Genetic diversity and cross-species transmissibility of bat-associated picornaviruses from Spain.

BACKGROUND: Emerging zoonotic diseases arise from cross-species transmission events between wild or domesticated animals and humans, with bats being one of the major reservoirs of zoonotic viruses. Viral metagenomics has led to the discovery of many viruses, but efforts have mainly been focused on some areas of the world and on certain viral families. METHODS: We set out to describe full-length genomes of new picorna-like viruses by collecting feces from hundreds of bats captured in different regions of Spain. Viral sequences were obtained by high-throughput Illumina sequencing and analyzed phylogenetically to classify them in the context of known viruses. Linear discriminant analysis (LDA) was performed to infer likely hosts based on genome composition. RESULTS: We found five complete or nearly complete genomes belonging to the family Picornaviridae, including a new species of the subfamily Ensavirinae. LDA suggested that these were true vertebrate viruses, rather than viruses from the bat diet. Some of these viruses were related to picornaviruses previously found in other bat species from distant geographical regions. We also found a calhevirus genome that most likely belongs to a proposed new family within the order Picornavirales, and for which genome composition analysis suggested a plant host. CONCLUSIONS: Our findings describe new picorna-like viral species and variants circulating in the Iberian Peninsula, illustrate the wide geographical distribution and interspecies transmissibility of picornaviruses, and suggest new hosts for calheviruses.

Comparing temporal changes and predictors of different types of mental health and socio-emotional wellbeing outcomes during COVID-19: an overlapping panel study of Spanish residents.

OBJECTIVES: Few panel studies have investigated how different types of mental health (MH) and socio-emotional wellbeing (SEW) outcomes have changed during the pandemic and if their burden has been equally distributed at the population-level. We aimed to examine temporal changes in these outcomes and their socio-ecological predictors using panel data. STUDY DESIGN: Longitudinal population-based survey with overlapping panels. METHODS: Analyses were carried out using four measurements of data from the Health and Social Survey (April 2020 to April 2021). Participants included Andalusian (Spanish) residents aged 16 years or older who participated in all four measurements (n = 1223). Seven dichotomous MH and SEW outcomes, as well as several socio-ecological predictors informed by a conceptual model, were examined in descriptive and multivariate analyses. RESULTS: Unadjusted odds of regular/bad perceived mental health (vs. excellent/very good/good), low socio-emotional wellbeing (vs. regular), low happiness (vs. regular), and feeling anxious (vs. not feeling anxious) decreased significantly from the first to the second measurement; however, in the fourth, low socio-emotional wellbeing significantly increased while low optimism decreased. Considering varying coefficients, objectively measured COVID-19 status and self-reported severity levels of the infection were statistically significant. Health status, social support, and household financial difficulty predicted higher adjusted odds in most of the seven assessed outcomes. CONCLUSIONS: Significant temporal variations in MH and SEW outcomes, along with their predictors, were observed during the first year of the pandemic. Some of these outcomes worsened as the pandemic progressed, whereas others improved. Findings also suggest that some individuals such as those experiencing poor health, limited social support, and low socioeconomic status are disproportionately impacted.

Colchicine and risk of hospitalization due to COVID-19: A population-based study.

Colchicine is one of the most widely studied and best-known anti-inflammatory treatments. This study aimed to assess the effect of colchicine on risk of hospitalization due to COVID-19; and its effect on susceptibility to and severity of the virus in patients with COVID-19. We carried out a population-based case-control study. The following groups were applied: (1) to assess risk of hospitalization, cases were patients with a positive PCR who were hospitalized due to COVID-19, and controls without a positive PCR; (2) to assess susceptibility to COVID-19, cases were patients with a positive PCR (hospitalized and non-hospitalized), and the same controls; (3) to determine potential severity, cases were subjects with COVID-19 hospitalized, and controls patients with COVID-19 nonhospitalised. Different electronic, linked, administrative health and clinical databases were used to extract data on sociodemographic variables, comorbidities, and medications dispensed. The study covered 3060 subjects with a positive PCR who were hospitalized, 26 757 with a positive PCR who were not hospitalized, and 56 785 healthy controls. After adjustment for sociodemographic variables, comorbidities and other treatments, colchicine did not modify risk of hospitalization due to COVID-19 (adjusted odd ratio [OR] 1.08 [95% confidence interval (CI) 0.76-1.53]), patients' susceptibility to contracting the disease (adjusted OR 1.12 (95% CI 0.91-1.37)) or the severity of the infection (adjusted OR 1.03 [95% CI 0.67-1.59]). Our results would neither support the prophylactic use of colchicine for prevention of the infection or hospitalization in any type of patient, nor justify the withdrawal of colchicine treatment due to a higher risk of contracting COVID-19.

