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Objectives: To assess the association of disability with suicide mortality, separately for women and men by age group., Methods: Information was obtained from a representative national sample of 161,809 community-dwelling adults (≥18 years). Participants contributed to follow-up time from baseline interview (2008) until suicide, death by other causes, or 2017. We calculated, by sex, standardized suicide mortality differences (SSMD), comparing persons with and without disabilities standardized to sociodemographic distribution of disability population., Results: 29 women died by suicide during 800,754 person-years follow-up and 97 men during 735,709 person-years. Among women with disabilities, SSMD (95% Confidence interval) per 100,000 person-years at 5 years was 54.4 deaths (-17.2 to 126.1) [100.0 (-27.4 to 227.4) in women <65 years and -4.8 (-27.3 to 17.7) in women ≥65 years (P homogeneity = 0.11)]. Among men, SSMD increased by 122.2 deaths (4.1 to 240.3) [37.2 (-40.2 to 114.6) in men <65 years and 74.7 (-51.8 to 200.5) in men ≥65 years (P homogeneity = 0.62)]., Conclusion: Suicide risk was higher in women and men with disability. In women higher risk was only notable for those <65. Men presented similar effects in both age groups. Nevertheless, due to imprecision of estimates, results should be viewed cautiously., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Pastor-Barriuso, Padrón-Monedero, Almazán-Isla, García López, de Pedro-Cuesta and Damián.)

Background: Disability and chronic diseases are prevalent conditions associated with mortality, but little information is available on their potential synergistic effects., Objective: This study aimed to describe additive interactions between disability and chronic diseases on mortality risk in middle-aged and older adults., Methods: A representative cohort of 22,800 community-dwelling Spanish people aged 50 years or older were interviewed for disability with the Global Activity Limitation Indicator and specific chronic diseases in the 2011-12 and 2014 National Health Surveys and subsequently followed up for mortality. Five-year all-cause mortality risks were standardized in each disability-by-comorbidity category through inverse probability weighting. We computed interaction contrasts as the departure of the standardized risk difference for people with both conditions from the sum of the standardized risk differences for those with any single condition., Results: The baseline prevalence of disability was 35.1 % (95 % confidence interval [CI] 34.4 %, 35.9 %). There was compelling evidence of synergistic effects of disability with chronic liver disease, heart diseases other than myocardial infarction, cancer, and cerebrovascular disease, with large positive interaction contrasts (95 % CIs) of 106.7 (-16.4, 229.9), 45.7 (6.9, 84.5), 45.1 (-15.0, 105.2), and 42.9 (-41.0, 126.9) excess deaths per 1000 persons. Less clear synergistic responses were observed for other comorbidities. We found some evidence of antagonism for osteoporosis, with a negative interaction contrast of -18.0 (95 % CI -82.2, 46.2) deaths per 1000 persons., Conclusion: Given the high mortality risk in people with disability, the study of its synergistic effects with target comorbidities can provide relevant information regarding preventive measures., Competing Interests: Declaration of competing interest Authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later., Design: Prospective cohort study., Settings and Participants: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals., Measurements: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores., Results: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time., Conclusions: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: It is unknown whether growth differentiation factor 15 (GDF-15) is associated with chronic musculoskeletal pain (CMP) and whether or not its association with incident cardiovascular disease (CVD) changes according to CMP status., Methods: In total, 1 957 randomly selected adults aged ≥65 years without prior CVD were followed up between 2015 and 2023. CMP was classified according to its intensity, frequency, and interference with daily activities. The association between GDF-15 levels and CMP was assessed using linear models with progressive inclusion of potential confounders, whereas the association between GDF-15 and CVD risk was evaluated with Cox proportional hazard models with similar adjustment and interaction terms between GDF-15 and CMP. The incremental predictive performance of GDF-15 over standard predictors was evaluated using discrimination and risk reclassification metrics., Results: GDF-15 concentrations were 6.90% (95% confidence interval [CI]: 2.56; 11.25) higher in individuals with CMP, and up to 8.89% (4.07; 15.71) and 15.79% (8.43; 23.16) higher in those with ≥3 CMP locations and interfering pain. These increased levels were influenced by a higher prevalence of cardiometabolic risk factors, functional impairments, depressive symptoms, and greater levels of inflammation in individuals with CMP. In fully adjusted models, a twofold increase in GDF-15 was associated with a 1.49 increased risk (95% CI: 1.08; 2.05) of a CVD event in individuals with CMP, but not among those without CMP (1.02 [0.77; 1.35]); p-interaction 0.041. Adding GDF-15 to models including the Framingham Risk Score improved predictive performance among individuals with CMP., Conclusions: We provide evidence that GDF-15 could serve as a biomarker to assess CMP, as well as to predict CVD incidence in individuals with CMP., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn exposure shows conflicting results., Objectives: To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC., Methods: In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008-2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models., Results: Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07-1.85). This association was slightly higher in high-grade PC [(ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01-1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06-2.54)] and in advanced tumours [(cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05-1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00-2.53)]. Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08-4.40)., Discussion: High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: The impact of residential green spaces on cardiovascular health in older adults remains uncertain., Methods: Cohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF-15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92)., Results: After adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of -5.56 % (95 %CI: -9.77; -1.35), -5.05 % (-9.58; -0.53), -4.24 % (-8.19, -0.19), and -4.16 % (-7.59; -0.74), respectively; and mean differences in hs-TnT among diabetic participants of -8.03 % (95 %CI: -13.30; -2.77), -9.52 % (-16.08; -2.96), -8.05 % (-13.94, -2.16) and -5.56 % (-10.75; -0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes., Conclusion: Increased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To estimate national and provincial prevalence of obesity and excess weight in the child and adolescent population in Spain by sex and sociodemographic characteristics, and to explore sources of inequalities in their distribution, and their geographical patterns., Methods: ENE-COVID is a nationwide representative seroepidemiological survey (68 287 participants) stratified by province and municipality size (April-June 2020). Participants answered a questionnaire which collected self-reported weight and height, that allowed estimating crude and model-based standardized prevalences of obesity and excess weight in the 10 543 child and adolescent participants aged 2-17 years., Results: Crude prevalences (WHO growth reference) were higher in boys than in girls (obesity: 13.4% vs. 7.9%; excess weight: 33.7% vs. 26.0%; severe obesity: 2.9% vs. 1.2%). These prevalences varied with age, increased with the presence of any adult with excess weight in the household, while they decreased with higher adult educational and census tract average income levels. Obesity by province ranged 1.8%-30.5% in boys and 0%-17.6% in girls; excess weight ranged 15.2%-49.9% in boys and 10.8%-40.8% in girls. The lowest prevalences of obesity and excess weight were found in provinces in the northern half of Spain. Sociodemographic characteristics only partially explained the observed geographical variability (33.6% obesity; 44.2% excess weight)., Conclusions: Childhood and adolescent obesity and excess weight are highly prevalent in Spain, with relevant sex, sociodemographic and geographical differences. The geographic variability explained by sociodemographic variables indicates that there are other potentially modifiable factors on which to focus interventions at different geographic levels to fight this problem., (© 2023 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Selenium is an essential trace element with an antioxidant and anti-inflammatory capacity that has been associated in experimental studies with beneficial effects on appetite control, the regulation of the gut microbiota, and control of the anabolic-catabolic balance. The main aim of the present study was to evaluate the association between circulating selenium concentrations and the risk of developing undernutrition in older adults., Methods: This was a cohort study with 1398 well-nourished community-dwelling individuals aged ≥ 65 years residing in Spain in 2017, who were followed for a mean of 2.3 years. Whole blood selenium was measured at baseline using inductively coupled plasma-mass spectrometry. Undernutrition was assessed at baseline and at follow-up, and defined as having at least one of the three GLIM phenotypic criteria (involuntary weight loss, a low body mass index, and a reduced muscle mass) and at least one of the two etiologic criteria (reduced food consumption or nutrient assimilation and inflammation/disease burden)., Results: During the follow-up, 142 participants (11%) developed moderate undernutrition and 113 (8.8%) severe undernutrition. The standardized relative risks of moderate and severe undernutrition at the 75th percentile of Se levels versus the 25th were 0.90 and 0.70, respectively. In dose-response analyses, the risk of severe undernutrition decreased linearly with increasing selenium concentrations. This association was independent of protein intake or diet quality and was stronger among participants with a diagnosis of a musculoskeletal disorder., Conclusions: The results suggest that an adequate dietary selenium status is needed to prevent undernutrition in older adults. Also, this may open the door for clinical trials with selenium supplementation, at doses considered as safe, to prevent undernutrition.

