Occupation as a risk factor of small cell lung cancer.

Small cell lung cancer (SCLC) comprises approximately 10% of all lung cancer cases. Tobacco is its main risk factor; however, occupation might play a role in this specific lung cancer subtype. The effect of occupation on SCLC risk has been hardly studied and therefore we aim to assess the role of occupation on the risk of SCLC. To do this, we designed a multicentric, hospital-based, case-control study. Cases consisted exclusively in SCLC patients and controls were recruited from patients having minor surgery at the participating hospitals. Face to face interviews emphasizing occupation and tobacco consumption were held and residential radon was also measured. Logistic regression models were adjusted with odds ratios with 95%CI as estimations of the effect. 423 cases and 905 controls were included. Smoking prevalence was higher in cases compared to controls. Those who worked in known-risk occupations for lung cancer showed an OR of 2.17 (95%CI 1.33; 3.52), with a similar risk when men were analysed separately. The results were adjusted by age, sex, smoking and indoor radon exposure. Those who worked in known-risk occupations and were moderate or heavy smokers had a SCLC risk of 12.19 (95%CI 5.68-26.38) compared with never or moderate smokers who had not worked in such occupations. Occupation is a relevant risk factor of SCLC, and it seems that its effect is boosted when tobacco smoking is present.

Residential Radon and Small Cell Lung Cancer. Final Results of the Small Cell Study.

INTRODUCTION: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study. METHODS: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. RESULTS: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. CONCLUSIONS: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure.

Radon, Tobacco Exposure and Non-Small Cell Lung Cancer Risk Related to BER and NER Genetic Polymorphisms.

INTRODUCTION: Tobacco consumption and radon exposure are considered the first and second most common causes of lung cancer, respectively. The aim of this study was to analyze both whether selected genetic polymorphisms in loci that are in DNA repair pathways, are related to non-small-cell lung cancer (NSCLC) and whether they may modulate the association between residential radon exposure and lung cancer in both smokers and never smokers. METHODS: A multicentre, hospital-based, case-control study with 826 cases and 1201 controls was designed in a radon-prone area. Genotyping was determined in whole blood and residential radon exposure was measured in participants' dwellings. RESULTS: Attending to tobacco exposure, the variant in the gene NBN (rs1805794) was associated with lung cancer in never smokers (OR 2.72; 95%1.44-5.2) and heavy smokers (OR 3.04; 95%CI 1.21-7.69). The polymorphism with the highest lung cancer association was OGG1 (rs125701), showing an OR of 8.04 (95%CI 1.64-58.29) for its homozygous variant genotype in heavy smokers. Attending to indoor radon exposure (>200Bq/m3), rs1452584, for its homozygous variant genotype, showed the highest association (OR 3.04 (95%CI 1.15-8.48). CONCLUSION: The genes analyzed seem to have no association with the fully adjusted model, but they might modulate lung cancer association when different categories of tobacco consumption are considered (i.e. heavy smokers). This association may similarly be elevated for those individuals having high indoor radon exposures, though at a minor extent.

Prescription of Potentially Inappropriate Medication in Older Inpatients of an Internal Medicine Ward: Concordance and Overlap Among the EU(7)-PIM List and Beers and STOPP Criteria.

