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Environmental exposures and gene-exposure interactions are the major causes of some diseases. Early-life exposome studies are needed to elucidate the role of environmental exposures and their complex interactions with biological mechanisms involved in childhood health. This study aimed to determine the contribution of early-life exposome to DNA damage and the modifying effect of genetic polymorphisms involved in air pollutants metabolism, antioxidant defense, and DNA repair. We conducted a cohort study in 416 Colombian children under five years. Blood samples at baseline were collected to measure DNA damage by the Comet assay and to determine GSTT1, GSTM1, CYP1A1, H2AX, OGG1, and SOD2 genetic polymorphisms. The exposome was estimated using geographic information systems, remote sensing, LUR models, and questionnaires. The association exposome-DNA damage was estimated using the Elastic Net linear regression with log link. Our results suggest that exposure to PM2.5 one year before the blood draw (BBD) (0.83, 95 %CI: 0.76; 0.91), soft drinks consumption (0.94, 0.89; 0.98), and GSTM1 null genotype (0.05, 0.01; 0.36) diminished the DNA damage, whereas exposure to PM2.5 one-week BBD (1.18, 1.06; 1.32), NO2 lag-5 days BBD (1.27, 1.18; 1.36), in-house cockroaches (1.10, 1.00; 1.21) at the recruitment, crowding at home (1.34, 1.08; 1.67) at the recruitment, cereal consumption (1.11, 1.04; 1.19) and H2AX (AG/GG vs. AA) (1.44, 1.11; 1.88) increased the DNA damage. The interactions between H2AX (AG/GG vs. AA) genotypes with crowding and PM2.5 one week BBD, GSTM1 (null vs. present) with humidity at the first year of life, and OGG1 (SC/CC vs. SS) with walkability at the first year of life were significant. The early-life exposome contributes to elucidating the effect of environmental exposures on DNA damage in Colombian children under five years old. The exposome-DNA damage effect appears to be modulated by genetic variants in DNA repair and antioxidant defense enzymes.

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Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

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BACKGROUND: There is no term for bloating in Spanish and distension is a very technical word. "Inflammation"/"swelling" are the most frequently used expressions for bloating/distension in Mexico, and pictograms are more effective than verbal descriptors (VDs) for bloating/distension in general GI and Rome III-IBS patients. However, their effectiveness in the general population and in subjects with Rome IV-DGBI is unknown. We analyzed the use of pictograms for assessing bloating/distension in the general population in Mexico. METHODS: The Rome Foundation Global Epidemiology Study (RFGES) in Mexico (n = 2001) included questions about the presence of VDs "inflammation"/"swelling" and abdominal distension, their comprehension, and pictograms (normal, bloating, distension, both). We compared the pictograms with the Rome IV question about the frequency of experiencing bloating/distension, and with the VDs. KEY RESULTS: "Inflammation"/"swelling" was reported by 51.5% and distension by 23.8% of the entire study population; while 1.2% and 25.3% did not comprehend "Inflammation"/"swelling" or distension, respectively. Subjects without (31.8%) or not comprehending "inflammation"/"swelling"/distension (68.4%) reported bloating/distension by pictograms. Bloating and/or distension by the pictograms were much more frequent in those with DGBI: 38.3% (95%CI: 31.7-44.9) vs. without: 14.5% (12.0-17.0); and in subjects with distension by VDs: 29.4% (25.4-33.3) vs. without: 17.2% (14.9-19.5). Among subjects with bowel disorders, those with IBS reported bloating/distension by pictograms the most (93.8%) and those with functional diarrhea the least (71.4%). CONCLUSIONS & INFERENCES: Pictograms are more effective than VDs for assessing the presence of bloating/distension in Spanish Mexico. Therefore, they should be used to study these symptoms in epidemiological research.