Background: In Spain, differences in the prevalence of obesity and excess weight according to sex and sociodemographic factors have been described at the national level, although current data do not allow to delve into geographical differences for these conditions. The aim was to estimate national and regional prevalences of adult obesity and excess weight in Spain by sex and sociodemographic characteristics, and to explore difference sources of inequalities in its distribution, as well as its geographical pattern., Method: ENE-COVID study was a nationwide representative seroepidemiological survey with 57,131 participants. Residents in 35,893 households were selected from municipal rolls using a two-stage random sampling stratified by province and municipality size (April-June 2020). Participants (77.0% of contacted individuals) answered a questionnaire which collected self-reported weight and height, as well as different socioeconomic variables, that allowed estimating crude and standardized prevalences of adult obesity and excess weight., Results: Crude prevalences of obesity and excess weight were higher in men (obesity: 19.3% vs. 18.0%; excess weight: 63.7% vs. 48.4%), while severe obesity was more prevalent in women (4.5% vs. 5.3%). These prevalences increased with age and disability, and decreased with education, census tract income and municipality size. Differences by educational level, relative census income, nationality or disability were clearly higher among women. Obesity by province ranged 13.3-27.4% in men and 11.4-28.1% in women; excess weight ranged 57.2-76.0% in men and 38.9-59.5% in women. The highest prevalences were located in the southern half of the country and some north-western provinces. Sociodemographic characteristics only explained a small part of the observed geographical variability (25.2% obesity)., Conclusion: Obesity and overweight have a high prevalence in Spain, with notable geographical and sex differences. Socioeconomic inequalities are stronger among women. The observed geographical variability suggests the need to implement regional and local interventions to effectively address this public health problem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gutiérrez-González, García-Solano, Pastor-Barriuso, Fernández de Larrea-Baz, Rollán-Gordo, Peñalver-Argüeso, Peña-Rey, Pollán, Pérez-Gómez and the ENE-COVID Study Group.)

Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. MH is data science adviser for ProPublica, Advisory Board Member of ADIA Lab, and consultant for Cytel.

Data System. The Spanish National Seroepidemiological Survey of SARS-CoV-2 (or ENE-COVID; SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] is the causative agent of COVID-19) was funded by the Spanish Ministry of Health, the Instituto de Salud Carlos III, and the Spanish National Health System. Data Collection/Processing. A stratified 2-stage probability sampling was used to select a representative cohort of the noninstitutionalized population of Spain. ENE-COVID collected longitudinal data from epidemiological questionnaires and 2 SARS-CoV-2 IgG antibody tests. From April 27 to June 22, 2020, 68 287 participants (77.0% of contacted persons) received a point-of-care test and 61 095 (68.9%) also underwent a laboratory immunoassay. A second follow-up phase was conducted between November 16 and 30, 2020. Data Analysis/Dissemination. Analyses use weights to adjust for oversampling and nonresponse and account for design effects of stratification and clustering. ENE-COVID data for research purposes will be available upon request from the official study Web page. Public Health Implications. ENE-COVID, a nationwide population-based study, allowed monitoring seroprevalence of antibodies against SARS-CoV-2 at the national and regional levels, providing accurate figures by gender, age (from babies to nonagenarians), and selected risk factors; characterizing symptomatic and asymptomatic infections; and estimating the infection fatality risk during the first pandemic wave. ( Am J Public Health . 2023;113(5):525-532. https://doi.org/10.2105/AJPH.2022.307167).

