Asbestos exposure and asbestosis mortality in Italian cement-asbestos cohorts: Dose-response relationship and the role of competing death causes.

OBJECTIVES: In Italy, asbestos was used intensively until its ban in 1992, which was extended for asbestos cement factories until 1994. The aim of this study was to evaluate the dose-response between asbestos exposure and asbestosis mortality across a pool of Italian occupational cohorts, taking into account the presence of competing risks. METHODS: Cohorts were followed for vital status and the cause of death was ascertained by a linkage with mortality registers. Cause-specific (CS) Cox-regression models were used to evaluate the dose-exposure relationship between asbestosis mortality and the time-dependent cumulative exposure index (CEI) to asbestos. Fine and Gray regression models were computed to assess the effect of competing risks of death. RESULTS: The cohort included 12,963 asbestos cement workers. During the follow-up period (1960-2012), of a total of 6961 deaths, we observed 416 deaths attributed to asbestosis, 879 to lung cancer, 400 to primary pleural cancer, 135 to peritoneal cancer, and 1825 to diseases of the circulatory system. The CS model showed a strong association between CEI and asbestosis mortality. Dose-response models estimated an increasing trend in mortality even below a CEI of 25 ff/mL-years. Lung cancer and circulatory diseases were the main competing causes of death. CONCLUSIONS: Asbestos exposure among Italian asbestos-cement workers has led to a very high number of deaths from asbestosis and asbestos-related diseases. The increasing risk trend associated with excess deaths, even at low exposure levels, suggests that the proposed limit values would not have been adequate to prevent disability and mortality from asbestosis.

Cause specific mortality in an Italian pool of asbestos workers cohorts.

BACKGROUND: Asbestos is a known human carcinogen and is causally associated with malignant mesothelioma, lung, larynx and ovarian cancers. METHODS: Cancer risk was studied among a pool of formerly asbestos-exposed workers in Italy. Fifty-two Italian asbestos cohorts (asbestos-cement, rolling-stock, shipbuilding, and other) were pooled and their mortality follow-up was updated to 2018. Standardized mortality ratios (SMRs) were computed for major causes of death considering duration of exposure and time since first exposure (TSFE), using reference rates by region, age and calendar period. RESULTS: The study included 63,502 subjects (57,156 men and 6346 women): 40% who were alive, 58% who died (cause known for 92%), and 2% lost to follow-up. Mortality was increased for all causes (SMR: men = 1.04, 95% confidence interval [CI] 1.03-1.05; women = 1.15, 95% CI 1.11-1.18), all malignancies (SMR: men = 1.21, 95% CI 1.18-1.23; women = 1.29, 95% CI 1.22-1.37), pleural and peritoneal malignancies (men: SMR = 10.46, 95% CI 9.86-11.09 and 4.29, 95% CI 3.66-5.00; women: SMR = 27.13, 95% CI 23.29-31.42 and 7.51, 95% CI 5.52-9.98), lung (SMR: men = 1.28, 95% CI 1.24-1.32; women = 1.26, 95% CI 1.02-1.53), and ovarian cancer (SMR = 1.42, 95% CI 1.08-1.84). Pleural cancer mortality increased during the first 40 years of TSFE (latency), reaching a plateau thereafter. CONCLUSIONS: Analyses by time-dependent variables showed that the risk for pleural neoplasms increased with latency and no longer increases at long TSFE, consistent with with asbestos clearance from the lungs. Peritoneal neoplasm risk increased over all observation time.

The perinatal health secondary to pandemic: association between women's delivery concerns and infant's behavioral problems.