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The level of clustering and the adjustment by cluster-robust standard errors have yet to be widely considered and reported in cross-sectional studies of tuberculosis (TB) in prisons. In two cross-sectional studies of people deprived of liberty (PDL) in Medellin, we evaluated the impact of adjustment versus failure to adjust by clustering on prevalence ratio (PR) and 95% confidence interval (CI). We used log-binomial regression, Poisson regression, generalized estimating equations (GEE), and mixed-effects regression models. We used cluster-robust standard errors and bias-corrected standard errors. The odds ratio (OR) was 20% higher than the PR when the TB prevalence was >10% in at least one of the exposure factors. When there are three levels of clusters (city, prison, and courtyard), the cluster that had the strongest effect was the courtyard, and the 95% CI estimated with GEE and mixed-effect models were narrower than those estimated with Poisson and binomial models. Exposure factors lost their significance when we used bias-corrected standard errors due to the smaller number of clusters. Tuberculosis transmission dynamics in prisons dictate a strong cluster effect that needs to be considered and adjusted for. The omission of cluster structure and bias-corrected by the small number of clusters can lead to wrong inferences.

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BACKGROUND: In Latin America, there are scarce data on the epidemiology of DGBI. The Rome Foundation Global Epidemiology Study (RFGES) Internet survey included 26 countries, four from Latin America: Argentina, Brazil, Colombia, and Mexico, with a 40.3% prevalence of Rome IV DGBI. We aimed at comparing the prevalence of DGBI and associated factors among these countries. METHODS: The frequency of DGBI by anatomical region, specific diagnoses, sex, age, diet, healthcare access, anxiety, depression, and HRQOL, were analyzed and compared. RESULTS: Subjects included Argentina n = 2057, Brazil = 2004, Colombia = 2007, and Mexico = 2001. The most common DGBI were bowel (35.5%), gastroduodenal (11.9%), and anorectal (10.0%). Argentina had the highest prevalence of functional diarrhea (p = 0.006) and IBS-D; Brazil, esophageal, gastroduodenal disorders, and functional dyspepsia; Mexico functional heartburn (all <0.001). Overall, DGBI were more common in women vs. men and decreased with age. Bowel disorders were more common in the 18-39 (46%) vs. 40-64-year (39%) groups. Diet was also different between those with DGBI vs. those without with subtle differences between countries. Subjects endorsing criteria for esophageal, gastroduodenal, and anorectal disorders from Mexico, more commonly consulted physicians for bowel symptoms vs. those from Argentina, Brazil, and Colombia. General practitioners were the most frequently consulted, by Mexicans (50.42%) and Colombians (40.80%), followed by gastroenterologists. Anxiety and depression were more common in DGBI individuals in Argentina and Brazil vs. Mexico and Colombia, and they had lower HRQOL. CONCLUSIONS: The prevalence of upper and lower DGBI, as well as the burden of illness, psychological impact and HRQOL, differ between these Latin American countries.

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OBJECTIVE: To estimate the association between Social Determinants of Health (structural and intermediate) and caries indicators in Chile's Metropolitan Region preschool children. METHODS: A multilevel cross-sectional study of Social Determinants of Health (SDH) and caries in children aged 1 to 6 years in Chile's Metropolitan Region was conducted in 2014-2015, with three levels: district, school and child. Caries were assessed by the dmft-index and the prevalence of untreated caries. The structural determinants analyzed were Community Human Development Index (CHDI), urban/rural location, school type, caregiver's education and family income. Poisson multilevel regression models were fit. RESULTS: The sample size was 2,275 children from 40 schools in 13 districts. While the highest CHDI district had an untreated caries prevalence of 17.1% (12.3-22.7%), in the most disadvantaged district it was 53.9% (95% CI 46.0-61.6%). As family income increased, the probability of untreated caries prevalence decreased (PR = 0.9 95% CI 0.8-1.0). Rural districts had an average dmft-index of 7.3 (95% CI 7.2-7.4), while in urban districts, it was 4.4 (95% CI 4.3-4.5). Higher probabilities of untreated caries prevalence (PR = 3.0 95% CI 2.3-3.9) were observed in rural children. Greater probabilities of untreated caries prevalence (PR = 1.3 95% CI 1.1-1.6) and prevalence of caries experience (PR = 1.3 95% CI 1.1-1.5) were observed in children whose caregivers had a secondary educational level. CONCLUSIONS: A strong association was observed between the social determinants of health, specifically the structural ones, and the caries indicators studied in children of the Metropolitan Region of Chile. There were notable differences in caries between districts according to social advantage. Rurality and caregiver's education were the most consistent predictors.

