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The article comments on a report by J. D. Jelinić et al which focused on the statistical analysis for occupational exposure measurements published in the 2005 issue of "Croatia Medical Journal." It addressed the effectiveness of a close relationship between occupational medicine and industrial hygiene and the importance of mean exposure concentration in chronic toxicants as the best indicator of health outcomes in industrial occupations.

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted. The study has a before-and-after design to demonstrate the immediate impact of short-term interventions. Accordingly, the urine concentrations of glyphosate and its main biodegradation product (amino-methylphosphonic acid- AMPA) were measured before and the day after the single herbicide application in 17 male winegrowers. Urine samples were analyzed by high performance liquid chromatography coupled with a triple quadrupole mass spectrometer equipped with an electrospray ionization source. Glyphosate and AMPA were not detectable in pre-application urine samples (limit of quantification for glyphosate (LOQ G ) was 0.1 μg/L; limit of quantification for AMPA (LOQ AMPA ) was 0.5 μg/L). After application, glyphosate urinary levels were above LOQ G in all workers. The median, min, and max values were 2.30, 0.51, and 47.2 μg/L, respectively. The same values were found for 50 %, 5 % and 95 % percentiles. After assigning numerical values, such as one half the LOQ, to each of the non-detects, the "z" of Wilcoxon matched-pairs signed-ranks test was -3.62 (p = 0.0003), suggesting the pre-application values being significantly lower than the post-application urinary glyphosate concentration. A similar analysis was not feasible with AMPA urinary levels, which were detectable only in 3 workers, after application. 12 (71 %) workers were significantly exposed to glyphosate, but adherence to the adoption of personal protective equipment was good: 14 (82 %) workers used gloves, 13 (76 %) used overalls and 13 (76 %) facial masks. Our data show that glyphosate can be absorbed by the workers after a single application and confirms the usefulness of biomonitoring in exposed workers. Further studies are needed in larger working populations and with multiple glyphosate applications, as well as to evaluate the correlations of glyphosate urine levels with exposure questionnaire data, in order to assess the actual relevance of risk and protection factors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Aging represents a serious health and socioeconomic concern for our society. However, not all people age in the same way and air pollution has been shown to largely impact this process. We explored whether polycyclic aromatic hydrocarbons (PAHs), excellent fossil and wood burning tracers, accelerate biological aging detected by lymphocytes DNA methylation age (DNAmAge) and telomere length (TL), early nuclear DNA (nDNA) hallmarks of non-mitotic and mitotic cellular aging, and mitochondrial DNA copy number (mtDNAcn)., Methods: The study population consisted of 49 male noncurrent-smoking coke-oven workers and 44 matched controls. Occupational and environmental sources of PAH exposures were evaluated by structured questionnaire and internal dose (urinary 1-pyrenol). We estimated Occup&#95;PAHs, the product of 1-pyrenol and years of employment as coke-oven workers, and Environ&#95;PAHs, from multiple items (diet, indoor and outdoor). Biological aging was determined by DNAmAge, via pyrosequencing, and by TL and mtDNAcn, via quantitative polymerase chain reaction. Genomic instability markers in lymphocytes as target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei), gene-specific (p53, IL6 and HIC1) and global (Alu and LINE-1 repeats) DNA methylation, and genetic polymorphisms (GSTM1) were also evaluated in the latent variable nDNA&#95;changes. Structural equation modelling (SEM) analysis evaluated these multifaceted relationships., Results: In univariate analysis, biological aging was higher in coke-oven workers than controls as detected by higher percentage of subjects with biological age older than chronological age (AgeAcc ≥ 0, p = 0.007) and TL (p = 0.038), mtDNAcn was instead similar. Genomic instability, i.e., genotoxic and epigenetic alterations (LINE-1, p53 and Alu) and latent variable nDNA&#95;changes were higher in workers (p < 0.001). In SEM analysis, DNAmAge and TL were positively correlated with Occup&#95;PAHs (p < 0.0001). Instead, mtDNAcn is positively correlated with the latent variable nDNA&#95;changes (p < 0.0001) which is in turn triggered by Occup&#95;PAHs and Environ&#95;PAHs., Conclusions: Occupational PAHs exposure influences DNAmAge and TL, suggesting that PAHs target both non-mitotic and mitotic mechanisms and made coke-oven workers biologically older. Also, differences in mtDNAcn, which is modified through nDNA alterations, triggered by environmental and occupational PAH exposure, suggested a nuclear-mitochondrial core-axis of aging. By decreasing this risky gerontogenic exposure, biological aging and the consequent age-related diseases could be prevented., (© 2023. The Author(s).)

