Association of perfluoroalkyl substances (PFAS) with liver function biomarkers in the highly exposed population of the Veneto Region.

INTRODUCTION: Epidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association. METHODS: The study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation. RESULTS: One ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects. CONCLUSION: Our findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators.

Decreases in serum PFAS are associated with decreases in serum lipids: A longitudinal study on a highly exposed population.

INTRODUCTION: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous and highly persistent man-made chemicals. Previous cross-sectional studies have consistently linked PFAS exposure to alterations in lipid profiles. However, longitudinal investigations are preferred to mitigate issues related to reverse causation and confounding. Hence, we aimed to investigate the association between changes in serum PFAS and changes in serum lipids, while shedding light on potential modifiers of the examined relationships. METHODS: We used data from a health surveillance program offered to residents of a vast area of the Veneto Region (North-Eastern Italy), who had been exposed to PFAS via contaminated drinking water until 2013. We included subjects aged ≥20 years who provided two blood samples over an average 4-year interval (n = 8101). We examined the relationships between changes in PFOA, PFOS and PFHxS and changes in total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and low-density lipoprotein cholesterol (LDL-C). Linear models were fitted for change in the natural logarithm (ln) of each lipid in relation to the change in the ln of PFAS. From the estimated regression coefficients, we calculated the predicted percentage change in the response for a ln-decrease in PFAS serum concentrations. RESULTS: Overall concentrations of PFOA, PFOS, PFHxS fell by 62.1 %, 24.4 % and 35.4 % from baseline, while small increases in lipids were observed. Declines in PFAS concentrations were associated with decreases in all lipids. For a ln-decrease in PFOA HDL-C decreased by 1.99 % (95 % CI: 1.28, 2.70), TC by 1.49 % (95 % CI: 0.88, 2.10), and LDL-C by 1.40 % (95 % CI: 0.45, 2.37). CONCLUSIONS: We found a positive association between changes in PFAS concentrations and changes in cholesterol levels, observing the most marked contrasts across sexes and age groups. Our findings support the reversibility of the associations identified in cross-sectional analyses, emphasizing the importance of water treatment measures in mitigating adverse health effects.

Safety profile assessment of HPV4 and HPV9 vaccines through the passive surveillance system of the Veneto Region (Italy) between 2008 and 2022: A 15-year retrospective observational study.

In Veneto Region, HPV vaccine has been actively offered to 12 year-old females since 2008, and to 12 year-old males since 2015. The study aims to analyze the safety profile of HPV4v and HPV9v vaccines and perform a case-by-case review of conditions of interest. Spontaneous reports related to HPV uploaded to the database of the Regional Pharmacovigilance Center between 2008-2022 were included. HPV vaccine doses administered until April 2022 in the Veneto Region were considered to calculate the reporting rate (RR). Potential "safety concerns" examined as conditions of interest were included through Standardized MedDRA or preferred terms searching queries. The level of diagnostic certainty was evaluated as per the Brighton Collaboration case definition criteria. A total of 637 reports and 1316 Adverse Events Following Immunizations (AEFI) were retrieved: 469 for HPV4v (73.6 %) and 168 for HPV9v (26.4 %). Serious reports were 71 (11.1 %): 49 (10.4 %) for HPV4v and 22 (13.1 %) for HPV9v. The RR for serious events between 2008-2022 was 6.9/100,000 administered doses, with no differences by vaccine type. Females and adults showed higher overall RR compared to males and to children and adolescents (p < 0.001), this result was confirmed by stratifying analysis by vaccine type. One case of Guillain Barré syndrome, anaphylactic shock, thrombocytopenia, Henoch Schoenlein purpura and four generalized seizures were reviewed. Vaccinovigilance data from the Veneto Region reaffirm a good safety profile for HPV vaccination and found no vaccine-related unexpected events. Such a detailed analysis may assist healthcare providers to advocate properly for HPV vaccination.

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region.

