Combination of toxicological and epidemiological approaches for estimating the health impact of atmospheric pollutants. A proof of concept for NO2.

BACKGROUND: Regular monitoring of the air pollutant nitrogen dioxide (NO2), an indicator for traffic-related emissions, is a priority in urban environments. The health impacts associated with NO2 exposure are the result of a combination of factors, including concentration, duration of exposure, and interactions with other pollutants. WHO has established air quality guidelines based on epidemiological studies. OBJECTIVE: This study develops a new concept "Health Impact Pathways (HIPs)" using adversity as a probabilistic indicator of health effects. For this purpose, it integrates available toxicological and epidemiological information, using Adverse Outcome Pathways (AOPs), in order to understand chemical-biological interactions and their consequences on health. METHODS: Literature review and meta-analysis of toxicological data supported by expert judgment were performed to establish: a) adversity pathways, b) quantitative criteria for scoring the observed toxicological effects (adversity indicators), c) NO2 exposure - adversity relationship for both long-term (1-36 months) and shortterm (1-7 days). The NO2 daily concentrations from January 2001 to December 2022, were obtained from Madrid city Air Quality network monitoring database. Adversity levels were compared with relative risk levels for all-cause and respiratory mortality estimated using linear equations from WHO 2021 guidelines. RESULTS: Non-linear relations were obtained for all long- and short-term NO2 related adversity indicators; for long-term effects, the best fitting was obtained with a modified Haber's law model with an exponential coefficient for the exposure time of 0.25. Estimations are presented for a set of case studies for Madrid city, covering temporal and spatial variability. A clear improvement trend along the two decades was observed, as well as high inter- and intra-station variability; the adversity indicators provided integrated information on the temporal and spatial evolution of population level risk. DISCUSSION: The proposed HIP conceptual approach offers promising advances for integrating experimental and epidemiological data. The next step is linking the concentration-adversity relationship with population health impacts through probability estimations, the preliminary estimations confirm the need for assessing independently different population groups.

Impact of the 2008 economic crisis on the burden of hepatitis B and C diseases in Southern European countries.

BACKGROUND: The economic crisis that began in 2008 has severely affected Southern (Greece, Italy, Portugal, Spain) Western European (SWE) countries of Western Europe (WE) and may have affected ongoing efforts to eliminate viral hepatitis. This study was conducted to investigate the impact of the economic crisis on the burden of HBV and HCV disease. METHODS: Global Burden of Diseases 2019 data were used to analyse the rates of epidemiological metrics of HBV and HCV acute and chronic infections in SWE and WE. Time series modelling was performed to quantify the impact of healthcare expenditure on the time trend of HBV and HCV disease burden in 2000-2019. RESULTS: Declining trends in incidence and prevalence rates of acute HBV (aHBV) and chronic HBV were observed in SWE and WE, with the pace of decline being slower in the post-austerity period (2010-2019) and mortality due to HBV stabilised in SWE. Acute HCV (aHCV) metrics and chronic HCV incidence and mortality showed a stable trend in SWE and WE, whereas the prevalence of chronic HCV showed an oscillating trend, decreasing in WE in 2010-2019 (p < 0.001). Liver cancer due to both hepatitis infections showed a stagnant burden over time. An inverse association was observed between health expenditure and metrics of both acute and chronic HBV and HCV. CONCLUSIONS: Epidemiological metrics for HBV and HCV showed a slower pace of decline in the post-austerity period with better improvement for HBV, a stabilisation of mortality and a stagnant burden for liver cancer due to both hepatitis infections. The economic crisis of 2008 had a negative impact on the burden of hepatitis B and C. Elimination of HBV and HCV by 2030 will be a major challenge in the SWE countries.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort.

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.

Exposure to residential traffic and trajectories of unhealthy ageing: results from a nationally-representative cohort of older adults.

