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PURPOSE: To investigate longitudinal associations between the vitamin D status and inflammatory markers in children and adolescents. METHODS: Children from eight European countries from the IDEFICS/I.Family cohort with repeated measurements were included in this study. A linear mixed-effect model was used to model the association of serum 25(OH)D as independent variable and z-scores of inflammatory markers [CRP, cytokines, adipokines, combined inflammation score] as dependent variables, where one level accounts for differences between individuals and the other for changes over age within individuals. RESULTS: A total of 1,582 children were included in the study. In the adjusted model, 25(OH)D levels were positively associated with adiponectin (ß = 0.11 [95% CI 0.07; 0.16]) and negatively with the inflammation score (ß = - 0.24 [95% CI - 0.40; - 0.08]) indicating that the adiponectin z-score increased by 0.11 units and the inflammation score decreased by 0.24 units per 12.5 nmol/l increase in 25(OH)D. In children with overweight or obesity, only a positive association between 25(OH)D and IP-10 was observed while in children with normal weight adiponectin was positively and the inflammation score was negatively associated. Associations of vitamin D with adiponectin and the inflammation score were stronger in girls than in boys and a positive association with TNF-α was observed only in girls. CONCLUSION: Our results suggest that an increase in vitamin D concentrations may help to regulate inflammatory biomarkers. However, it seems to be no benefit of a better vitamin D status in children with overweight/obesity unless their weight is managed to achieve an improved inflammatory marker status.
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INTRODUCTION: Despite international efforts, the number of individuals struggling with obesity is still increasing. An important aspect of obesity prevention relates to identifying individuals at risk at early stage, allowing for timely risk stratification and initiation of countermeasures. However, obesity is complex and multifactorial by nature, and one isolated (bio)marker is unlikely to enable an optimal risk stratification and prognosis for the individual; rather, a combined set is required. Such a multicomponent interpretation would integrate biomarkers from various domains, such as classical markers (eg, anthropometrics, blood lipids), multiomics (eg, genetics, proteomics, metabolomics), lifestyle and behavioural attributes (eg, diet, physical activity, sleep patterns), psychological traits (mental health status such as depression) and additional host factors (eg, gut microbiota diversity), also by means of advanced interpretation tools such as machine learning. In this paper, we will present a protocol that will be employed for a scoping review that attempts to summarise and map the state-of-the-art in the area of multicomponent (bio)markers related to obesity, focusing on the usability and effectiveness of such biomarkers. METHODS AND ANALYSIS: PubMed, Scopus, CINAHL and Embase databases will be searched using predefined key terms to identify peer-reviewed articles published in English until January 2024. Once downloaded into EndNote for deduplication, CADIMA will be employed to review and select abstracts and full-text articles in a two-step procedure, by two independent reviewers. Data extraction will then be carried out by several independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Peer Review of Electronic Search Strategies guidelines will be followed. Combinations employing at least two biomarkers from different domains will be mapped and discussed. ETHICS AND DISSEMINATION: Ethical approval is not required; data will rely on published articles. Findings will be published open access in an international peer-reviewed journal. This review will allow guiding future directions for research and public health strategies on obesity prevention, paving the way towards multicomponent interventions.
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Biomarcadores , Obesidade , Humanos , Antropometria , Bases de Dados Factuais , Obesidade/diagnóstico , Projetos de Pesquisa , Literatura de Revisão como AssuntoRESUMO
AIMS/HYPOTHESIS: There is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution. METHODS: Genotyping was successful in 2825 children aged 2-14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15-P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin. RESULTS: A variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10-8). Two variants associated with low z-insulin (P15, p value <5×10-6) were located on the RBFOX1 and SH3RF3 genes. These genes have previously been associated with both metabolic traits and dementia phenotypes. While variants associated with P50 showed stable associations across the insulin spectrum, we found that associations with variants identified through GWA analyses of P15 and P85 varied across quantiles of log-insulin. CONCLUSIONS/INTERPRETATION: The above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker-disease associations.
