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1.
Clin Epigenetics ; 13(1): 57, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741061

RESUMO

BACKGROUND: Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. METHODS: DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7-17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. RESULTS: None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). CONCLUSION: Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

2.
Sci Rep ; 11(1): 3257, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33547336

RESUMO

Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33622804

RESUMO

BACKGROUND: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures. METHODS: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs. RESULTS: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94). CONCLUSIONS: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

4.
Ann Emerg Med ; 77(4): 385-394, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33461884

RESUMO

STUDY OBJECTIVE: Accurate diagnostic testing to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical. Although highly specific, SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown in clinical practice to be affected by a noninsignificant proportion of false-negative results. This study seeks to explore whether the integration of lung ultrasonography with clinical evaluation is associated with increased sensitivity for the diagnosis of coronavirus disease 2019 pneumonia, and therefore may facilitate the identification of false-negative SARS-CoV-2 RT-PCR results. METHODS: This prospective cohort study enrolled consecutive adult patients with symptoms potentially related to SARS-CoV-2 infection who were admitted to the emergency department (ED) of an Italian academic hospital. Immediately after the initial assessment, a lung ultrasonographic evaluation was performed and the likelihood of SARS-CoV-2 infection, based on both clinical and lung ultrasonographic findings ("integrated" assessment), was recorded. RT-PCR SARS-CoV-2 detection was subsequently performed. RESULTS: We enrolled 228 patients; 107 (46.9%) had SARS-CoV-2 infection. Sensitivity and negative predictive value of the clinical-lung ultrasonographic integrated assessment were higher than first RT-PCR result (94.4% [95% confidence interval {CI} 88.2% to 97.9%] versus 80.4% [95% CI 71.6% to 87.4%] and 95% [95% CI 89.5% to 98.2%] versus 85.2% [95% CI 78.3% to 90.6%], respectively). Among the 142 patients who initially had negative RT-PCR results, 21 tested positive at a subsequent molecular test performed within 72 hours. All these false-negative cases were correctly identified by the integrated assessment. CONCLUSION: This study suggests that, in patients presenting to the ED with symptoms commonly associated with SARS-CoV-2 infection, the integration of lung ultrasonography with clinical evaluation has high sensitivity and specificity for coronavirus disease 2019 pneumonia and it may help to identify false-negative results occurring with RT-PCR.


Assuntos
/diagnóstico por imagem , Serviço Hospitalar de Emergência , Pulmão/diagnóstico por imagem , Adulto , Idoso , Reações Falso-Negativas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia
5.
Eur J Cancer ; 143: 33-39, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33278772

RESUMO

BACKGROUND: Although cancer is typically a disease of the older age groups, some types start emerging early in adulthood. This implies that exposures and stressors occurring before adulthood might play a role in the risk of cancer in adults. Little research has been conducted in this area. METHODS: We used European data from the Cancer in Five Continents Vol. XI to calculate cumulative risks by the end of subsequent adulthood decades of age (20-29, 30-39, 40-49) for 34 cancer sites and classified them as early-age emerging cancers if they reached 0.005% by 29 years old, intermediate-age emerging cancers by 39 years old, and late-age emerging cancers after 40 years old. We used data from Cancer in Five Continents Plus to analyse time trends in incidence rates by age groups over the period 1998-2012. FINDINGS: We identified 14 early-age emerging cancers. Nine of them showed significant increasing trends over calendar time in the early decades of adulthood, often more pronouncedly so in 20-29-year-olds than in 30-39 or 40-49-year-olds. The increase of colon cancer rates in the 20-29-year-olds was particularly high with an average annual percent change of 7.9% (95% confidence interval: 5.9%-10%). Decreases in incidence rates were only observed for cancer types classified as intermediate- or late-age emerging cancers. INTERPRETATION: Cancer prevention efforts seem to have favourably impacted intermediate- and late-age emerging cancer incidence rates. For early-age emerging cancers, aetiological research is needed to identify exposures and stressors occurring early in life, especially for those cancers that have been increasing in young adults. This knowledge will be essential to develop preventive strategies.