BACKGROUND: COVID-19 pandemic characterised a unique and vulnerable social, emotional, and health environment for pregnancy, with potential long-lasting risks to maternal and child health outcomes. In women who were pregnant at the peak of COVID-19 pandemic, we investigated the association between pandemic-related concerns about pregnancy and delivery and both the parent's (i.e. maternal parenting stress) and the infant's (i.e. emotional-behavioral problems) outcomes 12 months after birth. METHODS: A sample of 352 Italian pregnant women completed a web-based survey from 8 April to 4 May 2020 and a follow-up at 12 months after delivery. Maternal assessment in pregnancy covered prenatal measures for: pandemic-related concerns about pregnancy and childbirth, COVID-19 stressful events exposure, pandemic psychological stress, and mental-health symptoms (i.e. depression, anxiety). The 12 months' assessment covered post-partum measures of social support, parenting stress and maternal reports of infants' behavioral problems. RESULTS: The results of the Quasi-Poisson regression models on the association between COVID-19 related influencing factors and parenting stress and infant's behavioral problems showed that the presence of higher pandemic-related concerns about pregnancy and childbirth scores was associated with greater total and internalising behavioral problems but not with parenting stress levels. CONCLUSION: Perinatal mother-infant health has been sensitively threatened by pandemic consequences with maternal concerns about childbirth in pregnancy being associated with 12 months' children's behavioral outcomes. There is a need to invest in psychological support for perinatal women throughout the transition to parenthood to protect risk conditions before they get chronic or severe and influence offspring development.

Cholangiocarcinoma and Occupational Exposure to Asbestos: Insights From the Italian Pooled Cohort Study.

BACKGROUND: Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS: The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS: 47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION: Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

Rate advancement measurement for lung cancer and pleural mesothelioma in asbestos-exposed workers.

INTRODUCTION: Exposure to asbestos increases the risk of lung cancer and mesothelioma. Few studies quantified the premature occurrence of these diseases in asbestos-exposed workers. Focus on premature disease onset (rate advancement or acceleration) can be useful in risk communication and for the evaluation of exposure impact. We estimated rate advancement for total mortality, lung cancer and pleural mesothelioma deaths, by classes of cumulative asbestos exposure in a pooled cohort of asbestos cement (AC) workers in Italy. METHOD: The cohort study included 12 578 workers from 21 cohorts, with 6626 deaths in total, 858 deaths from lung cancer and 394 from pleural malignant neoplasm (MN). Rate advancement was estimated by fitting a competitive mortality Weibull model to the hazard of death over time since first exposure (TSFE). RESULT: Acceleration time (AT) was estimated at different TSFE values. The highest level of cumulative exposure compared with the lowest, for pleural MN AT was 16.9 (95% CI 14.9 to 19.2) and 33.8 (95% CI 29.8 to 38.4) years at TSFE of 20 and 40 years, respectively. For lung cancer, it was 13.3 (95% CI 12.0 to 14.7) and 26.6 (95% CI 23.9 to 29.4) years, respectively. As for total mortality, AT was 3.35 (95% CI 2.98 to 3.71) years at 20 years TSFE, and 6.70 (95% CI 5.95 to 7.41) at 40 years TSFE. CONCLUSION: The current study observed marked rate advancement after asbestos exposure for lung cancer and pleural mesothelioma, as well as for total mortality.

Behavioral outcomes and exposure to perfluoroalkyl substances among children aged 6-13 years: The TEDDY child study.

BACKGROUND: Although some studies report that exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and early life stages of a child could adversely impact neurodevelopment, literature shows mixed evidence. OBJECTIVES: Using an ecological framework for human development, we assessed the association of risk factors for environmental PFAS exposure and childhood PFAS concentrations with behavioral difficulties among school-age children exposed to PFAS from birth, while also controlling for the important influence of the parenting and familial environment. METHODS: The study participants included 331 school-age children (6-13 years) born in a PFAS-contaminated area in the Veneto Region (Italy). We study the associations between environmental risk factors of maternal PFAS exposure (residential time, consumption of tap water, residence in Red zone A or B), and breastfeeding duration with parent assessments of children's behavioral problems (using the Strengths and Difficulties Questionnaire [SDQ]), adjusting for socio-demographic, parenting and familial variables. The direct relationships between serum blood PFAS concentrations and SDQ scores was evaluated in a subset of children (n = 79), both with single PFAS and weighted quantile sum (WQS) regressions. RESULTS: Poisson regression models reported positive associations between high consumption of tap water and externalizing SDQ scores (Incidence Rate Ratio [IRR]: 1.18; 95% confidence interval [CI]: 1.04-1.32) and total difficulty scores (IRR: 1.14; 95% CI: 1.02-1.26). Childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with higher internalizing SDQ scores (4th vs. 1st quartile, PFOS IRR: 1.54, 95% CI: 1.06-2.25), externalizing scores (4th vs. 1st quartile, PFHxS IRR: 1.59, 95% CI: 1.09-2.32), and total difficulty scores (4th vs. 1st quartile, PFOS IRR: 1.37, 95% CI: 1.05-1.71; PFHxS IRR: 1.54, 95% CI: 1.09-1.90). The WQS regressions confirmed the associations reported by single-PFAS analyses. CONCLUSIONS: We observed cross-sectional associations of tap water consumption and childhood PFOS, and PFHxS concentrations with greater behavioral difficulties.