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Demência , Doenças Neurodegenerativas , Masculino , Feminino , Humanos , Estudo de Associação Genômica Ampla , Insulina , Jejum , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína LigasesRESUMO
CONTEXT: Vitamin D status has previously been associated with cardiometabolic risk markers in children and adolescents. In particular, it has been suggested that children with obesity are more prone to vitamin D deficiency and unfavorable metabolic outcomes compared with healthy-weight children. OBJECTIVE: To conduct a longitudinal study assessing this association in children and stratify by body mass index (BMI) category. METHODS: Children from the pan-European IDEFICS/I.Family cohort with at least one measurement of serum 25-hydroxyvitamin D [25(OH)D] at cohort entry or follow-up (n = 2171) were included in this study. Linear mixed-effect models were used to assess the association between serum 25(OH)D as an independent variable and z-scores of cardiometabolic risk markers (waist circumference, systolic [SBP] and diastolic blood pressure [DBP], high- [HDL] and low-density lipoprotein, non-HDL, triglycerides [TRG], apolipoprotein A1 [ApoA1] and ApoB, fasting glucose [FG], homeostatic model assessment for insulin resistance [HOMA-IR], and metabolic syndrome score) as dependent variables. RESULTS: After adjustment for age, sex, study region, smoking and alcohol status, sports club membership, screen time, BMI, parental education, and month of blood collection, 25(OH)D levels were inversely associated with SBP, DBP, FG, HOMA-IR, and TRG. The HOMA-IR z-score decreased by 0.07 units per 5 ng/mL increase in 25(OH)D. The 25(OH)D level was consistently associated with HOMA-IR irrespective of sex or BMI category. CONCLUSION: Low serum 25(OH)D concentrations are associated with unfavorable levels of cardiometabolic markers in children and adolescents. Interventions to improve vitamin D levels in children with a poor status early in life may help to reduce cardiometabolic risk.
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Doenças Cardiovasculares , Resistência à Insulina , Síndrome Metabólica , Deficiência de Vitamina D , Humanos , Criança , Adolescente , Estudos Longitudinais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Vitamina D , Vitaminas , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Triglicerídeos , Índice de Massa CorporalRESUMO
The effects of exposure to black carbon (BC) on various diseases remains unclear, one reason being potential exposure misclassification following modelling of ambient air pollution levels. Urinary BC particles may be a more precise measure to analyze the health effects of BC. We aimed to assess the risk of prediabetes and metabolic syndrome (MetS) in relation to urinary BC particles and ambient BC and to compare their associations in 5453 children from IDEFICS/I. Family cohort. We determined the amount of BC particles in urine using label-free white-light generation under femtosecond pulsed laser illumination. We assessed annual exposure to ambient air pollutants (BC, PM2.5 and NO2) at the place of residence using land use regression models for Europe, and we calculated the residential distance to major roads (≤250 m vs. more). We analyzed the cross-sectional relationships between urinary BC and air pollutants (BC, PM2.5 and NO2) and distance to roads, and the associations of all these variables to the risk of prediabetes and MetS, using logistic and linear regression models. Though we did not observe associations between urinary and ambient BC in overall analysis, we observed a positive association between urinary and ambient BC levels in boys and in children living ≤250 m to a major road compared to those living >250 m away from a major road. We observed a positive association between log-transformed urinary BC particles and MetS (ORper unit increase = 1.72, 95% CI = 1.21; 2.45). An association between ambient BC and MetS was only observed in children living closer to a major road. Our findings suggest that exposure to BC (ambient and biomarker) may contribute to the risk of MetS in children. By measuring the internal dose, the BC particles in urine may have additionally captured non-residential sources and reduced exposure misclassification. Larger studies, with longitudinal design including measurement of urinary BC at multiple time-points are warranted to confirm our findings.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Síndrome Metabólica , Estado Pré-Diabético , Masculino , Humanos , Criança , Adolescente , Poluentes Atmosféricos/análise , Síndrome Metabólica/epidemiologia , Poluentes Ambientais/análise , Estado Pré-Diabético/epidemiologia , Dióxido de Nitrogênio/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Fuligem/análise , Carbono/análise , Material Particulado/análiseRESUMO
AIMS: Family history is a known risk factor for early-onset myocardial infarction (EOMI). However, the role of modifiable lifestyle and metabolic factors in EOMI risk is unclear and may differ from that of older adults. METHODS: This case-control study included myocardial infarction (MI) patients aged ≤45 years from the Bremen ST-elevation MI Registry and matched controls randomly selected from the general population (German National Cohort) at the same geographical region. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the individual and combined associations of lifestyle and metabolic factors with EOMI risk, overall and according to family history for premature MI. RESULTS: A total of 522 cases and 1191 controls were included. Hypertension, current smoking, elevated waist-to-hip ratio, and diabetes mellitus were strongly associated with the occurrence of EOMI. By contrast, higher frequency of alcohol consumption was associated with decreased EOMI risk. In a combined analysis of the risk factors hypertension, current smoking, body mass index ≥25.0â kg/sqm, and diabetes mellitus, participants having one (OR = 5.4, 95%CI = 2.9-10.1) and two or more risk factors (OR = 42.3, 95%CI = 22.3-80.4) had substantially higher odds of EOMI compared to those with none of these risk factors, regardless of their family history. CONCLUSION: This study demonstrates a strong association of smoking and metabolic risk factors with the occurrence of EOMI. The data suggest that the risk of EOMI goes beyond family history and underlines the importance of primary prevention efforts to reduce smoking and metabolic syndrome in young persons.