BACKGROUND: Traffic exposure has been associated with biomarkers of increased biological ageing, age-related chronic morbidities, and increased respiratory, cardiovascular, and all-cause mortality. Whether it is associated with functional impairments and unhealthy ageing trajectories is unknown. METHODS: Nationally representative population-based cohort with 3,126 community-dwelling individuals aged ≥60 years who contributed 8,291 biannual visits over a 10 year period. Unhealthy ageing was estimated with a deficit accumulation index (DAI) based on the number and severity of 52 health deficits, including 22 objectively-measured impairments in physical and cognitive functioning. Differences in DAI at each follow-up across quintiles of residential traffic density (RTD) at 50 and 100 meters, and closest distance to a petrol station, were estimated using flexible marginal structural models with inverse probability of censoring weights. Models were adjusted for sociodemographic and time-varying lifestyle factors, social deprivation index at the census tract and residential exposure to natural spaces. RESULTS: At baseline, the mean (SD) age and DAI score of the participants were 69.0 (6.6) years and 17.02 (11.0) %, and 54.0% were women. The median (IQR) RTD at 50 and 100 meters were 77 (31-467) and 509 (182-1802) vehicles/day, and the mean (SD) distance to the nearest petrol station of 962 (1317) meters. The average increase in DAI (95%CI) for participants in quintiles Q2-Q5 (vs Q1) of RTD at 50 meters was of 1.51 (0.50, 2.53), 0.98 (-0.05, 2.01), 2.20 (1.18, 3.21) and 1.98 (0.90, 3.05), respectively. Consistent findings were observed at 100 meters. By domains, most of the deficits accumulated with increased RTD were of a functional nature, although RTD at 50 meters was also associated with worse self-reported health, increased vitality problems and higher incidence of chronic morbidities. Living closer to a petrol station was associated with a higher incidence of functional impairments and chronic morbidities. CONCLUSIONS: Exposure to nearby residential traffic is associated with accelerated trajectories of unhealthy ageing. Diminishing traffic pollution should become a priority intervention for adding healthy years to life in the old age.

Traffic Density Exposure, Oxidative Stress Biomarkers and Plasma Metabolomics in a Population-Based Sample: The Hortega Study.

Exposure to traffic-related air pollution (TRAP) generates oxidative stress, with downstream effects at the metabolic level. Human studies of traffic density and metabolomic markers, however, are rare. The main objective of this study was to evaluate the cross-sectional association between traffic density in the street of residence with oxidative stress and metabolomic profiles measured in a population-based sample from Spain. We also explored in silico the potential biological implications of the findings. Secondarily, we assessed the contribution of oxidative stress to the association between exposure to traffic density and variation in plasma metabolite levels. Traffic density was defined as the average daily traffic volume over an entire year within a buffer of 50 m around the participants' residence. Plasma metabolomic profiles and urine oxidative stress biomarkers were measured in samples from 1181 Hortega Study participants by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography, respectively. Traffic density was associated with 7 (out of 49) plasma metabolites, including amino acids, fatty acids, products of bacterial and energy metabolism and fluid balance metabolites. Regarding urine oxidative stress biomarkers, traffic associations were positive for GSSG/GSH% and negative for MDA. A total of 12 KEGG pathways were linked to traffic-related metabolites. In a protein network from genes included in over-represented pathways and 63 redox-related candidate genes, we observed relevant proteins from the glutathione cycle. GSSG/GSH% and MDA accounted for 14.6% and 12.2% of changes in isobutyrate and the CH2CH2CO fatty acid moiety, respectively, which is attributable to traffic exposure. At the population level, exposure to traffic density was associated with specific urine oxidative stress and plasma metabolites. Although our results support a role of oxidative stress as a biological intermediary of traffic-related metabolic alterations, with potential implications for the co-bacterial and lipid metabolism, additional mechanistic and prospective studies are needed to confirm our findings.

Epidemic Diffusion Network of Spain: A Mobility Model to Characterize the Transmission Routes of Disease.

Human mobility drives the geographical diffusion of infectious diseases at different scales, but few studies focus on mobility itself. Using publicly available data from Spain, we define a Mobility Matrix that captures constant flows between provinces by using a distance-like measure of effective distance to build a network model with the 52 provinces and 135 relevant edges. Madrid, Valladolid and Araba/Álaba are the most relevant nodes in terms of degree and strength. The shortest routes (most likely path between two points) between all provinces are calculated. A total of 7 mobility communities were found with a modularity of 63%, and a relationship was established with a cumulative incidence of COVID-19 in 14 days (CI14) during the study period. In conclusion, mobility patterns in Spain are governed by a small number of high-flow connections that remain constant in time and seem unaffected by seasonality or restrictions. Most of the travels happen within communities that do not completely represent political borders, and a wave-like spreading pattern with occasional long-distance jumps (small-world properties) can be identified. This information can be incorporated into preparedness and response plans targeting locations that are at risk of contagion preventively, underscoring the importance of coordination between administrations when addressing health emergencies.

Air Pollution and Birth Outcomes: Health Impact and Economic Value Assessment in Spain.