To vaccinate or not to vaccinate? The interplay between pro- and against- vaccination reasons.

BACKGROUND: By mid 2023, European countries reached 75% of vaccine coverage for COVID-19 and although vaccination rates are quite high, many people are still hesitant. A plethora of studies have investigated factors associated with COVID-19 vaccine hesitancy, however, insufficient attention has been paid to the reasons why people get vaccinated against COVID-19. Our work aims to investigate the role of reasons in the decision to get vaccinated against COVID-19 in a representative sample of 1,689 adult Italians (March-April 2021) balanced in terms of age, gender, educational level and area of residence. METHODS: Through an online questionnaire, we asked participants to freely report up to three reasons for and against COVID-19 vaccination, and the weight each had in the decision to get vaccinated. We first investigated the role of emotional competence and COVID-19 risk perception in the generation of both reasons using regression models. Next, we studied the role that the different reasons had in the vaccination decision, considering both the intention to vaccinate (using a beta regression model) and the decision made by the participants who already had the opportunity to get vaccinated (using a logistic regression model). Finally, two different classification tree analyses were carried out to characterize profiles with a low or high willingness to get vaccinated or with a low or high probability to accept/book the vaccine. RESULTS: High emotional competence positively influences the generation of both reasons (ORs > 1.5), whereas high risk perception increases the generation of positive reasons (ORs > 1.4) while decreasing reasons against vaccination (OR = 0.64). As pro-reasons increase, vaccination acceptance increases, while the opposite happens as against-reasons increase (all p < 0.001). One strong reason in favor of vaccines is enough to unbalance the decision toward acceptance of vaccination, even when reasons against it are also present (p < 0.001). Protection and absence of distrust are the reasons that mostly drive willingness to be vaccinated and acceptance of an offered vaccine. CONCLUSIONS: Knowing the reasons that drive people's decision about such an important choice can suggest new communication insights to reduce possible negative reactions toward vaccination and people's hesitancy. Results are discussed considering results of other national and international studies.

An SEIR Model with Time-Varying Coefficients for Analyzing the SARS-CoV-2 Epidemic.

In this study, we propose a time-dependent susceptible-exposed-infected-recovered (SEIR) model for the analysis of the SARS-CoV-2 epidemic outbreak in three different countries, the United States, Italy, and Iceland using public data inherent the numbers of the epidemic wave. Since several types and grades of actions were adopted by the governments, including travel restrictions, social distancing, or limitation of movement, we want to investigate how these measures can affect the epidemic curve of the infectious population. The parameters of interest for the SEIR model were estimated employing a composite likelihood approach. Moreover, standard errors have been corrected for temporal dependence. The adoption of restrictive measures results in flatten epidemic curves, and the future evolution indicated a decrease in the number of cases.

First steps into the pupillometry multiverse of developmental science.

Pupillometry has been widely implemented to investigate cognitive functioning since infancy. Like most psychophysiological and behavioral measures, it implies hierarchical levels of arbitrariness in preprocessing before statistical data analysis. By means of an illustrative example, we checked the robustness of the results of a familiarization procedure that compared the impact of audiovisual and visual stimuli in 12-month-olds. We adopted a multiverse approach to pupillometry data analysis to explore the role of (1) the preprocessing phase, that is, handling of extreme values, selection of the areas of interest, management of blinks, baseline correction, participant inclusion/exclusion and (2) the modeling structure, that is, the incorporation of smoothers, fixed and random effects structure, in guiding the parameter estimation. The multiverse of analyses shows how the preprocessing steps influenced the regression results, and when visual stimuli plausibly predicted an increase of resource allocation compared with audiovisual stimuli. Importantly, smoothing time in statistical models increased the plausibility of the results compared to those nested models that do not weigh the impact of time. Finally, we share theoretical and methodological tools to move the first steps into (rather than being afraid of) the inherent uncertainty of infant pupillometry.

