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Observational studies suggest that child maltreatment increases the risk of externalizing spectrum disorders such as attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), antisocial personality disorder (ASPD), and substance use disorder (SUD). Yet, only few of such associations have been investigated by approaches that provide strong evidence for causation, such as Mendelian Randomization (MR). Establishing causal inference is essential given the growing recognition of gene-environment correlations, which can confound observational research in the context of childhood maltreatment. Evaluating causality between child maltreatment and the externalizing phenotypes, we used genome-wide association study (GWAS) summary data for child maltreatment (143,473 participants), ADHD (20,183 cases; 35,191 controls), CD (451 cases; 256,859 controls), ASPD (381 cases; 252,877 controls), alcohol use disorder (AUD; 13,422 cases; 244,533 controls), opioid use disorder (OUD; 775 cases; 255,921 controls), and cannabinoid use disorder (CUD; 14,080 cases; 343,726 controls). We also generated a latent variable 'common externalizing factor' (EXT) using genomic structural equation modeling. Genetically predicted childhood maltreatment was consistently associated with ADHD (odds ratio [OR], 10.09; 95%-CI, 4.76-21.40; P = 1.63 × 10-09), AUD (OR, 3.72; 95%-CI, 1.85-7.52; P = 2.42 × 10-04), and the EXT (OR, 2.64; 95%-CI, 1.52-4.60; P = 5.80 × 10-04) across the different analyses and pleiotropy-robust methods. A subsequent GWAS on childhood maltreatment and the externalizing dimension from Externalizing Consortium (EXT-CON) confirmed these results. Two of the top five genes with the strongest associations in EXT GWAS, CADM2 and SEMA6D, are also ranked among the top 10 in the EXT-CON. The present results confirm the existence of a common externalizing factor and an increasing vulnerability caused by child maltreatment, with crucial implications for prevention. However, the partly diverging results also indicate that specific influences impact individual phenotypes separately.
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The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70-80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.
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COVID-19/prevenção & controle , Infarto do Miocárdio/terapia , Distanciamento Físico , Fatores Etários , Idoso , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Quarentena , Sistema de Registros , SARS-CoV-2 , Fatores Sexuais , Fatores de TempoRESUMO
BACKGROUND: Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. METHODS: In 350,512 UK Biobank participants aged 38-73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. RESULTS: During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95-1.07) and 1.04 (95% CI 0.97-1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08-1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96-1.26). CONCLUSION: Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.
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Exercício Físico/estatística & dados numéricos , Força da Mão/fisiologia , Melanoma/epidemiologia , Adulto , Idoso , Bancos de Espécimes Biológicos , Feminino , Humanos , Incidência , Masculino , Melanoma/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Comportamento Sedentário , Reino Unido/epidemiologiaRESUMO
AIMS: Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. METHODS AND RESULTS: We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. CONCLUSIONS: These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased.
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Doença da Artéria Coronariana/epidemiologia , Exercício Físico/estatística & dados numéricos , AVC Isquêmico/epidemiologia , Infarto do Miocárdio/epidemiologia , Acelerometria , Adulto , Idoso , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/genética , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/genética , Exercício Físico/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , AVC Isquêmico/etiologia , AVC Isquêmico/genética , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Comportamento SedentárioRESUMO
BACKGROUND: Fat mass and fat-free mass may play independent roles in mortality risk but available studies on body composition have yielded inconsistent results. OBJECTIVE: The aim was to determine the relations of body fat mass and fat-free mass to risk of mortality. METHODS: In pooled data from 7 prospective cohorts encompassing 16,155 individuals aged 20 to 93 y (median, 44 y), we used Cox regression and restricted cubic splines to estimate HRs and 95% CIs for the relation of body composition, measured by bioelectrical impedance analysis, to total mortality. We adjusted for age, study, sex, ethnicity, history of diabetes mellitus, education, smoking, physical activity, and alcohol consumption. RESULTS: During a median follow-up period of 14 y (range, 3-21 y), 1347 deaths were identified. After mutual adjustment for fat mass and fat-free mass, fat mass showed a J-shaped association with mortality (overall P value < 0.001; P for nonlinearity = 0.003). Using a fat mass index of 7.3 kg/m2 as the reference, a high fat mass index of 13.0 kg/m2 was associated with an HR of 1.56 (95% CI: 1.30, 1.87). In contrast, fat-free mass showed an inverse association with mortality (overall P value < 0.001; P for nonlinearity = 0.001). Compared with a low fat-free mass index of 16.1 kg/m2, a high fat-free mass of 21.9 kg/m2 was associated with an HR of 0.70 (95% CI: 0.56, 0.87). CONCLUSIONS: Fat mass and fat-free mass show opposing associations with mortality. Excess fat mass is related to increased mortality risk, whereas fat-free mass protects against risk of mortality. These findings suggest that body composition provides important prognostic information on an individual's mortality risk not provided by traditional proxies of adiposity such as BMI.
