Quantifying indoor radon levels and determinants in schools: a case study in the radon-prone area Galicia–Norte de Portugal Euroregion

Radon is a carcinogenic compound, and is particularly concerning in the education sector, where children and teachers may be exposed even longer than at home. Thus, this study intended to characterise radon in the indoor air of scholar environments in different provinces/districts of the Euroregion Galicia–Norte de Portugal. With a pioneering approach, this study evaluated the influence of specific factors/characteristics (location, type of management, construction material, season and floor within the building) and quantified their relative contribution to indoor radon levels. Radon was continuously monitored in 416 classrooms from school buildings located in urban and rural sites from different provinces/districts both in the regions of Galicia (A Coruña and Lugo provinces) and Portugal (Porto and Bragança districts), considering rooms for different age groups (from nursery schools to universities). Single and multivariate linear regression models were built considering the radon concentrations as the outcome variable and different room/building characteristics as predictor variables. Mean and median radon concentrations were 332 Bq·m−3 and 181 Bq·m−3, respectively. The radon concentrations observed are a public health concern, as almost 1/3 of the places monitored exceeded the reference limit value of the European legislation (300 Bq·m−3). Moreover, around 50 % of the indoor levels measured could be attributed to room/building characteristics: the building's location and the main construction material, as well as the occupants' age group, the floor within the building and the school's type of management (public/private). This study concluded that radon testing is needed in all school buildings and classrooms without exceptions. Thus, public administrations are urged to dedicate funds for testing, mitigation and public dissemination initiatives in schools. A special protocol for radon sampling in school buildings should also be developedThis work was financially supported by: LA/P/0045/2020 (ALiCE) and –(LEPABE) funded by national funds through FCT/MCTES (PIDDAC); competitive scholarship from Fundación Prevent (Beca I + D en PRL). PTBS Branco thanks the Portuguese Foundation for Science and Technology (FCT) for the financial support of his work contract through the Scientific Employment Stimulus – Individual Call – 2022.05461.CEECIND. The funding sources did not have any involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the article for publicationS

Clinical characteristics of chronic obstructive pulmonary disease in never-smokers: A systematic review

Introduction Chronic Obstructive Pulmonary Disease (COPD) is the third cause of death worldwide. While tobacco smoking is a key risk factor, COPD also occurs in never-smokers (NS). However, available evidence on risk factors, clinical characteristics, and natural history of the disease in NS is scarce. Here, we perform a systematic review of the literature to better describe the characteristics of COPD in NS. Methods We searched different databases following the PRISMA guidelines with explicit inclusion and exclusion criteria. A purpose-designed quality scale was applied to the studies included in the analysis. It was not possible to pool the results due to the high heterogeneity of the studies included. Results A total of 17 studies that met the selection criteria were included, albeit only 2 of them studied NS exclusively. The total number of participants in these studies were 57,146 subjects, 25,047 of whom were NS and 2,655 of the latter had NS-COPD. Compared to COPD in smokers, COPD in NS is more frequent in women and older ages, and is associated with a slightly higher prevalence of comorbidities. There are not enough studies to understand if COPD progression and clinical symptoms in NS are different to that of ever-smokers. Conclusions There is a significant knowledge gap on COPD in NS. Given that COPD in NS account for about a third of all COPD patients in the world, particularly in low-middle income countries, and the decrease in tobacco consumption in high income countries, understanding COPD in NS constitutes a public-health priorityThis work was supported by the Instituto de Salud Carlos III (ISCIII)/PI20/00476/Cofinanciado Unión Europea (UE-FEDER) and Grupo de referencia competitiva Xunta de GaliciaS

Small-area models to assess the geographical distribution of tobacco consumption by sex and age in Spain

Introduction: Complete and accurate data on smoking prevalence at a local level would enable health authorities to plan context-dependent smoking interventions. However, national health surveys do not generally provide direct estimates of smoking prevalence by sex and age groups at the subnational level. This study uses a small-area model-based methodology to obtain precise estimations of smoking prevalence by sex, age group and region, from a population-based survey. Methods: The areas targeted for analysis consisted of 180 groups based on a combination of sex, age group (15-34, 35-54, 55-64, 65-74, and ≥75 years), and Autonomous Region. Data on tobacco use came from the 2017 Spanish National Health Survey (2017 SNHS). In each of the 180 groups, we estimated the prevalence of smokers (S), ex-smokers (ExS) and never smokers (NS), as well as their coefficients of variation (CV), using a weighted ratio estimator (direct estimator) and a multinomial logistic model with random area effects. Results: When smoking prevalence was estimated using the small-area model, the precision of direct estimates improved; the CV of S and ExS decreased on average by 26%, and those of NS by 25%. The range of S prevalence was 11-46% in men and 4-37% in women, excluding the group aged ≥75 years. Conclusions: This study proposes a methodology for obtaining reliable estimates of smoking prevalence in groups or areas not covered in the survey design. The model applied is a good alternative for enhancing the precision of estimates at a detailed level, at a much lower cost than that involved in conducting large-scale surveys. This method could be easily integrated into routine data processing of population health surveys. Having such estimates directly after completing a health survey would help characterize the tobacco epidemic and/or any other risk factor more precisely.Instituto de Salud Carlos III (ISCIII), reference: PI19/00288, co-funded by the European Union. The sponsors did not participate in the study in any way.S

Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD's clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial.

Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting. We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader. We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions. ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823

Incidence, Clinical Characteristics, and Management of Psoriasis Induced by Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: A Nationwide Cohort Study.

Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained

DataSheet_2_Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease.csv

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD’s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.</p

DataSheet_1_Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease.pdf

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD’s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.</p