Who is likely to vacillate in their COVID-19 vaccination decision? Free-riding intention and post-positive reluctance.

Despite the actual availability of COVID-19 vaccines to combat the pandemic, many people are still vacillating in their decision to vaccinate. In this study, we considered the effect of two relevant contextual issues on vaccination intention: the number of people infected with COVID-19 is increasing, and the pace of vaccination is gaining speed. Specifically, we hypothesized that having already contracted SARS-CoV-2 (post-positive reluctance) could lead people to underestimate the importance of vaccination. Moreover, as the number of vaccinated people increases, more hesitant people could fall into the free-riding intention category, benefitting from the immunity provided by others' vaccinations. Vaccine hesitancy becomes more critical as the vaccination campaign proceeds: at one point, it will be inevitable to deal with hesitant people. This study is part of a WHO Regional Office for Europe project and involved a representative sample of 5006 Italians interviewed in January-February 2021. In case of post-positive reluctance, both young age and female gender increase vaccine hesitancy, while a high level of education reduces free-riding intention. Considering post-positive reluctance and free riding, a protective effect on hesitancy is associated with negative affective states, adherence to protective behaviors, trust in health information sources, and resilience. In contrast, increased vaccine hesitancy is associated with a high level of conspiracy-mindedness and trust in media information sources. Recognizing and studying the post-positive reluctance and the phenomenon of free-riding people can help us to become more efficient in combatting the virus.

Perfluoroalkyl substance mixtures and cardio-metabolic outcomes in highly exposed male workers in the Veneto Region: A mixture-based approach.

BACKGROUND: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production. METHODS: We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders. RESULTS: PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (ß: 8.41, 95% IC: 0.78-16.0), LDL-C (ß: 8.02, 95% IC: 1-15.0) and SBP (ß: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP. CONCLUSIONS: The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting.

Insomnia in primary care: a survey conducted on Italian patients older than 50 years-results from the "Sonno e Salute" study.

Insomnia affects one-third of the adult population and is associated with multiple medical conditions. We conducted an observational epidemiological survey to assess (1) the prevalence of insomnia in an Italian group of patients aged over 50 years, presenting directly to the general physician (GP); (2) the association of insomnia with sleepiness and comorbidities; and (3) the pharmacological treatment. The study was carried out by GPs. Each GP was asked to enroll the first patient over 50 years old spontaneously presenting for any medical problems for 5 consecutive days. The Italian version of the Sleep Condition Indicator (SCI) was administered; daytime sleepiness was evaluated by a visual analogic scale (VAS). For every patient, GPs collected information regarding comorbidities and pharmacological treatment for insomnia and evaluated the severity of insomnia using the Clinical Global Impression Severity (CGI-S) scale. A total of 748 patients (mean age 65.12 ± 9.45 years) were enrolled by 149 GPs. Prevalence of insomnia was 55.3%. SCI, VAS, and CGI-S scores were highly correlated between each other (p < 0.0001). At general linear model analysis, the comorbidities more associated with the presence of insomnia were anxiety-depressive disorder (p < 0.001), other psychiatric disorders (p = 0.017), cardiovascular disorders (p = 0.006), and dementia (p = 0.027). A statistically significant correlation was found between SCI score and the use of benzodiazepines (p < 0.001), z-drugs (p = 0.012), antidepressants (p < 0.001), and melatonin-prolonged release (p < 0.001). Insomnia affects half of Italian primary care patients over 50 years and is frequently associated with different medical conditions, sleepiness, and use of multiple-often off-label-drugs.

Misspecified modeling of subsequent waves during COVID-19 outbreak: A change-point growth model.