Air pollution is considered an ongoing major public health and environmental issue around the globe, affecting the most vulnerable, such as pregnant women and fetuses. The aim of this study is to estimate the health impact and economic value on birth outcomes, such as low birthweight (LBW), preterm birth (PTB), small for gestational age (SGA), attributable to a reduction of PM10 levels in Spain. Reduction based on four scenarios was implemented: fulfillment of WHO guidelines and EU limits, and an attributable reduction of 15% and 50% in annual PM10 levels. Retrospective study on 288,229 live-born singleton children born between 2009-2010, using data from Spain Birth Registry Statistics database, as well as mean PM10 mass concentrations. Our finding showed that a decrease in annual exposure to PM10 appears to be associated with a decrease in the annual cases of LBW, SGA and PTB, as well as a reduction in hospital cost attributed to been born with LBW. Improving pregnancy outcomes by reducing the number of LBW up to 5% per year, will result in an estimate associated monetary saving of 50,000 to 7,000,000 euros annually. This study agrees with previous literature and highlights the need to implement, and ensure compliance with, stricter policies that regulate the maximum exposure to outdoor PM permitted in Spain, contributing to decreased environmental health risk, especially negative birth outcomes.

Exploring Urban Green Spaces' Effect against Traffic Exposure on Childhood Leukaemia Incidence.

BACKGROUND: Several environmental factors seem to be involved in childhood leukaemia incidence. Traffic exposure could increase the risk while urban green spaces (UGS) exposure could reduce it. However, there is no evidence how these two factors interact on this infant pathology. OBJECTIVES: to evaluate how residential proximity to UGS could be an environmental protective factor against traffic exposure on childhood leukaemia incidence. METHODS: A population-based case control study was conducted across thirty Spanish regions during the period 2000-2018. It included 2526 incident cases and 15,156, individually matched by sex, year-of-birth, and place-of-residence. Using the geographical coordinates of the participants' home residences, a 500 m proxy for exposure to UGS was built. Annual average daily traffic (AADT) was estimated for all types of roads 100 m near the children's residence. Odds ratios (ORs) and 95% confidence intervals (95% CIs), UGS, traffic exposure, and their possible interactions were calculated for overall childhood leukaemia, and the acute lymphoblastic (ALL) and acute myeloblastic leukaemia (AML) subtypes, with adjustment for socio-demographic covariates. RESULTS: We found an increment of childhood leukaemia incidence related to traffic exposure, for every 100 AADT increase the incidence raised 1.1% (95% CI: 0.58-1.61%). UGS exposure showed an incidence reduction for the highest exposure level, Q5 (OR = 0.63; 95% CI = 0.54-0.72). Regression models with both traffic exposure and UGS exposure variables showed similar results but the interaction was not significant. CONCLUSIONS: Despite their opposite effects on childhood leukaemia incidence individually, our results do not suggest a possible interaction between both exposures. This is the first study about the interaction of these two environmental factors; consequently, it is necessary to continue taking into account more individualized data and other possible environmental risk factors involved.

Validity of Geolocation and Distance to Exposure Sources from Geographical Information Systems for Environmental Monitoring of Toxic Metal Exposures Based on Correlation with Biological Samples: a Systematic Review.

PURPOSE OF REVIEW: In epidemiologic studies, biomarkers are the best possible choice to assess individual exposure to toxic metals since they integrate all exposure sources. However, measuring biomarkers is not always feasible, given potential budgetary and time constraints or limited availability of samples. Alternatively, approximations to individual metal exposure obtained from geographic information systems (GIS) have become popular to evaluate diverse metal-related health outcomes. Our objective was to conduct a systematic review of epidemiological studies that evaluated the validity of GIS-based geolocation and distance to pollutant sources as an approximation of individual metal exposure based on correlation with biological samples. RECENT FINDINGS: We considered 11 toxic metals: lead (Pb), cadmium (Cd), antimony (Sb), aluminum (Al), arsenic (As), chromium (Cr), nickel (Ni), mercury (Hg), tungsten (W), uranium (U), and vanadium (V). The final review included 12 manuscripts which included seven metals (Pb, Cd, Al, As, Cr, Hg, and Ni). Many studies used geolocation of the individuals to compare exposed (industrial, urban, agricultural, or landfill sources) and unexposed areas and not so many studies used distance to a source. For all metals, except lead, there was more animal than human biosampling to conduct biological validation. We observed a trend towards higher levels of Cd, Cr, Hg, and Pb in biosamples collected closer to exposure sources, supporting that GIS-based proxies for these metals might approximate individual exposure. However, given the low number and heterogeneity of the retrieved studies, the accumulated evidence is, overall, not sufficient. Given the practical benefits and potential of modern GIS technologies, which allow environmental monitoring at a reasonable cost, additional validation studies that include human biosampling are needed to support the use of GIS-based individual exposure measures in epidemiologic studies.

