the study population during the study period. Neighborhood deprivation was associated with both incidence and mortality of lung cancer in patients with type 2 diabetes independently of the individual-level characteristics. In the fully adjusted models, comparing high- with low-deprivation neighborhoods, the HRs for lung cancer incidence were 1.21 (1.10 to 1.33) in men and 1.08 (0.95 to 1.21) in women. The corresponding HRs for lung cancer mortality were 1.04 (1.00 to 1.07) in men and 0.97 (0.94 to 1.00) in women. Competing risk analyses including cardiovascular mortality attenuated the results. CONCLUSION: In this large cohort of individuals with type 2 diabetes, we found higher lung cancer incidence and mortality in patients living in areas with high neighborhood deprivation, even after adjusting for individual-level characteristics. These findings may help develop a more contextual approach that includes the neighborhood environment when allocating resources for disease prevention and care in patients with type 2 diabetes. These findings could also help inform clinical care for patients with type 2 diabetes, particularly those living in deprived neighborhoods.

Risks of alcohol and drug use disorders in prostate cancer survivors: a national cohort study.

BACKGROUND: Prostate cancer (PC) survivors may potentially use substances to cope with psychological distress or poorly controlled physical symptoms. Little is known, however, about the long-term risks of alcohol use disorder (AUD) or drug use disorders in men with PC. METHODS: A national cohort study was conducted in Sweden of 180 189 men diagnosed with PC between 1998 and 2017 and 1 801 890 age-matched population-based control men. AUD and drug use disorders were ascertained from nationwide records through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors and prior psychiatric disorders. Subanalyses examined differences by PC treatment from 2005 to 2017. RESULTS: Men with high-risk PC had increased risks of both AUD (adjusted HR = 1.44, 95% confidence interval [CI] = 1.33 to 1.57) and drug use disorders (adjusted HR = 1.93, 95% CI = 1.67 to 2.24). Their AUD risk was highest in the first year and was no longer significantly elevated 5 years after PC diagnosis, whereas their drug use disorders risk remained elevated 10 years after PC diagnosis (adjusted HR = 2.26, 95% CI = 1.45 to 3.52), particularly opioid use disorder (adjusted HR = 3.07, 95% CI = 1.61 to 5.84). Those treated only with androgen-deprivation therapy had the highest risks of AUD (adjusted HR = 1.91, 95% CI = 1.62 to 2.25) and drug use disorders (adjusted HR = 2.23, 95% CI = 1.70 to 2.92). Low- or intermediate-risk PC was associated with modestly increased risks of AUD (adjusted HR = 1.38, 95% CI = 1.30 to 1.46) and drug use disorders (adjusted HR = 1.19, 95% CI = 1.06 to 1.34). CONCLUSIONS: In this large cohort, men with PC had significantly increased risks of both AUD and drug use disorders, especially those with high-risk PC and treated only with androgen-deprivation therapy. PC survivors need long-term psychosocial support and timely detection and treatment of AUD and drug use disorders.

Shared genetic and environmental etiology between substance use disorders and suicidal behavior.

BACKGROUND: Previous studies have demonstrated substantial associations between substance use disorders (SUD) and suicidal behavior. The current study empirically assesses the extent to which shared genetic and/or environmental factors contribute to associations between alcohol use disorders (AUD) or drug use disorders (DUD) and suicidal behavior, including attempts and death. METHODS: The authors used Swedish national registry data, including medical, pharmacy, criminal, and death registrations, for a large cohort of twins, full siblings, and half siblings (N = 1 314 990) born 1960-1980 and followed through 2017. They conducted twin-sibling modeling of suicide attempt (SA) or suicide death (SD) with AUD and DUD to estimate genetic and environmental correlations between outcomes. Analyses were stratified by sex. RESULTS: Genetic correlations between SA and SUD ranged from rA = 0.60-0.88; corresponding shared environmental correlations were rC = 0.42-0.89 but accounted for little overall variance; and unique environmental correlations were rE = 0.42-0.57. When replacing attempt with SD, genetic and shared environmental correlations with AUD and DUD were comparable (rA = 0.48-0.72, rC = 0.92-1.00), but were attenuated for unique environmental factors (rE = -0.01 to 0.31). CONCLUSIONS: These findings indicate that shared genetic and unique environmental factors contribute to comorbidity of suicidal behavior and SUD, in conjunction with previously reported causal associations. Thus, each outcome should be considered an indicator of risk for the others. Opportunities for joint prevention and intervention, while limited by the polygenic nature of these outcomes, may be feasible considering moderate environmental correlations between SA and SUD.