In the analysis of cumulative counts of SARS-CoV-2 infections, such as deaths or cases, common parametric models based on log-logistic growth curves adapt well to describe a single wave at a time. Unfortunately, in Italy, as well as all over the globe, from February 2020 to March 2021 more than one wave has been observed. In this paper, we propose a method to fit more than one wave in the same model. In particular, we discuss an approach based on a change-point model in a pseudo-likelihood framework that takes into account some model misspecification issues, such as those concerning the assumption of Poisson marginals and those relating to overdispersion and autocorrelation. An application to data collected in Italy is discussed.

Perceived Stress and Life Events in Patients Affected by Schizophrenia and Schizoaffective and Bipolar Disorder: Is There a Role for Self-Reported Basic Symptoms?

INTRODUCTION: The stress-diathesis model of psychotic disorders describes, in vulnerable individuals, the role of psychosocial stress in the onset and exacerbation of psychotic symptoms. Another interesting approach to the study of vulnerability in the development of psychosis is represented by the basic symptoms concept. OBJECTIVE: The present study aims at proposing an integration between these two models and investigating possible associations between psychotic symptoms, basic symptoms, perceived stress, and life events in a sample of patients affected by schizophrenia (SZ), schizoaffective (SA), and bipolar disorder with and without psychotic symptoms. METHODS: 112 patients were recruited in two university hospitals. Severity of psychiatric symptoms (Positive and Negative Syndrome Scale, PANSS), basic symptoms (Frankfurt Complaint Questionnaire, FCQ), perceived stress (Stress-related Vulnerability Scale, SVS), and life events (Paykel's interview for recent life events) were assessed. RESULTS: Patients affected by bipolar disorder (both with and without psychotic symptoms) showed a higher number of independent life events (p < 0.01) and tended to report more frequently at least 1 life event in the previous 6 months (p < 0.01) than patients affected by SZ or SA disorder. No differences emerged between the study groups in perceived stress nor in measures of basic symptoms. In the whole sample, a logistic regression analysis showed that the SVS total score (p < 0.05) and PANSS total score (p < 0.001) were associated with the presence of psychotic symptoms. CONCLUSIONS: In the study sample, life events and basic symptoms did not play a major role in influencing psychotic symptoms, compared to the subjective perception of stress and the severity of psychopathology. Taken together, these results can be informative for rehabilitation therapies aimed at enhancing resilience and coping strategies in this vulnerable group of patients.

Overall mortality and causes of death in newly admitted nursing home residents.

BACKGROUND: In spite of a rapidly ageing population, there is a lack of population-based data on mortality among nursing home residents in Southern Europe. AIMS: To assess mortality rates, their determinants, and causes of death in newly admitted nursing home residents in the Veneto region (northeastern Italy). METHODS: 19,392 subjects aged ≥ 65 years admitted to regional nursing homes during 2015-2017 were recruited in a cohort mortality study based on linked health records. Risk factors for mortality were investigated by Cox regression. The distribution of causes of death was retrieved from death certificates. RESULTS: Mortality peaked in the first 4 months after admission; thereafter the monthly mortality rate fluctuated around 3% in males and 2% in females. Overall mortality was 23% at 6 months and 34% at 1 year. In addition to age, gender, and dependency, main risk factors for mortality were recent hospitalization (first 4 months after entry into the facility), and the burden of comorbidities (subsequent follow-up period). The most represented causes of mortality were similar in the first and in the subsequent period after admission: cardio-cerebrovascular diseases, neurodegenerative diseases, respiratory diseases, and infections. DISCUSSION: The first months after admission represent a period at high risk of mortality, especially for patients with a recent hospitalization. Causes reported in death certificates suggest mainly an acute deterioration of pre-existing chronic conditions. CONCLUSION: Health care plans should be personalized for newly admitted vulnerable patients. Palliative care needs should be recognized and addressed for high-risk non-cancer patients.

Quetiapine Abuse Fourteen Years Later: Where Are We Now? A Systematic Review.