Exposure to Traffic Density during Pregnancy and Birth Weight in a National Cohort, 2000-2017.

The variation on birth weight is associated with several outcomes early on in life and low birth weight (LBW) increases the risk of morbidity and mortality. Some environmental exposures during pregnancy, such as particulate matters and other traffic-related pollutants can have a significant effect on pregnant women and fetuses. The aim of this study is to estimate the effect of exposure to traffic density during pregnancy over birth weight in Spain, from 2000-2017. This was a retrospective, cross-sectional study using the information from Spain Birth Registry Statistics database. The traffic density was measured using the Annual average daily traffic. Multivariate linear regression models using birth weight and traffic density were performed, as well as a logistic regression model to estimated Odds ratios for LBW and GAM models to evaluate the non-linear effect. Our findings showed that increases in traffic density were associated with reduction of birth weight and increases of LBW risk. Moreover, exposure to high and very-high traffic-density during pregnancy were associated with reduction of birth weight and increase on LBW risk comparing with exposure to low number of cars trespassing the neighborhoods. The results of this study agree with previous literature and highlights the need of effective policies for reducing traffic density in residential neighborhoods of cities and towns.

Exploring Blue Spaces' Effects on Childhood Leukaemia Incidence: A Population-Based Case-Control Study in Spain.

BACKGROUND: Blue spaces have been a key part of human evolution, providing resources and helping economies develop. To date, no studies have been carried out to explore how they may be linked to paediatric oncological diseases. OBJECTIVES: To explore the possible relationship of residential proximity to natural and urban blue spaces on childhood leukaemia. METHODS: A population-based case-control study was conducted in four regions of Spain across the period 2000-2018. A total of 936 incident cases and 5616 controls were included, individually matched by sex, year of birth and place of residence. An exposure proxy with four distances (250 m, 500 m, 750 m, and 1 km) to blue spaces was built using the geographical coordinates of the participants' home residences. Odds ratios (ORs) and 95% confidence intervals (95%CIs) for blue-space exposure were calculated for overall childhood leukaemia, and the acute lymphoblastic (ALL) and acute myeloblastic leukaemia (AML) subtypes, with adjustment for socio-demographic and environmental covariates. RESULTS: A decrease in overall childhood leukaemia and ALL-subtype incidence was found as we came nearer to children's places of residence, showing, for the study as a whole, a reduced incidence at 250 m (odds ratio (OR) = 0.77; 95%CI = 0.60-0.97), 500 m (OR = 0.78; 95%CI = 0.65-0.93), 750 m (OR = 0.80; 95%CI = 0.69-0.93), and 1000 m (OR = 0.84; 95%CI = 0.72-0.97). AML model results showed an increasing incidence at closest to subjects' homes (OR at 250m = 1.06; 95%CI=0.63-1.71). CONCLUSIONS: Our results suggest a possible association between lower childhood leukaemia incidence and blue-space proximity. This study is a first approach to blue spaces' possible effects on childhood leukaemia incidence; consequently, it is necessary to continue studying these spaces-while taking into account more individualised data and other possible environmental risk factors.

Assessing the effect of non-pharmaceutical interventions on COVID-19 transmission in Spain, 30 August 2020 to 31 January 2021.

BackgroundAfter a national lockdown during the first wave of the COVID-19 pandemic in Spain, regional governments implemented different non-pharmaceutical interventions (NPIs) during the second wave.AimTo analyse which implemented NPIs significantly impacted effective reproduction number (Rt) in seven Spanish provinces during 30 August 2020-31 January 2021.MethodsWe coded each NPI and levels of stringency with a 'severity index' (SI) and computed a global SI (mean of SIs per six included interventions). We performed a Bayesian change point analysis on the Rt curve of each province to identify possible associations with global SI variations. We fitted and compared several generalised additive models using multimodel inference, to quantify the statistical effect on Rt of the global SI (stringency) and the individual SIs (separate effect of NPIs).ResultsThe global SI had a significant lowering effect on the Rt (mean: 0.16 ± 0.05 units for full stringency). Mandatory closing times for non-essential businesses, limited gatherings, and restricted outdoors seating capacities (negative) as well as curfews (positive) were the only NPIs with a significant effect. Regional mobility restrictions and limited indoors seating capacity showed no effect. Our results were consistent with a 1- to 3-week-delayed Rt as a response variable.ConclusionWhile response measures implemented during the second COVID-19 wave contributed substantially to a decreased reproduction number, the effectiveness of measures varied considerably. Our findings should be considered for future interventions, as social and economic consequences could be minimised by considering only measures proven effective.