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BACKGROUND: Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. OBJECTIVE: This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. MATERIALS AND METHODS: A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. EXPECTED STUDY OUTCOMES/FINDINGS: To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

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Overlap of primary studies among systematic reviews (SRs) is one of the main methodological challenges when conducting overviews. If not assessed properly, overlapped primary studies may mislead findings, since they may have a major influence either in qualitative analyses or in statistical weight. Moreover, overlapping SRs may represent the existence of duplicated efforts. Matrices of evidence and the calculation of the overall corrected covered area (CCA) are appropriate methods to address this issue, but they seem to be not comprehensive enough. In this article we present Graphical Representation of Overlap for OVErviews (GROOVE), an easy-to-use tool for overview authors. Starting from a matrix of evidence, GROOVE provides the number of included primary studies and SRs included in the matrix; the absolute number of overlapped and non-overlapped primary studies; and an overall CCA assessment. The tool also provides a detailed CCA assessment for each possible pair of SRs (or "nodes"), with a graphical and easy-to-read representation of these results. Additionally, it includes an advanced optional usage, incorporating structural missingness in the matrix. In this article, we show the details about how to use GROOVE, what results it achieves and how the tool obtains these results. GROOVE is intended to improve the overlap assessment by making it easier, faster, and more friendly for both authors and readers. The tool is freely available at http://doi.org/10.17605/OSF.IO/U2MS4 and https://es.cochrane.org/es/groovetool.

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The relative roles of school context and individual student factors are of special interest to educators in measuring academic performance. Little is known about the effect of school violence on a student's academic performance and well-being. The aims of this study were to examine the effects of three types of school violence (direct violence, discrimination, and cyberbullying) on students' academic performance in standardized tests of mathematics, reading and history, and to identify individual student factors that contribute to reducing the negative effect of exposure to violence at school. We used 10th grade Chilean student data from the representative cross-sectional test of the Education Quality Measurement System (SIMCE in Spanish) from 2015. Multilevel linear models, adjusted for gender, incorporated other school and environmental contextual factors, as well as individual student factors. The results show that school violence in its three forms had a negative effect on academic performance. Student self-efficacy, educational expectations and satisfaction with interpersonal relations with their teachers, were important in reducing the negative effect of exposure to violence. The implications for the school are discussed.

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BACKGROUND: Although low levels of physical activity have slightly decreased globally, the need to reverse the physical inactivity remains urgent. One approach has been the installation of outdoor gyms (OGs). METHOD: A natural experiment arose from the installation of OGs in different neighborhoods of the city of Temuco, Chile. Baseline measurements were collected between 2006 and 2017 in a cohort of adults participating in the Prospective Urban & Rural Epidemiology study. Physical activity was assessed with the short version of the International Physical Activity Questionnaire, and time-varying covariates was assessed every 3 years. The multistage hierarchical, nested sampling process and the follow-up assessments led to data correlated at different levels, thus the authors analyzed the data using a logistic multilevel model. RESULT: 2463 urban adults from 16 neighborhoods, with an average age of 51.7 (9.8) years (67% female), were included. Having an adequate number of OGs improved the odds of complying with the World Health Organization's recommendations (adjusted odds ratio = 4.64, 3.95-5.45). In addition, being male (odds ratio = 1.53, 1.32-1.77) and under the age of 60 years (odds ratio = 0.83, 0.71-0.97) were associated with being physically active. CONCLUSION: The presence of more OGs can have a positive impact on physical activity recommendations.

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[RESUMEN]. Objetivo. Describir el papel que desempeñan la alfabetización estadística y la correcta comunicación de riesgo en las estrategias de comunicación relacionadas con la vacunación contra la COVID-19. Métodos. Se realizó una revisión de alcance en enero del 2021, con las palabras clave “ statistical literacy ”, “ risk communication”, “health communication ” y “ pandemic ” en las bases de datos de la Biblioteca Virtual en Salud de la Organización Panamericana de la Salud, PubMed, Web of Science, EBSCO y Google Académico. No se aplicaron filtros para fechas, idioma o tipos de publicación. Resultados. De los 87 artículos identificados, cuatro cumplieron con los criterios de inclusión. Se recono-cieron cuatro mensajes principales que relacionan la alfabetización estadística y la comunicación de riesgo: 1) la comunicación de riesgo y el nivel de alfabetización estadística afectan a la toma de decisión individual y colectiva, 2) la comunicación de la incertidumbre debe incluir lo que se sabe y no se sabe respecto a las estadísticas y los riesgos, 3) el uso de gráficos y visualizaciones es clave para informar apropiadamente a la población y 4) deben utilizarse diferentes formatos para mejorar la comunicación, siempre ajustados al nivel de alfabetización estadística de la población. Conclusiones. La alfabetización estadística desempeña un papel clave en la comunicación de los riesgos relacionados con la salud en general y la vacunación contra la COVID-19 en particular. En situaciones de emergencia sanitaria, la correcta comunicación de riesgo y de la incertidumbre asociada debe ser clara, transparente y oportuna.