6.
Environ Res ; 193: 110504, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33221306

RESUMO

BACKGROUND: Exposure to air pollution during the first 1000 days of life (from conception to the 2nd year of life) might be of particular relevance for long-term child health. Changes in molecular markers such as DNA methylation and telomere length could underlie the association between air pollution exposure and pollution-related diseases as well as serve as biomarkers for past exposure. The objective of this systematic review was to assess the association between air pollution exposure during pregnancy and the first two years of life and changes in DNA methylation or telomere length in children. METHODS: PubMed was searched in October 2020 by using terms relative to ambient air pollution exposure, DNA methylation, telomere length and the population of interest: mother/child dyads and children. Screening and selection of the articles was completed independently by two reviewers. Thirty-two articles matched our criteria. The majority of the articles focused on gestational air pollution exposure and measured DNA methylation/telomere length in newborn cord blood or placental tissue, to study global, candidate-gene or epigenome-wide methylation patterns and/or telomere length. The number of studies in children was limited. RESULTS: Ambient air pollution exposure during pregnancy was associated with global loss of methylation in newborn cord blood and placenta, indicating the beginning of the pregnancy as a potential period of susceptibility. Candidate gene and epigenome-wide association studies provided evidence that gestational exposure to air pollutants can lead to locus-specific changes in methylation, in newborn cord blood and placenta, particularly in genes involved in cellular responses to oxidative stress, mitochondrial function, inflammation, growth and early life development. Telomere length shortening in newborns and children was seen in relation to gestational pollutant exposure. CONCLUSIONS: Ambient air pollution during pregnancy is associated with changes in both global and locus-specific DNA methylation and with telomere length shortening. Future studies need to test the robustness of the association across different populations, to explore potential windows of vulnerability and assess the role of the methylation and telomere length as mediators in the association between early exposure to ambient air pollutants and specific childhood health outcomes.

7.
medRxiv ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33173887

RESUMO

Background: Congenital heart diseases (CHDs) are the most common congenital anomaly. The causes of CHDs are largely unknown. Higher prenatal body mass index (BMI), smoking and alcohol consumption are associated with increased risk of CHDs. Whether these are causal is unclear. Methods and Results: Seven European birth cohorts including 232,390 offspring (2,469 CHD cases [1.1%]) were included. We applied negative exposure paternal control analyses to explore the intrauterine effects of maternal BMI, smoking and alcohol consumption during pregnancy, on offspring CHDs and CHD severity. We used logistic regression and combined estimates using a fixed-effects meta-analysis. Analyses of BMI categories resulted in similar increased odds of CHD in overweight (mothers OR: 1.15 (1.01, 1.31) and fathers 1.10 (0.96, 1.27)) and obesity (mothers OR: 1.12 (0.93, 1.36) and fathers 1.16 (0.90, 1.50)). The association of mean BMI with CHD was null. Maternal smoking was associated with increased odds of CHD (OR: 1.11 (0.97, 1.25)) but paternal smoking was not (OR: 0.96 (0.85, 1.07)). The difference increased when removing offspring with genetic/chromosomal defects (mothers OR: 1.15 (1.01, 1.32) and fathers 0.93 (0.83, 1.05)). The positive association with maternal pregnancy smoking appeared to be driven by non-severe CHD cases (OR: 1.22 (1.04, 1.44)). Associations with maternal (OR: 1.16 (0.52, 2.58)) and paternal (OR: 1.23 (0.74, 2.06)) moderate/heavy pregnancy alcohol consumption were similar. Conclusions: We found evidence of an intrauterine effect for maternal smoking on offspring CHDs, but no evidence for higher maternal BMI or alcohol consumption. Our findings provide further support for why smoking cessation is important during pregnancy.

8.
BMC Infect Dis ; 20(1): 798, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115434

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), the causative agent of the coronavirus disease 19 (COVID-19), is a highly transmittable virus. Since the first person-to-person transmission of SARS-CoV-2 was reported in Italy on February 21st, 2020, the number of people infected with SARS-COV-2 increased rapidly, mainly in northern Italian regions, including Piedmont. A strict lockdown was imposed on March 21st until May 4th when a gradual relaxation of the restrictions started. In this context, computational models and computer simulations are one of the available research tools that epidemiologists can exploit to understand the spread of the diseases and to evaluate social measures to counteract, mitigate or delay the spread of the epidemic. METHODS: This study presents an extended version of the Susceptible-Exposed-Infected-Removed-Susceptible (SEIRS) model accounting for population age structure. The infectious population is divided into three sub-groups: (i) undetected infected individuals, (ii) quarantined infected individuals and (iii) hospitalized infected individuals. Moreover, the strength of the government restriction measures and the related population response to these are explicitly represented in the model. RESULTS: The proposed model allows us to investigate different scenarios of the COVID-19 spread in Piedmont and the implementation of different infection-control measures and testing approaches. The results show that the implemented control measures have proven effective in containing the epidemic, mitigating the potential dangerous impact of a large proportion of undetected cases. We also forecast the optimal combination of individual-level measures and community surveillance to contain the new wave of COVID-19 spread after the re-opening work and social activities. CONCLUSIONS: Our model is an effective tool useful to investigate different scenarios and to inform policy makers about the potential impact of different control strategies. This will be crucial in the upcoming months, when very critical decisions about easing control measures will need to be taken.