Background: Age-related comorbidities prone older adults to polypharmacy and to an increased risk of potentially inappropriate medication (PIM) use. This work aims to analyze the concordance and overlap among the EU(7)-PIM list, 2019 Beers criteria, and Screening Tool of Older Person's Prescriptions (STOPP) version 2 criteria and also to analyze the prevalence of PIM. Methods: A retrospective cohort study was conducted on older inpatients of an internal medicine ward. Demographic, clinical, and pharmacological data were collected, during March 2020. After PIM identification by the EU(7)-PIM list, Beers criteria, and STOPP v2 criteria, the concordance and overlap between criteria were analyzed. A descriptive analysis was performed, and all the results with a p-value lower than 0.05 were considered statistically significant. Results: A total of 616 older patients were included in the study whose median age was 85 (Q1-Q3) (78-89) years. Most of the older patients were male (51.6%), and the median (Q1-Q3) number of days of hospitalization was 17 (13-22) days. According to the EU(7)-PIM list, Beers criteria, and STOPP criteria, 79.7, 92.0, and 76.5% of older adults, respectively, used at least one PIM. A poor concordance (<63.4%) among criteria was observed. An association between PIM and the number of prescribed medicines was found in all applied criteria. Moreover, an association between the number of PIMs and diagnoses of endocrine, nutritional, and metabolic diseases, mental, behavioral, and neurodevelopmental disorders, and circulatory system diseases and days of hospitalization was observed according to Beers criteria, and that with diseases of the circulatory system and musculoskeletal system and connective tissue was observed according to STOPP criteria. Conclusion: Despite the poor concordance between the EU(7)-PIM list, 2019 Beers, and STOPP v2 criteria, this work highlights the need for more studies in inpatients to develop strategies to facilitate the identification of PIM to decrease the high prevalence of PIM in hospitalized patients. The poor concordance among criteria also highlights the need to develop new tools adapting the existing criteria to medical ward inpatients.

Residential Radon and Small Cell Lung Cancer. Final Results of the Small Cell Study.

INTRODUCTION: Residential radon is considered the second cause of lung cancer and the first in never smokers. Nevertheless, there is little information regarding the association between elevated radon levels and small cell lung cancer (SCLC). We aimed to assess the effect of residential radon exposure on the risk of SCLC in general population through a multicentric case-control study. METHODS: A multicentric hospital-based case-control study was designed including 9 hospitals from Spain and Portugal, mostly including radon-prone areas. Indoor radon was measured using Solid State Nuclear Track Detectors at the Galician Radon Laboratory. RESULTS: A total of 375 cases and 902 controls were included, with 24.5% of cases being women. The median number of years living in the measured dwelling was higher than 25 years for both cases and controls. There was a statistically significant association for those exposed to concentrations higher than the EPA action level of 148Bq/m3, with an Odds Ratio of 2.08 (95%CI: 1.03-4.39) compared to those exposed to concentrations lower than 50Bq/m3. When using a dose-response model with 100Bq/m3 as a reference, it can be observed a linear effect for small cell lung cancer risk. Smokers exposed to higher radon concentrations pose a much higher risk of SCLC compared to smokers exposed to lower indoor radon concentrations. CONCLUSIONS: Radon exposure seems to increase the risk of small cell lung cancer with a linear dose-response pattern. Tobacco consumption may also produce an important effect modification for radon exposure.

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer.

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients.

Lung cancer risk and residential radon exposure: A pooling of case-control studies in northwestern Spain.

BACKGROUND: Through a pooled case-control study design, we have assessed the relationship between residential radon exposure and lung cancer risk. Other objectives of the study were to evaluate the different risk estimates for the non-small cell lung cancer histological types and to assess the effect modification of the radon exposure on lung cancer risk by tobacco consumption. METHODS: We collected individual data from various case-control studies performed in northwest Spain that investigated residential radon and lung cancer. Cases had a confirmed anatomopathological diagnosis of primary lung cancer and controls were selected because they were undergoing ambulatory evaluation or surgical procedures that were unrelated to tobacco use. Residential radon was measured using alpha track detectors. Results were analyzed using logistic regression. RESULTS: 3704 participants were enrrolled, 1842 cases and 1862 controls. Data show that lung cancer risk increases with radon exposure, finding a significant association of radon exposure with lung cancer at radon exposures above 50 Bq/m3. The estimated adjusted OR for individuals exposed to concentrations >200 Bq/m3 was 2.06 (95% CI: 1.61-2.64) compared with those exposed to ≤50 Bq/m3. Within a smoking category, lung cancer risk increases markedly as radon concentration increases, reaching an OR of 29.3 (95% CI: 15.4-55.7) for heavy smokers exposed to more than 200 Bq/m.3 CONCLUSIONS: This study confirms that residential radon exposure is a risk factor for lung cancer well below action levels established by international organizations. As expected, there is also an effect modification between radon exposure and tobacco consumption.

Lung cancer survival in never-smokers and exposure to residential radon: Results of the LCRINS study.