Objectives. To describe participant characteristics associated with severe acute respiratory syndrome coronavirus 2 infection in Spain's first 2 COVID-19 waves per the Spanish National Seroepidemiological Survey of SARS-CoV-2 Infection (ENE-COVID). Methods. A representative cohort of the noninstitutionalized Spanish population, selected through stratified 2-stage sampling, answered a questionnaire and received point-of-care testing April to June 2020 (first wave: n = 68 287); previously seronegative participants repeated the questionnaire and test November 2020 (second wave: n = 44 451). We estimated seropositivity by wave and participant characteristics, accounting for sampling weights, nonresponse, and design effects. Results. We found that 6.0% (95% confidence interval [CI] = 5.7%, 6.4%) of Spain's population was infected by June and 3.8% (95% CI = 3.5%, 4.1%) more by November 2020. Both genders were equally affected. Seroprevalence decreased with age in adults 20 years and older in the second wave; socioeconomic differences increased. Health care workers were affected at 11.1% (95% CI = 9.0%, 13.6%) and 6.1% (95% CI = 4.4%, 8.5%) in the first and second waves, respectively. Living with an infected person increased infection risk to 22.1% (95% CI = 18.9%, 25.6%) in the first and 35.0% (95% CI = 30.8%, 39.4%) in the second wave. Conclusions. ENE-COVID characterized the first 2 pandemic waves, when information from surveillance systems was incomplete. ( Am J Public Health . 2023;113(5):533-544. https://doi.org/10.2105/AJPH.2023.307233).

Introduction: The protection of children is a major driver of behavior among those in charge of their care. We evaluated whether compliance with preventive measures against SARS-CoV-2 infection among adults living with children was different from that of those not living with them, in 2020., Methods: We used the COSMO-SPAIN ( N = 867) and the nationally representative ENE-COVID ( N = 29,926) surveys to estimate prevalence of compliance (95% confidence interval). Logistic model based standardization methods were applied to estimate standardized prevalence differences (SPrD) to the overall distribution of age, sex, education, history of COVID-19, and residence of other >60 yrs in the household., Results: We observed that adults living with children more frequently avoided bars (SPrD ENE-COVID : 4.2%; 95% CI: 2.3-6.1), crowded places (SPrD COSMO : 8.0%; 95% CI: 0.6-15.1) and did not use public transportation (SPrD ENE-COVID : 4.9%; 95% CI: 3.0-6.7). They were also more worried about work and family conciliation (SPrD COSMO : 12.2%; 95% CI: 4.8-19.5) and about closure of education centers (SPrD COSMO : 26.5%; 95% CI: 19.4-33.6)., Discussion: In general, adults living with children adopted slightly more frequently social distancing measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jroundi, Fernández de Larrea-Baz, Rodríguez-Blázquez, Pastor-Barriuso, Pollán-Santamaría, Forjaz, Pérez-Gómez and the ENE-COVID Study Group.)

The nephrotoxicity of low-chronic metal exposures is unclear, especially considering several metals simultaneously. We assessed the individual and joint association of metals with longitudinal change in renal endpoints in Aragon Workers Health Study participants with available measures of essential (cobalt [Co], copper [Cu], molybdenum [Mo] and zinc [Zn]) and non-essential (As, barium [Ba], Cd, chromium [Cr], antimony [Sb], titanium [Ti], uranium [U], vanadium [V] and tungsten [W]) urine metals and albumin-to-creatinine ratio (ACR) (N = 707) and estimated glomerular filtration rate (eGFR) (N = 1493) change. Median levels were 0.24, 7.0, 18.6, 295, 3.1, 1.9, 0.28, 1.16, 9.7, 0.66, 0.22 μg/g for Co, Cu, Mo, Zn, As, Ba, Cd, Cr, Sb, Ti, V and W, respectively, and 52.5 and 27.2 ng/g for Sb and U, respectively. In single metal analysis, higher As, Cr and W concentrations were associated with increasing ACR annual change. Higher Zn, As and Cr concentrations were associated with decreasing eGFR annual change. The shape of the longitudinal dose-responses, however, was compatible with a nephrotoxic role for all metals, both in ACR and eGFR models. In joint metal analysis, both higher mixtures of Cu-Zn-As-Ba-Ti-U-V-W and Co-Cd-Cr-Sb-V-W showed associations with increasing ACR and decreasing eGFR annual change. As and Cr were main drivers of the ACR change joint metal association. For the eGFR change joint metal association, while Zn and Cr were main drivers, other metals also contributed substantially. We identified potential interactions for As, Zn and W by other metals with ACR change, but not with eGFR change. Our findings support that Zn, As, Cr and W and suggestively other metals, are nephrotoxic at relatively low exposure levels. Metal exposure reduction and mitigation interventions may improve prevention and decrease the burden of renal disease in the population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn., Objectives: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism., Methods: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn., Results: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women., Discussion: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breast cancer (BC) survivors are advised to follow the WCRF/AICR cancer prevention recommendations, given their high risk of developing a second tumour. We aimed to explore compliance with these recommendations in BC survivors and to identify potentially associated clinical and sociodemographic factors. A total of 420 BC survivors, aged 31-80, was recruited from 16 Spanish hospitals. Epidemiological, dietary and physical activity information was collected through questionnaires. A 7-item score to measure compliance with the recommendations was built according to the 2018 WCRF/AICR scoring criteria. Standardized prevalences and standardized prevalence ratios of moderate and high compliance across participant characteristics were estimated using multinomial and binary logistic regression models. The mean score was 3.9 (SD: 1.0) out of 7 points. Recommendations with the worst adherence were those of limiting consumption of red/processed meats (12% of compliance, 95% CI: 8.2-15.0) and high fibre intake (22% of compliance, 95% CI: 17.6-27.0), while the best compliance was observed for the consumption of fruits and vegetables (73% of compliance, 95% CI: 69.2-77.7). Overall, adherence was worse in women with university education and in those with first-degree relatives with BC. This information may be of interest to design and implement personalized preventive measures adapted to the characteristics of these patients.

Background: The main aims of this study were to analyze trends of SARS-CoV-2 anti-nucleocapsid IgG throughout the four rounds of the seroepidemiologic study ENE-COVID, and compare the fourth-round results of two immunoassays detecting anti-nucleocapsid and anti-RBD IgG., Methods: ENE-COVID was developed in 2020 (two phases). Phase one included three rounds carried out in April 27-May 11, May 18-June 1, and June 8-June 22. Phase two included a fourth round in the same cohort (November 16-29). A chemiluminescent microparticle immunoassay was offered to participants in the first three rounds (Abbott; anti-nucleocapsid IgG). In the fourth round, we offered this test and a chemiluminescence immunoassay (Beckman; anti-RBD IgG) to i) a randomly selected sub-cohort, ii) participants who were IgG-positive in any of the three first rounds; and iii) participants who were IgG-positive in the fourth round by point-of-care immunochromatography., Results: 10,153 individuals (82.2% of people invited) participated in the fourth round. Of them, 2595 (35.1% of participants with results in the four rounds) were positive for anti-nucleocapsid IgG in at least one round. Anti-nucleocapsid IgG became undetectable in 43.3% of participants with positive first-round results. In fourth round, anti-nucleocapsid and anti-RBD IgG were detected in 5.5% (321/5827) and 5.4% (315/5827) participants of the randomly selected sub-cohort, and in 26.6% (867/3261) and 25.9% (846/3261) participants with at least one previous positive result, respectively., Conclusions: The IgG response is heterogeneous and conditioned by infection severity. A proportion of SARS-CoV-2 infected population may have negative serologic results in the post-infection months., (Copyright © 2022. Published by Elsevier B.V.)