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

Determinants of PFOA Serum Half-Life after End of Exposure: A Longitudinal Study on Highly Exposed Subjects in the Veneto Region.

BACKGROUND: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous, and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were overexposed to PFAS through drinking water until 2013, mainly to perfluorooctanoic acid (PFOA). OBJECTIVES: The aim of the present study was to estimate the rates of decline in serum PFOA and their corresponding serum half-lives, while characterizing their determinants. METHODS: We investigated 5,860 subjects more than 14 years of age who enrolled in the second surveillance round of the regional health surveillance program. Two blood samples were collected between 2017 and 2022 (average time between measurements: 4 years). Serum PFOA excretion rates and half-lives were estimated based on linear mixed effect models, modeling subject-specific serum PFOA concentrations over time and correcting for background concentrations. For modeling determinants of half-life [age, sex, body mass index (BMI), smoking-habit, alcohol consumption, and estimated glomerular filtration rate (eGFR)], we added interaction terms between each covariate and the elapsed time between measurements. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) apparent half-lives were also estimated. A separate analysis was conducted in children (n=480). All analyses were stratified by sex. RESULTS: Median initial serum concentrations of PFOA was 49 ng/mL (range: 0.5-1,090), with a median reduction of 62.45%. The mean estimated PFOA half-life was 2.36 years [95% confidence interval (CI): 2.33, 2.40], shorter in women (2.04; 95% CI: 2.00, 2.08) compared to men (2.83; 95% CI: 2.78, 2.89). Half-lives varied when stratified by some contributing factors, with faster excretion rates in nonsmokers and nonalcohol drinkers (especially in males). CONCLUSIONS: This study, to our knowledge the largest on PFOA half-life, provides precise estimates in young adults whose exposure via drinking water has largely ceased. For other PFAS, longer half-lives than reported in other studies can be explained by some ongoing exposure to PFAS via other routes. https://doi.org/10.1289/EHP13152.

COVID-19 Contact Tracing Strategies During the First Wave of the Pandemic: Systematic Review of Published Studies.

BACKGROUND: Contact tracing (CT) represented one of the core activities for the prevention and control of COVID-19 in the early phase of the pandemic. Several guidance documents were developed by international public health agencies and national authorities on the organization of COVID-19 CT activities. While most research on CT focused on the use digital tools or relied on modelling techniques to estimate the efficacy of interventions, poor evidence is available on the real-world implementation of CT strategies and on the organizational models adopted during the initial phase of the emergency to set up CT activities. OBJECTIVE: We aimed to provide a comprehensive picture of the organizational aspects of CT activities during the first wave of the pandemic through the systematic identification and description of CT strategies used in different settings during the period from March to June 2020. METHODS: A systematic review of published studies describing organizational models of COVID-19 CT strategies developed in real-world settings was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. PubMed, Embase, and Cochrane Library were searched. Studies not providing a description of the organizational aspects of CT strategies and studies reporting or modelling theoretical strategies or focusing on the description of digital technologies' properties were excluded. Quality of reporting was assessed by using the Template for Intervention Description and Replication Checklist for Population Health and Policy. We developed a narrative synthesis, using a conceptual framework to map the extracted studies broken down by target population. RESULTS: We retrieved a total of 1638 studies, of which 17 were included in the narrative synthesis; 7 studies targeted the general population and 10 studies described CT activities carried out in specific population subgroups. Our review identified some common elements across studies used to develop CT activities, including decentralization of CT activities, involvement of trained nonpublic health resources (eg, university students or civil servants), use of informatics tools for CT management, interagency collaboration, and community engagement. CT strategies implemented in the workplace envisaged a strong collaboration with occupational health services. Outreach activities were shown to increase CT efficiency in susceptible groups, such as people experiencing homelessness. Data on the effectiveness of CT strategies are scarce, with only few studies reporting on key performance indicators. CONCLUSIONS: Despite the lack of systematically collected data on CT effectiveness, our findings can provide some indication for the future planning and development of CT strategies for infectious disease control, mainly in terms of coordination mechanisms and the use of human and technical resources needed for the rapid development of CT activities. Further research on the organizational models of CT strategies during the COVID-19 pandemic would be required to contribute to a more robust evidence-making process.