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Diabetes Mellitus , Hipertensão , Infarto do Miocárdio , Humanos , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/complicações , Estilo de Vida , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Fatores de Risco , Adulto , Pessoa de Meia-IdadeRESUMO
PURPOSE: Subclinical systemic inflammation may lead to development of type 2 diabetes, but there has been no investigation into its relationship with early progression of glycaemic deterioration and insulin resistance, especially in younger population. In this study we assessed longitudinal associations of pro- and anti-inflammatory markers with markers that evaluate glycaemia and insulin resistance. METHODS: This study includes 6537 initially nondiabetic children (mean age at baseline = 6.2 years) with repeated measurements from the IDEFICS/I.Family cohort study (mean follow-up = 5.3 years) from eight European countries. Markers of inflammation were used as independent variables and markers of glycaemia/insulin resistance as dependent variables. Associations were examined using two-level growth model. Models were adjusted for sex, age, major lifestyle, metabolic risk factors, early life markers, and other inflammatory markers in final model. RESULTS: Children with 6 years of follow-up showed that a one-unit increase in z-score of leptin level was associated with 0.38 (95% CI = 0.32 to 0.44) unit increase in HOMA-IR z-scores. Leptin continued to be associated with HOMA-IR even when analysis was limited to children with no overall obesity, no abdominal obesity, and low to normal triglyceride levels. An inverse association was observed between IL-15 and HOMA-IR (ß = -0.11, 95% CI = -0.15 to -0.07). CONCLUSIONS: IL-15 should be evaluated further in the prevention or treatment of prediabetes whereas leptin may prove to be useful in early detection of prediabetes via their association with markers of insulin resistance in European children.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Glicemia/análise , Índice de Massa Corporal , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologiaRESUMO
Comorbidities and advanced stage diagnosis (ASD) are both associated with poorer cancer outcomes, but the association between comorbidities and ASD is poorly understood. We summarized epidemiological evidence on the association between comorbidities and ASD of selected cancers in a systematic review and meta-analysis. We searched PubMed and Web of Science databases up to June 3rd, 2021 for studies assessing the association between comorbidities and ASD of lung, breast, colorectal, or prostate cancer. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated using random-effects models. Also, potential variations in the associations between comorbidities and ASD by cancer type were investigated using random-effects meta-regression. Thirty-seven studies were included in this review, including 8,069,397 lung, breast, colorectal, and prostate cancer patients overall. The Charlson comorbidity index score was positively associated with ASD (stages III-IV) of breast cancer but was inversely associated with ASD of lung cancer (pinteraction = 0.004). Regarding specific comorbidities, diabetes was positively associated with ASD (OR = 1.17, 95%CI = 1.09-1.26), whereas myocardial infarction was inversely associated with ASD (OR = 0.84, 95%CI = 0.75-0.95). The association between renal disease and ASD differed by cancer type (pinteraction < 0.001). A positive association was found with prostate cancer (OR = 2.02, 95%CI = 1.58-2.59) and an inverse association with colorectal cancer (OR = 0.84, 95%CI = 0.70-1.00). In summary, certain comorbidities (e.g., diabetes) may be positively associated with ASD of several cancer types. It needs to be clarified whether closer monitoring for early cancer signs or screening in these patients is reasonable, considering the problem of over-diagnosis particularly relevant in patients with short remaining life expectancy such as those with comorbidities. Also, evaluation of the cost-benefit relationship of cancer screening according to the type and severity of comorbidity (rather than summary scores) may be beneficial for personalized cancer screening in populations with chronic diseases.