Background: Quetiapine, an atypical antipsychotic endowed with weak dopamine antagonist, potent 5-HT2A-blocking, partial 5-HT1A-agonist, anti-H1 histamine, adrenolytic, and sigma1 receptor agonist activities, since an original 2004 report is increasingly misused. Although some of its pharmacodynamics might explain some motives for voluptuary use, most of its actions are directed at setting-off those motives. Hence, it is possible that its popularity in special populations is due to the fact that the unpleasant or unwanted effects of addiction substances are somehow soothed by quetiapine. Currently, quetiapine is tested in substance use disorders, showing some promise, but it is likely to be misused in certain contexts. Objectives: To review the evidence for the use of quetiapine as addiction substance and investigate the characteristics of populations involved in such addiction. Methods: A systematic review of literature on various databases retrieved on September 7, 2018 87 records to comment. Results. We reviewed the evidence for quetiapine's addictive potential in the light of its pharmacodynamics properties and presented two cases of recreational quetiapine use, by a 35-year old male patient with past addictive behavior and by a 50-year-old woman with major depressive disorder and conversion disorder. We found quetiapine to be abused mainly by addict populations and people with law involvement. Conclusions/Importance: There is no reason to include quetiapine among regulated substances, but monitoring of its use in selected populations is warranted. Psychiatrists and physicians working in the penitentiary system should be aware of the addictive potential of quetiapine and adopt measures restricting its use.

Tryptophan and Kynurenine Metabolites: Are They Related to Depression?

BACKGROUND: Some previous studies found decreased concentrations of L-tryptophan (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of subjects with major depressive disorder (MDD), sometimes in association with suicidal behavior. Such changes might indicate a shift of TRY away from serotonin production, possibly via the effects of inflammatory peptides which activate indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and require replication. METHODS: We used sensitive liquid-chromatography mass spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n = 37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous suicide attempts, to 78 healthy, ambulatory controls of similar age and sex (total n = 127). FINDINGS: Contrary to expectation, TRY plasma concentrations were higher, KYN plasma concentrations were lower, and their ratio much higher in depressed subjects, with no relationship to suicidal history. Concentrations of 5-HIAA and the kynurenine metabolites did not differ between depressed and healthy subjects. CONCLUSIONS: These findings are opposite to expectations and not consistent with a hypothesized increased conversion from TRY to KYN in depressed subjects. In addition, we found no evidence of altered production of serotonin as 5-HIAA concentration was unchanged. None of the observed changes was associated with a history of suicide attempt.

Role of asbestos clearance in explaining long-term risk of pleural and peritoneal cancer: a pooled analysis of cohort studies.

OBJECTIVES: Models based on the multistage theory of cancer predict that rates of malignant mesothelioma continuously increase with time since first exposure (TSFE) to asbestos, even after the end of external exposure. However, recent epidemiological studies suggest that mesothelioma rates level off many years after first exposure to asbestos. A gradual clearance of asbestos from the lungs has been suggested as a possible explanation for this phenomenon. We analysed long-term trends of pleural and peritoneal cancer mortality in subjects exposed to asbestos to evaluate whether such trends were consistent with the clearance hypothesis. METHODS: We used data from a pool of 43 Italian asbestos cohorts (51 801 subjects). The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalised to include a term representing elimination of fibres over time. RESULTS: Rates of pleural cancer increased until 40 years of TSFE, but remained stable thereafter. On the other hand, we observed a monotonic increase of peritoneal cancer with TSFE. The model taking into account asbestos clearance fitted the data better than the traditional one for pleural (p=0.004) but not for peritoneal (p=0.09) cancer. CONCLUSIONS: Rates of pleural cancer do not increase indefinitely after the exposure to asbestos, but eventually reach a plateau. This trend is well described by a model accounting for a gradual elimination of the asbestos fibres. These results are relevant for the prediction of future rates of mesothelioma and in asbestos litigations.

A mortality study on male subjects exposed to polyfluoroalkyl acids with high internal dose of perfluorooctanoic acid.