Assuntos
Controle de Doenças Transmissíveis/métodos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Betacoronavirus/isolamento & purificação , Portador Sadio/diagnóstico , Portador Sadio/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Suscetibilidade a Doenças/diagnóstico , Suscetibilidade a Doenças/epidemiologia , Humanos , Itália/epidemiologia , Modelos Teóricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Quarentena
9.
Occup Environ Med ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115922

RESUMO

OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.

10.
Br J Cancer ; 123(9): 1456-1463, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32830199

RESUMO

BACKGROUND: Alcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk. METHODS: Data from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking. RESULTS: For all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx). CONCLUSIONS: Present results further encourage the reduction of alcohol intensity to mitigate HNC risk.

11.
Eur J Epidemiol ; 35(7): 709-724, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32705500

RESUMO

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.


Assuntos
Exposição Ambiental , Doenças não Transmissíveis , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Bases de Dados Factuais , Saúde Ambiental , União Europeia , Feminino , Humanos , Lactente , Masculino , Pais , Gravidez , Fatores de Risco , Fatores Socioeconômicos
12.
Front Public Health ; 8: 222, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574301

RESUMO

Italy was the first European country affected by the Sars-Cov-2 pandemic, with the first autochthonous case identified on Feb 21st. Specific control measures restricting social contacts were introduced by the Italian government starting from the beginning of March. In the current study we analyzed public data from the four most affected Italian regions. We (i) estimated the time-varying reproduction number (R t ), the average number of secondary cases that each infected individual would infect at time t, to monitor the positive impact of restriction measures; (ii) applied the generalized logistic and the modified Richards models to describe the epidemic pattern and obtain short-term forecasts. We observed a monotonic decrease of R t over time in all regions, and the peak of incident cases ~2 weeks after the implementation of the first strict containment measures. Our results show that phenomenological approaches may be useful to monitor the epidemic growth in its initial phases and suggest that costly and disruptive public health controls might have had a positive impact in limiting the Sars-Cov-2 spread in Northern Italy.

13.
J Dev Orig Health Dis ; : 1-9, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32452337

RESUMO

Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7-17) months were used to estimate Horvath's DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: -0.79 to 2.34 for low/medium education; 0.96, 95% CI: -1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath's method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.

15.
Am J Respir Crit Care Med ; 202(3): 412-421, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330394

RESUMO

Rationale: Millions of workers around the world are exposed to respirable crystalline silica. Although silica is a confirmed human lung carcinogen, little is known regarding the cancer risks associated with low levels of exposure and risks by cancer subtype. However, little is known regarding the disease risks associated with low levels of exposure and risks by cancer subtype.Objectives: We aimed to address current knowledge gaps in lung cancer risks associated with low levels of occupational silica exposure and the joint effects of smoking and silica exposure on lung cancer risks.Methods: Subjects from 14 case-control studies from Europe and Canada with detailed smoking and occupational histories were pooled. A quantitative job-exposure matrix was used to estimate silica exposure by occupation, time period, and geographical region. Logistic regression models were used to estimate exposure-disease associations and the joint effects of silica exposure and smoking on risk of lung cancer. Stratified analyses by smoking history and cancer subtypes were also performed.Measurements and Main Results: Our study included 16,901 cases and 20,965 control subjects. Lung cancer odds ratios ranged from 1.15 (95% confidence interval, 1.04-1.27) to 1.45 (95% confidence interval, 1.31-1.60) for groups with the lowest and highest cumulative exposure, respectively. Increasing cumulative silica exposure was associated (P trend < 0.01) with increasing lung cancer risks in nonsilicotics and in current, former, and never-smokers. Increasing exposure was also associated (P trend ≤ 0.01) with increasing risks of lung adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. Supermultiplicative interaction of silica exposure and smoking was observed on overall lung cancer risks; superadditive effects were observed in risks of lung cancer and all three included subtypes.Conclusions: Silica exposure is associated with lung cancer at low exposure levels. An exposure-response relationship was robust and present regardless of smoking, silicosis status, and cancer subtype.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Dióxido de Silício , Silicose/epidemiologia , Adulto , Idoso , Canadá/epidemiologia , Fumar Cigarros , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade
16.
Am J Respir Crit Care Med ; 202(3): 402-411, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32330395