Predictive capacity of FRAX in a spanish region with a hip fracture rate close to the national mean.

BACKGROUND: It is known that standardized incidence rates of hip fracture vary among older people in Spain. So far, the results published on the validation of the FRAX® tool in Spain have suggested that the major osteoporotic fractures (MOFs) risk in our country is underestimated. These studies have practically been based on Spanish cohorts evaluated in Catalonia, a higher hip fracture rate area. The purpose of this study is to analyse the ability of the FRAX® in a Spanish mid-fracture rate population. METHODS: Study design: Retrospective cohort study. MEASURES: MOFs: hip, humerus, wrist, spine fractures. Risk of fracture assessed by calculating odds ratios (ORs). Predictive capacity of FRAX® according to the osteoporotic fractures observed between 2009 and 2018 (ObsFr) to predicted by FRAX® without densitometry in 2009 (PredFr) ratio. RESULTS: 285 participants (156 women, 54.7%) with a mean ± SD of 61.5 ± 14 years. Twenty-four people sustained 27 fractures (15 MOFs). Significant ORs were observed for an age ≥ 65 (2.92; 95% CI, 1.07-7.96), female sex (3.18; 95% CI, 1.24-8.16), rheumatoid arthritis (0.62; 95% CI, 2.03-55.55), proton pump (2.71; 95% CI, 1.20-6.09) and serotonin reuptake (2.51; 95% CI, 1.02-6.16) inhibitors. The ObsFr/PredFr ratio in women were 1.12 (95% CI, 0.95-1.29) for MOFs and 0.47 (95% CI, 0-0.94) for hip fractures. Men had a ratio of 0.57 (95% CI, 0.01-1.14) for MOF, no hip fractures were observed. The ratios for the overall group were 1.29 (95% CI, 1.12-1.48) for MOFs and 0.70 (95% CI, 0.22-1.17) for hip fractures. CONCLUSIONS: FRAX® accurately predicted MOFs in women population with a hip fracture incidence rate close to the national mean compared to previous studies conducted in higher incidence regions in Spain.

Placebo Response and Its Predictors in Attention Deficit Hyperactivity Disorder: A Meta-Analysis and Comparison of Meta-Regression and MetaForest.

BACKGROUND: High placebo response in attention deficit hyperactivity disorder (ADHD) can reduce medication-placebo differences, jeopardizing the development of new medicines. This research aims to (1) determine placebo response in ADHD, (2) compare the accuracy of meta-regression and MetaForest in predicting placebo response, and (3) determine the covariates associated with placebo response. METHODS: A systematic review with meta-analysis of randomized, placebo-controlled clinical trial investigating pharmacological interventions for ADHD was performed. Placebo response was defined as the change from baseline in ADHD symptom severity assessed according to the 18-item, clinician-rated, DSM-based rating scale. The effect of study design-, intervention-, and patient-related covariates in predicting placebo response was studied by means of meta-regression and MetaForest. RESULTS: Ninety-four studies including 6614 patients randomized to placebo were analyzed. Overall, placebo response was -8.9 points, representing a 23.1% reduction in the severity of ADHD symptoms. Cross-validated accuracy metrics for meta-regression were R2 = 0.0012 and root mean squared error = 3.3219 for meta-regression and 0.0382 and 3.2599 for MetaForest. Placebo response among ADHD patients increased by 63% between 2001 and 2020 and was larger in the United States than in other regions of the world. CONCLUSIONS: Strong placebo response was found in ADHD patients. Both meta-regression and MetaForest showed poor performance in predicting placebo response. ADHD symptom improvement with placebo has markedly increased over the last 2 decades and is greater in the United States than the rest of the world.

Compositional and Bayesian inference analysis of the concentrations of air pollutants in Catalonia, Spain.