[ABSTRACT]. Objective. To describe the role of statistical literacy and proper risk communication in communication strate-gies related to COVID-19 vaccination.Methods. A scoping review was carried out in January 2021, with the keywords “statistical literacy,” “risk com-munication,” “health communication,” and “pandemic,” in the Pan American Health Organization Virtual Health Library, PubMed, Web of Science, EBSCO, and Google Scholar databases. No filters were applied for dates, language, or publication type.Results. Of the 87 articles identified, four met the inclusion criteria. Four main messages were recognized that relate statistical literacy and risk communication: 1) risk communication and statistical literacy level affect indi-vidual and collective decision-making; 2) communication of uncertainty should include what is known and not known with regard to statistics and risks; 3) the use of graphics and visuals is key to appropriately informing the population; and 4) different formats should be used to improve communication, always adjusted to the population’s statistical literacy level.Conclusions. Statistical literacy plays a key role in communicating risks related to health in general and COVID-19 vaccination in particular. In health emergencies, proper communication of risk and associated uncertainty should be clear, transparent, and timely.

[RESUMO]. Objetivo. Descrever o papel da literacia estatística e da comunicação correta de riscos nas estratégias de comunicação relacionadas à vacinação contra a COVID-19.Métodos. Em janeiro de 2021, foi realizada uma revisão de escopo com as palavras-chave “statistical lite-racy”, “risk communication”, “health communication” e “pandemic” nos bancos de dados da Biblioteca Virtual em Saúde da Organização Pan-Americana da Saúde, PubMed, Web of Science, EBSCO e Google Scholar. Não foi aplicado filtro de data, idioma ou tipo de publicação.Resultados. Dos 87 artigos identificados, quatro atenderam aos critérios de inclusão. Foram reconhecidas quatro mensagens principais relacionadas à literacia estatística e à comunicação de risco: 1) a comunicação de risco e o nível de literacia estatística afetam a tomada de decisão individual e coletiva; 2) a comunicação da incerteza deve incluir o que é conhecido e desconhecido sobre estatísticas e riscos; 3) o uso de gráficos e visualizações é fundamental para informar adequadamente a população; e 4) devem ser usados diferentes formatos para melhorar a comunicação, sempre ajustados ao nível de literacia estatística da população.Conclusões. A literacia estatística desempenha um papel fundamental na comunicação dos riscos relaciona-dos à saúde em geral e à vacinação contra a COVID-19 em particular. Em situações de emergência de saúde, a comunicação correta do risco e da incerteza a ele associada deve ser clara, transparente e oportuna.

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BACKGROUND: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. OBJECTIVES: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM. SEARCH METHODS: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events. MAIN RESULTS: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached. AUTHORS' CONCLUSIONS: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

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OBJECTIVE: The aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes. METHODS: A cross-sectional study was conducted between April and July 2019. Miners from five mines (N=338) at different altitudes were evaluated. We recorded sociodemographic, working and altitude information. Haemoglobin oxygen saturation (SaO2) and haemoglobin (Hb) were measured in situ, while PSA and testosterone were analysed at a low level. Linear mixed-effect models were used to evaluate the association between PSA level and two CIHH exposures: composite CIHH (with four descriptors) and ChileStd-CIHH (CIHH Chilean standard; based on the Chilean technical guide for occupational exposure to CIHH). All models were adjusted by age, body mass index and day of the work the samples were taken. RESULTS: Highest and lowest PSA levels were found in mines ≥3000 m above sea level (mine 3: median=0.75, IQR=-0.45; mine 4: median=0.46, IQR=-0.35). In the multilevel models, the wider altitude difference between mining operation and camp showed lower PSA levels (model D: ßPSA=-0.93 ng/mL, ßlogPSA=-0.07, p<0001), adjusted for other CIHH descriptors, SaO2, Hb and testosterone. The descriptors of composite CIHH explained better PSA variations than ChileStd-CIHH (model D: marginal R2=0.090 vs model A: marginal R2=0.016). CONCLUSIONS: Occupational health regulations and high altitude medicine should consider these results as initial evidence on the inclusion of new descriptors for CIHH and the possible effect of this exposure on PSA levels in this male-dominated occupational sector.