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Neoplasias Colorretais , Neoplasias da Próstata , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Comorbidade , Humanos , Pulmão , Masculino , Sobrediagnóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologiaRESUMO
COVID-19 poses a major challenge to individuals and societies around the world. Yet, it is difficult to obtain a good overview of studies across different medical fields of research such as clinical trials, epidemiology, and public health. Here, we describe a consensus metadata model to facilitate structured searches of COVID-19 studies and resources along with its implementation in three linked complementary web-based platforms. A relational database serves as central study metadata hub that secures compatibilities with common trials registries (e.g. ICTRP and standards like HL7 FHIR, CDISC ODM, and DataCite). The Central Search Hub was developed as a single-page application, the other two components with additional frontends are based on the SEEK platform and MICA, respectively. These platforms have different features concerning cohort browsing, item browsing, and access to documents and other study resources to meet divergent user needs. By this we want to promote transparent and harmonized COVID-19 research.
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COVID-19 , Estudos Epidemiológicos , Humanos , Metadados , Sistema de Registros , SARS-CoV-2RESUMO
Background: The coronavirus disease 2019 (COVID-19) global pandemic required a rapid and effective response. This included ethical and legally appropriate sharing of data. The European Commission (EC) called upon the Research Data Alliance (RDA) to recruit experts worldwide to quickly develop recommendations and guidelines for COVID-related data sharing. Purpose: The purpose of the present work was to explore how the RDA succeeded in engaging the participation of its community of scientists in a rapid response to the EC request. Methods: A survey questionnaire was developed and distributed among RDA COVID-19 work group members. A mixed-methods approach was used for analysis of the survey data. Results: The three constructs of radical collaboration (inclusiveness, distributed digital practices, productive and sustainable collaboration) were found to be well supported in both the quantitative and qualitative analyses of the survey data. Other social factors, such as motivation and group identity were also found to be important to the success of this extreme collaborative effort. Conclusions: Recommendations and suggestions for future work were formulated for consideration by the RDA to strengthen effective expert collaboration and interdisciplinary efforts.
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IMPORTANCE: Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women. OBJECTIVE: Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women. EVIDENCE REVIEW: Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form. FINDINGS: In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (-0.27âmmol/L [-0.41 to -0.13]), low-density lipoprotein (-0.25âmmol/L [-0.37 to -0.13]), triglycerides (-0.20âmmol/L [-0.28 to -0.11]), and apolipoprotein B (-0.13âg/L [-0.23 to -0.03]) and with an increase in serum apolipoprotein A-1 (0.04âg/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (-18.86âng/mL [-30.06 to -7.65]) and E-selectin (-2.32âng/mL [-4.05 to -0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34âµm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled. CONCLUSIONS AND RELEVANCE: Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health. : Video Summary: http://links.lww.com/MENO/A593.
Video Summary: http://links.lww.com/MENO/A593.
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Doenças Cardiovasculares , Fitoestrógenos , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Pós-Menopausa , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
OBJECTIVE: To assess the time point during infancy and early childhood at which greater than expected weight gain is associated with overweight in adolescence. STUDY DESIGN: Current height, weight, and body mass index (BMI) were assessed in 1520 adolescents (mean age of boys, 15.52 ± 0.84 years; mean age of girls, 15.37 ± 0.77 years). Information on weight and height trajectories during infancy and early childhood (birth and 6 other time points) was extracted from mother-child booklets. Conditional relative weights were computed to estimate greater or lower than expected weight gain (ie, soft tissue gain at a specific age independent of linear growth), and their association with BMI in adolescence was investigated using linear regression analysis. RESULTS: The mean BMI in adolescence was 21.77 ± 3.69 in boys and 21.70 ± 3.50 in girls. The proportion of overweight was 14.8% in each group. Overweight adolescents had significantly higher weight z-scores at birth, 1.2 month, 3.3 months, 7.6 months, 1 year, 2 years, and 4 years of age as compared with normal-weight adolescents. There were significant positive associations of weight z-scores and conditional relative weights with adolescent BMI at all ages except birth, which were strongest after the first year of life. In a majority of overweight adolescents, overweight had manifested within the first 4 years of life. CONCLUSIONS: Greater than expected weigh gain at any time in the first years of life is associated with an increased BMI in adolescence. The effect is strongest after the first year.