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Tecido Adiposo , Composição Corporal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Caracteres Sexuais , Adulto JovemRESUMO
STUDY OBJECTIVE: Long-term intake of proton pump inhibitors (PPIs) might increase the risk of cardiovascular events. One suggested mechanism is that PPIs inhibit the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and thereby block the degradation of endothelial asymmetrical dimethylarginine (ADMA). Excess ADMA in turn leads to impaired endothelial nitric oxide (NO) generation. So far, this mechanism has only been established in human cell cultures. Previous studies that examined this pathway in human populations measured circulating ADMA and found no association with PPI use and excess plasma ADMA. But in a recent study, plasma ADMA was not correlated with intracellular ADMA. We therefore focused on changes in plasma citrulline as an indicator for potential DDAH inhibition. DESIGN: We analyzed the association between regular daily PPI intake and flow-mediated dilation (FMD) of the brachial artery as well as plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine using inverse probability weighting to adjust for confounding and censoring. DATA SOURCE: Data of 1298 participants from two independent cohorts of the population-based Study of Health in Pomerania were used. PATIENTS: Participants of the population-based Study of Health in Pomerania are a stratified random sample of the study region. INTERVENTION: Regular daily intake of PPIs. MEASUREMENTS: FMD of the brachial artery and plasma concentrations of citrulline, arginine, ADMA, and symmetric dimethylarginine. MAIN RESULTS: Eighty-seven participants (57.5% female) were regular daily users of PPIs. In the fully adjusted models, associations were identified for FMD and plasma citrulline concentrations. PPI users revealed a 0.99% (95% CI: -1.96 to -0.02) lower FMD and 3.03 µmol/L (95% CI: -4.96 to -1.10) lower plasma citrulline levels as compared to non-users. CONCLUSION: Our data provide evidence that long-term intake of PPIs might inhibit human DDAH activity, resulting in impaired endothelial NO production and reduced vascular function. In the long run, this might explain an increased risk for cardiovascular diseases associated with long-term PPI use.
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Endotélio Vascular , Óxido Nítrico , Inibidores da Bomba de Prótons , Arginina , Citrulina , Estudos Transversais , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Masculino , Óxido Nítrico/metabolismo , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
OBJECTIVE: Identifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer. METHODS: We ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50-72 years (median follow-up 12.6 years), from the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body adiposity index, body shape index, and abdominal volume index. RESULTS: Anthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88-1.10). Similar associations were observed with measurements of body fat distribution. CONCLUSION: These results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women.
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Pesos e Medidas Corporais , Neoplasias Ovarianas/epidemiologia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Pós-Menopausa , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
PURPOSE: Due to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population. METHODS: Two surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use. RESULTS: No association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: - 2.06 to - 0.16) in immediate recall, and 0.72 lower (95% CI: - 1.22 to - 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score. CONCLUSIONS: The present study does not support a relationship between PPI use and brain aging.
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Envelhecimento/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Adulto JovemRESUMO
AIM: To assess whether cardiorespiratory fitness (CRF) and handgrip strength, two objective markers of physical fitness, are associated with age-related macular degeneration (AMD). METHODS: We analysed cross-sectional data from the population-based Study of Health in Pomerania (2008-2012) including 1173 adult men and women aged 20-79 years. Fundus photography of the central retina was recorded with a non-mydriatic camera, and images were graded according to an established clinical AMD classification scale by an experienced reader. CRF was measured using peak oxygen uptake (peakVO2), oxygen uptake at the anaerobic threshold (VO2@AT), and maximum power output (Wmax) from standardised cardiopulmonary exercise testing on a bicycle ergometer according to a modified Jones protocol. Handgrip strength was assessed using a handheld dynamometer. Adjusted prevalence ratios (PR) for the associations of peakVO2, VO2@AT, Wmax and handgrip strength with AMD were derived from multivariable Poisson regression models. RESULTS: PeakVO2, VO2@AT, Wmax and handgrip strength were not associated with AMD. Adjusted PR for AMD associated with a 1-SD increment in peakVO2, VO2@AT, Wmax and handgrip strength were 1.05 (95% CI 0.82 to 1.34), 0.96 (95% CI 0.78 to 1.18), 1.10 (95% CI 0.86 to 1.41) and 1.01 (95% CI 0.79 to 1.30), respectively. These associations were not modified by age, sex, smoking, body mass index and diabetes. Estimates in sensitivity analysis for confounding, selection bias and missing data were similar. CONCLUSION: In our study, CRF and handgrip strength were not associated with AMD. Nevertheless, longitudinal studies with bigger sample sizes are needed to furtherly examine these associations.