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Introduction: Infections in hematological cancer patients are common and usually life-threatening; avoiding them could decrease morbidity, mortality, and cost. Genes associated with antineoplastics' pharmacokinetics or with the immune/inflammatory response could explain variability in infection occurrence. Objective: To build a pharmacogenetic-based algorithm to predict the incidence of infections in patients undergoing cytotoxic chemotherapy. Methods: Prospective cohort study in adult patients receiving cytotoxic chemotherapy to treat leukemia, lymphoma, or myeloma in two hospitals in Santiago, Chile. We constructed the predictive model using logistic regression. We assessed thirteen genetic polymorphisms (including nine pharmacokinetic-related genes and four inflammatory response-related genes) and sociodemographic/clinical variables to be incorporated into the model. The model's calibration and discrimination were used to compare models; they were assessed by the Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve, respectively, in association with Pseudo-R2. Results: We analyzed 203 chemotherapy cycles in 50 patients (47.8 ± 16.1 years; 56% women), including 13 (26%) with acute lymphoblastic and 12 (24%) with myeloblastic leukemia. Pharmacokinetics-related polymorphisms incorporated into the model were CYP3A4 rs2242480C>T and OAT4 rs11231809T>A. Immune/inflammatory response-related polymorphisms were TLR2 rs4696480T>A and IL-6 rs1800796C>G. Clinical/demographic variables incorporated into the model were chemotherapy type and cycle, diagnosis, days in neutropenia, age, and sex. The Pseudo-R2 was 0.56, the p-value of the Hosmer-Lemeshow test was 0.98, showing good goodness-of-fit, and the area under the ROC curve was 0.93, showing good diagnostic accuracy. Conclusions: Genetics can help to predict infections in patients undergoing chemotherapy. This algorithm should be validated and could be used to save lives, decrease economic costs, and optimize limited health resources.

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PURPOSE: Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 -572C>G (rs1800796), IL-1ß -31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC. PATIENTS AND METHODS: We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin's lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike's information criterion (AIC). RESULTS: We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 -572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ~ 0.81 IC95% 0.02-1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ~ 0.95 IC95% 0.02-1.82). IL-1ß genetic polymorphism had no statistically significant association with ANC. CONCLUSION: IL-6 rs1800796 -572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.

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BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P=0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P=0.62 and P=0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.). (AU)