RESUMO

Rationale: Although the carcinogenicity of diesel engine exhaust has been demonstrated in multiple studies, little is known regarding exposure-response relationships associated with different exposure subgroups and different lung cancer subtypes.Objectives: We expanded on a previous pooled case-control analysis on diesel engine exhaust and lung cancer by including three additional studies and quantitative exposure assessment to evaluate lung cancer and subtype risks associated with occupational exposure to diesel exhaust characterized by elemental carbon (EC) concentrations.Methods: We used a quantitative EC job-exposure matrix for exposure assessment. Unconditional logistic regression models were used to calculate lung cancer odds ratios and 95% confidence intervals (CIs) associated with various metrics of EC exposure. Lung cancer excess lifetime risks (ELR) were calculated using life tables accounting for all-cause mortality. Additional stratified analyses by smoking history and lung cancer subtypes were performed in men.Measurements and Main Results: Our study included 16,901 lung cancer cases and 20,965 control subjects. In men, exposure response between EC and lung cancer was observed: odds ratios ranged from 1.09 (95% CI, 1.00-1.18) to 1.41 (95% CI, 1.30-1.52) for the lowest and highest cumulative exposure groups, respectively. EC-exposed men had elevated risks in all lung cancer subtypes investigated; associations were strongest for squamous and small cell carcinomas and weaker for adenocarcinoma. EC lung cancer exposure response was observed in men regardless of smoking history, including in never-smokers. ELR associated with 45 years of EC exposure at 50, 20, and 1 µg/m3 were 3.0%, 0.99%, and 0.04%, respectively, for both sexes combined.Conclusions: We observed a consistent exposure-response relationship between EC exposure and lung cancer in men. Reduction of workplace EC levels to background environmental levels will further reduce lung cancer ELR in exposed workers.


Assuntos
Adenocarcinoma de Pulmão/epidemiologia , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Fumar Cigarros/epidemiologia , Neoplasias Pulmonares/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Emissões de Veículos , Adulto , Idoso , Canadá/epidemiologia , Carbono , Europa (Continente)/epidemiologia , Feminino , Humanos , Exposição por Inalação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores Sexuais
17.
Eur J Epidemiol ; 35(3): 193-204, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32221742

RESUMO

The exposome represents the totality of life course environmental exposures (including lifestyle and other non-genetic factors), from the prenatal period onwards. This holistic concept of exposure provides a new framework to advance the understanding of complex and multifactorial diseases. Prospective pregnancy and birth cohort studies provide a unique opportunity for exposome research as they are able to capture, from prenatal life onwards, both the external (including lifestyle, chemical, social and wider community-level exposures) and the internal (including inflammation, metabolism, epigenetics, and gut microbiota) domains of the exposome. In this paper, we describe the steps required for applying an exposome approach, describe the main strengths and limitations of different statistical approaches and discuss their challenges, with the aim to provide guidance for methodological choices in the analysis of exposome data in birth cohort studies. An exposome approach implies selecting, pre-processing, describing and analyzing a large set of exposures. Several statistical methods are currently available to assess exposome-health associations, which differ in terms of research question that can be answered, of balance between sensitivity and false discovery proportion, and between computational complexity and simplicity (parsimony). Assessing the association between many exposures and health still raises many exposure assessment issues and statistical challenges. The exposome favors a holistic approach of environmental influences on health, which is likely to allow a more complete understanding of disease etiology.