We aimed to evaluate lung cancer survival in never-smokers, both overall and specifically by sex, exposure to residential-radon, age, histological type, and diagnostic stage. We included lung cancer cases diagnosed in a multicentre, hospital-based, case-control-study of never-smoker patients, diagnosed from January-2011 to March-2015 (Lung Cancer Research In Never Smokers study). 369 never-smokers (79% women; median age 71 years; 80% adenocarcinoma; 66% stage IV) were included. Median overall survival, and at one, 3 and 5 years of diagnosis was 18.3 months, 61%, 32% and 22%, respectively. Higher median survival rates were obtained for: younger age, adenocarcinoma, actionable mutations, and earlier-stage at diagnosis. Higher indoor radon showed a higher risk of death in multivariate analysis. Median lung cancer survival in never-smokers seems higher than that in ever-smokers. Patients with actionable mutations have a significantly higher survival. Higher indoor-radon exposure has a negative effect on survival.

Tobacco consumption and premenstrual syndrome: A case-control study.

OBJECTIVE: To assess whether tobacco smoking is associated with Premenstrual Syndrome (PMS) and its most severe form, Premenstrual Dysphoric Disorder (PMDD). DESIGN: Case-control study with incident cases using the Spanish public healthcare system. SETTING: 3 major public hospitals and one family counseling and planning center. POPULATION: Women consulting for troubles related to menstruation and for other motives such as screening for uterine cancer, contraception counseling or desire for pregnancy. METHODS: Logistic regression. MAIN OUTCOME MEASURES: Odds Ratios of PMS and PMDD. RESULTS: 285 incident PMS cases and 285 age-matched controls on the one hand, and 88 incident PMDD cases and 176 controls on the other hand participated in the study. The odds of premenstrual disorders was higher in current smokers compared with never smokers: Odds Ratio (OR) = 1.78, 95% Confidence Interval (CI): 1.20-2.63 for PMS and OR = 2.92, 95%CI: 1.55-5.50 for PMDD. For PMS, women who smoke 1 to 5 cigarettes/day presented an OR = 2.82, 95%CI: 1.57-5.06 and those who smoke more than 15 cigarettes/day an OR = 2.52, 95%CI: 0.99-6.40. Compared to non-smokers, current and ex-smokers who smoked < 3 pack-years presented an OR = 1.79, 95%CI: 1.04-3.08 for PMS, and an OR = 3.06, 95%CI: 1.27-7.35 for PMDD. Smokers of 3 to 8 pack-years presented an OR = 2.34, 95%CI: 1.33-4.13 for PMS and OR = 3.56, 95%CI: 1.55-8.17 for PMDD. These results were confirmed by the exposure-effect curve obtained from a cubic spline model. CONCLUSIONS: This study shows that smokers are more likely to develop PMS and PMDD.

Lung cancer and residential radon in never-smokers: A pooling study in the Northwest of Spain.

BACKGROUND: Using a pooled case-control study design, including only never-smokers, we have assessed the association of residential radon exposure with the subsequent occurrence of lung cancer. We also investigated whether residential radon poses a different risk specifically for adenocarcinoma. METHODS: We pooled individual data from different case-control studies conducted in recent years in Northwestern Spain which investigated residential radon and lung cancer. All participants were never-smokers. Cases had a confirmed biopsy of primary lung cancer. Hospital controls were selected at pre-surgery units, presenting for non-complex surgical procedures. They were interviewed using a standardized instrument. Residential radon was measured using alpha track detectors at the Galician Radon Laboratory at the University of Santiago de Compostela. RESULTS: A total of 1415 individuals, 523 cases and 892 controls were included. We observed an odds ratio of 1.73 (95%CI: 1.27-2.35) for individuals exposed to ≥ 200 Bq/m3 compared with those exposed to ≤100 Bq/m3. Lung cancer risk for adenocarcinoma was 1.52 (95%CI: 1.14-2.02) using the same categories for radon exposure. CONCLUSIONS: Residential radon is a clear risk factor for lung cancer in never-smokers. Our data suggest that radon exposure is associated with all histological types of lung cancer and also with adenocarcinoma, which is currently the most frequent histological type for this disease.

Residential radon exposure and brain cancer: an ecological study in a radon prone area (Galicia, Spain).