Background : COVID-19 is an asymptomatic condition in 40% of cases, and most symptomatic patients present with mild/moderate disease not requiring hospitalization or intensive care, especially during the Omicron wave, when the hospitalization rate was estimated to be 0.3%. The main port of entry for SARS-CoV-2 in the human body is the nasal cavity and the upper respiratory tract is affected since the early stages of the infection. Nasal irrigation or aerosol by isotonic or hypertonic saline solution is a traditional therapeutic approach for respiratory or nasal inflammation, also featured by prophylactic properties against upper respiratory infections. Methods : We conducted a prospective open-label controlled study to assess the superiority of an already existing medication (Tonimer Lab Panthexyl 800)-a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid-to reduce the viral shedding time in patients affected by asymptomatic or mild COVID-19. COVID-19 patients (N = 108) were split into two groups: a treatment arm (50 participants receiving standard of care plus nasal spray 3 times/day with Tonimer Lab Panthexyl 800) and a control arm (58 participants receiving standard of care but nasal spray with Tonimer Lab Panthexyl 800). The two groups, both testing initially positive for SARS-CoV-2 at real-time PCR (RT-PCR) on nasal swab, were followed up over time to assess the daily number of positive swab tests turning negative (study endpoint). Treatment effectiveness at various time lags since the first positive RT-PCR swab test was measured by rate of events in the experimental arm (EER) and in the control arm (CER), absolute risk increase (ARI) = (EER - CER), and number needed to treat (NNT) = (1/ARI). To investigate the endpoint, we used logistic and Cox regression models, expressing the result as odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (95%CI), respectively. The symptoms recorded with a modified COVID-Q questionnaire at both diagnosis and first negative antigenic swab test were compared in each group (treated versus controls) by exact symmetry test. Results : During the first five days of treatment, COVID-19 patients treated with Tonimer Lab Panthexyl 800 were more likely to become negative two days before controls. According to NNT, four subjects had to be treated for five days to achieve the study endpoint in one individual. The negativization rate in patients treated with Tonimer Lab Panthexyl 800 was significantly higher than patients' treated with standard of care alone (OR = 7.39, 95%CI: 1.83-29.8; HR = 6.12, 95%CI: 1.76-21.32). There was no evidence of side effects. Conclusions : Nasal spray with Tonimer Lab Panthexyl 800 was effective against SARS-CoV-2, stopping viral shedding in the treatment arm two days before the control group. This treatment should be continued for at least five days after the first positive swab test for SARS-CoV-2.

Health and safety of occupations entailing extensive skin contact with cinnabar-enriched sand in beaches of Friuli-Venezia Giulia (FVG) Region (North-eastern Italy) have been questioned for possible skin absorption of mercury (Hg). One hundred mg hair was collected from the occipital scalp of 50 male workers of Grado beach and 121 males from FVG general population. Factors associated with hair Hg content were investigated by multivariable logistic (considering Hg levels >1 vs ≤1 mg/kg) and log-transformed linear regression. The median hair concentration of Hg in male beach workers was 0.70 (IQR = 0.42; 1.34) mg/kg, lower than FVG general population's [1.29 (IQR = 0.87-2.06) mg/kg (p < 0.001)]. In both regression models the hair Hg increased with fish consumption, both among beach workers of Grado and FVG general population. The mean Hg levels in beach workers of Grado fell within an acceptable range, not requiring restrictions of their occupational activities., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Several reports suggested that acute kidney injury (AKI) is a relatively common occurrence in hospitalized COVID-19 patients, but its prevalence is inconsistently reported across different populations. Moreover, it is unknown whether AKI results from a direct infection of the kidney by SARS-CoV-2 or it is a consequence of the physiologic disturbances and therapies used to treat COVID-19. We aimed to estimate the prevalence of AKI since it varies by geographical settings, time periods, and populations studied and to investigate whether clinical information and laboratory findings collected at hospital admission might influence AKI incidence (and mortality) in a particular point in time during hospitalization for COVID-19., Methods: Herein we conducted a prospective longitudinal study investigating the prevalence of AKI and associated factors in 997 COVID-19 patients admitted to the Baqiyatallah general hospital of Tehran (Iran), collecting both clinical information and several dates (of: birth; hospital admission; AKI onset; ICU admission; hospital discharge; death). In order to examine how the clinical factors influenced AKI incidence and all-cause mortality during hospitalization, survival analysis using the Cox proportional-hazard models was adopted. Two separate multiple Cox regression models were fitted for each outcome (AKI and death)., Results: In this group of hospitalized COVID-19 patients, the prevalence of AKI was 28.5% and the mortality rate was 19.3%. AKI incidence was significantly enhanced by diabetes, hyperkalemia, higher levels of WBC count, and blood urea nitrogen (BUN). COVID-19 patients more likely to die over the course of their hospitalization were those presenting a joint association between ICU admission with either severe COVID-19 or even mild/moderate COVID-19, hypokalemia, and higher levels of BUN, WBC, and LDH measured at hospital admission. Diabetes and comorbidities did not increase the mortality risk among these hospitalized COVID-19 patients., Conclusions: Since the majority of patients developed AKI after ICU referral and 40% of them were admitted to ICU within 2 days since hospital admission, these patients may have been already in critical clinical conditions at admission, despite being affected by a mild/moderate form of COVID-19, suggesting the need of early monitoring of these patients for the onset of eventual systemic complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer AA declared a shared affiliation with the author SS to the handling editor at the time of review., (Copyright © 2022 Rostami, Mastrangelo, Einollahi, Nemati, Shafiee, Ebrahimi, Javanbakht, Saadat, Amini, Einollahi, Beyram and Cegolon.)

Vinyl-chloride monomer (VCM) is classified as a known carcinogen of the liver; for lung cancer, some results suggest a potential association with polyvinyl chloride (PVC) dust. We evaluated the relationship between lung cancer mortality and exposure as PVC baggers in a cohort of workers involved in VCM production and polymerization in Porto Marghera (Venice, Italy) considering both employment status and smoking habits. The workers were studied between 1973 and 2017. A subset of them (848 over 1658) was interviewed in the 2000s to collect information about smoking habits and alcohol consumption. Missing values were imputed by the Multivariate Imputation by Chained Equations (MICE) algorithm. We calculated standardized mortality ratios (SMR) and 95% confidence intervals (95% CIs) using regional reference rates by task (never, ever, and exclusively baggers) and by smoking habits. Mortality rate ratios (MRR), adjusted for age, calendar time, time since first exposure, and smoking habits, were obtained via Poisson regression using Rubin's rule to combine results from imputed datasets calculating the fraction of information due to non-response. Lung cancer mortality was lower than the regional reference in the whole cohort (lung cancer SMR = 0.92; 95% CI 0.75-1.11). PVC baggers showed a 50% increase in lung cancer mortality compared to regional rates (SMR = 1.48; 95% CI 0.82-2.68). In the cohort analyses, a doubled risk of lung cancer mortality among PVC baggers was confirmed after adjustment for smoking and time-dependent covariates (MRR = 1.99, 95% CI 1.04-3.81). Exposure to PVC dust resulting from activity as bagger in a polymerization PVC plant was associated with an increase in lung cancer mortality risk after adjustment for smoking habits.