Looking Towards 2030: Strengthening the Environmental Health in Childhood-Adolescent Cancer Survivor Programs.

Childhood and adolescent cancer survivors (CACS) are a high-risk population for non-communicable diseases and secondary carcinogenesis. The Environmental and Community Health Program for Longitudinal Follow-up of CACS in the region of Murcia, Spain, is an ongoing pioneering program that constitutes a model for social innovation. This study aims to present the program tools and protocol as a whole, as well as a profile of the incidence, survival, and spatiotemporal distribution of childhood cancer in the region of Murcia, Spain, using 822 sample cases of cancer diagnosed in children under 15 years of age (1998-2020). While the crude incidence rate across that entire period was 149.6 per 1 million, there was an increase over that time in the incidence. The areas with a higher standardized incidence ratio have shifted from the northwest (1998-2003) to the southeast (2016-2020) region. Overall, the ten-year survival rate for all tumor types was 80.1% over the entire period, increasing the five-year survival rate from 76.1 (1998-2003) to 85.5 (2014-2018). CACS living in areas with very poor outdoor air quality had lower survival rates. Furthermore, integrating environmental health into clinical practice could improve knowledge of the etiology and prognosis, as well as the outcomes of CACS. Finally, monitoring individual carbon footprints and creating healthier lifestyles, alongside healthier environments for CACS, could promote wellbeing, environmental awareness, and empowerment in order to attain Sustainable Development Goals for non-communicable diseases in this population.

Cadmium (Cd) and Lead (Pb) topsoil levels and incidence of childhood leukemias.

There are few well-established risk factors for childhood leukemias. While the frequency of childhood leukemias might be partially attributable to some diseases (accounting for a small fraction of cases) or ionizing radiation, the role of heavy metals has not been assessed. The objective of our study was to assess the potential association between levels of cadmium (Cd) and lead (PB) in soil and childhood leukemias incidence. We conducted a population-based case-control study of childhood leukaemia in Spain, covering 2897 incident cases gathered from the Spanish Registry of Childhood Tumours and including 14 Spanish Regions with a total population of 5,307,433 children (period 1996-2015). Cd and Pb bioavailable levels at every children's home address were estimated using data from the Geochemical Atlas of Spain. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (95%CIs); we included as covariates: sex, rurality, employment rate and socioeconomic status. Metal levels were analysed according to two definitions: as continuous variable assuming linearity and as categorical variables to explore a potentially nonlinear association (quantiles). Increases in both Cd and Pb topsoil levels were associated with increased probability of childhood leukemias incidence. The results for the models with the continuous variables showed that a unit increase on the topsoil level was associated with an OR of 1.11 for Cd (95%CI 1.00-1.24) and an OR of 1.10 for Pb (95%CI 0.99-1.21). Our study may point towards a possible link between residential Cd and Pb topsoil levels and the probability of childhood leukemias incidence. Residing in a location with the highest concentrations of these heavy metals compared to those locations with the lowest could increase the risk around a 20%, for both Cd and Pb.

Geographical Variability in Mortality in Urban Areas: A Joint Analysis of 16 Causes of Death.

The geographical distribution of mortality has frequently been studied. Nevertheless, those studies often consider isolated causes of death. In this work, we aim to study the geographical distribution of mortality in urban areas, in particular, in 26 Spanish cities. We perform an overall study of 16 causes of death, considering that their geographical patterns could be dependent and estimating the dependence between the causes of death. We study the deaths in these 26 cities during the period 1996-2015 at the census tract level. A multivariate disease mapping model is used in order to solve the potential small area estimation problems that these data could show. We find that most of the geographical patterns found show positive correlations. This suggests the existence of a transversal geographical pattern, common to most causes of deaths, which determines those patterns to a higher/lower extent depending on each disease. The causes of death that exhibit that underlying pattern in a more prominent manner are chronic obstructive pulmonary disease (COPD), lung cancer, and cirrhosis for men and cardiovascular diseases and dementias for women. Such findings are quite consistent for most of the cities in the study. The high positive correlation found between geographical patterns reflects the existence of both high and low-risk areas in urban settings, in general terms for nearly all the causes of death. Moreover, the high-risk areas found often coincide with neighborhoods known for their high deprivation. Our results suggest that dependence among causes of death is a key aspect to be taken into account when mapping mortality, at least in urban contexts.