Improving the Quality of Healthcare Provision Regarding HPV Immunization for Women with CIN2+ Lesions: The Experience of the Veneto Region in Italy.

HPV is the most common cause of sexually-transmitted infections the world over. The aim of this study was to assess the impact of a healthcare quality improvement strategy designed to increase the rate of vaccination against HPV in women diagnosed with cervical lesions graded as CIN2 or higher (CIN2+) during routine screening. The Veneto Regional Health Service developed a 22-item questionnaire to measure the gap between ideal procedure and real practice regarding the offer of vaccination against HPV for women undergoing routine cervical screening. The questionnaire was administered to nine expert doctors, one at each of the region's Local Health Units (LHUs). An additional specific assessment concerned the quality of the related web pages available on the LHU websites. Strategies to close the gap between ideal procedure and real practice were decided collegially, and a checklist to support good practices was developed and shared with operators at the LHUs. Changes in practice were measured using data relating to women diagnosed with CIN2+ lesions extracted from the regional oncological screening database before and after the publication of a Regional Procedure on the topic. The LHUs differed considerably in how they managed each step, in terms of training for healthcare personnel, organization and assessment of the pathway from cervical screening to HPV vaccination, and in dedicated website communication. After implementing the quality improvement strategy, the proportion of women given a first dose of HPV vaccine within 3 months of being diagnosed with CIN2+ lesions at 1st-level screening rose to 50% (compared with 30.85% beforehand), and the median time elapsing between a diagnosis of CIN2+ lesion and a first dose of HPV vaccine dropped from 158 to 90 days. These findings underscore the importance of providing training to promote vaccination for general practitioners and other clinicians. The study also confirms the need for more efforts in communication to ensure that any citizen has the opportunity to access preventive healthcare.

COVID-19 Vaccine Effectiveness against Omicron Variant among Underage Subjects: The Veneto Region's Experience.

Even if most of the complications due to COVID-19 are observed in the elderly, in Italy the impact of COVID-19 among young people has not been negligible. Furthermore, their contribution to SARS-CoV-2 circulation is still unclear. These reasons have driven policy makers to involve subjects aged 5 to 17 years in the COVID-19 vaccination campaign. However, the trade-off of vaccinating this age-group should be further investigated, especially in view of the rise of new immunologically evasive variants of concern (VOCs). We used regional databases to retrospectively estimate vaccine effectiveness over time of each approved vaccination schedule among children (5-11) and adolescents (12-17). Our findings suggest that COVID-19 vaccines were highly effective and their protection levels lasted longer during a period of Delta variant predominance, whereas they offered just mild to moderate levels of protection-apparently affected by a rapid waning effect-in a period of Omicron variant predominance. Considering these results, it is plausible to evaluate a reformulation of possible future COVID-19 vaccination campaigns among underage subjects. However, effectiveness against serious complications due to COVID-19, as well as indirect benefits of underage vaccinations, should first be addressed. Furthermore, vaccine effectiveness should be kept monitored, as new VOCs may arise, but also new adapted vaccines may start being administered.

Differences in Immunological Evasion of the Delta (B.1.617.2) and Omicron (B.1.1.529) SARS-CoV-2 Variants: A Retrospective Study on the Veneto Region's Population.