Background: There is a risk of novel mutations of SARS-CoV-2 that may render COVID-19 resistant to most of the therapies, including antiviral drugs and vaccines. The evidence around the application of therapeutic plasma exchange (TPE) for the management of critically ill patients with COVID-19 is still provisional, and further investigations are needed to confirm its eventual beneficial effects., Aims: To assess the effect of TPE on the risk of mortality in patients with COVID-19-associated pneumonia, using three statistical procedures to rule out any threats to validity., Methods: We therefore carried out a single-centered retrospective observational non-placebo-controlled trial enrolling 73 inpatients from Baqiyatallah Hospital in Tehran (Iran) with the diagnosis of COVID-19-associated pneumonia confirmed by real-time polymerase chain reaction (RT-qPCR) on nasopharyngeal swabs and high-resolution computerized tomography chest scan. These patients were broken down into two groups: Group 1 (30 patients) receiving standard care (corticosteroids, ceftriaxone, azithromycin, pantoprazole, hydroxychloroquine, lopinavir/ritonavir), and Group 2 (43 patients) receiving the above regimen plus TPE (replacing 2 l of patients' plasma by a solution, 50% of normal plasma, and 50% of albumin at 5%) administered according to various time schedules. The follow-up time was 30 days and all-cause mortality was the endpoint., Results: Deaths were 6 (14%) in Group 2 and 14 (47%) in Group 1. However, different harmful risk factors prevailed among patients not receiving TPE rather than being equally split between the intervention and control group. We used an algorithm of structural equation modeling (of STATA) to summarize a large pool of potential confounders into a single score (called with the descriptive name "severity"). Disease severity was lower (Wilkinson rank-sum test p < 0.001) among patients with COVID-19 undergoing TPE (median: -2.82; range: -5.18; 7.96) as compared to those not receiving TPE (median: -1.35; range: -3.89; 8.84), confirming that treatment assignment involved a selection bias of patients according to the severity of COVID-19 at hospital admission. The adjustment for confounding was carried out using severity as the covariate in Cox regression models. The univariate hazard ratio (HR) of 0.68 (95%CI: 0.26; 1.80; p = 0.441) for TPE turned to 1.19 (95%CI: 0.43; 3.29; p = 0.741) after adjusting for severity., Conclusions: In this study sample, the lower mortality observed among patients receiving TPE was due to a lower severity of COVID-19 rather than the TPE effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cegolon, Einollahi, Panahi, Imanizadeh, Rezapour, Javanbakht, Nikpouraghdam, Abolghasemi and Mastrangelo.)

Background . The peak of sexually transmitted infections (STI) among adolescents/young adults suggests a low level of prevention. In order to assess whether the level of sexual health education (SHE), received by several channels, was effective at improving sexual behaviors, we conducted a survey among freshmen from four Italian universities. Methods . This observational cross-sectional study was carried out with an anonymous self-reported paper questionnaire, administered during teaching lectures to university freshmen of the northern (Padua, Bergamo, and Milan campuses) and southern (Palermo campus) parts of the country. Knowledge of STI (a linear numerical score), knowledge of STI prevention (dichotomous variable: yes vs. no) and previous STI occurrence (polytomous variable: "no"; "don't know"; "yes") were the outcomes in the statistical analysis. Results . The final number of freshmen surveyed was 4552 (97.9% response rate). The mean age of respondents was 21.4 ± 2.2 years and most of them (70.3%) were females. A total of 60% of students were in a stable romantic relationship. Only 28% respondents knew the most effective methods to prevent STI (i.e., condom and sexual abstinence), with a slightly higher prevalence of correct answers among females (31.3%) than males (25.8%). Students with history of STIs were 5.1%; they reported referring mostly to their general practitioner (GP) (38.1%) rather than discussing the problem with their partner (13.1%). At multivariable analysis, a significantly higher level of STI knowledge was observed in older students (25+ years of age), biomedical students, and those from a non-nuclear family; lower levels were found among students of the University of Palermo, and those who completed a vocational secondary school education. Those who had less knowledge about the most effective tools to prevent STIs included males, students from the University of Palermo, students registered with educational sciences, economics/political sciences, those of foreign nationality, and those whose fathers had lower educational levels. The risk of contracting a STI was significantly lower only in students not in a stable relationship (relative risk ratio, RRR = 0.67; 95% confidence interval, 95%CI = 0.48; 0.94), whereas such risk was significantly higher in students with higher STI knowledge (RRR = 1.15; 95%CI = 1.08; 1.22). Discussion and Conclusions . University freshmen investigated in this study had poor knowledge of STIs and their prevention. Unexpectedly, those with higher levels of knowledge had an increased risk of STIs. There have been no educational interventions-with good quality and long-term follow-ups-that increased the confidence that such SHE programs could have population level effects. A new high-quality study is therefore recommended to assess the effectiveness of an intervention generating behavioral changes; increasing only STI knowledge may not be sufficient.