Long-term Risks of Depression and Suicide Among Men with Prostate Cancer: A National Cohort Study.

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear. OBJECTIVE: To determine the long-term risks of major depression and death by suicide in a large population-based cohort. DESIGN, SETTING, AND PARTICIPANTS: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard ratios (HRs) adjusted for sociodemographic factors and comorbidities. Subanalyses assessed differences by PC treatment during 2005-2017. RESULTS AND LIMITATIONS: Men diagnosed with high-risk PC had higher relative rates of major depression (adjusted HR [aHR] 1.82, 95% confidence interval [CI] 1.75-1.89) and death by suicide (aHR 2.43, 95% CI 2.01-2.95). These associations persisted for ≥10 yr after PC diagnosis. The relative increase in major depression was lower among those treated with radiation (aHR 1.44, 95% CI 1.31-1.57) or surgery (aHR 1.60, 95% CI 1.31-1.95) in comparison to androgen deprivation therapy (ADT) alone (aHR 2.02, 95% CI 1.89-2.16), whereas the relative rate of suicide death was higher only among those treated solely with ADT (aHR 2.83, 95% CI 1.80-4.43). By contrast, men with low- or intermediate-risk PC had a modestly higher relative rate of major depression (aHR 1.19, 95% CI 1.16-1.23) and higher relative rate of suicide death at 3-12 mo after PC diagnosis (aHR 1.88, 95% CI 1.11-3.18) but not across the entire follow-up period (aHR 1.02, 95% CI 0.84-1.25). This study was limited to Sweden and will need replication in other populations. CONCLUSIONS: In this large cohort, high-risk PC was associated with substantially higher relative rates of major depression and death by suicide, which persisted for ≥10 yr after PC diagnosis. PC survivors need close follow-up for timely detection and treatment of psychosocial distress. PATIENT SUMMARY: In a large Swedish population, men with aggressive prostate cancer had higher long-term relative rates of depression and suicide.

Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study.

OBJECTIVE: To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers. DESIGN: National cohort study. SETTING: Sweden. PARTICIPANTS: All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015. MAIN OUTCOME MEASURES: The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and environmental) factors. RESULTS: During 53.6 million person years of follow-up, ischemic heart disease was diagnosed in 83 881 (3.8%) women. All five adverse pregnancy outcomes were independently associated with increased risk of ischemic heart disease. In the 10 years after delivery, adjusted hazard ratios for ischemic heart disease associated with specific adverse pregnancy outcomes were 2.09 (95% confidence interval 1.77 to 2.46) for other hypertensive disorders of pregnancy, 1.72 (1.55 to 1.90) for preterm delivery, 1.54 (1.37 to 1.72) for pre-eclampsia, 1.30 (1.09 to 1.56) for gestational diabetes, and 1.10 (1.00 to 1.21) for small for gestational age. The hazard ratios remained significantly increased even 30-46 years after delivery: 1.47 (1.30 to 1.66) for other hypertensive disorders of pregnancy, 1.40 (1.29 to 1.51) for gestational diabetes, 1.32 (1.28 to 1.36) for pre-eclampsia, 1.23 (1.19 to 1.27) for preterm delivery, and 1.16 (1.13 to 1.19) for small for gestational age. These findings were only partially (<45%) explained by shared familial (genetic or environmental) factors. Women who experienced multiple adverse pregnancy outcomes showed further increases in risk (eg, <10 years after delivery, adjusted hazard ratios associated with 1, 2, or ≥3 adverse pregnancy outcomes were 1.29 (1.19 to 1.39), 1.80 (1.59 to 2.03), and 2.26 (1.89 to 2.70), respectively)). CONCLUSIONS: In this large national cohort, women who experienced any of five major adverse pregnancy outcomes showed an increased risk for ischemic heart disease up to 46 years after delivery. Women with adverse pregnancy outcomes should be considered for early preventive evaluation and long term risk reduction to help prevent the development of ischemic heart disease.