Season of birth and other perinatal risk factors for melanoma.

Ultraviolet radiation (UVR) exposure is the main risk factor for cutaneous malignant melanoma (CMM), but its specific effect in infancy is unknown. We examined whether season of birth, a proxy for solar UVR exposure in the first few months of life, is associated with CMM in childhood through young adulthood

Perinatal and Familial Risk Factors for Acute Lymphoblastic Leukemia in a Swedish National Cohort

BACKGROUNDPerinatal factors including high birth weight have been found to be associated with acute lymphoblastic leukemia (ALL) in case-control studies. However, to the best of our knowledge, these findings have seldom been examined in large population-based cohort studies, and the specific contributions of gestational age and fetal growth remain unknown. METHODSThe authors conducted a national cohort study of 3,569,333 individuals without Down syndrome who were born in Sweden between 1973 and 2008 and followed for the incidence of ALL through 2010 (maximum age, 38 years) to examine perinatal and familial risk factors. RESULTSThere were 1960 ALL cases with 69.7 million person-years of follow-up. After adjusting for potential confounders, risk factors for ALL included high fetal growth (incidence rate ratio [IRR] per additional 1 standard deviation, 1.07; 95% confidence interval [95% CI], 1.02-1.11 [P =.002]; and IRR for large vs appropriate for gestational age, 1.22; 95% CI, 1.06-1.40 [P =.005]), first-degree family history of ALL (IRR, 7.41; 95% CI, 4.60-11.95 [P<.001]), male sex (IRR, 1.20; 95% CI, 1.10-1.31 [P<.001]), and parental country of birth (IRR for both parents born in Sweden vs other countries, 1.13; 95% CI, 1.00-1.27 [P =.045]). These risk factors did not appear to vary by patient age at the time of diagnosis of ALL. Gestational age at birth, season of birth, birth order, multiple birth, parental age, and parental education level were not found to be associated with ALL. CONCLUSIONSIn this large cohort study, high fetal growth was found to be associated with an increased risk of ALL in childhood through young adulthood, independent of gestational age at birth, suggesting that growth factor pathways may play an important long-term role in the etiology of ALL. Cancer 2015;121:1040-1047. (c) 2014 American Cancer Society. The authors conducted what, to their knowledge, is the largest population-based cohort study to date to examine perinatal and familial risk factors for acute lymphoblastic leukemia (ALL) among approximately 3.5 million individuals born in Sweden between 1973 and 2008. High fetal growth was found to be associated with an increased risk of ALL in childhood through young adulthood, independent of gestational age at birth, suggesting that growth factor pathways may play an important long-term role in the etiology of ALL

Perinatal risk factors for Wilms tumor in a Swedish national cohort

Perinatal risk factors including high birth weight have been associated with Wilms tumor in case-control studies. However, these findings have seldom been examined in large cohort studies, and the specific contributions of gestational age at birth and fetal growth remain unknown. We conducted the largest population-based cohort study to date consisting of 3,571,574 persons born in Sweden in 1973-2008, followed up for Wilms tumor incidence through 2009 to examine perinatal risk factors. There were 443 Wilms tumor cases identified in 66.3 million person-years of follow-up. After adjusting for gestational age and other perinatal factors, high fetal growth was associated with increased risk of Wilms tumor among girls (hazard ratio per 1 standard deviation (SD), 1.36; 95 % CI 1.20-1.54; P < 0.001), but not boys (1.10; 95 % CI 0.97-1.25; P = 0.14) (P (interaction) = 0.02). Among girls, high fetal growth was associated with disease onset before age 5 years (odds ratio per 1 SD, 1.47; 95 % CI 1.28-1.69; P < 0.001), but not beyond (1.00; 95 % CI 0.76-1.31; P = 0.99). No clear associations were found for gestational age at birth or other perinatal factors. In this large cohort study, high fetal growth was associated with Wilms tumor before age 5 years among girls. These findings suggest that early-life growth factor pathways for Wilms tumor may be more common among girls than boys. Further elucidation of these mechanisms may reveal better targets for prevention or treatment of specific subtypes of Wilms tumor

Risk of Depression in Persons With alzheimer\u27s Disease: a National Cohort Study

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer\u27s 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 \u3e2-fold subsequent risk of depression.Risks were highest in the first year (\u3e3-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

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

Familial and neighborhood effects on psychiatric disorders in childhood and adolescence

Background: More knowledge is needed on potential associations between individual-, family-, and neighborhood-level factors and psychiatric disorders in children and adolescents. Aims: To examine associations between, individual-, family-, and neighborhood-level factors and incident internalizing (anxiety and mood) disorders and externalizing (ADHD and conduct) disorders in children and adolescents, and to estimate the relative contributions of family and neighborhood to individual variation in these disorders. Method: We performed a three-level logistic regression on all 542,195 children born in Sweden in 1992-1996, nested in 427,954 families, which in turn were nested in 8475 neighborhoods. The children were followed from 2000 to 2010 for incident internalizing and externalizing psychiatric disorders, assessed from medical records. Results: 26,514 children (4.8%) were diagnosed with internalizing or externalizing psychiatric disorders. Approximately 29% of the total individual variance in internalizing disorders could be attributed to the family level, which includes both genetic and family environmental effects, and 5% to the neighborhood level. The corresponding figures for externalizing disorders were 43.5% and 5.5%, respectively. After adjustment for individual-level sociodemographic factors, high neighborhood deprivationwas associated with increased risks of externalizing and internalizing psychiatric disorders (odds ratio [OR] = 1.37, 95% credible interval [CI] = 1.25-1.50 and OR = 1.34, 95% CI = 1.25-1.45, respectively), including conduct disorder (OR = 2.01, 95% CI = 1.58-2.55), anxiety disorders (OR = 1.40, 95% CI = 1.29-1.52), and mood disorders (OR = 1.21, 95% CI, 1.09-1.35). The strongest association between neighborhood deprivation and ADHD was observed in moderately deprived neighborhoods (OR = 1.31, 95% CI = 1.19-1.44). Conclusions: These findings call for policies to promote mental health that consider potential influences from children's family and neighborhood environments. Trial registration: Not applicable

Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals

AbstractObjectivesThis study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.BackgroundEnd-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.MethodsWe analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level ≥1.5 mg/dl in men or ≥1.3 mg/dl in women.ResultsAn elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.ConclusionsElevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological p ..