Background: During the first wave of the COVID-19 pandemic (April to May 2020), 6,169 Polish and 939 Italian residents were surveyed with an online questionnaire investigating socio-demographic information and personality traits (first section) as well as attitudes, position, and efficacy perceptions on the impact of lockdown (second section) and various health protection measures enforced (third section). Methods: The "health protection attitude score" (HPAS), an endpoint obtained by pooling up the answers to questions of the third section of the survey tool, was investigated by multiple linear regression models, reporting regression coefficients (RC) with 95% confidence intervals (95% CI). Results: Concerns for business and health due to COVID-19 were associated with a positive attitude toward risk reduction rules. By contrast, male sex, concerns about the reliability of information available online on COVID-19 and its prevention, along with the feeling of not being enough informed on the transmissibility/prevention of SARS-CoV-2 were associated with a negative attitude toward risk mitigation measures. Discussion: A recent literature review identified two social patterns with different features in relation to their attitude toward health protection rules against the spread of COVID-19. Factors positively associated with adherence to public health guidelines were perceived threat of COVID-19, trust in government, female sex, and increasing age. Factors associated with decreased compliance were instead underestimation of the COVID-19 risk, limited knowledge of the pandemic, belief in conspiracy theories, and political conservativism. Very few studies have tested interventions to change attitudes or behaviors. Conclusion: To improve attitude and compliance toward risk reduction norms, a key intervention is fostering education and knowledge on COVID-19 health risk and prevention among the general population. However, information on COVID-19 epidemiology might be user-generated and contaminated by social media, which contributed to creating an infodemic around the disease. To prevent the negative impact of social media and to increase adherence to health protection, stronger content control by providers of social platforms is recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lorettu, Mastrangelo, Stepien, Grabowski, Meloni, Piu, Michalski, Waszak, Bellizzi and Cegolon.)

Background: The COVID-19 pandemic has imposed radical behavioral and social changes in the general population, significantly impacting the lives of individuals affected by disabilities. The aim of this study was to investigate the impact of COVID-19 on non-institutionalized subjects with sensorineural disabilities during the first COVID-19 wave in Italy., Methods: A 39-item online national survey was disseminated from 1 April 2020 to 31 June 2020 via social media throughout Italy to communities of individuals with proven severe sensorineural disabilities, affiliated to five national patient associations. The survey collected extensive information on the socio-demographic profile, health, everyday activities, and lifestyle of individuals with hearing and visual disabilities., Results: One hundred and sixty-three respondents with hearing (66.9%) and visual (33.1%) disabilities returned a usable questionnaire. The mean age of interviewees was 38.4 ± 20.2 years and 56.3% of them were females. Despite the vast majority of respondents (77.9%) perceiving their health status as unchanged (68.8% of interviewees with hearing deficits vs. 96.3% of those with visual impairments), about half the interviewees reported sleep disorders during lock-down, more likely those with visual deficits. Remote services were seemingly more effective for business than school activities. Furthermore, although just 18.8% of respondents rated remote rehabilitation care unsatisfactory, only 12.8% of interviewees felt supported by health and social services during the COVID-19 emergency. The vast majority of respondents were concerned about the future and the risk of SARS-CoV-2 contagion, particularly individuals with hearing impairments. Among the various risk mitigation measures, facemasks caused the greatest discomfort due to communication barriers, particularly among interviewees affected by hearing disabilities (92.2% vs. 45.7%). The most common request (46.5%) of respondents to reduce the inconveniences of the COVID-19 emergency country lock-down was improving the access to and delivery of health and social services for individuals with sensorineural disabilities (19.3%), followed by the use of transparent masks (17.5%)., Conclusions: Although health protection measures such as face masks and social distancing play a key role in preventing and controlling the spread of SARS-CoV-2, the unmet needs of disabled individuals should be carefully considered, especially those affected by sensory disabilities. Tailored access to health and social services for individuals affected by sensorineural disabilities should be implemented. Additional actions should include the use of to face masks to reduce communication barriers linked to hearing-impairment, as well as the improvement of remote services, especially distance learning at school.

Background: Cutaneous melanoma (CM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CM in several Italian centers, which are part of the Clinical National Melanoma Registry (CNMR)., Methods: Melanoma-specific survival and overall survival were calculated. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors., Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CM were included in the analysis with completed information about therapies. All types of immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by anti-PD-1 (HR=0.25), globally immunotherapy was significantly associated with improved survival, either for anti-CTLA4 monotherapy or combined with anti-PD-1 (HR=0.47 and 0.26, respectively) and BRAFI+MEKI (HR=0.62)., Conclusions: The nivolumab/pembrolizumab in combination of ipilimumab and the addition of ant-MEK to the BRAFi can be considered the best therapies to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment., Competing Interests: PA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Array, Merck Serono, Pierre-Fabre, Incyte, Medimmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Pfizer. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Array and travel support from MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Crispo, Corradin, Giulioni, Vecchiato, Del Fiore, Queirolo, Spagnolo, Vanella, Caracò, Tosti, Pennacchioli, Giudice, Nacchiero, Quaglino, Ribero, Giordano, Marussi, Barruscotti, Guida, De Giorgi, Occelli, Grosso, Cairo, Gatti, Massa, Atzori, Calvani, Fabrizio, Mastrangelo, Toffolutti, Celentano, Budroni, Gandini, Rossi, Testori, Palmieri, Ascierto and the Clinical National Melanoma Registry Study Group at the Italian Melanoma Intergroup.)

Background: Further knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE-DNA) adducts., Methods: The study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE-DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships., Results: Anti-B[a]PDE-DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE-DNA (p = 0.028 and p = 0.018), particularly in males (p = 0.006 and p = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE-DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003)., Conclusion: New findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases., Capsule: Everyday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.

Competing Interests: Competing interests: None declared.