While most countries have networks of stations for monitoring pollutant concentrations, they do not cover the whole territory continuously. Therefore, to be able to carry out a spatial and temporal study, the predictions for air pollution from unmeasured sites and time periods need to be used. The objective of this study is to predict the air pollutant concentrations of PM10, O3, NO2, SO2 and CO in sites throughout Catalonia (Spain) and time periods without a monitoring station. Compositional data (CoDa) studies the relative importance of pollutants. A novel feature in this article is combining CoDa with an indicator of total pollution. Predictions are then made using a combination of spatio-temporal models and the Bayesian Laplace Integrated Approach (INLA) inference method. The most relevant results obtained indicate that the log-ratio between NO2 and O3 has the highest variance and the best predictive accuracy in time and space. Total pollution levels are second in variance but have low spatial predictive accuracy. Third in variance is the low temporal accuracy found in the log-ratio between SO2 and the remaining pollutants. Globally, the combination of CoDa and the INLA method is suitable for making effective spatio-temporal predictions of air pollutants.

Analysis of the geographic pattern of the police reports for domestic violence in Girona (Spain).

BACKGROUND: There are many studies that address the issue of gender-based violence, but few analyse the police-reported cases. It is as important to analyse the temporal and geographic distribution of these incidents as it is the sociodemographic profile of the accuser. To this effect, the present study aims to analyse the sociodemographic profile of the victims of the particular case of domestic violence that report the incident to the police and to evaluate the spatial-temporal distribution of these reports. METHODS: Using the data from a database containing the police-reported incidents of domestic violence in Girona in the period 2012-2018, the risk of a police-reported incident was estimated by adjusting the two-part Hurdle model. RESULTS: The risk of reporting incidents of domestic violence to the police is higher in the less deprived areas of the city, and the spatial distribution of these police reports corroborate this finding. Nevertheless, those areas with the greatest socio-economic deprivation were also the ones where there were less police reports filed. Also the prediction of less police reports in the census tract with the highest percentage of the population with an insufficient educational level coincides with the largest number of police reports made by women with a medium and university level education (56.1%) compared with 9.5% of police reports made by women with insufficient schooling. CONCLUSIONS: These results can be useful for social protection services to design policies specifically aimed at women residing in those areas with the highest risk. Moreover, the use of spatial statistical techniques together with geographic information systems tools is a good strategy to analyse domestic violence and other types of offences because they not only allow to graphically identify the spatial distribution, but it is also a good tool to identify problems related to this type of offence.

Past-season, pre-season and in-season risk assessment of groin problems in male football players: a prospective full-season study.

OBJECTIVE: We assessed past-season, pre-season and in-season risk factors to investigate their association with an in-season groin problem in male amateur football players. METHODS: Past-season groin-pain information and pre-season short-lever and long-lever adductor squeeze strength were obtained at baseline, together with anthropometrics (weight, lower limb lever length) and player age. In-season hip-related and groin-related sporting function was monitored every 4 weeks using the Sports and Recreation (Sport) subscale from the Hip And Groin Outcome Score questionnaire (HAGOS (Sport)). Groin problems, including time-loss groin injuries and groin pain irrespective of time loss, were collected over a 39-week competitive in-season. We estimated relative risk (RR), and 95% credibility interval (ICr) from logistic regressions fitted in a Bayesian framework. RESULTS: Players (n=245) suffering from groin pain during the past-season had 2.4 times higher risk of experiencing a groin problem in the new season (2.40 RR; 95% ICr 1.5 to 3.7). This risk was reduced by 35% (0.65 RR; 95% ICr 0.42 to 0.99) per unit (N·m/kg) increase in the long-lever adductor squeeze test. Player age, short-lever squeeze test and the HAGOS (Sport) scores were not associated with the risk of a groin problem. CONCLUSIONS: Past-season groin pain increased the risk of a groin problem in the new in-season. This risk was reduced by higher pre-season long-lever adductor squeeze strength. Past-season groin-pain information and long-lever adductor squeeze strength can be quickly obtained during pre-season to identify players with an elevated risk of in-season groin problems. This may be key to reduce these problems in the new season.

Inflammatory potential of diet and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition.