OBJECTIVES: The aim of the present study was to examine the association between exposure to polyfluoroalkyl substances (PFASs) and mortality (1970-2018) in a cohort of 462 male employees who had worked at least six months before 2009 for a factory (14,658 person-years; 107 deaths, average follow-up time 31.7 years), which had been producing perfluorooctanoic acid (PFOA), perfluorooctanesulfonyl fluoride (PFOS) and other chemicals since 1968. METHODS: Employees were classified as follows: 1) by probability of exposure to PFASs; 2) by tertiles of PFOA serum concentrations. In a fraction (n = 120) of workers measurements of internal PFOA serum concentration were used to predict a cumulative serum PFOA concentration of each cohort member. Mortality rates were compared to that of the regional population using the standardized mortality ratio (SMR), and to that of the workers of a nearby metalworking factory in terms of risk ratio (RR), across categories of probability of PFASs exposure and tertiles of cumulative serum PFOA concentrations. RESULTS: Internal PFOA serum concentration among 120 workers in the 2000-2013 period was very high (Geometric Mean: 4048 ng/mL; range 19-91,900 ng/mL). The mortality of the chemical cohort was increased for liver cancer (SMR: 2.32; CI: 1.11-4.87), malignant neoplasm of lymphatic and haematopoietic tissue (SMR: 2.26; CI: 1.08-4.73). In the comparison with the cohort of workers from the metalworking factory, the RRs for mortality of the cohort were increased for overall mortality (RR: 1.42; CI: 1.12-1.79), diabetes (RR: 5.95; CI: 1.08-32.8), liver cancer (RR: 6.69; CI: 1.71-26.2) and liver cirrhosis (RR: 3.87; CI: 1.18-12.7). Mortality for these causes increased in association with probability of PFASs exposure and with tertiles of cumulative PFOA serum concentrations. CONCLUSION: The present is a small observational study with limited control over confounding factors. The cohort showed increased mortality for all causes and subjects in the highest cumulative internal dose of PFOA had a statistically significant increase for mortality of liver cancer, liver cirrhosis, diabetes, malignant neoplasms of lymphatic and haematopoietic tissue in both comparisons. Toxicological studies on PFOA and PFOS provide support for causality for the observed association with the risk for liver cirrhosis and liver cancer.

Cumulative asbestos exposure and mortality from asbestos related diseases in a pooled analysis of 21 asbestos cement cohorts in Italy.

BACKGROUND: Despite the available information on cancer risk, asbestos is used in large areas in the world, mostly in the production of asbestos cement. Moreover, questions are raised regarding the shape of the dose response relation, the relation with time since exposure and the association with neoplasms in various organs. We conducted a study on the relationship between cumulative asbestos exposure and mortality from asbestos related diseases in a large Italian pool of 21 cohorts of asbestos-cement workers with protracted exposure to both chrysotile and amphibole asbestos. METHODS: The cohort included 13,076 workers, 81.9% men and 18.1% women, working in 21 Italian asbestos-cement factories, with over 40 years of observation. Exposure was estimated by plant and period, and weighted for the type of asbestos used. Data were analysed with consideration of cause of death, cumulative exposure and time since first exposure (TSFE), and by gender. SMRs were computed using reference rates by region, gender and calendar time. Poisson regression models including cubic splines were used to analyse the effect of cumulative exposure to asbestos and TSFE on mortality for asbestos-related diseases. 95% Confidence Intervals (CI) were computed according to the Poisson distribution. RESULTS: Mortality was significantly increased for 'All Causes' and 'All Malignant Neoplasm (MN)', in both genders. Considering asbestos related diseases (ARDs), statistically significant excesses were observed for MN of peritoneum (SMR: men 14.19; women 15.14), pleura (SMR: 22.35 and 48.10), lung (SMR: 1.67 and 1.67), ovary (in the highest exposure class SMR 2.45), and asbestosis (SMR: 507 and 1023). Mortality for ARDs, in particular pleural and peritoneal malignancies, lung cancer, ovarian cancer and asbestosis increased monotonically with cumulative exposure. Pleural MN mortality increased progressively in the first 40 years of TSFE, then reached a plateau, while peritoneal MN showed a continuous increase. The trend of lung cancer SMRs also showed a flattening after 40 years of TSFE. Attributable proportions for pleural, peritoneal, and lung MN were respectively 96, 93 and 40%. CONCLUSIONS: Mortality for ARDs was associated with cumulative exposure to asbestos. Risk of death from pleural MN did not increase indefinitely with TSFE but eventually reached a plateau, consistently with reports from other recent studies.