Portal hypertension, liver fibrosis, and angiosarcoma of the liver (ASL) have been reported among workers exposed to vinyl chloride monomer (VCM) since the 1970s. In 2007, the International Agency for Research on Cancer established the association of VCM with hepatocellular carcinoma (HCC), though only on the basis of the few cases available. Thereafter, recent reports from the United States cohort and a European sub-cohort of vinyl chloride workers provided compelling evidence of a strong association between cumulative VCM exposure and HCC risk. Further areas of research include the risk of liver cancer at lower levels of exposure and different patterns of risk of ASL and HCC with the time since exposure. The evidence of interaction between VCM exposure and other known liver carcinogens such as alcohol and chronic viral infection provides clues for the health surveillance of exposed workers. Notably, also the risk of VCM-associated chronic liver disease is modulated by alcohol consumption, viral infection, and genetic polymorphism. A counter-intuitive finding from cohort studies of exposed workers is the lower mortality from liver cirrhosis with respect to the general population; this can be attributed to the healthy worker effect and to the selection of liver cancer as the cause of death in the presence of concomitant chronic liver disease. Studies designed to overcome these intricacies confirmed an association between cumulative VCM exposure and the risk of liver cirrhosis., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.

Background: Births by cesarean section (CS) usually require longer recovery time, and as a result women remain hospitalized longer following CS than vaginal delivery (VD). A number of strategies have been proposed to reduce avoidable health care costs associated with childbirth. Among these, the containment of length of hospital stay (LoS) has been identified as an important quality indicator of obstetric care and performance efficiency of maternity centres. Since improvement of obstetric care at hospital level needs quantitative evidence, we compared the maternity services of an Italian region on LoS post CS., Methods: We conducted a population-based study in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from all its 12 maternity centres (coded from A to K) during 2005-2015. We fitted a multivariable logistic regression using LoS as a binary outcome, higher/lower than the international early discharge (ED) cutoffs for CS (4 days), controlling for hospitals as well as several factors related to the clinical conditions of the mothers and the newborn, the obstetric history and socio-demographic background. Results were expressed as adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Population attributable risks (PARs) were also calculated as proportional variation of LoS>ED for each hospital in the ideal scenario of having the same performance as centre J (the reference) during calendar year 2015. Results were expressed as PAR with 95%CI. Differences in mean LoS were also investigated with a multivariable linear regression model including the same explanatory factors of the above multiple logistic regression. Results were expressed as adjusted regression coefficients (aRC) with 95%CI., Results: Although decreasing over the years (5.0 ± 1.7 days in 2005 vs. 4.4 ± 1.7 days in 2015), the pooled mean LoS in the whole FVG during these 11 years was still 4.7 ± 1.7 days, higher than respective international ED benchmark. The significant decreasing trend of LoS>ED over time in FVG (aOR = 0.89; 95%CI: 0.88; 0.90) was marginal as compared to the variability of LoS>ED observed among the various maternity services. Regardless it was expressed as aRC or aOR, LoS after CS was lowest in hospital C, highest in hospital D and intermediate in centres I, K, G, F, A, H, E, B and J (in descending order). The aOR of LoS being longer than ED ranged from 1.63 (95%CI:1.46; 1.81) in hospital B up to 32.09 (95%CI: 25.68; 40.10) in facility D. When hospitals were ranked by PAR the same pattern was found, even if restricting the analysis to low risk pregnancies., Conclusions: Although significantly decreasing over time, the mean LoS in FVG during 2005-2015 was 4.7 days, higher than the international threshold recommended for CS. There was substantial variability in LoS by facility centre, suggesting that internal organizational processes of single hospitals should be improved by enforcing standardized guidelines and using audits, economic incentives and penalties if need be., Competing Interests: The authors have declared that no competing interests exist.

Transcripts of human endogenous retrovirus K are expressed in most breast cancers (BCs). Yellow fever vaccine 17D (YFV) expresses a protein with a closely homologous epitope. Cross-reactive immunity could hypothetically inhibit BC growth at least in women aged around 50 years at diagnosis, in whom the prognosis of BC was found to be better than that in women younger or older. A cohort of 12 804 women who received YFV in the Veneto Region, Italy, was divided into two subcohorts according to age at vaccination and followed up through the Veneto Tumor Registry. The time since vaccination until cancer incidence was categorized (≤1.9; 2-3.9; 4-5.9; 6-7.9; 8-10.9; ≥11 years) and, using the lowest class as a reference, the incidence rate ratio for BC with a 95% confidence interval and P-value was estimated by Poisson regression in each time since vaccination class, adjusting for age and calendar period. In 3140 women vaccinated at 40-54 years of age, YFV administration resulted in a protective effect of long duration slowly fading over time with a U-shaped pattern of response. Overall, BC risk was reduced by about 50% (incidence rate ratio=0.46; 95% confidence interval=0.26-0.83; P=0.009) 2 years after vaccination. Cross-reactive antigens could not be the mechanism because no protection was observed in women vaccinated before 40 or after 54 years of age. BC cells in a microscopic stage of disease can be destroyed or severely damaged by YFV if BC is not very aggressive. To prove that treatment is truly effective, a placebo-controlled double-blind trial should be conducted.

Background : Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods : Within the framework of a hospital-based case ( n = 96)/control ( n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results : The SEM analysis indicates negative direct links ( p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk ( p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects ( p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link)., Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention., Competing Interests: The authors declare no conflict of interest.

Objectives: validation of codes of hospital discharge records (SDO) for identification of new cases of malignant testicular tumour in the Veneto Region (Northern Italy)., Design: record linkage between the regional archive of SDO and the archive of the Veneto Tumour Registry (VTR)., Setting and Participants: extraction of cases from SDO source with ICD-9-CM 186 code for diagnosis and 62.3-62.4 codes for surgical procedure, and from VTR database using ICD-O-3 C62 code for site and 9060-9062, 9064-9066, 9070, 9071, 9080-9083, 9085, 9100, 9101 codes for morphology, with 5th digit behaviour code equal to "/3". Comparison of the two sources in a classification table using VTR data as gold standard., Main Outcome Measures: positive predictive value and sensitivity of SDO, with 95% confidence interval (95%CI) based on binomial distribution., Results: from 2006 to 2008, in areas covered by the registry, SDO and VTR identified, respectively, 221 and 216 cases of testicular cancer. SDO procedure showed a sensitivity of 92% (95%CI 87%- 95%) and a positive predictive value of 90% (95%CI 85%-93%)., Conclusions: the SDO procedure can be considered an acceptable proxy for testis cancer incidence, thus allowing a wider spatiotemporal observation of the epidemiological trends.