The main objective was to identify sociodemographic characteristics of the population at risk for a greater clustering of unhealthy behaviors and to evaluate the association of such clustering with self-rated health status and disability. Data come from the 2017 Spanish National Health Survey with a sample of 21,947 participants of 15 years of age or older. Based on tobacco consumption, risk drinking, unbalanced diet, sedentarism, and body mass index <18.5/≥25 we created two indicators of risk factor clustering: 1) Number of unhealthy behaviors (0-5); and 2) Unhealthy lifestyle index (score: 0-15). Self-rated health was dichotomized into "optimal" and "suboptimal," and disability was classified as "no disability," "mild," and "severe" based on the Global Activity Limitation Index (GALI). We estimated prevalence ratios (PR) adjusted for covariates using generalized linear models using the clustering count variable, and dose-response curves using the unhealthy lifestyle index. Most participants (77.4%) reported 2 or more risk factors, with men, middle-age individuals, and those with low socioeconomic status being more likely to do so. Compared to those with 0-1 risk factors, the PR for suboptimal health was 1.26 (95% CI:1.18-1.34) for those reporting 2-3 factors, reaching 1.43 (95% CI:1.31-1.55) for 4-5 factors. The PR for severe activity limitation was 1.66 (95% CI:1.35-2.03) for those reporting 2-3 factors and 2.06 (95% CI:1.59-2.67) for 4-5 factors. The prevalence of both health indicators increased in a non-linear fashion as the unhealthy lifestyle index score increased, increasing rapidly up to 5 points, slowing down between 5 and 10 points, and plateauing afterwards., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This systematic review discusses long-term NSW and female BC risk, with special attention to differences between pre- and postmenopausal BC, to test the association with recent NSW. The review follows PRISMA guidelines (Prospero registry: CRD42018102515). We searched PubMed, Embase, and WOS for case-control, nested case-control, and cohort studies addressing long-term NSW (≥15 years) as risk exposure and female BC as outcome until 31 December 2020. Risk of bias was evaluated with the Newcastle-Ottawa scale. Eighteen studies were finally included (eight cohorts; five nested case-control; five case-control). We performed meta-analyses on long-term NSW and BC risk; overall and by menopausal status; a subanalysis on recent long-term NSW, based on studies involving predominantly women below retirement age; and a dose-response meta-analysis on NSW duration. The pooled estimate for long-term NSW and BC was 1.13 (95%CI = 1.01-1.27; 18 studies, I 2 = 56.8%, p = 0.002). BC risk increased 4.7% per 10 years of NSW (95%CI = 0.94-1.09; 16 studies, I 2 = 33.4%, p = 0.008). The pooled estimate for premenopausal BC was 1.27 (95%CI = 0.96-1.68; six studies, I 2 = 32.0%, p = 0.196) and for postmenopausal BC 1.05 (95%CI = 0.90-1.24,I 2 = 52.4%; seven studies, p = 0.050). For recent long-term exposure, the pooled estimate was 1.23 (95%CI = 1.06-1.42; 15 studies; I 2 = 48.4%, p = 0.018). Our results indicate that long-term NSW increases the risk for BC and that menopausal status and time since exposure might be relevant.

Background: There are scant studies focused on measuring the association between disability and all-cause mortality based on large representative national samples of the community-dwelling adult population; moreover, the number of such studies which also include cause-specific mortality is yet lower., Methods: Longitudinal cohort study that used baseline data from 162 381 adults who participated in a countrywide disability survey (2008). A nationally representative sample was selected and interviewed in their homes. We present data on people ≥18 years. Disability was considered as any substantial limitation found on a list of 44 life activities that have lasted or are expected to last more than 1 year and originate from an impairment. Cause-specific mortality data were obtained from the Spanish Statistical Office. Subjects contributed follow-up time from baseline interview until death or the censoring date (31 December 2017). We computed standardised rate ratios (SRRs), with age, sex, living with a partner and education level distribution of the total group as standard population., Results: Adults with disability (11%) had an adjusted mortality rate more than twice as high as adults without disability (SRR 2.37, 95% CI 2.24 to 2.50). The increased mortality risk remained over the 10-year follow-up period. Mortality due to diseases of the nervous system (SRR 4.86, 95% CI 3.93 to 6.01), diseases of the musculoskeletal system (SRR 3.45, 95% CI 2.18 to 5.47), infectious diseases (SRR 3.38, 95% CI 2.27 to 5.01) and diabetes mellitus (SRR 3.56, 95% CI 2.71 to 4.68) was particularly high in those with disability., Conclusions: All-cause mortality rates are markedly higher among adults with disability. Preventive measures and health promotion initiatives are needed to reduce mortality risk in this population. Special attention should be paid to disabled people with certain specific diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterize asymptomatic SARS-CoV-2 infections and develop a symptom-based risk score useful in primary healthcare., Study Design and Setting: Sixty-one thousand ninty-two community-dwelling participants in a nationwide population-based serosurvey completed a questionnaire on COVID-19 symptoms and received an immunoassay for SARS-CoV-2 IgG antibodies between April 27 and June 22, 2020. Standardized prevalence ratios for asymptomatic infection were estimated across participant characteristics. We constructed a symptom-based risk score and evaluated its ability to predict SARS-CoV-2 infection., Results: Of all, 28.7% of infections were asymptomatic (95% CI 26.1-31.4%). Standardized asymptomatic prevalence ratios were 1.19 (1.02-1.40) for men vs. women, 1.82 (1.33-2.50) and 1.45 (0.96-2.18) for individuals <20 and ≥80 years vs. those aged 40-59, 1.27 (1.03-1.55) for smokers vs. nonsmokers, and 1.91 (1.59-2.29) for individuals without vs. with case contact. In symptomatic population, a symptom-based score (weights: severe tiredness = 1; absence of sore throat = 1; fever = 2; anosmia/ageusia = 5) reached standardized seroprevalence ratio of 8.71 (7.37-10.3), discrimination index of 0.79 (0.77-0.81), and sensitivity and specificity of 71.4% (68.1-74.4%) and 74.2% (73.1-75.2%) for a score ≥3., Conclusion: The presence of anosmia/ageusia, fever with severe tiredness, or fever without sore throat should serve to suspect COVID-19 in areas with active viral circulation. The proportion of asymptomatics in children and adolescents challenges infection control., (Copyright © 2021. Published by Elsevier Inc.)