INTRODUCTION: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study. METHODS: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders. RESULTS: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13). CONCLUSIONS: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings.

Effects of long-term exposure to air pollutants on the spatial spread of COVID-19 in Catalonia, Spain.

BACKGROUND: The risk of infection and death by COVID-19 could be associated with a heterogeneous distribution at a small area level of environmental, socioeconomic and demographic factors. Our objective was to investigate, at a small area level, whether long-term exposure to air pollutants increased the risk of COVID-19 incidence and death in Catalonia, Spain, controlling for socioeconomic and demographic factors. METHODS: We used a mixed longitudinal ecological design with the study population consisting of small areas in Catalonia for the period February 25 to May 16, 2020. We estimated Generalized Linear Mixed models in which we controlled for a wide range of observed and unobserved confounders as well as spatial and temporal dependence. RESULTS: We have found that long-term exposure to nitrogen dioxide (NO2) and, to a lesser extent, to coarse particles (PM10) have been independent predictors of the spatial spread of COVID-19. For every 1 µm/m3 above the mean the risk of a positive test case increased by 2.7% (95% credibility interval, ICr: 0.8%, 4.7%) for NO2 and 3.0% (95% ICr: -1.4%,7.44%) for PM10. Regions with levels of NO2 exposure in the third and fourth quartile had 28.8% and 35.7% greater risk of a death, respectively, than regions located in the first two quartiles. CONCLUSION: Although it is possible that there are biological mechanisms that explain, at least partially, the association between long-term exposure to air pollutants and COVID-19, we hypothesize that the spatial spread of COVID-19 in Catalonia is attributed to the different ease with which some people, the hosts of the virus, have infected others. That facility depends on the heterogeneous distribution at a small area level of variables such as population density, poor housing and the mobility of its residents, for which exposure to pollutants has been a surrogate.

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from 10 European countries between 1991 and 2001. Adherence to the MD was estimated through the adapted relative MD (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow-up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma [HL], 2,606 non-HL and 395 lymphoma not otherwise specified) were identified. Overall, a 1-unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p-trend = 0.03) while a statistically nonsignificant inverse association between a high versus low arMED score and risk of lymphoma was observed (hazard ratio [HR]: 0.91 [95% CI 0.80; 1.03], p-trend = 0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N = 135), a suggestive inverse association was found for HL (HR 1-unit increase = 0.93 [95% CI: 0.86; 1.01], p-trend = 0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC but not by subtypes. Further large prospective studies are warranted to confirm these findings.

Correction to: Financial crisis and income-related inequalities in the universal provision of a public service: the case of healthcare in Spain.

Following publication of the original article [1], the autor reported 5 references should be indicated in Spanish. The correct references can be found below.

Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.

PURPOSE: To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials. METHODS: A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used. RESULTS: A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one. CONCLUSIONS: The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.

A randomized controlled trial for overweight and obesity in preschoolers: the More and Less Europe study - an intervention within the STOP project.

BACKGROUND: Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. METHODS/DESIGN: A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. DISCUSSION: This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT03800823; 11 Jan 2019.

Challenges in assessing the real incidence of chronic lymphocytic leukemia: 16 years of epidemiological data from the province of Girona, Spain.

Determining chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) incidence is challenging for two reasons: cancer registries tend to underreport CLL cases and its diagnostic criteria changed markedly in 2008. No studies have reported incidence rates dealing with both difficulties, and thus CLL/SLL burden in Europe is currently uncertain. Herein, we present accurate CLL/SLL incidence in a Spanish region during 1998-2013, using the population-based Girona Cancer Registry (GCR). We detected an 18.2% under-reporting of CLL/SLL cases when combining records from the GCR and additional information sources (i.e., records of flow cytometry laboratories, hospital registries and hematologists' databases). In addition, age-adjusted rates (using the 2013 European population) changed from 7.57 (95% CI 6.87; 8.30) in 1998-2008 to 6.35 (95% CI 5.51; 7.30) in 2009-2013. Overall, completeness of CLL/SLL data requires accurate diagnosis and reporting of cases. Revision of cancer registry operations to include CLL/SLL-specific surveillance is likely to ensure that the monitoring of this malignancy is entirely accurate.