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Aptidão Cardiorrespiratória/fisiologia , Força da Mão/fisiologia , Degeneração Macular/fisiopatologia , Adulto , Idoso , Estudos Transversais , Ergometria , Teste de Esforço , Feminino , Humanos , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: Evidence from observational studies for the effect of physical activity on the risk of Alzheimer disease (AD) is inconclusive. We performed a 2-sample mendelian randomization analysis to examine whether physical activity is protective for AD. METHODS: Summary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 patients with AD and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at p < 5 × 10-8 to be associated with average accelerations and 8 SNPs associated at p < 5 × 10-7 with vigorous physical activity (fraction of accelerations >425 milligravities) served as instrumental variables. RESULTS: There was no association between genetically predicted average accelerations with the risk of AD (inverse variance weighted odds ratio [OR] per SD increment: 1.03, 95% confidence interval 0.97-1.10, p = 0.332). Genetic liability for fraction of accelerations >425 milligravities was unrelated to AD risk. CONCLUSION: The present study does not support a causal association between physical activity and risk of AD.
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Doença de Alzheimer/genética , Exercício Físico , Predisposição Genética para Doença/genética , Análise da Randomização Mendeliana , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: Physical activity is a complex behavior that is difficult to measure validly and reliably in large, population-based studies. Data on physical activity are available for the initial 100,000 participants of the German National Cohort. OBJECTIVES: To describe the baseline physical activity assessment in the cohort and to present initial descriptive results. MATERIAL AND METHODS: Physical activity was assessed using a combination of tools, including two self-administered questionnaires, the Questionnaire on Annual Physical Activity Pattern (QUAP) and the Global Physical Activity Questionnaire (GPAQ); a computer-based 24h physical activity recall (cpar24); and 7day accelerometry (Actigraph GT3X/+; ActiGraph, Pensacola, FL, USA). RESULTS: The availability of data varied between assessment instruments (QUAP: nâ¯= 16,372; GPAQ: nâ¯= 90,900; cpar24: nâ¯= 23,989; accelerometry: nâ¯= 35,218). Analyses across measurement tools showed that on average, women spent 75 to 216â¯min/d, and men spent 73 to 224â¯min/d in moderate or higher intensity total physical activity. Persons aged 20-39 years spent 66 to 200â¯min/d, and persons aged 40-69 years spent 78 to 244â¯min/d in moderate or higher intensity total physical activity. CONCLUSIONS: Initial baseline analyses of physical activity in this cohort show the value of using a combination of questionnaires, 24h recalls, and a movement sensor. The comprehensive data collection represents a valuable resource for future analyses and will improve our understanding of the association between physical activity and disease prevention.
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Exercício Físico , Acelerometria , Adulto , Idoso , Estudos de Coortes , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes. PARTICIPANTS AND METHODS: We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO2peak), oxygen uptake at the anaerobic threshold (VO2@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume. RESULTS: Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1-standard deviation increase in VO2peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO2peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels). CONCLUSION: Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.