Real time surveillance of COVID-19 space and time clusters during the summer 2020 in Spain.

BACKGROUND: On June 21st de-escalation measures and state-of-alarm ended in Spain after the COVID-19 first wave. New surveillance and control strategy was set up to detect emerging outbreaks. AIM: To detect and describe the evolution of COVID-19 clusters and cases during the 2020 summer in Spain. METHODS: A near-real time surveillance system to detect active clusters of COVID-19 was developed based on Kulldorf's prospective space-time scan statistic (STSS) to detect daily emerging active clusters. RESULTS: Analyses were performed daily during the summer 2020 (June 21st - August 31st) in Spain, showing an increase of active clusters and municipalities affected. Spread happened in the study period from a few, low-cases, regional-located clusters in June to a nationwide distribution of bigger clusters encompassing a higher average number of municipalities and total cases by end-August. CONCLUSION: STSS-based surveillance of COVID-19 can be of utility in a low-incidence scenario to help tackle emerging outbreaks that could potentially drive a widespread transmission. If that happens, spatial trends and disease distribution can be followed with this method. Finally, cluster aggregation in space and time, as observed in our results, could suggest the occurrence of community transmission.

Approximate Bayesian inference for multivariate point pattern analysis in disease mapping.

We present a novel approach for analysing multivariate case-control georeferenced data in a Bayesian disease mapping context using stochastic partial differential equations (SPDEs) and the integrated nested Laplace approximation (INLA) for model fitting. In particular, we propose smooth terms based on SPDE models to estimate the underlying spatial variation as well as risk associated to pollution sources. Log-Gaussian Cox processes are used to estimate the intensity of the cases and controls, to account for risk factors and include a term to measure spatial residual variation. Each intensity is modelled on a baseline spatial effect (estimated from both controls and cases), a disease-specific spatial term and the effects of some covariates. By fitting these models, the residual spatial terms can be easily compared to detect high-risk areas not explained by the covariates. Three different types of effects to model exposure to pollution sources are considered on the distance to the source: a fixed effect, a smooth term to model non-linear effects by means of a discrete random walk of order one and a Gaussian process in one dimension with a Matérn covariance function. Spatial terms are modelled using a Gaussian process in two dimensions with a Matérn covariance function and are approximated using an approach based on solving an SPDE through INLA. Finally, this new framework is applied to a dataset of three different types of cancer and a set of controls from Alcalá de Henares (Madrid, Spain). Covariates available include the distance to several polluting industries and socioeconomic indicators. Our findings point to a possible risk increase due to the proximity to some of these industries.

Environment, lifestyle behavior and health-related quality of life in childhood and adolescent cancer survivors of extracranial malignancies.

BACKGROUND: Childhood cancer is a chronic disease with high survival rates. Childhood cancer survivors (CCS) can still face health effects later in their lives. Health-related quality of life (HRQoL) and the factors that modify it allow CCS and their families to improve care in the long-term follow-up. This study aims to: (1) examine the differences in HRQoL between CCS of extracranial malignancies and a comparison group, and (2) explore the clinical, environmental and lifestyles factors implicated in the HRQoL of CCS. METHODS: In this cross-sectional study with a case vs. non-case comparison, the HRQoL of 117 CCS between 8 and 18 years old was compared with healthy non-cases paired by sex and age. The Pediatric Environmental History (PEHis) was applied to obtain information on sociodemographic, clinical, environmental and lifestyle factors. The PedsQL™ Generic Core Scales questionnaire was used to evaluate HRQoL. RESULTS: In the multivariate analysis among the CCS, the following variables were significantly associated with HRQoL: Poor outdoor air quality (Total, Psychosocial, Emotional, Social and School domains); household income (Total, Psychosocial and School domains); and the presence of late effects (Total, Physical, Psychosocial, and Social domains); regular contact with nature (Physical domain); and the daily hours of screen-time (Emotional domain). CCS present HRQoL results superior to the non-cases group in the physical domain (86.10 vs. 80.34; p=0.001), finding no differences in the other domains evaluated. CONCLUSIONS: An environmental and community health approach, such as PEHis, in CCS long-term programs promoting the creation of healthier environments and lifestyles contributes to improving their HRQoL and secondarily other chronic diseases.