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Peso ao Nascer , Índice de Massa Corporal , Obesidade Infantil/epidemiologia , Aumento de Peso , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
As the prevalence of metabolic syndrome (MetS) in children and young adults is increasing, a better understanding of genetics that underlie MetS will provide critical insights into the origin of the disease. We examined associations of common genetic variants and repeated MetS score from early childhood to adolescence in a pan-European, prospective IDEFICS/I.Family cohort study with baseline survey and follow-up examinations after two and six years. We tested associations in 3067 children using a linear mixed model and confirmed the results with meta-analysis of identified SNPs. With a stringent Bonferroni adjustment for multiple comparisons we obtained significant associations(p < 1.4 × 10-4) for 5 SNPs, which were in high LD (r2 > 0.85) in the 16q12.2 non-coding intronic chromosomal region of FTO gene with strongest association observed for rs8050136 (effect size(ß) = 0.31, pWald = 1.52 × 10-5). We also observed a strong association of rs708272 in CETP with increased HDL (p = 5.63 × 10-40) and decreased TRG (p = 9.60 × 10-5) levels. These findings along with meta-analysis advance etiologic understanding of childhood MetS, highlighting that genetic predisposition to MetS is largely driven by genes of obesity and lipid metabolism. Inclusion of the associated genetic variants in polygenic scores for MetS may prove to be fundamental for identifying children and subsequently adults of the high-risk group to allow earlier targeted interventions.
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Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , Cromossomos Humanos Par 16/genética , Síndrome Metabólica/genética , Obesidade Infantil/genética , Polimorfismo de Nucleotídeo Único , Adulto , Criança , Pré-Escolar , Família , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
INTRODUCTION: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). METHODS: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. RESULTS: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays. CONCLUSIONS: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Adolescente , Adulto , Neoplasias Encefálicas/classificação , Estudos de Casos e Controles , Criança , Diagnóstico Tardio , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Prevalência , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for clinicians, researchers, policy- and decision-makers, funders, publishers, public health experts, disaster preparedness and response experts, infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations), and other potential users. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.
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Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease ( CVD ) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow-up of 4.2 years, 4066 CVD events were recorded. In a random-effects meta-analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12-1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias ( P value from Egger's test=0.013). Correction for publication bias using the trim-and-fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03-1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow-up. Conclusions In populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.
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Angina Pectoris/sangue , Doenças Cardiovasculares/sangue , Infarto do Miocárdio/sangue , Osteoprotegerina/sangue , Acidente Vascular Cerebral/sangue , Síndrome Coronariana Aguda/epidemiologia , Angina Pectoris/epidemiologia , Biomarcadores/sangue , Doenças Cardiovasculares/mortalidade , Comorbidade , Diabetes Mellitus/epidemiologia , Cardiopatias/epidemiologia , Humanos , Nefropatias/epidemiologia , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Gallbladder cancer is highly lethal, with notable differences in incidence by geography and ethnic background. The aim of this study was to identify common genetic susceptibility alleles for gallbladder cancer. METHODS: In this case-control genome-wide association study (GWAS), we did a genome-wide scan of gallbladder cancer cases and hospital visitor controls, both of Indian descent, followed by imputation across the genome. Cases were patients aged 20-80 years with microscopically confirmed primary gallbladder cancer diagnosed or treated at Tata Memorial Hospital, Mumbai, India, and enrolled in the study between Sept 12, 2010, and June 8, 2015. We only included patients who had been diagnosed less than 1 year before the date of enrolment and excluded patients with any other malignancies. We recruited visitor controls aged 20-80 years with no history of cancer visiting all departments or units of Tata Memorial Hospital during the same time period and frequency matched them to cases on the basis of age, sex, and current region of residence. We estimated association using logistic regression, adjusting for age, sex, and five eigenvectors. We recruited samples for a replication cohort from patients visiting Tata Memorial Hospital between Aug 4, 2015, and May 17, 2016, and patients visiting the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, between July, 2010, and May, 2015. We used the same inclusion and exclusion criteria for the replication set. We examined three of the most significant single-nucleotide polymorphisms (SNPs) in the replication