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BACKGROUND: Hypertension is the leading cause of cardiovascular disease globally. Despite proven benefits, hypertension control is poor. We hypothesised that a comprehensive approach to lowering blood pressure and other risk factors, informed by detailed analysis of local barriers, would be superior to usual care in individuals with poorly controlled or newly diagnosed hypertension. We tested whether a model of care involving non-physician health workers (NPHWs), primary care physicians, family, and the provision of effective medications, could substantially reduce cardiovascular disease risk. METHODS: HOPE 4 was an open, community-based, cluster-randomised controlled trial involving 1371 individuals with new or poorly controlled hypertension from 30 communities (defined as townships) in Colombia and Malaysia. 16 communities were randomly assigned to control (usual care, n=727), and 14 (n=644) to the intervention. After community screening, the intervention included treatment of cardiovascular disease risk factors by NPHWs using tablet computer-based simplified management algorithms and counselling programmes; free antihypertensive and statin medications recommended by NPHWs but supervised by physicians; and support from a family member or friend (treatment supporter) to improve adherence to medications and healthy behaviours. The primary outcome was the change in Framingham Risk Score 10-year cardiovascular disease risk estimate at 12 months between intervention and control participants. The HOPE 4 trial is registered at ClinicalTrials.gov, NCT01826019. FINDINGS: All communities completed 12-month follow-up (data on 97% of living participants, n=1299). The reduction in Framingham Risk Score for 10-year cardiovascular disease risk was -6·40% (95% CI 8·00 to -4·80) in the control group and -11·17% (-12·88 to -9·47) in the intervention group, with a difference of change of -4·78% (95% CI -7·11 to -2·44, p<0·0001). There was an absolute 11·45 mm Hg (95% CI -14·94 to -7·97) greater reduction in systolic blood pressure, and a 0·41 mmol/L (95% CI -0·60 to -0·23) reduction in LDL with the intervention group (both p<0·0001). Change in blood pressure control status (<140 mm Hg) was 69% in the intervention group versus 30% in the control group (p<0·0001). There were no safety concerns with the intervention. INTERPRETATION: A comprehensive model of care led by NPHWs, involving primary care physicians and family that was informed by local context, substantially improved blood pressure control and cardiovascular disease risk. This strategy is effective, pragmatic, and has the potential to substantially reduce cardiovascular disease compared with current strategies that are typically physician based. FUNDING: Canadian Institutes of Health Research; Grand Challenges Canada; Ontario SPOR Support Unit and the Ontario Ministry of Health and Long-Term Care; Boehringer Ingelheim; Department of Management of Non-Communicable Diseases, WHO; and Population Health Research Institute. VIDEO ABSTRACT.

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Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality. However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status­wealth and education­differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorized as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. (AU)

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Introducción.La hipercolesterolemia en los padres sería mejor predictor de hipercolesterolemia en niños que la historia clínica familiar. Objetivos. Comparar las fuerzas de asociación y los valores de predicción de la hipercolesterolemia en padres y la historia clínica familiar positiva con la hipercolesterolemia en hijos. Material y métodos. Estudio analítico, transversal. Se dosó colesterolemia en niños ≥ 6 y < 12 años y sus padres biológicos. Se realizó una encuesta a los padres. Se evaluó la asociación mediante el cálculo de odds ratio. Se determinó su valor de predicción. Se estudió la relación entre la hipercolesterolemia en padres y en hijos usando la regresión multinivel. Resultados. Se evaluaron 332 niños, 304 madres y 206 padres. El análisis entre uno/ambos progenitores con colesterolemia ≥ 240 mg/dl y niños ≥ 200 mg/dl mostró OR= 6,40; IC95 % =2,85-14,48; p <0,0001; sensibilidad= 69 %; espedhcidad= 74 %; valor predictivo positivo (VPP)= 34 %; valor predictivo negativo (VPN)= 93 %; razones de verosimilitud positiva (RVP)= 2,69; negativa (RVN)= 0,42. La historia clínica familiar vs. niños con colesterolemia ≥ 200 arrojó OR= 1,86; IC95 %= 0,84-4,11; p= 0,1272; sensibilidad= 69 %; especificidad= 46 %; VPP= 19 %; VPN= 89 %; RVP= 1,27; RVN= 0,68. Los hijos tuvieron 2,9 y 2,5 más mg/dl de colesterol por cada 10 mg/dl de aumento en colesterol en madres y padres, respectivamente. Conclusiones: La hipercolesterolemia en padres se asoció significativamente con la hipercolesterolemia en hijos y mostró mayor poder de predicción que la historia clínica familiar positiva.

Introduction. Parental hypercholesterolemia would be a better predictor of hypercholesterolemia than family medical history in children. Objectives. To compare the strength of association and predictive values of parental hypercholesterolemia versus a positive family history in pediatric hypercholesterolemia. Material and methods. Cross-sectional, analytical study. Cholesterol levels were measured in children aged ≥ 6 and < 12 years and in their biological parents. A survey was administered to parents. The association was estimated using the odds ratio (OR), and its predictive value was determined. The relationship between hypercholesterolemia in parents and their children was studied with multilevel regression. Results. A total of 332 children, 304 mothers, and 206 fathers were assessed. A cholesterol level ≥ 240 mg/dL in one or both parents and ≥ 200 mg/dL in children showed: OR= 6.40; 95 % confidence interval (CI)= 2.85-14.48; p < 0.0001; sensitivity= 69 %; specihcity= 74 %; positive predictive value (PPV)= 34 %; negative predictive value (NPV)= 93 %; positive likelihood ratio (LR+)= 2.69; negative likelihood ratio (LR-)= 0.42. Family medical history versus children with cholesterol level ≥ 200 showed: OR= 1.86; 95 % CI= 0.84-4.11; p= 0.1272; sensitivity= 69 %; specihcity= 46 %; PPV= 19 %; NPV= 89 %; LR+= 1.27; LR-= 0.68. Cholesterol was 2.9 and 2.5 mg/dL higher per every 10 mg/dL of increased cholesterol in mothers and fathers, respectively. Conclusions: Parental hypercholesterolemia was significantly associated with hypercholesterolemia in children and showed a higher predictive power than a positive family medical history.