Assuntos
Exposição Ambiental/efeitos adversos , Expossoma , Saúde Ambiental , Monitoramento Ambiental , Poluentes Ambientais/efeitos adversos , Epigenômica , Nível de Saúde , Humanos , Estilo de Vida
18.
Artigo em Inglês | MEDLINE | ID: mdl-32150940

RESUMO

The assessment of early life socioeconomic position (SEP) is essential to the tackling of social inequalities in health. Although different indicators capture different SEP dimensions, maternal education is often used as the only indicator in birth cohort research, especially in multi-cohort analyses. Household income, as a direct measure of material resources, is one of the most important indicators, but one that is underused because it is difficult to measure through questionnaires. We propose a method to construct a standardized, cross-cohort comparable income indicator, the "Equivalized Household Income Indicator (EHII)", which measures the equivalized disposable household income, using external data from the pan-European Union Statistics on Income and Living Conditions (EUSILC) surveys, and data from the cohorts. We apply this method to four studies, Piccolipiù and NINFEA from Italy and ELFE and EDEN from France, comparing the distribution of EHII with other SEP-related variables available in the cohorts, and estimating the association between EHII and child body mass index (BMI). We found that basic parental and household characteristics may be used, with a fairly good performance, to predict the household income. We observed a strong correlation between EHII and both the self-reported income, whenever available, and other individual socioeconomic-related variables, and an inverse association with child BMI. EHII could contribute to improving research on social inequalities in health, in particular in the context of European birth cohort collaborative studies.


Assuntos
Renda , Classe Social , Fatores Socioeconômicos , Índice de Massa Corporal , Criança , Estudos de Coortes , França , Humanos , Itália , Padrões de Referência
19.
Pediatr Obes ; 15(8): e12632, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32174046

RESUMO

BACKGROUND/OBJECTIVES: Several exposures during pregnancy are associated with offspring body mass index (BMI). The objective of this study was to evaluate whether third trimester antibiotic use and vaginal infections are associated with BMI in preschool children. SUBJECTS/METHODS: The study population included singletons from the NINFEA birth cohort with available anthropometric measurements at the age of 4 (3151 born with vaginal and 1111 born with caesarean delivery). Self-reported use of antibiotics and the presence of vaginal infection in the third trimester were analysed in association with the child's BMI, classified into three categories: thinness, normal and overweight/obesity, using both the International Obesity Task Force (IOTF) and the World Health Organization (WHO) recommended cut-offs. RESULTS: Maternal vaginal infections in the third trimester of pregnancy were associated with higher relative risk ratios (RRR) for overweight/obesity at age of four in children delivered vaginally: 1.92 (95% confidence interval [CI]: 1.37 to 2.70). This association appeared stronger for children born to women with pre-pregnancy BMI >25 kg/m2 (RRR: 4.78; 95% CI 2.45 to 9.35), and was robust when different obesity cut-offs were used. The results regarding third trimester antibiotic use in vaginal deliveries were less conclusive (RRRs for overweight/obesity: 1.43 (0.92 to 2.21) and 1.11 (0.57 to 2.20), for the IOTF and WHO cut-offs, respectively). Third trimester vaginal infections were not associated with BMI in children delivered by caesarean section. CONCLUSIONS: Maternal third trimester vaginal infections are associated with an increased overweight/obesity risk in children born by vaginal delivery, and especially in children of mothers with pre-pregnancy overweight/obesity.

20.
Calcif Tissue Int ; 106(6): 599-607, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32076748

RESUMO

PURPOSE: Hyponatremia and hypokalemia are common among elderly and have been associated with osteoporosis, we evaluate the role of these electrolytes as risk for fragility fractures. METHODS: This study is divided in two parts: one retrospective and one prospective. We retrospectively collected data on urgently admitted patients for femoral fragility fractures (Fx) or for acute myocardial infarction (AMI), and patients admitted for elective hip/knee replacement surgery for osteoarthrosis (OA). Age, sex, serum sodium, potassium, creatinine, and comorbidities were recorded. We enrolled prospectively in-patients from our unit: age, sex, comorbidities, drugs, and fragility fractures were recorded. Blood electrolytes were measured. Cognitive function, nutrition, muscular strength, and balance were evaluated by standard tests. The mortality rate was recorded with a follow-up after hospital discharge. RESULTS: The retrospective study included 2166 subjects: 702 Fx and 1464 controls (907 AMI, 557 OA): the prevalence of hyponatremia was similar in Fx and AMI, whereas it was higher in Fx with respect to OA (p < 0.001) as well as hypokalemia (p < 0.001). Sodium decrease was associated with higher fracture risk. Among the 284 subjects included in the prospective study, 50 patients were hyponatremic, more likely malnourished, and presented a higher prevalence of fragility fractures (p = 0.008). They had a higher mortality after hospital discharge (HR = 1.80, p = 0.005), however, this association disappears after correction for confounding variables. CONCLUSIONS: We suggest that hyponatremia and hypokalemia have to be considered as a marker of poor health more than an independent fracture risk.

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