Background: Literature suggests that more research is needed to clarify the effect of workplace inspections by governmental officers on injury rates. This paper aims to compare comprehensive and partial inspections in Italian manufacturing companies., Methods: Survival analysis was applied to the period free from injuries following inspection by means of the Kaplan-Meier method and of Cox models., Results: Kaplan-Meier curves show that, compared to companies with a partial inspection, companies which had a comprehensive inspection had a higher survival through the entire period. Adjusting for confounders, the Cox model confirms a significant preventive effect of comprehensive inspection for companies with 10-30 employees, but not for those with >30 employees., Conclusions: The results suggest that the effect on injuries is greater if all aspects of safety are addressed during the inspection instead of focusing on a single aspect. These findings are interesting because they can help in planning effective prevention activities., (© 2016 Wiley Periodicals, Inc.)

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer., (Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: to define an Italian national protocol of post-occupational health surveillance for asbestos workers according to effectiveness, appropriateness, saving, and social utility., Design: data for 1,071 former asbestos workers from several Italian Regions were collected and analysed. For these workers, a retrospective estimate of asbestos exposure was carried out. A cohort study of 1,588 asbestos workers recruited from 2000 onward during statutory health examinations in Veneto and followed-up for lung cancer mortality until December 2010 was executed. A literature search on methods of follow-up of asbestos workers (imaging, spirometry, and questionnaires) and diagnosis of non-malignant (asbestosis and pleural plaques) and malignant (lung cancer) asbestos disease was done. A consensus, i.e., a process of agreeing on one result among the participants, was made., Setting and Participants: 19 Italian Regions (North: Veneto, Emilia-Romagna, Lombardia, Piemonte, Valle d'Aosta, Autonomous Province of Trento, Autonomous Province of Bolzano, Friuli Venezia Giulia, Liguria; Centre:Toscana, Umbria; South and Islands: Calabria, Abruzzo, Puglia, Campania, Basilicata,Marche, Sicilia, Sardegna), Department of Occupational Medicine at Italian National Institute for Compensation ofWork-Related Diseases and Accidents (INAIL), and Department of Cardiac, Thoracic, and Vascular Sciences at University of Padova., Main Outcome Measures: analysis of current regional experiences on health surveillance; retrospective estimate of asbestos exposure; data collection and analysis of a cohort of asbestos workers; search of the relevant literature; final report with the consensus document., Results: the results obtained in each of the above areas of research, along with the relevant findings of the literature, were presented and discussed among the participants. The several phases of expression and evaluation of the participants' opinions were conducted according to an iterative method of investigation (Delphi method), which allows a progressive converging of different views into one shared result., Conclusion: based on all the above, a consensus has been reached on a proposal for an Italian national protocol of health surveillance for asbestos workers.

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci., (Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer., (Published by Oxford University Press 2014.)

Background: In a mesothelioma lawsuit, the Public Prosecutor commissioned an expert evidence on the legal accountability for the disease, because the patient experienced multiple exposures to asbestos in both occupational and environmental settings., Objectives: To collect information on asbestos exposure from all available sources and to quantify the contribution of each source of exposure as a percentage of the total risk., Methods: We retrieved information on jobs done and asbestos exposure from a work colleague and a database maintained by the National Institute for Insurance of Occupational Accidents/Diseases, respectively. Information on environmental exposure was searched through the scientific literature. The contribution of each source of exposure was quantified with a method of risk apportionment, taking into account time elapsed since first and last exposure, intensity and frequency of exposure and carcinogenic potency of asbestos fiber mix., Results: The subject worked in the maintenance of railway electrification system. The mechanical compression stress induced on the ballast during passage of trains released chrysotile (from fragmented stones) and crocidolite (through abrasive action of crushed gravel on the underbody of rolling stocks insulated with friable crocidolite). Despite the low cumulative exposure (about 2 ff×years/cc), 99% of the mesothelioma risk was attributable to the work done because of the high content of crocidolite of inhaled asbestos., Conclusions: The report of an uncommon source of occupational asbestos exposure and a scientifically based method to allocate mesothelioma risk among multiple exposure could help to recognize mesothelioma as occupational disease in the workers employed in maintenance of the railway electrification system under the Italian National Railways.

Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2422 bladder cancer cases and 5751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6911 cases and 11 814 controls of European descent. TaqMan genotyping of 13 promising single nucleotide polymorphisms with P < 1 × 10(-5) was pursued in a follow-up set of 801 cases and 1307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P = 4.53 × 10(-9)) and rs907611 on 11p15.5 (P = 4.11 × 10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P = 7.13 × 10(-7)) and rs4510656 on 6p22.3 (P = 6.98 × 10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.

Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The objectives of this study were to measure the incidence of sarcomas, including viscerally sited tumors that are not reported in cancer statistics, and to draw explanatory clues from a large and reliable sarcoma incidence data set., Methods: Cases of sarcomas regardless of primary site (except bone and joints) were collected during 2 years in 3 European regions totaling approximately 26,000,000 person-years. The sources used were pathology reports and hospital discharges forms. Diagnoses were reviewed by expert sarcoma pathologists and were classified according to 2002 World Health Organization criteria. Soft tissue sarcomas (STS) were considered those located in arms, legs, trunk, head, neck, and retroperitoneum; visceral sarcomas (VS) were considered those that arose in internal organs. Rates were age standardized using the European (ASR-E) and the USA standard population. The rate of coexistence of VS and STS was calculated by dividing the 2 corresponding ASRs., Results: There were 1558 sarcomas, 968 STS, and 590 VS. The ASRs-USA per 100,000 person-years was 5.12 × 10(5) among males and 4.58 × 10(5) among females for all sarcomas. For males and females, respectively, the ASR-E per 100,000 person-years was 3.58 × 10(5) and 2.55 × 10(5) , respectively, for STS; 1.47 × 10(5) and 1.97 × 10(5) , respectively, for VS; and 0.55 × 10(5) and 0.10 × 10(5) , respectively, for Kaposi sarcoma. The coexistence rate of VS and STS was 0.41 for males and 0.77 for females. For dermatofibrosarcoma (both sexes), uterine sarcoma, liposarcoma (females), and leiomyosarcoma, including or excluding the uterus (females), the age-specific rates depicted a curve with a rapid increasing trend until ages 40 to 50 years and little variation thereafter., Conclusions: Compared with the incidence of STS, VS incidence made up an additional 41% in males and 77% in females. Because the shape of age-specific curves for some histotypes was similar to that of breast cancer, the authors concluded that sex hormones (plus many chemicals that act as endocrine disruptors) may be involved in carcinogenesis. This evidence could pave the way to investigate alternative treatments and to explore etiology. Cancer 2012. © 2012 American Cancer Society., (Copyright © 2012 American Cancer Society.)

Background: Although the management of sarcoma is improving, non adherence to clinical practice guidelines (CPGs) remains high, mainly because of the low incidence of the disease and the variety of histological subtypes. Since little is known about the health economics of sarcoma, we undertook a cost-effectiveness analysis (within the CONnective TIssue CAncer NETwork, CONTICANET) comparing costs and outcomes when clinicians adhered to CPGs and when they did not., Methods: Patients studied had a histological diagnosis of sarcoma, were older than 15 years, and had been treated in the Rhône-Alpes region of France (in 2005/2006) or in the Veneto region of Italy (in 2007). Data collected retrospectively for the three years after diagnosis were used to determine relapse free survival and health costs (adopting the hospital's perspective and a microcosting approach). All costs were expressed in euros (€) at their 2009 value. A 4% annual discount rate was applied to both costs and effects. The incremental cost-effectiveness ratio (ICER) was expressed as cost per relapse-free year gained when management was compliant with CPGs compared with when it was not. To capture uncertainty surrounding ICER, a probabilistic sensitivity analysis was performed based on a non-parametric bootstrap method., Results: A total of 219 patients were included in the study. Compliance with CPGs was observed for 118 patients (54%). Average total costs reached 23,571 euros when treatment was in accordance with CPGs and 27,313 euros when it was not. In relation to relapse-free survival, compliance with CPGs strictly dominates non compliance, i.e. it is both less costly and more effective. Taking uncertainty into account, the probability that compliance with CPGs still strictly dominates was 75%., Conclusions: Our findings should encourage physicians to increase their compliance with CPGs and healthcare administrators to invest in the implementation of CPGs in the management of sarcoma.

Cytochrome P4501A2 (CYP1A2) is a key enzyme for activation of bladder carcinogens. Polymorphisms in the 5'-noncoding promoter region of CYP1A2 gene [mainly -2467T/delT(rs35694136) and -163C/A(rs762551)], are crucial in modifying CYP1A2 activity in smokers. Within the framework of a hospital-based case/control study, we investigated the relationship between CYP1A2 polymorphisms, occupational/environmental exposures and bladder cancer (BC) risk. The study population included 185 BC cases and 180 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). A case-only design was applied to study the interaction between CYP1A2 -2467T/delT (or -163C/A) and occupational and environmental factors. Multiple logistic regression showed a significantly increased risk among heavy smokers (> or =50 packyears; OR 5.6, 95% CI: 2.5-12.5) and heavy coffee drinkers (>5 cups/day; OR 3.1, 95% CI: 1.2-7.9). Exposure to AAs showed a significant trend of BC risk with increasing cumulative exposure (CE) (P = 0.04), with heavy smoking as possible confounder. A decreased risk was noted for large leaf vegetable consumption, with significant trend from <1/month to >3 times/week (P = 0.008). The case-only analysis showed an interaction between -2467T/delT and tobacco smoking >25 packyears (P = 0.04); no interaction was detected between such polymorphisms and coffee consumption, dietary habits and occupational exposure to AAs. No effects were shown with -163C/A genotype as well as no overall effect of CYP1A2 by itself on BC risk. This is the first study suggesting that CYP1A2 -2467T/delT modifies the effect of cigarette smoking on BC risk.

Background: Since previous studies have provided conflicting results, we investigated the relationship between the risk of benign asbestos-related diseases and different aspects of asbestos exposure in previous asbestos workers who underwent low-dose computed tomography (CT)., Methods: CT scans were carried out in 772 subjects. A questionnaire was employed to collect data on smoking habits and duration, peak and cumulative exposure, and time since first exposure to asbestos. Multiple logistic regression models with stepwise selection of variables were used to evaluate the associations., Results: Fourteen (1.8%) cases of asbestosis, 187 (24.2%) of pleural plaques (PP), and 50 (6.5%) of diffuse pleural thickening (DPT) were found. The significant risk factors were: cumulative exposure for asbestosis (P for trend = 0.004); time since first exposure (P for trend <0.001), and peak exposure (P for trend <0.001) for PP; and time since first exposure for DPT (P for trend = 0.024)., Conclusions: Parenchymal asbestosis and PP are associated with different aspects of asbestos exposure. DPT appears to be less specific for asbestos exposure.