Spatial Assessment of the Association between Long-Term Exposure to Environmental Factors and the Occurrence of Amyotrophic Lateral Sclerosis in Catalonia, Spain: A Population-Based Nested Case-Control Study.

BACKGROUND: It is believed that an interaction between genetic and non-genetic factors may be involved in the development of amyotrophic lateral sclerosis (ALS). With the exception of exposure to agricultural chemicals like pesticides, evidence of an association between environmental risk factors and ALS is inconsistent. Our objective here was to investigate the association between long-term exposure to environmental factors and the occurrence of ALS in Catalonia, Spain, and to provide evidence that spatial clusters of ALS related to these environmental factors exist. METHODS: We carried out a nested case-control study constructed from a retrospective population-based cohort, covering the entire region. Environmental variables were the explanatory variables of interest. We controlled for both observed and unobserved confounders. RESULTS: We have found some spatial clusters of ALS. The results from the multivariate model suggest that these clusters could be related to some of the environmental variables, in particular agricultural chemicals. In addition, in high-risk clusters, besides corresponding to agricultural areas, key road infrastructures with a high density of traffic are also located. CONCLUSION: Our results indicate that some environmental factors, in particular those associated with exposure to pesticides and air pollutants as a result of urban traffic, could be associated with the occurrence of ALS.

The association between exposure to environmental factors and the occurrence of attention-deficit/hyperactivity disorder (ADHD). A population-based retrospective cohort study.

BACKGROUND: A number of factors contribute to attention deficit hyperactivity disorder (ADHD) and although they are not fully known, the occurrence of ADHD seems to be a consequence of an interaction between multiple genetic and environmental factors. However, apart from pesticides, the evidence is inadequate and inconsistent as it differs not only in the population and time period analysed, but also in the type of study, the control of the confounding variables and the statistical methods used. In the latter case, the studies also differ in the adjustment of spatial and temporal variability. Our objective here, is to provide evidence on an association between environmental factors and ADHD. METHODS: In our study, we used a population-based retrospective cohort in which we matched cases and controls (children free of the disease) by sex and year of birth (n = 5193, 78.9% boys). The cases were children born between 1998 and 2012 and diagnosed with ADHD (n = 116). To evaluate whether there was a geographical pattern in the incidence of ADHD, we first represented the smoothed standardized incidence rates on a map of the region being studied. We then estimated the probability of being a case by using a generalized liner mixed model with a binomial link. As explanatory variables of interest, we included the following environmental variables: distance to agricultural areas, distance to roads (stratified into three categories according to traffic density and intensity), distance to petrol stations, distance to industrial estates, and land use. We control for both observed (individual and family specific variables and deprivation index) and unobserved confounders (in particular, individual and familial heterogeneity). In addition, we adjusted for spatial extra variability. RESULTS: We found a north-south pattern containing two clusters (one in the centre of the study region and another in the south) in relation to the risk of developing ADHD. The results from the multivariate model suggest that these clusters could be related to some of the environmental variables. Specifically, living within 100 m from an agricultural area or a residential street and/or living fewer than 300 m from a motorway, dual carriageway or one of the industrial estates analysed was associated (statistically significant) with an increased risk of ADHD. CONCLUSION: Our results indicate that some environmental factors could be associated with ADHD occurring, particularly those associated with exposure to pesticides, organochlorine compounds and air pollutants because of traffic.

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

Financial crisis and income-related inequalities in the universal provision of a public service: the case of healthcare in Spain.

BACKGROUND: The objective of this paper is to analyse whether the recent recession has altered health care utilisation patterns of different income groups in Spain. METHODS: Based on information concerning individuals 'income and health care use, along with health need indicators and demographic characteristics (provided by the Spanish National Health Surveys from 2006/07 and 2011/12), econometric models are estimated in two parts (mixed logistic regressions and truncated negative binominal regressions) for each of the public health services studied (family doctor appointments, appointments with specialists, hospitalisations, emergencies and prescription drug use). RESULTS: The results show that the principle of universal access to public health provision does not in fact prevent a financial crisis from affecting certain income groups more than others in their utilisation of public health services. CONCLUSIONS: Specifically, in relative terms the recession has been more detrimental to low-income groups in the cases of specialist appointments and hospitalisations, whereas it has worked to their advantage in the cases of emergency services and family doctor appointments.