Background: Increasing physical activity (PA) and reducing sedentary behaviour (SB) have been associated with healthy ageing, but their effects when adjusted for reverse causation and selection bias remain unclear., Methods: A deficits accumulation (DA) index based on the number and severity of 51 health deficits (0-100%) was calculated at baseline and three biannual follow-up visits, in a representative cohort of 3 228 community-dwelling older adults in Spain. Average differences in DA index by previous recreational PA, household PA, mentally-active SB and passive SB were estimated using marginal structural models with inverse probability of exposure and censoring weights., Results: Compared with participants with previous recreational PA of 10-19.9 metabolic equivalent hours/week (MET-hours/week), average differences in DA index (95% confidence intervals) were 0.19 (-1.09, 1.48), 0.69 (-0.23, 1.61), -0.66 (-1.34, 0.02), -0.87 (-1.59, -0.13) and -0.55 (-1.37, 0.28) for 0, 0.1-9.9, 20-29.9, 30-39.9 and ≥40 MET-hours/week, respectively (P for trend = 0.006). Household PA showed no effect on subsequent DA after adjusting for reverse causation. Women, but not men, who spent 7-14.9, 15-20.9 and ≥21 h/week on mentally active SB had DA decreases of 0.09 (-1.00, 1.19), 1.08 (-0.28, 2.45) and 2.17 (0.58, 3.75), respectively, compared with 1-6.9 h/week (P for trend = 0.005); whereas women who spent 3-3.9, 4-4.9 and ≥5 h/day on passive SB showed DA increases of 0.41 (-0.52, 1.35), 1.35 (0.13, 2.57) and 2.13 (0.78, 3.47), respectively, compared with 2-2.9 h/day (P for trend = 0.001)., Conclusions: The proposed methodology allows estimation of the causal effects of PA and SB on ageing, by simulating a random assignment in which all subjects have the same probability of exposure., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Toenails have been used as biomarkers of exposure to toxic metals, but their validity for this purpose is not yet clear and might differ depending on the specific agent. To evaluate this issue, we reviewed the literature on: a) the time-window of exposure reflected by toenails; b) the reproducibility of toenail toxic-metal levels in repeated measures over time; c) their relationship with other biomarkers of exposure, and; d) their association with potential determinants (i.e. sociodemographic, anthropometric, or lifestyle characteristics) or with sources of exposure like diet or environmental pollution. Thus, we performed a systematic review, searching for articles that provided original data for levels of any of the following toxic metals in toenails: aluminum, beryllium, cadmium, chromium, mercury, nickel, lead, thallium and uranium. We identified 88 articles, reporting data from 67 different research projects, which were quite heterogeneous with regard to population profile, sample size and analytical technique. The most commonly studied metal was mercury. Concerning the time-window of exposure explored by toenails, some reports indicate that toenail cadmium, nickel and lead may reflect exposures that occurred 7-12 months before sampling. For repeated samples obtained 1-6 years apart, the range of intraindividual correlation coefficients of aluminum, chromium and mercury was 0.33-0.56. The correlation of toxic metal concentrations between toenails and other matrices was higher for hair and fingernails than for urine or blood. Mercury levels were consistently associated with fish intake, while other toxic metals were occasionally associated with specific sources (e.g. drinking water, place of residence, environmental pollution, and occupation). The most frequently evaluated health endpoints were cardiovascular diseases, cancer, and central nervous system diseases. Available data suggest that toenail mercury levels reflected long-term exposures and showed positive associations with fish intake. The lack of standardization in sample collection, quality control, analytical techniques and procedures - along with the heterogeneity and conflicting results among studies - mean it is still difficult to conclude that toenails are a good biomarker of exposure to toxic metals. Further studies are needed to draw solid conclusions about the suitability of toenails as biomarkers of exposure to toxic metals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Cadmium (Cd) is a toxic metal found in tobacco, air and food. Recent cross-sectional studies have suggested that Cd negatively impacts physical performance, but the prospective association is uncertain., Methods: We used data from 2548 older adults from the Seniors-ENRICA II cohort in Madrid, Spain. Whole blood Cd levels were measured at baseline using inductively coupled plasma-mass spectrometry. At baseline (2017) and follow-up (2019), overall physical function was evaluated using the physical component summary (PCS) of the SF 12-Item Health questionnaire, lower-extremity performance with the Short Physical Performance Battery (SPPB), muscle weakness with a hand dynamometer, and frailty with a Deficit Accumulation index. Mobility limitations and disability in instrumental activities of daily living (IADL) were ascertained with standardized questionnaires. Analyses were adjusted for relevant confounders, including tobacco smoke, number of cigarettes smoked per day and time since cessation in former smokers., Results: In cross-sectional analyses, odds ratios (95% confidence interval) per two-fold increase in blood Cd were 1.16 (1.03; 1.31) for low PCS scores, 1.08 (0.97; 1.20) for impaired lower-extremity performance, 1.10 (0.98; 1.23) for low grip strength, 1.11 (1.02; 1.20) for mobility limitations, 1.16 (1.02; 1.31) for frailty, and 1.26 (1.08; 1.47) for IADL disability. In longitudinal analyses, corresponding hazard ratios were 1.25 (1.03; 1.51) for low PCS scores, 1.14 (1.03; 1.27) for impaired lower-extremity performance, 1.02 (0.92; 1.13) for low grip strength, 1.03 (0.91; 1.16) for mobility limitations, and 1.16 (1.00; 1.35) for frailty. All the associations where consistent when current smokers were excluded from the analyses., Conclusions: Our results support the role of Cd as a risk factor for physical function impairments in older adults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This systematic review summarizes the current evidence related to the reliability of toenail total arsenic concentrations (thereafter "arsenic") as a biomarker of long-term exposure. Specifically, we reviewed literature on consistency of repeated measures over time, association with other biomarkers and metal concentrations, factors influencing concentrations, and associations with health effects. We identified 129 papers containing quantitative original data on arsenic in toenail samples covering populations from 29 different countries. We observed geographic differences in toenail arsenic concentrations, with highest median or mean concentrations in Asian countries. Arsenic-contaminated drinking water, occupational exposure or living in specific industrial areas were associated with an increased toenail arsenic content. The effects of other potential determinants and sources of arsenic exposure including diet, gender and age on the concentrations in toenails need further investigations. Toenail arsenic was correlated with the concentrations in hair and fingernails, and with urine arsenic mainly among highly exposed populations with a toenail mean or median ≥1 μg/g. Overall, there is a growing body of evidence suggesting that arsenic content from a single toenail sample may reflect long-term internal dose-exposure. Toenail arsenic can serve as a reliable measure of toxic inorganic arsenic exposure in chronic disease research, particularly promising for cancer and cardiovascular conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Social engagement (SE) has been consistently shown to improve survival among community-dwelling older people, but the evidence in nursing home residents is inconclusive and prone to short-term reverse causation and confounding by major health determinants. Our main objective was to study the potential causal effect of within-the-facility social engagement (SE) on long-term all-cause mortality in care home residents., Methods: A representative cohort of 382 nursing home residents in Madrid without severe physical and cognitive impairments at baseline was followed up for 10-year all-cause mortality. Standardized mortality curves for residents with low/null, moderate, and high levels of SE at baseline were estimated using Kaplan-Meier methods and spline-based survival models with inverse probability of exposure weights conditional on baseline sociodemographic characteristics, facility features, comorbidity, and disability. Standardized 5-year mortality risks and median survival times were compared across levels of SE., Results: The baseline prevalences of low/null, moderate, and high SE were 36, 44, and 20%, respectively. Compared with residents with low/null SE at baseline, the standardized differences (95% confidence intervals) in 5-year mortality risk were - 2.3% (- 14.6 to 10.0%) for moderately engaged residents and - 18.4% (- 33.8 to - 2.9%) for highly engaged residents. The median survival time increased by 0.4 (- 1.4 to 2.2) and 3.0 (0.8 to 5.2) years, respectively., Conclusion: Residents with high SE within the nursing home had an 18% lower 5-year mortality risk and a 3-year increase in their median survival, as compared with residents with similar health determinants but low/null SE. The development of adequate tailored intervention programs, addressed to increase SE in nursing home residents, could improve their long-term survival, in addition to expected gains in quality of life.