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INTRODUCTION: Parental hypercholesterolemia would be a better predictor of hypercholesterolemia than family medical history in children. OBJECTIVES: To compare the strength of association and predictive values of parental hypercholesterolemia versus a positive family history in pediatric hypercholesterolemia. Material and methods. Cross-sectional, analytical study. Cholesterol levels were measured in children aged ≥ 6 and < 12 years and in their biological parents. A survey was administered to parents. The association was estimated using the odds ratio (OR), and its predictive value was determined. The relationship between hypercholesterolemia in parents and their children was studied with multilevel regression. RESULTS: A total of 332 children, 304 mothers, and 206 fathers were assessed. A cholesterol level ≥ 240 mg/dL in one or both parents and ≥ 200 mg/dL in children showed: OR= 6.40; 95 % confidence interval (CI)= 2.85-14.48; p < 0.0001; sensitivity= 69 %; specihcity= 74 %; positive predictive value (PPV)= 34 %; negative predictive value (NPV)= 93 %; positive likelihood ratio (LR+)= 2.69; negative likelihood ratio (LR-)= 0.42. Family medical history versus children with cholesterol level ≥ 200 showed: OR= 1.86; 95 % CI= 0.84-4.11; p= 0.1272; sensitivity= 69 %; specihcity= 46 %; PPV= 19 %; NPV= 89 %; LR+= 1.27; LR-= 0.68. Cholesterol was 2.9 and 2.5 mg/dL higher per every 10 mg/dL of increased cholesterol in mothers and fathers, respectively. CONCLUSIONS: Parental hypercholesterolemia was significantly associated with hypercholesterolemia in children and showed a higher predictive power than a positive family medical history.

Introducción.La hipercolesterolemia en los padres sería mejor predictor de hipercolesterolemia en niños que la historia clínica familiar. Objetivos. Comparar las fuerzas de asociación y los valores de predicción de la hipercolesterolemia en padres y la historia clínica familiar positiva con la hipercolesterolemia en hijos. Material y métodos. Estudio analítico, transversal. Se dosó colesterolemia en niños ≥ 6 y < 12 años y sus padres biológicos. Se realizó una encuesta a los padres. Se evaluó la asociación mediante el cálculo de odds ratio. Se determinó su valor de predicción. Se estudió la relación entre la hipercolesterolemia en padres y en hijos usando la regresión multinivel. Resultados. Se evaluaron 332 niños, 304 madres y 206 padres. El análisis entre uno/ambos progenitores con colesterolemia ≥ 240 mg/dl y niños ≥ 200 mg/dl mostró OR= 6,40; IC95 % =2,85-14,48; p <0,0001; sensibilidad= 69 %; espedhcidad= 74 %; valor predictivo positivo (VPP)= 34 %; valor predictivo negativo (VPN)= 93 %; razones de verosimilitud positiva (RVP)= 2,69; negativa (RVN)= 0,42. La historia clínica familiar vs. niños con colesterolemia ≥ 200 arrojó OR= 1,86; IC95 %= 0,84-4,11; p= 0,1272; sensibilidad= 69 %; especificidad= 46 %; VPP= 19 %; VPN= 89 %; RVP= 1,27; RVN= 0,68. Los hijos tuvieron 2,9 y 2,5 más mg/dl de colesterol por cada 10 mg/dl de aumento en colesterol en madres y padres, respectivamente. Conclusiones: La hipercolesterolemia en padres se asoció significativamente con la hipercolesterolemia en hijos y mostró mayor poder de predicción que la historia clínica familiar positiva.

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