In December 2021-January 2022 the Veneto region in Italy faced an unprecedented wave of SARS-CoV-2 infections, even though both the vaccine coverage and the number of previously infected individuals keep increasing. In this study we address the protection against the SARS-CoV-2 infection offered by natural immunity and a three-dose regimen through a retrospective study based on Veneto's regional databases. In particular, we compared these protection levels during two distinct periods respectively representative of the Delta (B.1.617.2) and the Omicron (B.1.1.529) variants, in order to investigate and quantify the immunological evasion, especially of the Omicron. For each period we compared the incidence rate of infection among the population with various immunological protections against SARS-CoV-2 and performed a multivariable proportional hazard Cox binomial regression to assess the effectiveness afforded by both forms of active immunization. We found out that a previous SARS-CoV-2 infection (irrespective of its timing) offers 85% (83-87%) and 36% (33-39%) protection against being reinfected by Delta and Omicron, respectively. In addition, we estimated the third dose to be more effective in both periods and to have a minor proportional loss of effectiveness due to the rise of the Omicron variant, with an afforded effectiveness against SARS-CoV-2 Delta and Omicron infection of 97% (96-97%) and 47% (45-48%), respectively. Our findings suggest that viral variant factors may affect any form of active immunization but that receiving a booster vaccination cycle is more effective and less variable than natural immunity in terms of afforded protection against SARS-CoV-2 infections.

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.

Surveillance of Outbreaks of SARS-CoV-2 Infections at School in the Veneto Region: Methods and Results of the Public Health Response during the Second and Third Waves of the Pandemic between January and June 2021.

During the COVID-19 pandemic, many countries adopted various non-pharmacological interventions to contain the number of infections. The most often used policy was school closures. We describe the strategy adopted by the Veneto Regional Authority to contain transmission in school settings. This included a detailed school surveillance system, strict contact tracing, and maintaining school attendance with self-monitoring for symptoms whenever possible. All analyzed COVID-19 cases among children, adolescents (0-19 years old), and school staff were registered using a web-based application between 4 January 2021 and 13 June 2021. During the study period, 6272 episodes of infection in schools were identified; 87% were linked to a student index case and 13% to school staff; 69% generated no secondary cases; 24% generated one or two; and only 7% caused more than two. Our data may help to clarify the role of school closures, providing useful input for decisions in the months to come. Good practice in public health management needs tools that provide a real-time interpretation of phenomena like COVID-19 outbreaks. The proposed measures should be easy to adopt and accessible to policymakers.

Association of Influenza Vaccination and Prognosis in Patients Testing Positive to SARS-CoV-2 Swab Test: A Large-Scale Italian Multi-Database Cohort Study.

To investigate the association of the 2019-2020 influenza vaccine with prognosis of patients positive for SARS-CoV-2A, a large multi-database cohort study was conducted in four Italian regions (i.e., Lazio, Lombardy, Veneto, and Tuscany) and the Reggio Emilia province (Emilia-Romagna). More than 21 million adults were residing in the study area (42% of the population). We included 115,945 COVID-19 cases diagnosed during the first wave of the pandemic (February-May, 2020); 34.6% of these had been vaccinated against influenza. Three outcomes were considered: hospitalization, death, and intensive care unit (ICU) admission/death. The adjusted relative risk (RR) of being hospitalized in the vaccinated group when compared with the non-vaccinated group was 0.87 (95% CI: 0.86-0.88). This reduction in risk was not confirmed for death (RR = 1.04; 95% CI: 1.01-1.06), or for the combined outcome of ICU admission or death. In conclusion, our study, conducted on the vast majority of the population during the first wave of the pandemic in Italy, showed a 13% statistically significant reduction in the risk of hospitalization in some geographical areas and in the younger population. No impact of seasonal influenza vaccination on COVID-19 prognosis in terms of death and death or ICU admission was estimated.

Exposure to Perfluoroalkyl Substances and Mortality for COVID-19: A Spatial Ecological Analysis in the Veneto Region (Italy).