We aimed to know if radon concentration is associated with municipal mortality due to brain cancer in Galicia, Spain. We designed an ecological study taking as study unit Galician municipalities. To be included, municipalities had to have at least three radon measurements. We correlated radon concentrations with municipal mortality due to these malignant tumors during the period 1999-2008. We calculated the relative risk of dying of brain cancers for each municipality and correlated this value with municipal radon concentration using Spearman's Rho. 251 municipalities were included, with close to 3,500 radon measurements and an average of 14 radon measurements at each municipality. We observed a significant correlation between residential radon with brain cancer mortality for males and females and the intensity of the correlation was higher for females. These results were reinforced when the analysis was restricted to municipalities with more than 5 radon measurements: Spearman's Rho 0.286 (p-value < 0.001) and Spearman's Rho 0.509 (p-value < 0.001) for males and females, respectively. These results suggest an association between residential radon and brain cancer mortality. More research using more robust epidemiological designs is needed to confirm these findings.

Bacteremia nosocomial asociada a catéter vascular central en unidades de cuidados intensivos en 2 hospitales en Galicia (España) / Bloodstream infections associated with central venous catheters in intensive careunits in 2 hospitals in Galicia (Spain)

Fundamento y objetivo: Las infecciones asociadas a la asistencia sanitaria suponen una parte sustancial de los efectos adversos que los pacientes sufren durante la atención médica. Las bacteremias asociadas a catéter vascular central (CVC) suponen una causa importante de estas infecciones. Los objetivos fueron determinar la tasa de incidencia de bacteremia asociada a CVC en unidades de cuidados intensivos y la identificación de los principales factores de riesgo involucrados en el desarrollo de bacteremia asociada a CVC. Sujetos y métodos: El estudio se llevó a cabo en 2 hospitales de Galicia (España) y se realizó un estudio de cohorte o incidencia y posteriormente, anidado en este, un subestudio de casos y controles. Se incluyeron a pacientes atendidos en unidades de cuidados intensivos de 2 hospitales (hospital A y hospital B) durante un período de 2 meses, de los años 2009, 2010 y 2011. Se calcularon las tasas de incidencia y los factores de riesgo asociados al desarrollo de bacteremia asociada a CVC. Resultados: Las tasas de incidencia encontradas fueron 3,21; 2,91 y 5,76 bacteremias por 1.000 días en riesgo para el hospital A para los años 2009, 2010 y 2011 respectivamente. Estas tasas fueron de 2,10; 0 y 4,74 bacteremias por 1.000 días en riesgo para el hospital B para los mismos años. Se identificaron como factores de riesgo, el estado de coma (OR = 3,72; IC95% 1,06-13,02) y el número de catéteres (OR = 1,90; IC95% 1,21-2,97). Conclusiones: Se observan tasas superiores al estándar recomendado en la mayoría de los períodos de estudio. Se debe prestar especial atención a los pacientes en coma y con varios catéteres, al presentar estos un riesgo mayor de desarrollo de bacteremias asociadas a CVC.

Background: Healthcare-associated infections lead to a high proportion of the adverse effects that patients experience during medical care. Among them, central-line associated bloodstreaminfections (CLABSIs) represent a significant proportion (14-52%). Objective: To calculate the incidence rates of CLABSI and to identify the risk factors for infection at intensive care units at 2 hospitals (hospital A and hospital B). Design: This study was conducted at two Galician hospitals (Spain) and was designed as an observational study that included patients attended in intensive care units from 2009 to 2011.We calculated incidence rates and risks related with intrinsic or extrinsic factors. Results: The incidence rates found at hospital A were 3.21, 2.91 and 5.76 bloodstream infections per 1,000 days at risk in 2009, 2010 and 2011, respectively, and at hospital B 2.10, 0 and4.74 bloodstream infections per 1,000 days at risk in those same years. The risk factors identified in the multivariate analysis were coma (OR = 3.72; 95% CI 1.06-13.02) and the number of catheters (OR = 1.90; 95% CI 1.21-2.97). Conclusion: The observed incidence rates are higher than the recommended standards. Intensive care unit staff should focus special attention on to patients with coma and with a high numbers of catheters.