cohort and did a meta-analysis of the GWAS discovery and replication sets to get combined estimates of association. FINDINGS: The discovery cohort comprised 1042 gallbladder cancer cases and 1709 controls and the replication cohort contained 428 gallbladder cancer cases and 420 controls. We observed genome-wide significant associations for several markers in the chromosomal region 7q21.12 harbouring both the ABCB1 and ABCB4 genes, with the most notable SNPs after replication and meta-analysis being rs1558375 (GWAS p=3·8â×â10-9; replication p=0·01; combined p=2·3â×â10-10); rs17209837 (GWAS p=2·0â×â10-8; replication p=0·02; combined p=2·3â×â10-9), and rs4148808 (GWAS p=2·4â×â10-8; replication p=0·008; combined p=2·7â×â10-9). Combined estimates of per-allele trend odds ratios were 1·47 (95% CI 1·30-1·66; p=2·31â×â10-10) for rs1558375, 1·61 (1·38-1·89; p=2·26â×â10-9) for rs17209837, and 1·57 (1·35-1·82; p=2·71â×â10-9) for rs4148808. GWAS heritability analysis suggested that common variants are associated with substantial variation in risk of gallbladder cancer (sibling relative risk 3·15 [95% CI 1·80-5·49]). INTERPRETATION: To our knowledge, this study is the first report of common genetic variation conferring gallbladder cancer risk at genome-wide significance. This finding, along with in-silico and biological evidence indicating the potential functional significance of ABCB1 and ABCB4, underlines the likely importance of these hepatobiliary phospholipid transporter genes in the pathology of gallbladder cancer. FUNDING: The Tata Memorial Centre and Department of Biotechnology.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Vesícula Biliar/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/epidemiologia , Neoplasias da Vesícula Biliar/patologia , Predisposição Genética para Doença , Genótipo , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
To date, no studies have investigated the association of the GWAS-identified SNPs with BC risk in Indian population. We investigated the association of 30 previously reported and replicated BC susceptibility SNPs in 1,204 cases and 1,212 controls from a hospital based case-control study conducted at the Tata Memorial Hospital, Mumbai. As a measure of total susceptibility burden, the polygenic risk score (PRS) for each individual was defined by the weighted sum of genotypes from 21 independent SNPs with weights derived from previously published estimates of association odds-ratios. Logistic regression models were used to assess risk associated with individual SNPs and overall PRS, and stratified by menopausal and receptor status. A total of 11 SNPs from eight genomic regions (FGFR2, 9q31.2, MAP3K, CCND1, ZM1Z1, RAD51L11, ESR1 and UST) showed statistically significant (p-value ≤ 0.05) evidence of association, either overall or when stratified by menopausal status or hormone receptor status. BC SNPs previously identified in Caucasian population showed evidence of replication in the Indian population mainly with respect to risk of postmenopausal and hormone receptor positive BC.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Índia , Pessoa de Meia-Idade , Medição de Risco , Adulto JovemRESUMO
PURPOSE: Although cancer registry data indicate that there are large differences in breast cancer (BC) rates between rural and urban regions of India, the reasons for these differences are not well understood. METHODS: We conducted a hospital based case-control study (1,637 breast cancer cases; 1,515 visitor controls) in Mumbai, India, during the years 2009-2013. Extensive questionnaire data, anthropometry measurement and blood samples were collected on all participants. Using logistic regression models, we estimated risk based on odds ratio (OR) and 95 % confidence intervals (CI) for various reproductive and anthropometric measures, stratified by rural-urban status depending upon residence in first 20 years of life. RESULTS: Waist-to-hip ratio of ≥0.95 compared to ratio ≤0.84 was strongly associated with risk of BC in both rural and urban populations (ORurban = 4.10, 95 % CI 3.03-5.56; ORrural = 3.01, 95 % CI 1.85-4.90). First full-term pregnancy after the age of 25 compared to first full-term pregnancy below 20 years of age was associated with risk of BC in both urban and rural women (ORurban = 1.78, 95 % CI 1.32-2.41; ORrural = 2.24, 95 % CI 1.13-4.43). The prevalence of age at first full-term pregnancy was significantly lower in rural (mean age at first full-term pregnancy = 19.39 years) versus urban women (mean age at first full-term pregnancy = 22.62 years), whereas mean waist circumference was much higher in urban women (82.13 cm) compared to rural women (79.26 cm). We did not observe any association between breast feeding and risk of BC. CONCLUSIONS: Differences in the prevalence of central adiposity and age at first full-term pregnancy between rural and urban women from India may explain some differences in breast cancer rates between these two populations.
Assuntos
Neoplasias da Mama/epidemiologia , Idade Materna , Obesidade Abdominal/epidemiologia , História Reprodutiva , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Idoso , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Anticoncepcionais Orais/uso terapêutico , Feminino , Humanos , Índia/epidemiologia , Modelos Logísticos , Menarca , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Prevalência , Fatores de Risco , Relação Cintura-Quadril , Adulto JovemRESUMO
The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.