BACKGROUND: In the context of the COVID-19 pandemic, there is interest in assessing if per- and polyfluoroalkyl substances (PFAS) exposures are associated with any increased risk of COVID-19 or its severity, given the evidence of immunosuppression by some PFAS. The objective of this paper is to evaluate at the ecological level if a large area (Red Zone) of the Veneto Region, where residents were exposed for decades to drinking water contaminated by PFAS, showed higher mortality for COVID-19 than the rest of the region. METHODS: We fitted a Bayesian ecological regression model with spatially and not spatially structured random components on COVID-19 mortality at the municipality level (period between 21 February and 15 April 2020). The model included education score, background all-cause mortality (for the years 2015-2019), and an indicator for the Red Zone. The two random components are intended to adjust for potential hidden confounders. RESULTS: The COVID-19 crude mortality rate ratio for the Red Zone was 1.55 (90% Confidence Interval 1.25; 1.92). From the Bayesian ecological regression model adjusted for education level and baseline all-cause mortality, the rate ratio for the Red Zone was 1.60 (90% Credibility Interval 0.94; 2.51). CONCLUSION: In conclusion, we observed a higher mortality risk for COVID-19 in a population heavily exposed to PFAS, which was possibly explained by PFAS immunosuppression, bioaccumulation in lung tissue, or pre-existing disease being related to PFAS.

Emergence of Lyme borreliosis in the province of Verona, Northern Italy: Five-years of sentinel surveillance.

We investigated the epidemiology, clinical manifestations, laboratory data and antibiotic treatment of Lyme borreliosis in the province of Verona, Northern Italy, during the period 2015-2019. One hundred and 29 cases of Lyme borreliosis were diagnosed in a single hospital representing 27 % of all cases reported in the Veneto region in the same period. The mean annual incidence of Lyme borreliosis was 0.992/100,000 inhabitants. A peak incidence of 2/100,000 inhabitants was observed in 2018. Early localized Lyme borreliosis was the most common presentation (74 %), followed by early disseminated Lyme borreliosis (21 %). One possible early Lyme neuroborreliosis and two cranial neuropathies were diagnosed. IgM and/or IgG borrelia antibodies were positive in 90 % of the cases. This significant increase of Lyme borreliosis incidence in the province of Verona highlights the need to increase knowledge on its epidemiology and clinical manifestation among both the general population and clinicians to allow early diagnosis and treatment.

Epidemiology and public health response in early phase of COVID-19 pandemic, Veneto Region, Italy, 21 February to 2 April 2020.

BackgroundVeneto was one of the Italian regions hit hardest by the early phase of the coronavirus disease (COVID-19) pandemic.AimThis paper describes the public health response and epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the Veneto Region from 21 February to 2 April 2020.MethodsInformation on the public health response was collected from regional health authorities' official sources. Epidemiological data were extracted from a web-based regional surveillance system. The epidemic curve was represented by date of testing. Characteristics of hospitalised COVID-19 cases were described and compared to those never admitted to hospital. Age- and sex-stratified case-fatality ratios (CFRs) were calculated.ResultsKey elements of the regional public health response were thorough case-finding and contact tracing, home care for non-severe cases, creation of dedicated COVID-19 healthcare facilities and activation of sub-intensive care units for non-invasive ventilation. As at 2 April 2020, 91,345 individuals were tested for SARS-CoV-2 and 10,457 (11.4%) were positive. Testing and attack rates were 18.6 per 1,000 and 213.2 per 100,000 population, respectively. The epidemic peaked around 20 to 24 March, with case numbers declining thereafter. Hospitalised cases (n = 3,623; 34.6%) were older and more frequently male compared with never-hospitalised cases. The CFR was 5.6% overall, and was higher among males and people > 60 years of age.ConclusionIn the Veneto Region, the strict social distancing measures imposed by the Italian government were supported by thorough case finding and contact tracing, as well as well-defined roles for different levels of care.

Serum Levels of Perfluoroalkyl Substances (PFAS) in Adolescents and Young Adults Exposed to Contaminated Drinking Water in the Veneto Region, Italy: A Cross-Sectional Study Based on a Health Surveillance Program.

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. https://doi.org/10.1289/EHP5337.

Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy).