Background: Low-dose computed tomography (CT) has been found to detect more Stage IA lung cancer than chest x-ray., Aims: To investigate whether lung cancer screening with CT was effective and acceptable in former asbestos workers., Methods: CT scanning was carried out following the protocol previously described in the literature. A questionnaire was used to assess cumulative asbestos exposure. An economic analysis was also performed. Informed consent was obtained from all patients., Results: A total of 1119 male asbestos workers (58% of invited) were examined, of whom 65% were smokers or ex-smokers. Mean age was 57.1 years with mean cumulative exposure to asbestos of 123 fibres/ml x years. Pleural plaques were found in 375 workers (32%), while 338 workers (29%) were included in the radiological follow-up, which led to 25 biopsies (13 of lung, 9 of pleura, 3 of both) and five screen-detected lung cancers (0.4%), one in Stage I. Incidence rate was 149 per 10(5), equal to that in the male general population of similar age. The expenses for diagnosis were 1014 and 244962 Euro per screened subject and screen-detected lung cancer case, respectively., Conclusions: Screening adherence and frequency of detection were low, while costs and radiation dose were high. In spite of a high cumulative asbestos exposure, lung cancer risk was not increased relative to the general population. The screening programme was not felt to be cost-effective from the perspective of the government as a third-party funding agency.

There is conflicting evidence on the level of anesthetics that impairs neurobehavioral performance, leading to differences in exposure standards (25 or 50 ppm for N(2)O). Thirty-eight operating room nurses and 23 unexposed nurses were asked to provide information on confounding variables: age, gender, years of schooling, alcohol and coffee consumption, smoking, length of work, symptoms (Euroquest) and results of Block Design test. Afterward, all workers were repeatedly examined (on Monday and Friday of a working week, before and after workshift) for stress and arousal (Mood Scale) and complex reaction times (Color Word Vigilance, CWV), the latter being the outcome. Individual exposure was assessed through urinary end-shift concentrations of nitrous oxide (N(2)O) and isoflurane. According to the highest value of urinary excretion of N(2)O in the week, exposed workers were subdivided in three groups (<13; > or =13 and <27; and > or = 27 microg/l). The values of 13 and 27 microg/l correspond to environmental concentrations of 25 and 50 ppm, respectively. In order to take into account the pre-existing abilities of exposed and reference workers, and investigate the neurobehavioral changes over time, longitudinal data were analyzed by a two-stage regression model and analysis of variance for repeated measures (MANOVA). The former method, controlling for confounding factors and Monday morning CWV (which conveyed the pre-existing ability of the subjects), showed that, with respect to unexposed nurses, reaction times were significantly (p<0.020) higher only in workers with urinary N(2)O> or = 27 microg/l. Therefore, at MANOVA, all subjects were categorized in two classes (N(2)O urinary concentrations or = 27 microg/l), and CWV results were adjusted for the confounding variables and effects of stress and arousal, taken concurrently with CWV. CWV significantly (p<0.039) decreased over a working week (indicating a learning effect) in workers with urinary N(2)O<27 microg/l, while remained steady (indicating impairment of neurobehavioral performance) in those with urinary N(2)O> 27 microg/l.

In old subjects exposed to extreme high temperature during a heat wave, studies have consistently reported an excess of death from cardio- or cerebro-vascular disease. By contrast, dehydration, heat stroke, acute renal insufficiency, and respiratory disease were the main causes of hospital admission in the two studies carried out in elderly during short spells of hot weather. The excess of circulatory disease reported by mortality studies, but not by morbidity studies, could be explained by the hypothesis that deaths from circulatory disease occur rapidly in isolated people before they reach a hospital. Since the contrasting patterns of hospital admission and mortality during heat waves could also be due to chance (random variation over time and space in the spectrum of diseases induced by extreme heat), and bias (poor quality of diagnosis on death certificate and other artifacts), it should be confirmed by a concurrent study of mortality and morbidity. Many heat-related diseases may be preventable with adequate warning and an appropriate response to heat emergencies, but preventive efforts are complicated by the short time interval that may elapse between high temperatures and death. Therefore, prevention programs must be based around rapid identification of high-risk conditions and persons. The effectiveness of the intervention measures must be formally evaluated. If cardio- and cerebro-vascular diseases are rapidly fatal health outcomes with a short time interval between exposure to high temperature and death, deaths from circulatory disease might be an useful indicator in evaluating the effectiveness of a heat watch/warning system.

Previous studies have suggested that those in occupations exposed to endotoxin have a reduced rate of lung/respiratory cancer. An initial investigation found a significantly reduced risk of all sites malignant neoplasms in white male crop and livestock farmers, and black male and female crop farmers. This study provides data on lung/respiratory cancers in the same workers. Data were obtained from occupation and industry-coded US death certificates collected from 26 states for the period 1984-1993. Cause, sex, and race specific proportionate mortality ratios (PMRs) were calculated using a National Institute of Occupational Safety and Health computer program. A pooled relative risk (PRR) was obtained by summing up separately and then dividing the sex-race specific observed and expected cases, separately in crop and livestock farmers. Deaths from respiratory cancer were 12,482 and 2,290, and deaths from lung cancer were 12,091 and 2,201. In each sex and race group respiratory and lung cancer PMRs are generally lower than unity. Lung cancer PRR was 0.80 (0.78-0.81) in crop farmers and 0.70 (0.67-0.73) in livestock farmers, a significant difference (p < 0.0001). Comparison of our findings with those by Nieuwenhuijsen et al. [1999] reporting personal exposure measurements in groups of Californian farmers (endotoxin averaging 132.5 EU/m(3) during livestock farming against 19.9 EU/m(3) during field crop and fruit farming), suggests a decreasing lung cancer risk with increasing endotoxin exposure, and supports a possible dose-response relationship between the two.