Background: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level., Methods: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test)., Findings: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test., Interpretation: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave., Funding: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study investigates the still uncertain association between serum phospholipid fatty acids (PL-FA), and anthropometric and adiposity variables. A cross-sectional study was conducted with 1443 Spanish premenopausal women. Participants answered an epidemiological and a food frequency questionnaire. Anthropometric variables were measured using a bioimpedance scale. Serum PL-FAs levels were determined by gas chromatography-mass spectrometry. The association between body mass index (BMI), weight gain, body fat percentage, visceral fat index, and waist circumference with serum PL-FAs and desaturation indices was evaluated using multivariable linear regression models. BMI was positively associated with the relative concentration of saturated fatty acids (SFAs) (β = 0.94, q-val = 0.001), and with palmitoleic, dihomo-γ-linolenic (DGLA), arachidonic (AA) and α-linolenic acids, and was inversely associated with oleic, gondoic, trans-vaccenic, linoleic and γ-linolenic acids. Total fat percentage was positively associated with DGLA and AA, and inversely with linoleic and γ-linolenic acids. Low relative concentrations of some SFAs and high levels of n-6 PUFAs were associated with greater waist circumference. While the oleic/stearic and AA/DGLA acid ratios were inversely associated with BMI, DGLA/linoleic acid ratio was positively related to almost all variables. In addition to BMI, total fat percentage and waist circumference were also associated with certain individual fatty acids.