OBJECTIVES: To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). DESIGN: Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. RESULTS: We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). CONCLUSION: The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We present the main results of the 2011-2012 survey of the Italian screening programmes for colorectal cancer carried out by the National centre for screening monitoring (Osservatorio nazionale screening, ONS) on behalf of the Ministry of Health. By the end of 2012, 112 programmes were active, of which 11 had been activated during 2012 and 4 during 2011. The national theoretical extension increased from 66% of Italians aged 50-69 years residing in areas covered by organized screening programmes in 2010 to 73.7% in 2012. The majority of programmes employ the fecal immunochemical test (FIT), while some have adopted flexible sigmoidoscopy (FS) once in a lifetime and FIT for non-responders to FS. Overall, about 7,744,000 subjects were invited to undergo FIT, 53.1% of those to be invited within the two years. The adjusted attendance rate was 47.1%and 3,531,937 subjects were screened. Large differences in the attendance rate were observed among regions. Positivity rate of FIT programmes was 5.2% at first screening (range: 1.0-12.4%) and 4.0% at repeat screening (range: 3.4-6.4%). The average attendance rate to total colonoscopy (TC) was 81.2% and in two regions (Molise and Campania) it was lower than 70%. Completion rate for total colonoscopy (TC) was 91%. Among the 1,316,327 subjects attending screening for the first time, the detection rate (DR) per 1,000 screened subjects was 2.0 for invasive cancer and 9.1 ‰ for advanced adenomas (AA, adenomas with a diameter ≥1 cm, with villous/tubulo-villous type or high-grade dysplasia). As expected, the corresponding figures in the 2,215,610 subjects at repeat screening were lower (1.0‰ and 6.8‰ for invasive cancer and AA, respectively). Many programmes reported some difficulties in guaranteeing TC in the appropriate time frame to FIT+ subjects: in 15% of cases the waiting time was longer than two months. Ten programmes in 2011 and eight in 2012 employed FS as the screening test: 24,549 subjects were screened in the two years, with an attendance rate of 24.5%. Overall, 85.9% of FSs were classified as complete. Overall, TC referral rate was 9.8% and the DR per 1,000 screened subjects was 3.0 and 48.2 for invasive cancer and AA, respectively.

Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study.

BACKGROUND: The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. MATERIALS AND METHODS: We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4-14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). RESULTS: CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31-15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07-36.9), CIN3+ excision (OR 6.02, 95% CI 1.73-20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8-62.6; OR for other hrHPV types: 18.3, 95% CI 5.9-57.0). CONCLUSION: Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6-12 months of follow-up.

Quality of colonoscopy in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy).

OBJECTIVES: To assess variation in the main colonoscopy quality indicators in organised colorectal cancer (CRC) screening programmes based on faecal immunochemical test (FIT). DESIGN: Data from a case-series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected. The adenoma detection rate (ADR) and caecal intubation rate (CIR) were assessed for the whole population and the individual endoscopists. To explore variation in the quality indicators, multilevel analyses were performed according to patient/centre/endoscopist characteristics. RESULTS: We analysed 75 569 (mean age: 61.3 years; men: 57%) colonoscopies for positive FIT performed by 479 endoscopists in 79 centres. ADR ranged from 13.5% to 75% among endoscopists (mean: 44.8%). ADR was associated with gastroenterology specialty (OR: 0.87 for others, 95% CI 0.76 to 0.96) and, at the endoscopy centre level, with the routine use of sedation (OR: 0.80 if occasional (<33%); 95% CI 0.64 to 1.00) and availability of screening-dedicated sessions (OR: 1.35; 95% CI 1.11 to 1.66). CIR ranged between 58.8% and 100% (mean: 93.1%). Independent predictors of CIR at the endoscopist level were the yearly number of screening colonoscopies performed (OR: 1.51 for endoscopists with >600 colonoscopies; 95% CI 1.11 to 2.04) and, at the endoscopy centre level, screening-dedicated sessions (OR: 2.18; 95% CI 1.24 to 3.83) and higher rates of sedation (OR: 0.47 if occasional; 95% CI 0.24 to 0.92). CONCLUSIONS: The quality of colonoscopy was affected by patient-related, endoscopist-related and centre-related characteristics. Policies addressing organisational issues should improve the quality of colonoscopy in our programme and similar programmes.