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Limiar Anaeróbio , Encéfalo , Aptidão Cardiorrespiratória/fisiologia , Substância Cinzenta , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Correlação de Dados , Teste de Esforço/métodos , Teste de Esforço/estatística & dados numéricos , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do ÓrgãoRESUMO
Increased cardiorespiratory fitness is related to decreased risk of major chronic illnesses, including cardiovascular disease, type 2 diabetes, and cancer, but its association with colorectal cancer specifically has received very little attention. We examined the relation of cardiorespiratory fitness to colorectal cancer in 59,191 UK Biobank participants aged 39-70 years without prevalent cancer at baseline, followed from 2009 to 2014. Submaximal bicycle ergometry was conducted at study entry, and cardiorespiratory fitness was defined as physical work capacity at 75% of the maximum heart rate, standardised to body mass (PWC75%). Multivariable Cox proportional hazards regression was performed to obtain hazard ratios (HR) and corresponding 95% confidence intervals (CI). During a mean follow-up of 4.6 years, 232 participants developed colorectal cancer (151 colon cancers; 79 rectal cancers). When comparing the 75th to the 25th percentiles of PWC75%, the multivariable-adjusted HR of colorectal cancer was 0.78 (95% CI 0.62-0.97). That relation was largely driven by an inverse association with colon cancer (HR 0.74, 95% CI 0.56-0.97) and less so with rectal cancer (HR 0.88, 95% CI 0.62-1.26; p value for difference by colorectal cancer endpoint = 0.056). The inverse relation of cardiorespiratory fitness with colorectal cancer was more evident in men (HR 0.72, 95% CI 0.55-0.94) than women (HR 0.99, 95% CI 0.71-1.38), although the gender difference was not statistically significant (p value for interaction = 0.192). Increased cardiorespiratory fitness is associated with decreased risk of colorectal cancer. Potential heterogeneity by colorectal cancer anatomic subsite and gender requires further study.
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Aptidão Cardiorrespiratória , Neoplasias Colorretais/epidemiologia , Frequência Cardíaca/fisiologia , Adulto , Idoso , Bancos de Espécimes Biológicos , Índice de Massa Corporal , Estudos de Coortes , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/epidemiologia , Neoplasias Colorretais/diagnóstico , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias Retais/diagnóstico , Neoplasias Retais/epidemiologia , Fatores Sexuais , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Little is known about outpatient health services use following critical illness and intensive care. We examined the association of intensive care with outpatient consultations and quality of life in a population-based sample. METHODS: Cross-sectional analysis of data from 6,686 participants of the Study of Health in Pomerania (SHIP), which consists of two independent population-based cohorts. Statistical modeling was done using Poisson regression, negative binomial and generalized linear models for consultations, and a fractional response model for quality of life (EQ-5D-3L index value), with results expressed as prevalence ratios (PR) or percent change (PC). Entropy balancing was used to adjust for observed confounding. RESULTS: ICU treatment in the previous year was reported by 139 of 6,686 (2,1%) participants, and was associated with a higher probability (PR 1.05 [CI:1.03;1.07]), number (PC +58.0% [CI:22.8;103.2]) and costs (PC +64.1% [CI:32.0;103.9]) of annual outpatient consultations, as well as with a higher number of medications (PC +37.8% [CI:17.7;61.5]). Participants with ICU treatment were more likely to visit a specialist (PR 1.13 [CI:1.09; 1.16]), specifically internal medicine (PR 1.67 [CI:1.45;1.92]), surgery (PR 2.42 [CI:1.92;3.05]), psychiatry (PR 2.25 [CI:1.30;3.90]), and orthopedics (PR 1.54 [CI:1.11;2.14]). There was no significant effect regarding general practitioner consultations. ICU treatment was also associated with lower health-related quality of life (EQ-5D index value: PC -13.7% [CI:-27.0;-0.3]). Furthermore, quality of life was inversely associated with outpatient consultations in the previous month, more so for participants with ICU treatment. CONCLUSIONS: Our findings suggest that ICU treatment is associated with an increased utilization of outpatient specialist services, higher medication intake, and impaired quality of life.
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Assistência Ambulatorial/estatística & dados numéricos , Cuidados Críticos/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Qualidade de Vida , Adulto , Idoso , Assistência Ambulatorial/economia , Cuidados Críticos/economia , Estudos Transversais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Adulto JovemRESUMO
Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d-1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.
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Consumo de Bebidas Alcoólicas/genética , Genes/genética , Predisposição Genética para Doença/genética , Transtornos Mentais/genética , Adulto , Idoso , Alcoolismo/genética , Encéfalo/fisiopatologia , Feminino , Genes/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Esquizofrenia/genética , População Branca/genéticaRESUMO
The present study evaluated the ability of the visceral adiposity index (VAI), the lipid accumulation product (LAP), and product of triglycerides and glucose (TyG), three novel, insulin resistance-related markers, to discriminate prediabetes/diabetes in the general German population. Altogether 2,045 Germans (31-72 years, 53.3% women) without known diabetes and a history of Myocardial Infarction (MI)/stroke from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study were eligible. The discriminatory accuracy of the markers for oral glucose tolerance test (OGTT)-defined prediabetes/diabetes according to the American Diabetes Association (ADA) criteria was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The Youden Index (YI) was used to determine optimal cut-off values, and a non-parametric ROC regression was used to examine whether the discriminatory accuracy varied by sex and age. 365 men (38.2%) and 257 women (23.6%) were newly diagnosed with prediabetes/diabetes. AUCs for TyG, LAP and VAI were 0.762 (95% CI 0.740-0.784), 0.743 (95% CI 0.720-0.765), and 0.687 (95% CI 0.662-0.712), respectively. The optimal cut-off values for the LAP and TyG were 56.70 and 8.75 in men, and 30.40 and 8.53 in women. In conclusion, TyG and LAP provide good discrimination of persons with prediabetes/diabetes.