Objectives: To assess the association between having suffered a fall in the month prior to interview and long-term overall survival in nursing-home residents., Methods: Retrospective cohort study conducting an overall survival follow-up of 689 representative nursing-home residents from Madrid, Spain. Residents lived in three types of facilities: public, subsidized and private and its information was collected by interviewing the residents, caregivers and/or facility physicians. Residents contributed to follow-up time from their baseline interviews until death or being censored at the end of the 5-year follow-up period. The association between suffering a fall during the month prior to interview and long-term overall survival was analyzed using Cox proportional hazards models. To adjust for potential confounders we used progressive adjusted models. We then repeated the analyses with severity of the fall (no fall, non-severe, severe) as the main independent variable., Results: After a 2408 person-year follow-up (median 4.5 years), 372 participants had died. In fully-adjusted models, residents who had suffered any kind of fall in the previous month showed virtually the same survival rates compared to non-fallers (hazard ratio (HR) = 1.03; 95% CI = 0.75-1.40). There was a weak graded relationship between increased fall severity and survival rates for the non-severe fall group (HR = 0.92; 95% CI = 0.58-1.45) and the severe fall group (HR = 1.36; 95% CI = 0.73-2.53) compared with residents who had not suffered any kind of fall. The hazard ratios for severe falls were higher in men, residents with less comorbidity, fewer medications, and those functionally independent., Conclusion: We found no associations between having suffered a fall in the month prior to interview and long-term survival; neither did we find a marked association when severity of fall was accounted for in the whole population. In some subgroups, however, the results merit further scrutiny., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease associated with an increased risk of cardiovascular disease (CVD), diabetes, and chronic kidney disease. Indeed, CVD is the most common cause of death in NAFLD patients. This study aimed to evaluate the association between NAFLD and the risk of incident myocardial infarction., Methods: This is a retrospective cohort study involving 111 492 adults over 40 years old without history of CVD, liver disease, or cancer at baseline who participated in a regular health screening exam between 2003 and 2013. Fatty liver was diagnosed by ultrasonography., Results: During 725 706.9 person-years of follow-up, 183 participants developed myocardial infarction (incidence rate 0.3 cases per 1000 person-years). The age, sex, and year of visit-adjusted hazard ratio (HR) for incident myocardial infarction comparing participants with NAFLD with those without it was 2.14 (95% confidence interval 1.59, 2.89). This association remained significant in fully adjusted models (HR 1.54; 95% confidence interval 1.11, 2.14). Compared with participants without NAFLD, in participants with low NAFLD fibrosis score (NFS) (< -1.455) and with intermediate-to-high NFS (≥ -1.455), the fully adjusted HRs for incident myocardial infarction were 1.70 (1.22, 2.36) and 1.88 (1.24, 2.87), respectively., Conclusion: In this large cohort study, NAFLD was associated with an increased incidence of myocardial infarction independently of established risk factors. In addition, this association was similar in participants with and without evidence of more advanced NAFLD as indicated by the NFS. NAFLD patients may need to be carefully monitored and managed early to prevent myocardial infarction., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: In contrast to the recognized role of Helicobacter pylori in the etiology of non-cardia gastric cancer (GC), there is still insufficient epidemiological evidence for the involvement of Epstein-Barr virus (EBV) in gastric carcinogenesis. We aimed to evaluate the relation of antibody profile and antibody reactivity intensity against four individual EBV proteins to GC risk., Methods: We used information from 281 GC cases and 2071 age and sex frequency matched controls recruited in the frame of the MCC-Spain multicase-control study, between 2008 and 2013. Sociodemographic, lifestyle and environmental factors were assessed in face-to-face interviews. Antibody responses to four EBV proteins (EBNA-1, ZEBRA, EA-D, and VCA-p18) were analyzed by multiplex serology. Odds ratios (OR) and 95% confidence intervals were calculated by using logistic regression mixed models to evaluate the association of seropositivity and antibody reactivity against EBV proteins with GC, adjusting for GC risk factors. Stratified analyses by tumor location (cardia vs. non-cardia) and morphology (intestinal vs. diffuse) were done., Results: Among controls, seropositivity for EA-D, ZEBRA, EBNA-1 and VCA-p18 was 85%, 91%, 97% and 99%, respectively. Even though seropositivity for none of the studied proteins was associated with a higher GC risk, increasing antibody reactivity against EBNA-1 and VCA-p18 was associated with higher OR of GC. This association was present for cardia and non-cardia cancer cases, and for intestinal and diffuse types., Conclusion: Our results support the hypothesis that EBV may play a role in GC etiology, and highlight the importance of evaluating specific antibodies and the dose-response relations when studying widespread infections., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To analyze sex- and education-specific trajectories of health deficits accumulation (DA) throughout old age and to examine whether these trajectories differ according to health domains., Design: Population-based prospective cohort study., Setting: and participants: In Spain, 3228 community-dwelling individuals aged 60 years or older were followed up for 10 years., Measures: At baseline and 3 follow-up visits, a DA index (0 to 100% deficit) was calculated based on the number and severity of 52 health deficits across the domains of physical and cognitive function, self-rated health and vitality, mental health, and morbidity. Trajectories of overall and domain-specific DA indexes were estimated using mixed models for repeated measurements, allowing for homogeneous linear, piecewise linear, and smooth nonlinear DA trends over age., Results: Women showed greater DA than men, but differences leveled out with age: annual increments in DA index (95% confidence interval) for participants aged <70, 70-80, and ≥80 years were, respectively, 0.40 (0.30-0.50), 0.68 (0.57-0.80), and 1.30 (1.07-1.54) in men and 0.63 (0.53-0.73), 0.99 (0.89-1.10), and 1.31 (1.09-1.53) in women. These changes were mainly driven by a progressive accumulation of chronic diseases and by quadratic declines in physical and cognitive function. Both men and women showed improvements in mental health with age. In general, women and participants with lower education had decreased physical and cognitive function and accumulated morbidities faster than their counterparts. Only individuals with very fast declines in function and fast accumulation of morbidities showed a significant worsening of self-rated health and vitality over time., Conclusions: Public health interventions aimed at promoting healthy ageing should focus on prevention and early control of chronic diseases, as well on the preservation of function and early rehabilitation, with the latter being more relevant during the latter stages of life. Post-acute and long-term care services should incorporate adequate physical therapy and nursing facilities to promote attainable levels of functionality in older adults., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Blacks have a higher incidence of out-of-hospital sudden cardiac death (SCD) in comparison with whites. However, the racial differences in the cumulative risk of SCD and the reasons for these differences have not been assessed in large-scale community-based cohorts. The objective of this study is to compare the lifetime cumulative risk of SCD among blacks and whites, and to evaluate the risk factors that may explain racial differences in SCD risk in the general population., Methods: This is a cohort study of 3832 blacks and 11 237 whites participating in the Atherosclerosis Risk in Communities Study (ARIC). Race was self-reported. SCD was defined as a sudden pulseless condition from a cardiac cause in a previously stable individual, and SCD cases were adjudicated by an expert committee. Cumulative incidence was computed using competing risk models. Potential mediators included demographic and socioeconomic factors, cardiovascular risk factors, presence of coronary heart disease, and electrocardiographic parameters as time-varying factors., Results: The mean (SD) age was 53.6 (5.8) years for blacks and 54.4 (5.7) years for whites. During 27.4 years of follow-up, 215 blacks and 332 whites experienced SCD. The lifetime cumulative incidence of SCD at age 85 years was 9.6, 6.6, 6.5, and 2.3% for black men, black women, white men, and white women, respectively. The sex-adjusted hazard ratio for SCD comparing blacks with whites was 2.12 (95% CI, 1.79-2.51). The association was attenuated but still statistically significant in fully adjusted models (hazard ratio, 1.38; 95% CI, 1.11-1.71). In mediation analysis, known factors explained 65.3% (95% CI 37.9-92.8%) of the excess risk of SCD in blacks in comparison with whites. The single most important factor explaining this difference was income (50.5%), followed by education (19.1%), hypertension (22.1%), and diabetes mellitus (19.6%). Racial differences were evident in both genders but stronger in women than in men., Conclusions: Blacks had a much higher risk for SCD in comparison with whites, particularly among women. Income, education, and traditional risk factors explained ≈65% of the race difference in SCD. The high burden of SCD and the racial-gender disparities observed in our study represent a major public health and clinical problem.

