BACKGROUND: In spring 2013, groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by perfluoroalkyl substances (PFAS) from a PFAS manufacturing plant active since the late 1960s. Residents were exposed to high concentrations of PFAS, particularly perfluorooctanoic acid (PFOA), through drinking water until autumn 2013. A publicly funded health surveillance program is under way to aid in the prevention, early diagnosis, and treatment of chronic disorders possibly associated with PFAS exposure. OBJECTIVES: The objectives of this paper are: a) to describe the organization of the health surveillance program, b) to report serum PFAS concentrations in adolescents and young adults, and c) to identify predictors of serum PFAS concentrations in the studied population. METHODS: The health surveillance program offered to residents of municipalities supplied by contaminated waterworks includes a structured interview, routine blood and urine tests, and measurement of 12 PFAS in serum by high-performance liquid chromatography-tandem mass spectrometry. We studied 18,345 participants born between 1978 and 2002, 14-39 years of age at recruitment. Multivariable linear regression was used to identify sociodemographic, lifestyle, dietary, and reproductive predictors of serum PFAS concentrations. RESULTS: The PFAS with the highest serum concentrations were PFOA [median 44:4 ng=mL, interquartile range (IQR) 19.3-84.9], perfluorohexanesulfonic acid (PFHxS) (median 3:9 ng=mL, IQR 1.9-7.4), and perfluorooctanesulfonic acid (PFOS) (median 3:9 ng=mL, IQR 2.6-5.8). The major predictors of serum levels were gender, municipality, duration of residence in the affected area, and number of deliveries. Overall, the regression models explained 37%, 23%, and 43% of the variance of PFOA, PFOS, and PFHxS, respectively. CONCLUSIONS: Serum PFOA concentrations were high relative to concentrations in populations with background residential exposures only. Interindividual variation of serum PFAS levels was partially explained by the considered predictors.

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Introduction COVID-19 case fatality rate in hospitalized patients varies across countries and studies. Reliable estimates, specific for age, sex, and comorbidities, are needed to monitor the epidemic, to compare the outcome in different settings, and to correctly design trials for COVID-19 interventions. The aim of this study was to provide population-based survival curves of hospitalized COVID-19 patients. Materials and Methods A cohort study was conducted in three areas of Northern Italy, heavily affected by SARS-CoV-2 infection (Lombardy and Veneto Regions, and Reggio Emilia province), using a loco-regional COVID-19 surveillance system, linked to hospital discharge databases. We included all patients testing positive for SARS-CoV-2 RNA by RT-PCR on nasopharyngeal/throat swab samples who were hospitalized from 21 February to 21 April 2020. Kaplan–Meier survival estimates were calculated at 14 and 30 days for death in any setting, stratifying by age, sex, and the Charlson Index. Results Overall, 42,926 hospitalized COVID-19 patients were identified. Patients’ median age was 69 years (IQR: 57–79), 62.6% were males, and 6.0% had a Charlson Index ≥3. Survival curves showed that 22.0% (95% CI 21.6–22.4) of patients died within 14 days and 27.6% (95% CI 27.2–28.1) within 30 days from hospitalization. Survival was higher in younger patients and in females. The negative impact of comorbidities on survival was more pronounced in younger age groups. Conclusion The high fatality rate observed in the study (28% at 30 days) suggests that studies should focus on death as primary endpoint during a follow-up of at least one month.

Background Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study comprised 16,224 individuals aged 20–39 years. Pregnant women (n = 327), or individuals with missing information on the selected covariates (n = 111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP ≥ 140 mmHg)/diastolic blood pressure (DBP ≥ 90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61–2.47), 1.60 mmHg (95%CI 0.92–2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR = 1.06 (1.01–1.11), PFOS OR = 1.13 (1.03–1.23), PFHxS OR = 1.08 (1.02–1.15), PFNA OR = 1.20 (1.02–1.40). Conclusions Our findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

Background: Residents of a large area in the Veneto Region (Northeastern Italy) were exposed to drinking water contaminated by perfluoroalkyl substances (PFAS) for decades. While exposure to PFAS has been consistently associated with elevated serum lipids, combined exposures to multiple PFASs have been poorly investigated. Utilising different statistical approaches, we examine the association between chemical mixtures and lipid parameters. Methods: Cross-sectional data from the regional health surveillance program (34,633 individuals aged 20–64 years) were used to examine the combined effects of PFAS mixture (Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS)) on total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Weighted Quantile Sum (WQS) regression, Quantile-based G-computation (Q-Gcomp) and Bayesian Kernel Machine Regression (BKMR) were used based on their ability to handle highly correlated chemicals. Results: We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 4.09, 95% CI: 3.47–4.71), HDL-C (β: 1.13, 95% CI: 0.92–1.33) and LDL-C (β: 3.14, 95% CI: 2.65–3.63). Q-Gcomp estimated that a quartile increase in the PFAS mixture was associated with increased TC (ψ: 4.04, 95% CI 3.5–4.58), HDL-C (ψ: 1.07, 95% CI 20.87–1.27) and LDL-C (ψ: 2.71, 95% CI 2.23–3.19). In the BKMR analysis, the effect of PFAS mixture on serum lipids increased significantly when their concentrations were at their 75th percentiles or above, compared to those at their 50th percentile. All methods revealed a major contribution of PFOS and PFNA, although the main exposure was due to PFOA. We found suggestive evidence that associations varied when stratified by gender. Conclusions: The PFAS mixture was positively associated with lipid parameters, regardless of the applied method. Very similar results obtained from the three methods may be attributed to the linear positive association with the outcomes and no interaction between each PFAS.