Assuntos
Adiposidade , Diabetes Mellitus Tipo 2/diagnóstico , Glucose/metabolismo , Gordura Intra-Abdominal/fisiopatologia , Produto da Acumulação Lipídica , Obesidade Abdominal/fisiopatologia , Estado Pré-Diabético/diagnóstico , Triglicerídeos/metabolismo , Adulto , Idoso , Biomarcadores/análise , Diabetes Mellitus Tipo 2/epidemiologia , Diagnóstico Diferencial , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Curva ROC , Fatores de RiscoRESUMO
BACKGROUND: Physical inactivity is an established risk factor for several cancers of the digestive system and female reproductive organs, but the evidence for liver cancers is less conclusive. METHODS: The aim of this study was to synthesize prospective observational studies on the association of physical activity and liver cancer risk by means of a systematic review and meta-analysis. We searched Medline, Embase, and Scopus from inception to January 2019 for prospective studies investigating the association of physical activity and liver cancer risk. We calculated mean hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. We quantified the extent to which an unmeasured confounder or an unaccounted selection variable could shift the mean hazard ratio to the null. RESULTS: Fourteen prospective studies, including 6,440 liver cancers, were included in the systematic review and meta-analysis. The mean hazard ratio for high compared with low physical activity was 0.75 (95% CI = 0.63 to 0.89; 95% prediction interval = 0.52 to 1.07; I² = 64.2%). We estimated that 67.6% (95% CI = 56.6% to 78.5%) of all true effect estimates would have a hazard ratio less than 0.8. Bias analysis suggested than an unobserved confounder would have to be associated with a 1.99-fold increase in the risk of physical activity or liver cancer to explain away the observed mean hazard ratio. An unaccounted for selection variable would have to be related to exposure and endpoint with a relative risk of 1.58 to explain away the mean hazard ratio. CONCLUSIONS: Physical activity is inversely related to the risk of liver cancer. Further studies with objectively measured physical activity and quasi-experimental designs addressing confounding are needed.
Assuntos
Atividades Cotidianas , Terapia por Exercício , Neoplasias Hepáticas/prevenção & controle , Comportamento Sedentário , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Estudos Prospectivos , Fatores de RiscoAssuntos
Consumo de Bebidas Alcoólicas/tendências , Autorrelato , Classe Social , Adolescente , Adulto , Fatores Etários , Estudos de Coortes , Feminino , Alemanha , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
OBJECTIVE: To revise the German guidelines and recommendations for ensuring Good Epidemiological Practice (GEP) that were developed in 1999 by the German Society for Epidemiology (DGEpi), evaluated and revised in 2004, supplemented in 2008, and updated in 2014. METHODS: The executive board of the DGEpi tasked the third revision of the GEP. The revision was arrived as a result of a consensus-building process by a working group of the DGEpi in collaboration with other working groups of the DGEpi and with the German Association for Medical Informatics, Biometry and Epidemiology, the German Society of Social Medicine and Prevention (DGSMP), the German Region of the International Biometric Society (IBS-DR), the German Technology, Methods and Infrastructure for Networked Medical Research (TMF), and the German Network for Health Services Research (DNVF). The GEP also refers to related German Good Practice documents (e.g. Health Reporting, Cartographical Practice in the Healthcare System, Secondary Data Analysis). RESULTS: The working group modified the 11 guidelines (after revision: 1 ethics, 2 research question, 3 study protocol and manual of operations, 4 data protection, 5 sample banks, 6 quality assurance, 7 data storage and documentation, 8 analysis of epidemiological data, 9 contractual framework, 10 interpretation and scientific publication, 11 communication and public health) and modified and supplemented the related recommendations. All participating scientific professional associations adopted the revised GEP. CONCLUSIONS: The revised GEP are addressed to everyone involved in the planning, preparation, execution, analysis, and evaluation of epidemiological research, as well as research institutes and funding bodies.