Aim: To investigate the effect of selenium supplementation at different dose levels on changes in HbA1c after 6 months and 2 years in a population of low selenium status., Materials and Methods: The Denmark PRECISE study was a single-centre, randomized, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. In total, 491 volunteers aged 60 to 74 years were randomly assigned to treatment with 100, 200 or 300 μg selenium/day as selenium-enriched yeast or placebo-yeast. HbA1c measurements were available for 489 participants at baseline, 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat., Results: The mean (SD) age, plasma-selenium concentration, and blood HbA1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6-month intervention period, mean HbA1c (95% CI) decreased by 1.5 (-2.8 to -0.2) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (-2.0 to 0.6) mmol/mol for the 200 and 300 μg/d groups compared with placebo (P = 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA1c had decreased significantly in all treatment groups, with no difference between active treatment and placebo., Conclusions: Selenium supplementation in an elderly European population of low selenium status did not significantly affect HbA1c levels after 2 years. Our findings corroborate a possible U-shaped response of selenium supplementation on glucose metabolism., (© 2018 John Wiley & Sons Ltd.)

Background and Objectives: Nursing or care home characteristics may have a long-term impact on the residents' mortality risks that has not been studied previously. The study's main objective was to assess the association between facility ownership and long-term, all-cause mortality., Research Design and Methods: We conducted a mortality follow-up study on a cohort of 611 nursing-home residents in the city Madrid, Spain, from their 1998-1999 baseline interviews up to September 2013. Residents lived in three types of facilities: public, subsidized and private, which were also sub-classified according to size (number of beds). Residents' information was collected by interviewing the residents themselves, their caregivers and facility physicians. We used time-to-event multivariable models and inverse probability weighting to estimate standardized mortality risk differences., Results: After a 3728 person-year follow-up (median/maximum of 4.8/15.2 years), 519 participants had died. In fully-adjusted models, the standardized mortality risk difference at 5 years of follow-up between medium-sized private facilities and large-sized public facilities was -18.9% (95% confidence interval [CI]: -33.4 to -4.5%), with a median survival (95% CI) of 3.6 (0.5 to 6.8) additional years. The fully-standardized 5-year mortality difference (95% CIs) between for-profit private facilities and not-for-profit public institutions was -15.1% (-31.1% to 0.9%), and the fully-standardized median survival difference (95% CIs) was 3.0 (-1.7 to 7.7) years., Discussion and Implications: These results are compatible with an association between factors related with the ownership of facilities and the long-term mortality risk of their residents. One of these factors, the facility size, could partly explain this association., Competing Interests: The authors have declared that no competing interests exist.

Background: The effect of chronic hepatitis B virus (HBV) infection on the risk of chronic kidney disease (CKD) is controversial. We examined the prospective association between hepatitis B surface antigen (HBsAg) serology status and incident CKD in a large cohort of men and women., Methods: Cohort study of 299,913 adults free of CKD at baseline who underwent health screening exams between January 2002 and December 2016 in South Korea. Incident CKD was defined as the development of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m 2 and/or proteinuria., Results: Over 1,673,701 person-years of follow-up, we observed 13,924 incident cases of CKD (3225 cases of eGFR < 60 ml/min/1.73m 2 and 11,072 cases of proteinuria). In fully adjusted models comparing positive to negative HBsAg participants, the hazard ratio (HR, 95% confidence interval) for incident CKD was 1.11 (1.03-1.21; P = 0.01). The corresponding HR for incident proteinuria and for eGFR < 60 ml/min/1.73m 2 were 1.23 (1.12-1.35; P <  0.001) and 0.89 (0.73-1.07; P = 0.21), respectively. The associations were similar across categories of liver enzyme levels at baseline., Conclusion: In this large cohort, HBsAg positive serology was associated with higher risk of incident CKD, and we provide novel evidence that this association was due to a higher incidence of proteinuria in HBsAg positive participants. Our study adds to the growing body of evidence suggesting that chronic HBV infection may be a contributor to the increasing incidence of CKD.

Background: Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ~ 125 µg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained concentrations higher than this are beneficial, or indeed detrimental, is unknown., Objective: In a population of relatively low selenium status, we aimed to determine the effect on mortality of long-term selenium supplementation at different dose levels., Design: The Denmark PRECISE study was a single-centre, randomised, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. Participants were 491 male and female volunteers aged 60-74 years, recruited at Odense University Hospital, Denmark. The trial was initially designed as a 6-month pilot study, but supplemental funding allowed for extension of the study and mortality assessment. Participants were randomly assigned to treatment with 100, 200, or 300 µg selenium/d as selenium-enriched-yeast or placebo-yeast for 5 years from randomization in 1998-1999 and were followed up for mortality for a further 10 years (through March 31, 2015)., Results: During 6871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat analysis, the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 µg selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46) over the entire follow-up period. The 100 and 200 µg/d doses showed non-significant decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects on cancer and cardiovascular mortality appeared similar., Conclusions: A 300 µg/d dose of selenium taken for 5 years in a country with moderately-low selenium status increased all-cause mortality 10 years later. While our study was not initially designed to evaluate mortality and the sample size was limited, our findings indicate that total selenium intake over 300 µg/d and high-dose selenium supplements should be avoided., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is often accompanied by multiple comorbidities, which are associated with an increased risk of exacerbation, a poor health-related quality of life, and high mortality. However, differences in comorbidity profile by race and ethnicity in COPD patients have not been fully elucidated., Methods: Participants aged 40 to 79 years with spirometry-defined COPD from the U.S. National Health and Nutrition Examination Survey (NHANES) (2007-2012) and from the Korea NHANES (2007-2015) were analyzed to compare the prevalence of comorbidities by race and ethnicity group. Comorbidities were defined using questionnaire data, physical exams, and laboratory tests., Results: Non-Hispanic Whites had the highest prevalence of dyslipidemia (65.5%), myocardial infarction (6.2%), osteoarthritis (40.1%), and osteoporosis (13.6%), while non-Hispanic Blacks had the highest prevalence of asthma (24.0%), hypertension (70.2%), stroke (7.3%), diabetes mellitus (DM) (23.3%), anemia (16.4%), and rheumatoid arthritis (11.9%). Compared to non-Hispanic Whites, non-Hispanic Blacks had a significantly higher prevalence of hypertension, stroke, DM, anemia, and rheumatoid arthritis after adjusting for age, sex, body mass index, and smoking status, while Hispanics had a significantly higher prevalence of DM and anemia, and Koreans had significantly lower prevalences of all comorbidities except stroke, DM, and anemia., Conclusions: COPD-related comorbidities varied significantly by race and ethnicity, and different strategies may be required for the optimal management of COPD and its comorbidities in different race and ethnicity groups.